Volume 1 Issue 2 www.ijrpb.com March-April 2013
Indian Journal of Research in Pharmacy and Biotechnology
ISSN: 2320-3471 (...
Volume 1 Issue 2 www.ijrpb.com March-April 2013
Indian Journal of Research in Pharmacy and Biotechnology
ISSN: 2320-3471 (...
ISSN: 2320 – 3471(Online)
Indian Journal of Research in Pharmacy and Biotechnology
Volume 1 Issue2 www.ijrpb.com March –Ap...
ISSN: 2320 – 3471(Online)
Indian Journal of Research in Pharmacy and Biotechnology
Volume 1 Issue2 www.ijrpb.com March –Ap...
ISSN: 2320 – 3471(Online)
Shashank Mathew et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) March...
ISSN: 2320 – 3471(Online)
Shashank Mathew et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) March...
ISSN: 2320 – 3471(Online)
Shashank Mathew et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) March...
ISSN: 2320 – 3471(Online)
V Lakshmi Prasanna et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Ma...
ISSN: 2320 – 3471(Online)
V Lakshmi Prasanna et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Ma...
ISSN: 2320 – 3471(Online)
V Lakshmi Prasanna et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Ma...
ISSN: 2320 – 3471(Online)
V Lakshmi Prasanna et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Ma...
ISSN: 2320 – 3471(Online)
V Lakshmi Prasanna et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Ma...
ISSN: 2320 – 3471(Online)
Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Marc...
ISSN: 2320 – 3471(Online)
Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Marc...
ISSN: 2320 – 3471(Online)
Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Marc...
ISSN: 2320 – 3471(Online)
Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Marc...
ISSN: 2320 – 3471(Online)
Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Marc...
ISSN: 2320 – 3471(Online)
Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Marc...
ISSN: 2320 – 3471(Online)
Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Marc...
ISSN: 2320 – 3471(Online)
Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) Marc...
ISSN: 2320 – 3471(Online)
J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) March-April...
ISSN: 2320 – 3471(Online)
J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) March-April...
ISSN: 2320 – 3471(Online)
J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) March-April...
ISSN: 2320 – 3471(Online)
J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) March-April...
ISSN: 2320 – 3471(Online)
J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) March-April...
ISSN: 2320 – 3471(Online)
J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology
Volume 1(2) March-April...
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Ijrpb 1(2) for print
Upcoming SlideShare
Loading in …5
×

Ijrpb 1(2) for print

3,644 views

Published on

Published in: Technology, Business
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
3,644
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
14
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Ijrpb 1(2) for print

  1. 1. Volume 1 Issue 2 www.ijrpb.com March-April 2013 Indian Journal of Research in Pharmacy and Biotechnology ISSN: 2320-3471 (Online) Editor B.Pragati Kumar, M.Pharm, Assistant Professor, Nimra College of Pharmacy Consulting editor Dr. S Duraivel, M.Pharm, Ph.D., Principal, Nimra College of Pharmacy Associate Editors Dr. A. Ravi Kumar, M.Pharm., Ph D. Dr. Emdad Hossain, M. Pharm., Ph D. Dr. S. Sangeetha, M.Pharm., Ph.D. Dr. Ramana Reddy, M.Pharm., Ph.D., F.I.C. Dr. M. Janardhan, M.Pharm., Ph.D. Mr. Lokesh Deb, M.Pharm.,(Ph.D) Mr. Debjit Bowmick, M.Pharm., (Ph.D) Mr. Harish Gopinath, M.Pharm., (Ph.D) Dr. Sankhadip Bose, M.Pharm., Ph.D. Dr. K.P.Sampath Kumar, M. Pharm., Ph D. Editorial Advisory Board Dr.Y.Narasimaha Reddy, M. Pharm., Ph D. Mr.Digpati Roy, M.Pharm.,(Ph.D) Dr.V.Gopal, M. Pharm., Ph D. Mr.Praneta Desale, M.Pharm. Dr. J.Balasubramanium, M. Pharm., Ph D. Mr.Nikhil P Jogad, M.Pharm.,(Ph.D) Dr.P.Ram Reddy, M. Pharm., Ph D. Mr.Shambaditya Goswami, M.Pharm.,(Ph.D) Dr. V.Prabhakar Reddy, M. Pharm., Ph D. Mr.Samaresh Pal Roy, M.Pharm.,(Ph.D) Dr. S.D.Rajendran, M. Pharm., Ph D. Mr. Pulak Majumder, M.Pharm.,(Ph.D) Dr. Chinnala Krishnamohan, M. Pharm., Ph D. Dr. R.Margret Chandira, M.Pharm., Ph.D. Dr.T.Venkateswara Rao, M.Pharm., Ph.D. Mr.Akhilesh Prasad Yadav, M.Pharm.,(Ph.D) Dr. Vijay Kumar, M.Pharm., Ph.D. Mr.Rajnish Kumar Singh, M.Pharm. Mr. A.Madhusudhan Reddy, M.Pharm.,(Ph.D) Mr. Supriya Das, M.Pharm.,(Ph.D) Prof.M.Ravi, M.Pharm, (Ph.D) Mr.Pradip Das, M.Pharm. Mr. C. Narendhar, M.Pharm. Mr. Vinod Raghuwanshi, M.Pharm. Mr.Subhashis Debnath, M.Pharm.,(Ph.D) Mr. Shravan Kumar Paswan, M.Pharm. Mr. Diptanu Biswas, M.Pharm. Mr. Praveen Khirwadkar M.Pharm.,(Ph.D)
  2. 2. Volume 1 Issue 2 www.ijrpb.com March-April 2013 Indian Journal of Research in Pharmacy and Biotechnology ISSN: 2320-3471 (Online) Indian Journal of Research in Pharmacy and Biotechnology is a bimonthly journal, developed and published in collaboration with Nimra College of Pharmacy, Ibrahimpatnam, Vijayawada, Krishna District, Andhra Pradesh, India-521456 Printed at: F. No: 501, Parameswari Towers, Ibrahimpatnam, Vijayawada, India -521456 Contact us/ send your articles to: Email: ijrpb@yahoo.com Phone no: 9490717845; 9704660406 Visit us at www.ijrpb.com
  3. 3. ISSN: 2320 – 3471(Online) Indian Journal of Research in Pharmacy and Biotechnology Volume 1 Issue2 www.ijrpb.com March –April 2013 Contents Page Nos. Antidepressant activity of ethanolic extract of plant Kalanchoe pinnata (lam) pers in mice Shashank Matthew, Ajay Kumar Jain, Cathrin Matthew, M.Kumar, Debjit Bhowmik 153-155 Antinociceptive and anti-inflammatory activity of Tecoma stans leaf extracts V Lakshmi Prasanna, K Lakshman, Medha M Hegde and Vinutha Bhat 156-160 Recent trends in usage of polymers in the formulation of dermatological gels Shaik Arif Bhasha, Syed Abdul Khalid, S.Duraivel, Debjit Bhowmik, K.P.Samapth Kumar 161-168 Recent trends of polymer usage in the formulation of orodispersible tablets J.Preethi, MD Farhana, B.Chelli Babu, MD.Faizulla, Debjit Bhowmik, S.Duraivel 169-174 Design and development of amlodipine besylate fast dissolving tablets by using natural superdisintegrants N.Narasimha Rao, B.Radha Krishna Murthy, D.Rajasekhar, P. Suri Babu, K. Phaneendra Babu, Srinivasa Babu. P 175-179 Formulation optimization and evaluation of liposomal gel of prednisolone by applying statistical design Varde Neha M, Thakor Namita M, C.Sini Srendran, Shah Viral H 180-187 ADR monitoring in hypertension outpatient department of hospital Sreenu Thalla, K.Venkatta Ramana, Sk.Sheherbanu, Sk.Ashya, A.Manikanteswara Reddy, B.Lakshmi 188-190 Evaluation of the antioxidant and hepatoprotective activity of Madhuca longifolia (koenig) leaves Arun Kumar, Kaushik Biswas, S Ramachandra Setty 191-196 Formulation and evaluation of sustained release matrix tablets of Metformin hydrhocloride A Madhusudhan Reddy, Ayesha Siddika, P Surya Bhaskara Rao, 197-200 Herbal medicine Atheeq-ur-Rahman, Ismail Shaik , K.P.Samapth Kumar 201-205 Microsponge drug delivery system SK Shafi, S.Duraivel, Debjit Bhowmik, K.P.Sampath Kumar 206-209 Nanotherapeutics – an era of drug delivery system in nanoscience Bhargavi, Ch.Anil, Debjit Bhowmik, Praneta Desale, K.P.Sampath Kumar 210-214 A validated RP-HPLC method for the estimation of Baclofen in bulk drug and pharmaceutical formulations Rajesh M, Manzoor Ahmed, Maanasa Rajan BN 215-218 A validated RP-HPLC method for the estimation of Cisapride in bulk drug and pharmaceutical formulations Maanasa Rajan.B.N, Manzoor Ahmd, Rajesh M 219-222 Review article on antimicrobial resistance Maryam Bincy Thomas, Suruchi Singh 223-225 Urinary tract infection: causes, symptoms, diagnosis and it’s management M. Komala, K.P.Sampath Kumar 226-233 Diabetes epidemic in India: risk factors, symptoms and treatment Abhinov T, Md Aasif Siddique Ahmed Khan, Ashrafa, Shabana Parveen, K.P.Samapth Kumar 234-243 Simultaneous estimation of Olmesartan and Atorvastatin in bulk and fromulation by using UV spectroscopy and RP-HPLC Revanth Reddy B, Aravind G 244-254 Development and validation of RP-HPLC method for the determination of Cefdinir in bulk and capsule dosage form P.Ravisankar, G.DevalaRao, M.KrishnaChaitanya 255-263 Simultaneous separation of six Fluoroquinolones using an isocratic hplc system with uv detection: application to analysis of levofloxacin in pharmaceutical formulations Ravisankar Panchumarthy, Devala Rao Garikapati, Krishna Chaitanya Manukonda, Sandhya Rani Nagabhairava 264-274
  4. 4. ISSN: 2320 – 3471(Online) Indian Journal of Research in Pharmacy and Biotechnology Volume 1 Issue2 www.ijrpb.com March –April 2013 INDIAN JOURNAL OF RESEARCH IN PHARMACY AND BIOTECHNOLOGY Instructions to Authors Manuscripts will be subjected to peer review process to determine their suitability for publication provided they fulfill the requirements of the journal as laid out in the instructions to authors. After the review, manuscripts will be returned for revision along with reviewer’s and/or editor’s comments. Kindly follow the below guidelines for preparing the manuscript: 1. Prepare the manuscript in Times New Roman font using a font size of 12. There shall not be any decorative borders anywhere in the text including the title page. 2. Don’t leave any space between the paragraphs. 3. Divide the research article into a. Abstract b. Introduction c. Materials and Methods d. Results e. Discussion f. conclusion g. References 4. References should include the following in the same order given below a) Author name followed by initials b) Title of the book/ if the reference is an article then title of the article c) Edition of the book/ if the reference is an article then Journal name d) Volume followed by issue of the journal e) Year of publication followed by page numbers 5. Download the author declaration form from the web site www.ijrpb.com, fill it and submit it after signing by corresponding and co-authors to IJRPB. You can send the filled in form by post or scanned attachment to ijrpb@yahoo.com. 6. Keep in touch with the editor through mail or through phone for further clarifications as well as for timely publication of your article.
  5. 5. ISSN: 2320 – 3471(Online) Shashank Mathew et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 153 ANTIDEPRESSANT ACTIVITY OF ETHANOLIC EXTRACT OF PLANT KALANCHOE PINNATA (LAM) PERS IN MICE Shashank Matthew1 *, Ajay Kumar Jain2 , Cathrin Matthew2 , M.Kumar3 , Debjit Bhowmik4 1. Department of Pharmaceutical Sciences, Sardar Patel College of technology, Balaghat 2. Government district hospital, Balaghat 3. Vinayaka missions college of Pharmacy, Salem 4. Karpagam University, Coimbatore * Corresponding author: Email: sheak1980@gmail.com ABSTRACT The main objective of present work is to find out good pharmacological activities in herbal source with their preliminary phytochemical study, and also it is aimed to investigate anti-diabetic activity of ethenolic and aqueous extracts of dried stem of plant Kalanchoe pinnata (LAM)PERS against CNS- Depressant activity in rats. Normally herbal products are free from side effects/adverse effects and they are low cost medicines, which will be beneficial for human being. The main objective of this work is to develop potent CNS-Depressant agent having no or minimum side effects from indigenous plants for the therapeutic management. KEYWORDS: Phytochemical study, Kalanchoe pinnata, 1. INTRODUCTION The World Health Organization (WHO) defined health as “a complete state of physical, mental, and social well-being and not merely the absence of disease or infirmity”. So during the past decade, traditional systems of medicine have become a topic of global importance. Current estimate suggest that, in many developing countries a large proportion of the population relies heavily on traditional practitioners and medicinal plants to meet primary health care needs. Although modern medicine may be available in these countries, herbal medicines (phytomedicines) have often maintained popularity for historical and cultural reasons. Concurrently, many people in developed countries have begun to turn to alternative or complementary therapies, including medicinal herbs. 2. MATERIAL AND METHODS 2.1. Collection and authentication of plant material: The specimen copy (Herbarium) of selected plant collected in month of july-2007 from ABS Botanical garden, Karripatty, Distt. - Salem, Tamil Nadu Mr.A. Balsubramnian, (Consultant-central siddha research) Executive Director ABS botanical garden, Salem, authenticated the plant as Kalanchoe Pinnata (LAM) PERS (Family- Crassulaceae). 2.2. Preparation of extract: The stem of Kalanchoe Pinnata (LAM) PERS were dried under shade and then powdered with a mechanical grinder. The powder was passed through sieve No. 30 and stored in an airtight container for further use. 2.3. Solvent for extraction: • Petroleum Ether (60-80o C) • Alcohol (95% v/v) • Distilled water with chloroform (0.25%) 2.4. Extraction procedure: The dried powders of stem of Kalanchoe pinnata were defatted with petroleum ether (60-80ºc) in a Soxhlet Apparatus by continuous hot- percolation. The defatted powder material (marc) thus obtained was Further extracted with ethanol (95% v/v) with same method and fresh powder used for aqueous extraction by Cold maceration method. The solvent was removed by distillation under low pressure and evaporation. The resulting semisolid mass was vacuum dried by using rotary flash evaporator. The resultant dried extracts were used for further study. 2.5. Procurement of experimental animals: Swiss albino mice (20-25 g) and albino Wister rats (150-200 g) of either sex and of approximate same age are used in the present studies were procured from listed suppliers of Sri Venkateswara Enterprises, Bangalore, India. The animals were fed with standard pellet diet (Hindustan lever Ltd. Bangalore) and water ad libitum. All the animals were housed in polypropylene cages. The animals were kept under alternate cycle of 12 hours of darkness and light. The animals were acclimatized to the laboratory condition for 1 week before starting the experiment. The animals were fasted for at least 12 hours before the onset of each activity. The experimental protocols were approved by Institutional Animal Ethics Committee (IAEC No.-P.Col. / /2007) after scrutinization. The animals received the drug treatments by oral gavage tube. 2.6. CNS- depressant activity: Most of the central nervous system acting drugs influence the locomotor activities in man and animals. The CNS - Depressant drugs such as barbiturates and alcohols reduce the motor activity,
  6. 6. ISSN: 2320 – 3471(Online) Shashank Mathew et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 154 while the stimulants such as caffeine and amphetamine increase the activity, in other words, the locomotor activity can be an index of wakefulness (alertness) of mental activity. In the present study the attempt has been focused to evaluate the CNS-Depressant activity of extracts of stem of plant Kalanchoe pinnata (LAM) PERS on the locomotor activity of mice using actophotometer. Table.1. Treatment design Group I Normal control (Normal saline 0.9%) Group II Positive control (Chlorpromazine 3 mg / kg i.p.) Group III Ethanolic extract (300mg / kg) Group IV Ethanolic extract (600mg / kg) Group V Aqueous extract (300mg / kg) Group VI Aqueous extract (600mg / kg) Procedure:- 1. Albino mice weighing between 150-200 gm was purchased from Venkateshwara Enterprises, Bangalore 2. Animals are divided into 6 groups. 3. The equipment was turned on and each animal are placed in activity cage and for 10 min. and the basal activity score is noted down. 4. Normal saline is administrated in the dose of 2 ml / kg to the first group (normal control). 5. Chlorpromazine (3mg / kg) was administered to II group of animal. 6. The animals of group III, IV, were treated with ethanolic extracts and V, VI with aqueous extracts. 7. After 45 min of the treatment, once again the animals were placed in the activity cage and the score was noted. The difference in the activity before and after treatment was noted. The percent decrease in motor activity was calculated and compared with control group of animals (Kulkarni, S. K- 2005). 8. CNS -- Depressant activity of alcoholic and aqueous extract of dried stem of plant kalanchoe pinnata (LAM.)PERS., on the locomotor activity of mice using actophotometer. Table 2. Evaluations of CNS-depressant activity Group Treatment design Dose Locomotor activity in 10mins. % decrease in activityBefore treatment after treatment 1 Normal control 2ml/kg 224.5 ± 1.88 220.5 ± 1.75 ----- 2 Standard (Chlorpromazine) 3mg/kg 280.33 ± 0.55* * 106.00 ± 1.03* * 62.18 3 Ethanolic extract 300mg/kg 216.83 ± 0.74* * 110.16 ± 0.65* * 49.19 4 Ethanolic extract 600mg/kg 209.00 ± 0.57* * 94.8 ± 0.83* * 54.62 5 Aqueous extract 300mg/kg 223.00 ± 0.41 170.00 ± 1.53* * 23.76 6 Aqueous extract 600mg/kg 229.160 ± 0.98* * 176.5 ± 1.89* * 32.98 Values are expressed by Mean ± SEM P values: * * P< 0.01; * P <0.05. One way ANOVA followed by DUNNETT’S, multiple comparison tests 3. CONCLUSION Alcoholic extract of plant Kalanchoe pinnata (LAM) PERS have more CNS-depressant activity as compared to aqueous extract but as compare to standard drug it shows near about same action. REFERENCES Dhanurkar RA, Kulkarni NN, Pharmacology of medicinal plants and natural products, Ind J Pharmacology, 32, 2000, 81-118. Gupta SS, Prospects and perspective of natural plant products in medicine, Indian J of pharmacology 1994, 26, 1-12. John AO, Ojewole, Antinociceptive, anti-inflammatory and antidiabetic effects of Bryophyllum pinnatum (Crassulaceae) leaf aqueous extract, Journal of Ethnopharmacology 99, 1, 13-19.
  7. 7. ISSN: 2320 – 3471(Online) Shashank Mathew et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 155 Joshi Shashank R, Shah Siddhart N, Rising global burden of Diabetes, The Asian J of Diabetology, 1(3), 1999, 13-15. Lenzen S, and Munday R, Thiol-group reactivity, hydrophilicity and stability of alloxan, its reduction products and its N-methyl derivatives and a comparison with ninhydrin, Biochemical Pharmacology, 42, 1991, 1385-1391. Lenzen S, Panten U, Alloxan: history and mechanism of action, Diabetologia, 31, 1988, 337-342. Lipnick RL, Cotruvo JA, Hill RN, Comparison of the up and down method and the fixed dose procedure acute toxicity procedures, Fd Chen, Toxic, 33, 1995, 223-231. Pincus I J, Hurwitz, Scott M E, effect of rate of injection of alloxan on development of diabetes in Rabbits, J Am Physio Soc, 86, 1954, 553-555. Ramachandran A, Snehlata C, Viswanthan V, burden of type 2 Diabetes and its complications, The Indian scenario, Current science, 83, 2002, 1471-1476. Salahdeen HM and Yemitan OK, Neuropharmacological effects of aqueous leaf extract of Bryophyllum Pinnatum in mice, African journal of biomedical research, 9, 2006, 101-107. Shukla R, Sharma S B, Puri D, Prabhu M K, and Murth P S, Medicinal plants useful in diabetes, Indian J Clinic Biochem, 15, 2002, 169. Siddharta P, Chaudhuri AKN, Further studies on the anti-inflammatory profile of the methanolic fraction of the fresh leaf extract of Bryouphyllum pinnatum, Fitoterapia, 63(5), 1992, 451-459. V Babu, Gangadevi T, Subramonian A, Antihyperglycemic activity of cassia Kleinl leaf extract in glucose fed normal rats and alloxan induced diabetic rats; Indian Journal of Pharmacology 2002, 34, 409-415.
  8. 8. ISSN: 2320 – 3471(Online) V Lakshmi Prasanna et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 156 ANTINOCICEPTIVE AND ANTI-INFLAMMATORY ACTIVITY OF TECOMA STANS LEAF EXTRACTS V Lakshmi Prasanna1 *, K Lakshman2 , Medha M Hegde2 and Vinutha Bhat2 1.Department of Pharmacognosy, Creative Educational Society’s College of Pharmacy, Kurnool. A.P. 2. Department of Pharmacognosy, PES College of Pharmacy, Bangalore, Karnataka. *Corresponding author: E-mail:vlakshmi.prasanna.14@gmail.com ABSTRACT Tecoma stans (Bignoniaceae) is used in the treatment of diabetes, stomach pains, rheumatism, diuretic, vermifuge and tonic in traditional medicine. The present study has been design to evaluate antinociceptive and anti-inflammatory activities of alcohol and aqueous extracts of Tecoma stans leaves and to determine total phenolic and flavonoid contents. Both extracts shows dose dependent activity. The antinociceptive activity was investigated using hot plate, acetic acid induced writhing and formalin induced paw licking methods. Anti-inflammatory activity was evaluated using carrageenan induced paw oedema method. Total phenolic and flavonoid content determined using standard chemical methods. Alcohol extract (500 mg/kg) showed highest 76.92% inhibition of inflammation after 24 hrs. Both the extracts produced increased in latency time compared to vehicle but alcohol extract showed highest activity after 150 min in hot plate method (4.63 ± 0.08 sec) and inhibit nocipeptive response in both phase. Extracts also produced significant inhibition of writhing. Content of total phenolic and flavonoid also found more in alcoholic extract. These findings demonstrate that the alcohol leaf extract of Tecoma stans have excellent antinociceptive and anti-inflammatory activity, which may due to presence of higher phenolic and flavonoid content. Key-words: Tecoma stans leaves; antinociceptive; anti-inflammatory; phenolic content; flavonoid content. 1. INTRODUCTION Tecoma stans (Bignoniaceae) is a fast growing small evergreen shrub tree, that grows to a height of 7.5meters. Leaves are compound and imparipinnate with 2 to 5 pairs of leaflets. Flowers occur in clusters at the ends of the branches and are trumpet shaped with 5 rounded lobes, 6 cm long, pale to bright yellow in color. Fruits are narrow, slightly flattened to pointed capsules, up to 20 cm long (Orwa C, 2009). The chemical constituents of Tecoma stans are triterpenes, hydrocarbons, resins, volatile oil. Leaves and stems contain flavonoids, chrysoeriol, luteolin, hyperoside, indole oxygenase. Alkaloids like tecomanine, tecostanine, 4- noractinidine, 4-norskytanthine and boschniakine. Flowers contain β-carotene and Zeaxanthin. Roots are used as vermifuge, diuretic, tonic (Yoganarasimhan, 1904). The leaves are claimed to be useful in the treatment of inflammation and pain. Even though, Tecoma stans was reported to be useful in many ailments, there are no reports regarding its antinociceptive and anti- inflammatory activity. Hence in the current study, the anti-inflammatory and antinociceptive activity of alcohol and aqueous extracts of Tecoma stans leaves was studied using different animal models. This study is a scientific approach to validate the traditional use of the leaves of Tecoma Stans. 2. MATERIALS AND METHODS 2.1. Plant material: Dried leaves of Tecoma stans (Bignoniaceae) were collected from GKVK and authenticated by Dr.Rajanna from GKVK, Bangalore. A voucher specimen has been deposited at departmental herbarium for future reference (TS-10-03).The plant material was dried, powdered and stored in air tight containers for further studies. The powdered material weighing 500 g was extracted by Soxhlet using alcohol and water. The solvent was completely removed by using a rotary flash evaporator to get a semisolid mass. The Alcohol and aqueous extract yield is 10.80 and 21.75% W/W. 2.2. Animals: Albino mice and Wistar rats of either sex weighing 18-24 g and 150-200 g respectively, housed under standardized animal house conditions were used in all the experiments. They had access to standard pellet and water ad libitum. Animals were divided into six groups of six each. All the experiments are approved by Institutional Animal Ethics Committee, PES College of Pharmacy, India. 2.3. Preliminary phytochemical studies: Alcoholic & aqueous extracts of Tecoma stans were investigated for qualitative chemical examination which gives an idea regarding the chemical constituents present in the extracts. Phytochemical screening was done as explained in literature (Ikhiri, 1992).
  9. 9. ISSN: 2320 – 3471(Online) V Lakshmi Prasanna et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 157 2.4. Determination of total phenolic content: The amount of phenol in the alcohol and aqueous leaf extract of Tecoma stans was determined with Folin-Ciocalteu reagent using the method (Olayinka A Aiyegoro, Anthony I Okoh, 2010). Gallic acid (0-0.5 mg/ml) was used as standard and results were expressed as mg/g gallic acid equivalent of dry extract. 2.5. Estimation of total flavonoids: Aluminum chloride colorimetric method was used for flavonoids determination (Hole K, Hunskaar S, 1987). The content was determined from extrapolation of calibration curve which was made by preparing quercetin solution (0-0.8 mg/ml) in distilled water. The concentration of flavonoid was expressed in terms of mg/g quercetine equivalent. 2.6. Antinociceptive activity 2.6.1. Hot plate method: The animals were placed on Eddy's hot plate maintained at a temperature of 55 ± 0.5°C. A cut-off period of 15 s was observed to avoid damage to the paw. Reaction time and the type of response were noted using a stopwatch. The response is in the form of jumping, withdrawal of the paws or the licking of the paws. Pentazocine was used as standard (10 mg/kg) which was administered i.p. The alcohol and aqueous extracts of Tecoma stans (250 and 500 mg/kg) were administered orally (Koster R, 1959). The response was observed at 0, 30, 60, 120 and 150 min. 2.6.2. Formalin induced paw licking model: One hour after oral administration of test compounds (250 and 500 mg/kg alcohol and aqueous extracts of Tecoma stans), 20 µl of 1% formalin was injected into the paw of each animal. Duration of paw licking was monitored 0-5min (first phase) and 15-30min (second phase) after formalin injection. Pentazocine was used as a standard (10mg/kg) which was administered i.p (Winter CA, 1962). 2.6.3. Acetic acid induced writhing test: Albino mice were administered with different treatments orally one hour before acetic acid injection. Control group received only vehicle, and animals under standard group received Diclofenac sodium (10 mg/kg, p.o.). One hour after drug administration, 1% v/v acetic acid (0.1ml/10 g, i.p.) was injected. Five minutes after the intraperitoneal injection of acetic acid, number of writhing were counted for the period of 20 minutes (Ahamed KN, 2005). 2.7. Anti-inflammatory activity 2.7.1. Carrageenan-induced rat paw edema: Acute inflammation was produced by injecting 0.1ml of (1%) carrageenan (in a normal saline solution) into plantar surface of rat hind paw. The alcohol and aqueous extracts (250 and 500 mg/kg, orally), Diclofenac sodium (10 mg/kg, orally) as a reference agent were administered 60min before carrageenan injection. The paw edema volume was recorded using a plethysmometer at a different time intervals (Tjolsen A, 1992). 2.7.2. Statistical analysis: The results and data obtained in this study were evaluated using one-way analysis of variance (ANOVA) followed by Dunnett’s multiple comparison test. The values are expressed as mean + SEM and p < 0.05 was considered significant. 3. RESULTS 3.1. Preliminary phytochemical analysis: Our qualitative preliminary phytochemical tests showed the presence of alkaloids, glycosides, saponins, phenols, tannins, proteins, carbohydrates, phytosterols in alcoholic extract of Tecoma stans, and aqueous extract of the plant showed similar constituents positive except phyosterols, while fixed oils & fats are absent in both the extracts. 3.2. Total phenolic and total flavonoid content: The total phenolic & flavonoid content is more in alcohol extract (72.3 mg/g GAE and 49.6 mg/g QE) than aqueous extract (64.2 mg/g GAE and 38.5 mg/g QE) (Table 1). Table 1: Presence of total phenolic and flavonoid content in the extracts Extract Total phenolic content (mg/g gallic acid equivalent) Total flavonoid content (mg/g quercetine equivalent) Alcohol extract 72.3±1.23 49.6±0.99 Aqueous extract 64.2±1.02 38.5±0.80 Results were expressed as mean±SEM (n=3). 3.3. Antinociceptive activity: The extracts of Tecoma stans has shown significant dose dependent antinociceptive activity, however the alcohol extract (500 mg/kg) produced better activity than the aqueous extract. The alcohol extract (500 mg/kg) showed highest activity after 150 min in hot plate method as latency time increases to 4.63 ± 0.08 sec after 150 min compare to 1.08 ± 0.08 of control (Table 2).
  10. 10. ISSN: 2320 – 3471(Online) V Lakshmi Prasanna et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 158 Table 2: Effect of alcohol and aqueous leaf extract of Tecoma stans on Hot plate model Treatment Dose(mg/kg) Initial 30min 60min 120min 150min Control 10 1.02±0.09 0.94±0.05 1.16±0.07 1.27±0.01 1.08±0.08 Pentazocine 10 1.14±0.04 2.42±0.19*** 4.06±0.03*** 5.36±0.08*** 5.80±0.06*** Alcohol extract 250 0.97±0.01 1.08±0.05 1.94±0.01*** 2.62±0.06*** 3.26±0.03*** Alcohol extract 500 0.93±0.04 1.17±0.01* 2.69±0.04*** 3.74±0.07*** 4.63±0.08*** Aqueous extract 250 1.01±0.02 1.09±0.05 1.18±0.01 2.10±0.01*** 2.35±0.06*** Aqueous extract 500 0.95±0.07 1.15±0.02* 2.06±0.03*** 3.17±0.07*** 3.98±0.03*** Values are mean ± SE, n=6, ***P < 0.001, **P < 0.01 and *P < 0.05 using one-way ANOVA followed by Dunnett’s test. Oral administration of alcohol extract (250 and 500 mg/kg) produced inhibition of 28.48% and 37.43% pain response in first phase and inhibition of 53.41% and 74.56% paw licking response in second phase. Aqueous extract produce comparatively less effect than the alcohol extract and produced inhibition of 23.98% and 29.73% pain response in first phase and inhibition of 40.33% and 59.46% pain response in second phase at a dose of 250 mg and 500 mg/kg respectively (Table 3). Table 3. Effect of alcohol and aqueous leaf extract of Tecoma stans on Formalin induced paw licking model Treatment Dose mg/kg %inhibition of Paw licking in early phase 0-5min %inhibition of Paw licking in late phase 15-30min Control 10 - - Pentazocine 10 47** 80.22*** Alcohol extract 250 28.48* 53.41*** Alcohol extract 500 37.43** 74.56*** Aqueous extract 250 23.98 40.33*** Aqueous extract 500 29.73* 59.46*** Values are mean ± SE, n=6, ***P < 0.001, **P < 0.01 and *P < 0.05 using one-way ANOVA followed by Dunnett’s test. Alcohol extract produced 36.5% and 53.5% inhibition of writhing response in low and high dose respectively. Aqueous extract has produced less inhibition than the alcohol extract (Table 4). Table 4: effect of alcohol and aqueous leaf extract of Tecoma stanus on acetic acid induced writhing model Treatment Dose (mg/kg) Number of writhing % inhibition Control 70.5 Diclofenac sodium 3 25.8 63.4*** Alcohol extract 250 44.7 36.5** Alcohol extract 500 32.9 53.3*** Aqueous extract 250 50.2 28.7* Aqueous extract 500 39.3 44.2*** 3.4. Anti-inflammatory activity: The test extracts at doses of 250 and 500 mg/kg as well as diclofenac sodium (10 mg/kg), showed significant inhibition of edema in dose dependent manner 3 h after carrageenan-induced inflammation, when compared with the control. Both alcohol extract and aqueous extract of Tecoma stans produced dose dependent inhibition of paw edema, The percentage inhibition of edema was 63.3%, 76.92%, 57.05% and 64.74% against alcohol extract (250 mg/kg and 500 mg/kg) and aqueous extract (250 mg/kg and 500 mg/kg) respectively after 24h (Table 5).
  11. 11. ISSN: 2320 – 3471(Online) V Lakshmi Prasanna et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 159 Table 5: Effect of alcohol and aqueous leaf extract of Tecoma stans on Carrageenan induced rat paw edema model. Treatment Dose (mg/kg) % inhibition of paw edema Inflammation 3h 24h Control - 0.00 0.00 Diclofenac sodium 10 35.60*** 79.48*** Alcohol extract 250 23.48 63.34*** Alcohol extract 500 30.06*** 76.92*** Aqueous extract 250 11.36 57.05*** Aqueous extract 500 21.20 64.74*** Values are mean ± SEM, n=6, ***P < 0.001, **P < 0.01 and *P < 0.05 using one-way ANOVA followed by Dunnett’s test. 4. DISCUSSION Both the extracts showed activity in a dose dependent manner. The alcohol extracts showed potent antinociceptive and anti-inflammatory activity compare to aqueous extract. The hot plate test is considered to be selective for opioid like compounds, which are centrally acting analgesic in several animal species. The hot plate method has been found to be suitable for evaluation of centrally acting analgesic (Shibata, 1989).The alcoholic and aqueous extracts at low and high doses (250 and 500 mg/kg) increase the reaction time in dose dependent manner to the thermal stimulus. The highest antinociception of thermal stimulus was exhibited at higher dose of alcohol extract than aqueous extract. This could be the possible explanation for its central analgesic activity observed in hot plate test. The formalin induced paw licking test is a valid and reliable model for analgesic activity and it is sensitive for various classes of analgesic drugs. Formalin test produces a distinct biphasic response and different analgesics may act differently in the early and late phases of this test. Therefore, the test can be used to clarify the possible mechanism of the antinociceptive effect of a proposed analgesic (Rosland, 1990). Centrally acting drugs such as opioids inhibit both phases equally (Taesotikul, 2003). But peripherally acting drugs such aspirin; indomethacin and dexamethasone only inhibit the late phase. The late phase seems to be anti inflammatory response with inflammatory pain that can be inhibited by anti-inflammatory drugs (Marsha, 2002). The alcoholic and aqueous extracts exhibited a significant antinociception in both early and late phase of the formalin test. Acetic acid induced writhing test, a model of chemo-nociception and it induced pain by increasing fluids of PGE2 and PGE2α. Acetic acid also induces sympathetic nervous system mediators, which are found in high level at first 30 min after acetic acid injection. This probably indicates that the analgesic activity of the extracts was mediated by inflammatory as well as neurogenic mechanisms. The alcohol and aqueous extract exhibited significant, dose-dependent decrease in the number of abdominal constrictions. However alcohol extract has shown good activity compare to aqueous extract. Carrageenan induced paw edema is characterized by a biphasic events, with involvement of different inflammatory mediators (Marsha KMG, 2002). In first phase (during the first 2h after carrageenan injection) chemical mediators such as histamines and serotonin play a role (Marsha, 2002) while in second phase (3-5h) after carrageenan infection kinin and prostaglandins are also released. Administration of alcohol extract at 250 and 500 mg/kg inhibited the edema from the 3h after carrageenan challenge, and aqueous extract at dose of 250 and 500 mg/kg inhibited the edema from 4h after carrageenan challenge, which probably inhibits the different aspects and chemical mediators of inflammation. The phytochemical analysis of various extracts showed the presence of carbohydrates, alkaloids, glycosides, tannins, saponins, phytosterols, phenolic compounds, proteins, amino acids, flavonoids, gums and mucilage. Our result also showed that extract contain significant amount of total phenolic and flavonoid content. The anti-inflammatory effect of Tecoma stans may be due to the presence of flavonoids. It has been reported that flavonoids possess anti-inflammatory and analgesic activity. Flavonoids are known to target prostaglandins which are involved in the late phase of acute inflammation and pain perception. Hence, the presence of flavonoids may be contributory to the anti-inflammatory and analgesic activities of Tecoma stans. This study confirms the antinociceptive and anti-inflammatory activity of leaves of Tecoma stans. Both activities were found to be comparable with reference drug. Further studies need to be done to identify and separate the
  12. 12. ISSN: 2320 – 3471(Online) V Lakshmi Prasanna et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 160 group of active constituents responsible for antinociceptive and anti-inflammatory activity from alcohol and aqueous extracts. ACKNOWLEDGEMENT Authors are thankful to the Management, Director, Principal, Dr.S.Mohan, PES college of Pharmacy for providing necessary facilities to carry out this work & Dr.Rajanna, GKVK, Bangalore, for identifying the plant. REFERENCES Ahamed KN, Kumar V, Raja S, Mukherjee K, Mukherjee PK. Anti- nociceptive and anti- inflammatory activity of Araucaria bidwilli Hook, IJPT, 1, 2005, 105-109. Hole K, Hunskaar S, The formalin test in mice dissociation between inflammatory and non inflammatory pain. Pain, 30, 1987, 103-111. Ikhiri K, Boureima D, Dan-Kouloudo D. Chemical screening of medicinal plants used in traditional pharmacopoeia of Niger, Int J Pharmacog, 30, 1992, 251–262. Koster R, Anderson M, De-Beer EJ, Acetic acid analgesic screen Fed Proc Fed Am Soc Exp Biol, 18, 1959, 418-420. Marsha KMG, Everton TA, Oswald SR. Preliminary investigation of the Anti-inflammatory properties of an aqueous extract from Morinda citrifolia (Noni), Proc West Pharmacol Soc, 45, 2002, 76-78. Olayinka A Aiyegoro, Anthony I Okoh, Preliminary phytochemical screening and In vitro antioxidant activities of the aqueous extract of Helichrysum longifolium, BMC Complementary and Alternative Medicine, 10, 2010, 1472-6882. Orwa C, Mutua A, Kindt R, Jamnadass R, Anthony S, Agroforestry Database:a tree reference and selection guide version. Available at: http://www.worldagroforestry.org/sites/treedbs/treedatabases.asp.2009, Accessed on 14 June 2010. Rosland JH, Tjoisen A, Maehle B, Hole K, The formalin test in mice: effect of formalin concentration. Pain, 1990, 42, 235. Shibata M, Ohkubo T, Takahashi H, Inoki R. Modified formalin test characteristic biphasic pain response. Pain, 38, 1989, 347. Taesotikul T, Panthong A, Kanjanapothi D, Verpoorte R, Scheffer JJC. Anti- inflammatory,antipyretic and antinoceceptive activities of Tabernaemontaa pandacaqui Poir, J of Epharmacol, 84, 2003, 31-35. Tjolsen A, Berge OG, Hunskaar S, Rosland JH, Hole K, The formalin test: an evaluation of the method. Pain, 51, 1992, 5. Winter CA, Risley EA, Nuss GW, Carragenan induced edema in hind paw of the rat as assay for anti inflammatory drugs, Proceedings of the society for experimental biology and medicine, 1962, 11, 544-547. Yoganarasimhan SN, Medicinal plants of India, Bangalore, India, 10th ed, Interline publisher pvt limited. 1904, 81.
  13. 13. ISSN: 2320 – 3471(Online) Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 161 RECENT TRENDS IN USAGE OF POLYMERS IN THE FORMULATION OF DERMATOLOGICAL GELS Shaik Arif Bhasha1 , Syed Abdul Khalid1 , S.Duraivel1 , Debjit Bhowmik1 , K.P.Samapth Kumar2 * 1. Nimra college of pharmacy, Vijayawada, India 2. Department of Pharmaceutical Sciences, Coimbatore medical college, Coimbatore, India Corresponding author: Email:debjit_cr@yahoo.com ABSTRACT Topical preparations can be applied directly to an external body surface by spreading, rubbing, and spraying. The topical route of administration has been utilized either to produce local effect for treating skin disorder or to produce systemic drug effects. Within the major group of semisolid preparations, the use of transparent gels has expanded both in cosmetics and in pharmaceutical preparations. Gels often provide a faster release of drug substance, independent of the water solubility of the drug, as compared to creams and ointments. They are highly biocompatible with a lower risk of inflammation or adverse reactions, easily applied and do not need to be removed. Gels for dermatological use have several favorable properties such as being thixotropic, greaseless, easily spreadable, easily removed, emollient, non-staining, and compatible with several excipients and water soluble or miscile. Dosage form selection should include those delivery systems that are non- comedogenic. Gels tend to be most effective as they have faster absorption than creams. Gels containing only water tend to be slow to dry; so the addition of ethyl or isopropyl alcohol to the gel hastens their drying to a film. But some patients may need the less drying lotions or creams for dry or sensitive skin or for use during dry winter weather. INTRODUCTION Gels are semisolid systems in which a liquid phase is constrained within a three-dimensional polymeric matrix (consisting of natural or synthetic gums) in which a high degree of physical (or sometimes chemical) cross- linking has been introduced. Some of these systems are as clear as water in appearance, visually aesthetically pleasing as in gelatin deserts and other are turbid. The clarity range is from clear to a whitish translucent. The polymers are used between 0.5-15% and in most of the cases they are usually at the concentration between 0.5-2%. Gels are usually clear, transparent, semisolids, containing the solubilised active substances (Lachman, 1987). The term “Gel” was introduced in the late 1800 to name some semisolid material according to pharmacological, rather then molecular criteria. The U.S.P. defines gels as a semisolid system consisting of dispersion made up of either small inorganic particle or large organic molecule enclosing and interpenetrated by liquid. The inorganic particles form a three-dimensional “house of cards” structure. Gels consist of two-phase system in which inorganic particles are not dissolved but merely dispersed throughout the continuous phase and large organic particles are dissolved in the continuous phase, randomly coiled in the flexible chains. Advantages:  Avoidance of first pass metabolism.  Convenient and easy to apply.  Avoidance of the risks and inconveniences of intravenous therapy and of the varied conditions of absorption, like pH changes, presence of enzymes, gastric emptying time etc.  Achievement of efficacy with lower total daily dosage of drug by continuous drug input.  Avoids fluctuation in drug levels, inter- and intrapatient variations.  Ability to easily terminate the medications, when needed.  A relatively large area of application in comparison with buccal or nasal cavity  Ability to deliver drug more selectively to a specific site.  Avoidance of gastro-intestinal incompatibility.  Providing utilization of drugs with short biological half-life, narrow therapeutic window.  Improving physiological and pharmacological response.  Improve patient compliance.  Provide suitability for self-medication. Disadvantages:  Skin irritation of contact dermatitis may occur due to the drug and/or excipients.  Poor permeability of some drugs through the skin.
  14. 14. ISSN: 2320 – 3471(Online) Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 162  Possibility of allergenic reactions.  Can be used only for drugs which require very small plasma concentration for action  Enzyme in epidermis may denature the drugs.  Drugs of larger particle size not easy to absorb through the skin. Characteristics of gels: 1. Ideally gelling agents for pharmaceutical and cosmetic use should be inert, safe and nonreactive with other formulation components. A potential incompatibility is illustrated by the combination of cationic drug, preservative or surfactant with an anionic gel former. For example sodium alginate has been shown to reduce the concentration of cationic preservatives in solution as well as complex with chlorpheniramine, reduce the drug release rate from gelled formulation. Polyether has been shown to interact with phenols and carboxylic acids, leading to loss of potency. 2. The inclusion of a gelling agent in a formulation should provide a reasonable solid like nature during storage that can be broken when subjected to the shear force generated in shaking a bottle, squeezing a tube, or during topical application. A cost consideration requires a low concentration of gallant to produce the desired characteristics. 3. The gel should exhibit little viscosity change under the temperature variations of normal use and storage. For e.g. plastic base exhibits a lesser decrease in consistency than petrolatum over the some temperature range. This minimizes unacceptable changes in the products’ characteristics. 4. The gels particularly those of polysaccharide nature are susceptible to microbial degradation. Incorporation of a suitable preservative may prevent contamination and subsequent loss of gel characteristics due to microbial attack. 5. The gel characteristics should match the intended use. A topical gel should not be tacky. Too high a concentration of gel former or the use of an excessive molecular weight may produce a gel difficult to dispense or apply. An ophthalmic gel must be sterile. The aim in to produce a stable elegant, economic gel product adequately suited for its intended use. 6. Swelling: Gels can swell, absorbing liquid with an increase in volume (e.g. Xerogels). This is referred to as swelling and the pressure developed is known as swelling pressure. The swelling can be looked on as the initial phase of dissolution as osmosis occurs, where solvent penetrates the gel matrix. Gel-gel interactions are replaced by gel- solvent interactions. Limited swelling is usually the result of some degree of cross linking in the gel matrix that prevents total dissolution. Such gels swell considerably when the solvent mixture posses a solubility parameter comparable to that of the gallant. 7. Syneresis: Many gels systems undergo a contraction upon standing. The interstitial liquid is expressed, collecting at the surface of the gel. This process is referred to as syneresis or bleeding. Syneresis is not limited to organic hydrogels but has been seen in organogels and inorganic hydrogels. Typically syneresis becomes more pronounced as the concentration of polymer decreases. 8. Structure: Inorganic particles are capable of gelling a vehicle due to formation of a “house of card” structure. Clays e.g. bentonite or kaolin posses a lamellar structure that can be extensive hydrated. The flat surface of bentonite particles are negatively charged while the edges are positively hydrated. The flat surface of bentonite particles are negatively charged while the edges are positively charged. The attraction of face to edge of these colloidal lamellae creates a three-dimension network of particles throughout the liquid, immobilizing the solvent. The interactions between the particles are fairly weak, being broken by stirring or shaking. 9. Rheology: Solutions of gelling agents and dispersions of flocculated solids are typically pseudo plastic, exhibiting non-Newtonian flow behavior characterized by decreasing viscosity with increasing shear rate. Such behavior is due to progressive breakdown of the structure of the system. The tenuous structure of inorganic particles dispersed in water is disrupted by an applied shear stress. As shear stress is increased, more and more interparticulate associations are broken, resulting in a greater tendency to flow. Similarly, for macromolecules dispersed in a solvent, the applied shear tends to align the molecules in the direction of flow. The molecules straighten out, becoming less entangled as shear increases, thus lessening the resistance to flow. CLASSIFICATION: Based on colloidal phases: Gels are classified into inorganic (two phase system) and organic (single phase) gels on the basis of their nature of colloidal phase present. In a two phase system, if the particle size of the dispersed phase is relatively large and forms the three dimensional “house of cards” structures throughout the gel, then the gel mass sometime is referred to as magma (eg.bentonite magma). A gel with two phase system generally consists of floccules of small particles rather than large molecules and gel structure in such a system is not always stable. Both gels and magma may be thixotropic forming semisolids on standing and becomes liquid an agitation.
  15. 15. ISSN: 2320 – 3471(Online) Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 163 A single phase gel consists of large organic molecules existing on twisted matted strands, dissolved in a continuous phase, such that no apparent boundaries exist between the dispersed macromolecules and the liquid. this large organic molecule either natural or synthetic polymers often referred as gel formers, tends to entangle with each other due to their random motion or bounded together by stronger types of vander-waals force so as to form crystalline or amorphous regions throughout the entire system. Single phase in macro sense considers the molecule to be dissolved in continuous solvent phase; however the unique behaviors of long macromolecules in solutions, leading to fairly high viscosities and gel formation makes it possible to consider such a system as two phase, at micro level- the dispersion of lyophillic colloidal polymer molecule and the continuous phase solvent. Single phase gels may be made from synthetic macromolecules (E.g. carbomer), semi-synthetic natural polymer (E.g. Cellulose derivatives) or natural gums (tragacanth). The later preparations are also called aqueous, alcohol and oils may be used as the continuous phase. For ex. Mineral oil can be combined with a polyethylene resin to form an oleaginous ointment base. Based on nature of solvent: Gels may be classified even as hydrogels (water based) or organo gels (with a nonaqueous solvent) based on the type of solvent used as continuous liquid phase. Bentonite magma, gelatin, cellulose derivative, carbomer, polaxomer gels are example of hydrogel. Examples of hydrogels are plastibase (low molecular weight polyethylene dissolved in mineral oil and stock cooled), olag (aerosil) gel and dispersion of metallic stearates in oils. Organogels: Organogels contain a nonaqueous solvent as the continuous phase. Example of organogel are plastibase(low molecular weight polyethylene dissolved in mineral oil and stock cooled) and dispersions of metallic stearates in oils. An organogel is a non-crystalline, non-glassy thermo reversible (thermoplastic) solid material composed of a liquid organic phase entrapped in a three-dimensionally cross-linked network. The liquid can be e.g. an organic solvent, a mineral oil or a vegetable oil. The solubility and particle dimensions of the structurant are important characteristics for the elastic properties and firmness of the organogel. Often, these systems are based on self-assembly of the structurant molecules. Organogels have potential for use in a number of applications, such as in pharmaceuticals, cosmetics, art conservation, and food. An example of formation of an undesired thermo reversible network is the occurrence of wax crystallization in crude oil. Sorbitan monostearate, a hydrophobic nonionic surfactant, gels a number of organic solvents such as hexadecane, isopropyl myristate, and a range of vegetable oils. Gelation is achieved by dissolving/dispersing the organogelator in hot solvent to produce an organic solution/dispersion, which, on cooling sets to the gel state. Cooling the solution/dispersion causes a decrease in the solvent-gelator affinities, such that at the gelation temperature, the surfactant molecules self-assemble into inverse toroidal vesicles. Further cooling results in the conversion of the toroids into rod-shaped tubules. Once formed, the tubules associate with others, and a three- dimensional network is formed which immobilizes the solvent. An organogel is thus formed. Sorbitan monostearate gels are opaque, thermoreversible semisolids, and they are stable at room temperature for weeks. Such organogels are affected by the presence of additives such as the hydrophilic surfactant, polysorbate 20, which improves gel stability and alters the gel microstructure from a network of individual tubules to star-shaped "clusters" of tubules in the liquid continuous phase. Another solid monoester in the sorbitan ester family, sorbitan monopalmitate, also gels organic solvents to give opaque, thermoreversible semisolids. Like sorbitan monostearate gels, the microstructure of the palmitate gels comprises an interconnected network of rod like tubules. Unlike the stearate gels, however, the addition of small amounts of a polysorbate monoester causes a large increase in tubular length instead of the clustering effect seen in stearate gels. The sorbitan stearate and palmitate organogels may have potential applications as delivery vehicles for drugs and antigens. Xerogels: solid gels with low solvent concentration are known as xerogels. Xerogels are often produced by evaporation of the solvent, leaving the gel framework behind. They can be returned to the gel state by introduction of an agent that,on imbition, swells the gel matrix. Example of xerogels include dry gelatin,tragacanth ribbons and acacia tears and dry cellulose and polystyrene. A xerogel is a solid formed from a gel by drying with unhindered shrinkage. Xerogels usually retain high porosity (25%) and enormous surface area (150–900 m2 /g), along with very small pore size (1-10 nm). When solvent removal occurs under hypercritical (supercritical) conditions, the network does not shrink and a highly porous, low- density material known as an aerogel is produced. Heat treatment of a xerogel at elevated temperature produces viscous sintering (shrinkage of the xerogel due to a small amount of viscous flow) and effectively transforms the porous gel into a dense glass.
  16. 16. ISSN: 2320 – 3471(Online) Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 164 Hydrogel: Hydrogel (also called Aquagel) is a network of polymer chains that are water-insoluble, sometimes found as a colloidal gel in which water is the dispersion medium. Hydrogels are superabsorbent (they can contain over 99% water) natural or synthetic polymers. Hydrogels also possess a degree of flexibility very similar to natural tissue, due to their significant water content. Common uses for hydrogels include  Currently used as scaffolds in tissue engineering. When used as scaffolds, hydrogels may contain human cells in order to repair tissue.  Environmentally sensitive hydrogels. These hydrogels have the ability to sense changes of pH, temperature, or the concentration of metabolite and release their load as result of such a change.  As sustained-release delivery systems  Provide absorption, desloughing and debriding capacities of necrotics and fibrotic tissue.  Hydrogels that are responsive to specific molecules, such as glucose or antigens can be used as biosensors as well as in DDS.  Used in disposable diapers where they "capture" urine, or in sanitary napkins  Contact Lenses (silicone hydrogels, polyacrylamides)  Medical Electrodes using hydrogels composed of cross linked polymers (polyethylene oxide, polyAMPS and polyvinylpyrrolidone)  Water gel explosives  Other, less common uses include  breast implants  granules for holding soil moisture in arid areas  Dressings for healing of burn or other hard-to-heal wounds. Wound gels are excellent for helping to create or maintain a moist environment.  Reservoirs in topical drug delivery; particularly ionic drugs, delivered by iontophoresis (see ion exchange resin)  Common ingredients are e.g. polyvinyl alcohol, sodium polyacrylate, acrylate polymers and copolymers with an abundance of hydrophilic groups.  Natural hydrogel materials are being investigated for tissue engineering, these materials include agarose, methylcellulose, hylaronan, and other naturally derived polymers. Based on Rheological properties: Gels are considers to exhibit non-Newtonian properties. Gels may be classified based a rheological properties as plastic, pseudo plastic and thixotropic gels. Plastic gels for example Bingham bodies, flocculated suspension of Al (OH) 2 exhibit a plastic floe and the plot of rheogram gives yield value of gels above which the elastic gels distorts and begin to flow. Pseudo plastic gels e.g. liquid dispersion of natural gums like tragacanth, sodium alginate, methyl cellulose, sodium CMC, exhibit pseudo plastic flow. The viscosity of pseudo plastic gels decreases with increasing rate of shear, with no yield value. The rheogram for pseudo plastic material results from a shearing action on the long chain molecules of the linear polymers. As the shearing stress is increased, the disarranged molecules begin to align their long axis in the direction of flow with release of solvent from gel matrix. Thixotropic gels: The bonds between particles in these gels are very weak and can be broken down by a shaking or stirring. The resultant sol will revert back to gel due to the particle colliding and linking together again the reversible isothermal sol gel transformation is termed thixotropy. It is most likely to occur in colloidal system with non- spherical particles, to build up a scaffold like structure eg. Bentonite, kaolin and agar 0.5%. Based on the physical nature: Based on the physical nature i.e. consistency of gel they are classified as elastic and rigid gels. Elastic gel: Gel of agar, pectin, gaur gum, gelatin, and alginate exhibit a elastic behavior. The fibrous molecules being linked at the point of junction by relatively posses weak bounds such as hydrogen bounds and dipole attraction. If the molecule posses free –COOH group then additional bounding takes by salt bridge of type –COO-X2 + -COO between two adjacent strands network (ex. Alginate and carbopols) where “X” is linking atom/molecule. The type of link imparts elastic behavior to the gel and builds coulombs force, hydrogen bounding, and vander-waals force of attraction between gelling polymers. Rigid gels: It can be formed from macromolecule in which the framework linked by primary valence bound e.g. in solid silica gel, silicic acid molecules are held by Si-O-Si-O bound to give a polymer structure possessing a network
  17. 17. ISSN: 2320 – 3471(Online) Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 165 of pores. The rigid gels are even formed in case of polaxomers by thermal changes or reaction between poly vinyl alcohols with glycidyl ether or toluene disocyanate or methane diphenyl isocynate. GEL FORMING SUBSTANCES: A number of polymers are used to provide the structural network that is the essence of a gel system. These include natural gums, cellulose derivatives, and carbomers. Although most of these function in aqueous media, several polymers that can gel nonpolar liquids are also available. Certain colloidal solids behave as gallants as a result of asymmetric flocculation of the particles. High concentration of some nonionic surfactants can be used to produce clear gel in systems containing up to about 15% mineral oil. These are employed mostly as hair dressings. Gel forming polymers are classified as follows: A. Natural polymer 1. Agar 2. Alginates 3. carageenan 4. Tragacanth 5. Pectin 6. Xanthan 7. Gellan Gum 8. Guar Gum 9. Other gums 10. Chitosan etc. B. Semi synthetic polymers 1. Cellulose derivatives 2. Carboxymethyl cellulose 3. Methylcellulose 4. Hydroxypropyl cellulose 5. Hydroxy propyl (methyl cellulose) 6. Hydroxyethyl cellulose etc. C. Synthetic polymers 1. Carbomer 2. Carbopol 934 3. Carbopol 940 4. Carbopol 980 etc. 5. Poloxamer/surfactants 6. Polyacrylamide 7. Polyethylene and its co-polymers D. Inorganic substances 1. Microcrystalline silica 2. Clays E. Other gallants 1. Beeswax 2. Cetyl ester wax 3. Aluminum staerate etc. A. Natural polymers: Natural gums have been used in commerce since the beginning of recorded history. Typically, they are branched-chain polysaccharides. Most are anionic (negative charged in aqueous solution or dispersion), although a few, such as gaur, are neutral molecules. Differences in proportion of the sugar building blocks that make up these molecules and their arrangement and molecular weight result in significant variations in gum properties. Because of their chemical makeup, neutral gums are subjected to microbial degradation and support microbial growth. Aqueous systems containing gums should contain a suitable preservative. As mentioned earlier, cationic antimicrobials are not generally compatible with the anionic gums and should usually be avoided. Although many of the most familiar gums are plant exudates of extracts, other sources are also used. 1. Alginates: These polysaccharides containing varying proportion of D-mannuronic and L-guluronic acids are derived from brown seaweed in the form of monovalent and divalent salts. Although other alginate salts are available commercially, sodium alginate is by far the most widely used. Gelation occurs by reduction of pH or reaction with
  18. 18. ISSN: 2320 – 3471(Online) Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 166 divalent cations. Reduction of pH converts the carboxylate ions to free carboxyl groups. This reduces hydration of polymer segments as well as the repulsion between them. Generally, some calcium must be present; the small amounts contributed by the alginate may be sufficient. The pH at which gelation occurs calcium begins to gel below a pH 4. Gel strength is a function of alginate concentration; 0.5% is a practical minimum. 2. Carrageenan: All the carrageenans are anionic. Carrageenan, the hydrocolloid extracted from red seaweed, is a variable mixture of sodium, potassium, ammonium, calcium and magnesium sulfate esters of polymerized galactose, and 3,6-anhydrogalactose. The main copolymer types are labeled kappa-, iota-, and lambda-carrageenan. Kappa and iota fraction form thermally reversible gels in water. This has been ascribed to a temperature-sensitive molecular rearrangement. At high temperature, the copolymers exist as random coils; cooling result in formation of double helices that act as cross-links. 3. Tragacanth: Trgacanth is defined in the NFas the “dried gummy exudation from Astragalus gummifer Labillardiere, or other Asiatic species of Astragalus. Tragacanth is a complex material composed of chiefly of acidic polysaccharide (tragacanth acid) containing calcium, magnesium, and potassium, and a smaller amount of a neutral polysaccharide, tragacanthin. The gum swells in water; concentrations of 2 % or above a “high-quality” gum produce a gel. 4. Pectin: Pectin, the polysaccharide extracted from the inner skin of citrus fruit or apple pomance, may be used in pharmaceutical jellies as well as in foods. The gel is formed at an acid pH in aqueous solutions containing calcium and possibly another agent that acts to dehydrate the gum. 5. Xanthan gum: Although xanthan gum is used most frequently as a stabilizer in suspensions and emulsions at concentrations below 0.5%, higher concentrations in aqueous media yield viscid solutions that are jellylike in nature. Xanthan gum is produced by bacterial fermentation, and other its availability and quality are not subject to many of the uncertainties that affect other natural products, particularly those that are extracted from plants whose habitat falls within politically unsettled part of the world. Thermally reversible gels result from combinations of xanthan with gaur or locust bean gum. 6. Gellan gum: Gellan gum is another polysaccharide produced by fermentation that has FDA clearance for use in foods. The gum is highly efficient; as little as 0.05% is required for gel formation. Gels will not form in the absence of free cations. While both monovalent and divalent ions can include gelation, the divalent ions are required in much lower concentration, roughly 1/25 the concentration of monovalent ions. To produce a uniform gel, the gum is first dissolved in deionized water heated to 70-75°C. 7. Guar gum: Guar gum is a nonionic polysaccharide derived from seeds. Aqueous guar solutions can be cross- linked by several polyvalent cations to form gels. The mechanism is believed to involve chelate formation between groups in different polymer chains. A disadvantage of these gels is the presence of insoluble plant residue. 8. Other gums: Gelatin is used widely as a bodying agent and gel former in the food industry, and occasionally in pharmaceutical products. Agar can be used to make firm gels, it is most frequently used in culture media. 9. Chitosan: Chitosan is a natural biopolymer derived from the outer shell of crustaceans. Chitin is extracted and partially deacetylated to produce chitosan. Unlike most gums, chitosan carries a positive charge and is thus attracted to a variety of biological tissues and surfaces that are negatively charged. Various derivatives are being explored for specific applications. Concentrated aqueous solutions have a gel-like consistency. Firmer gels result from interaction with polysaccharides, such as alginate. B. Semi synthetic polymers Cellulose derivatives: Many useful derivatives are fashioned from cellulose, a natural structure polymer found in plants. Treatment in the presence of various active substances results in breakdown of the cellulose backbone as well as substitution of a portion of its hydroxyl moieties. The major factors affecting rheological properties of the resultant material are the nature of the substitution(s), degree of substitution, and average molecular weight of the resultant polymer. Carboxymethylacellulose: Carboxymethylcellulose, also known as sodium carboxymethylcellulose, CMC, and cellulose gum, is an anionic polymer available in a variety of grades that differ in molecular weight and degree of substitution. Gelation requires addition of an electrolyte with a polyvalent cation to a solution of the polymer; aluminum salts are proffered. Methylcellulose: Methylcellulose is an example of a polymer whose solubility in water decreases as the temperature is raised. If an aqueous solution is heated, viscosity increases markedly at a certain point as the result of aqueous solution is heated, viscosity increases markedly at a certain point as the result of formation of gel structure. This property, known as thermal gelation, is a function of polymer chemistry and the presence of additives. The gelation
  19. 19. ISSN: 2320 – 3471(Online) Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 167 temperature range for methocel type A is 50-55 °C. Salts and sugars with a high affinity for water lower the gelation temperature whereas alcohol and propylene glycol have the opposite effect. Other cellulose derivatives: Hydroxypropyl cellulose is soluble in water as well as many polar organic solvents. Consequently, it is useful as a gelling agent for such liquids and for mixture of water and various organic liquids, such as alcohol, that adversely affect the rheological properties of gums and certain other hydrophilic agents. High molecular weight grades of hydroxypropyl cellulose and hydroxyethyl cellulose, though highly viscous, behave as fluids and do not exhibit a yield value. C. Synthetic polymers Carbomer: Carbopol® polymers, along with Pemulen® polymeric emulsifiers are all cross-linked. They swell in water up to 1000 times their original volume (and ten times their original diameter) to form a gel when exposed to a pH environment between 4.0 - 6.0. Since the pKa of these polymers is 6.0 ± 0.5, the carboxylate groups on the polymer backbone ionize, resulting in repulsion between the negative charges, which adds to the swelling of the polymer. Cross-linked polymers do not dissolve in water. The glass transition temperature of Carbopol® polymer is 105°C in powder form. However, the glass transition temperature drops dramatically as the polymer comes into contact with water. The polymer chains starts gyrating and the radius of gyration becomes larger. Macroscopically, this phenomenon manifests itself as swelling. Carbopol® polymers and co-polymers are used mainly in liquid or semisolid pharmaceutical formulations as suspending or viscosity increasing agents. Formulations include creams, gels and ointments. Carbopol® polymers are also employed as emulsifying agents in the preparation of o/w emulsions for external use and are also employed in cosmetics (C. Rowe, 2003). Poloxamer/surfactants: Poloxamer is a synthetic block copolymer of ethylene oxide and propylene oxide. Their molecular weight ranges from 1000-15000. In a molecule the hydrophilic poly (oxyethylene) sand witches the hydrophilic poly (oxypropylene) thereby the polo oxypropylene occupies a central position in the molecule and it is flanked by two hydrophilic polyoxyethylene blocks. The differences in the chain length of the polyoxyethylene and polyoxypropylene chains in different products are responsible for the divergences in their physical, chemical and practical properties. Polyethylene and its co-polymers: Various forms of polyethylene and its copolymers are used to gel hydrophobic liquids. The result is a soft, easily spreadable semisolid that forms a water-resistant film on the skin surface. Polyethylene itself is a suitable gellant for simple aliphatic hydrocarbon liquids but may lack compatibility with many other oils found in personal care products. For, these, copolymers with vinyl acetate and acrylic acid may be used, perhaps with the aid of a co-solvent. To form the gels, it is necessary to disperse the polymer in the oil at elevated temperature (above 80 °C) and then shock cool to precipitate fine crystals that make up the matrix. D. Inorganic Substances: Certain finely divided solids can function efficiently as thickening agents in various liquid media. Gel formation depends on establishment of a network in which colloidal particles of the solid are connected in an asymmetric fashion. This requires mutual attraction of the particles (flocculation) and partial wetting by the liquid. Microcrystalline silica: Microcrystalline silica can functions as a gallant in a wide range of liquids. Network formation results from attraction of the particles by polar forces, principally hydrogen bonding. An important commercial application of silica is its use in dentifrices. Microcrystalline silica acts as a bonding agent that provides thixotropy to the formation; at the same time, the required concentration of polishing agents is required. Clays: Montmorillonite clays are capable of swelling in water as the result of hydration of exchangeable cations and electrostatic repulsion between the negatively charged faces. At high concentration in water, thixotropic gels are fromed because the particles combine in a flocculated structure in which the face of one particle is attracted to the edge of another. METHOD OF PREPARATION OF GELS Gels are normally in the industrial scale prepared under room temperature. However few of the polymers need special treatment before processing. The gel preparation can be categorized under the following headings: Gel prepared by thermal change: The solubility of most lyophilic colloids e.g. Gelatin, agar is reduced on lowering the temperature, so that cooling a concentrated hot sol will often produce a gel. In contrast to this, some material such as the cellulose ethers owe their water solubility to hydrogen bonding with the water. Raising the temperature of these sols will disrupt the hydrogen bonding and the reduced solubility will cause gelation. Gel prepared by flocculation with neutralizers: Gelation is produced by adding just sufficient precipitation to produce the gel state but insufficient to bring about complete precipitation. It is necessary to ensure rapid mixing to avoid local high concentrations of precipitant. Solutions of ethyl cellulose, polystyrene in benzene can be gelled by rapid mixing with suitable amounts of a nonsolvent such as petroleum ether. The additions of salts to hydropholic
  20. 20. ISSN: 2320 – 3471(Online) Shaik Arif basha et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 168 sols bring coagulation, and gelation is rarely observed. The additions of suitable proportion of salts to moderately hydrophilic sols such as aluminum hydroxide, bentonite, etc. produce gels. The gels formed are frequently thixotropic in behavior. Hydrophilic colloids such as gelatin and acacia are only affected by high concentration of electrolytes, when the effect is to “salt out” the colloid and gelation does not occur. Gel prepared by chemical reaction: In the preparation of sols by precipitation from solution e.g. aluminum hydroxide sol prepared by interaction in aqueous solution of an aluminum salt and sodium carbonate, an increased concentration of reactants will produce a gel structure. USES The uses of gels and gelling are quite widespread, but discussion here is limited to the pharmaceutical and cosmetic fields only. Gels find use as delivery system for oral administration as gels proper or as capsule shells made from gelatin; for topical drug applied directly to the skin,mucous membranes, or eye ; and for long-acting forms of drug injected intramuscularly or implanted into the body. Geliing agents are useful as binders in tablet granulations,protective colloids in suspensions, thickeners in oral liquids, and suppository bases. Cosmetically, gels have been employed in a wide variety of products,including shampoos,fragrance products,dentifrices, and skin and hair-care preparation. CONLUSION Dermatological formulations are among the most frequently compounded products because of their wide range of potential uses. These include solutions (i.e., collodions, liniments, aqueous and oleaginous solutions), suspensions and gels, emulsions, lotions, and creams. Lotions can be either suspensions or emulsions but are fluid liquids that are typically used for their lubricating effect. Creams are emulsions and are typically opaque, thick liquids or soft solids used for their emollient properties. Creams also have the added feature that they tend to "vanish" or disappear with rubbing. REFERENCES Alfred Martin, James Swarbrick, Arthur Cammarala, Physical Pharmacy 3rd Edition, 1983, 56-569, 522, 542. C. Rowe, P. J. Sheskey, P. J. Weller, Handbook of Pharmaceutical Excipients 4th Edition, Pharmaceutical Press, London, UK, 2003, 89 - 92. Fresno,M. J. C. Ramírez A. D., Jiménez M. M..Systematic study of the flow behaviour and mechanical properties of Carbopol hydroalcoholic gels. European Journal of Pharmaceutics and Biopharmaceutics, 2002, 54, 329 - 335. Herbert A Libermen, Martin M Rieger, Gilbert S Banker, Gels: In Pharmaceutical Dosage Forms, Dispersed Systems, Informa Health Care,1996, 399-419 Herbert A. Libermen,Martin M.Rieger, Gilbert S. Banker, Gels. In Pharmaceutical Dosage Forms, Dispersed Systems, Informa Health Care, 1996, 399-419. Herbert A. Libermen,Martin M.Rieger, Gilbert S. Banker. Gels. In Pharmaceutical Dosage Forms, Informa Health Care, 1996, 399-419. Lachman HP, Lieberman JL, Kanig, Theory and Practice of Industrial Pharmacy, 3rd Edition, Varghese Publishing House, Bombay, 1987, 534-548. MN Nutimer, Chromatograph, Biomed App, 420, 1987, 228-230.
  21. 21. ISSN: 2320 – 3471(Online) J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 169 RECENT TRENDS OF POLYMER USAGE IN THE FORMULATION OF ORODISPERSIBLE TABLETS J.Preethi, MD Farhana, B.Chelli Babu, MD.Faizulla, Debjit Bhowmik* , S.Duraivel Nimra College Pharmacy, Nimranagar, Vijayawada, Andhra Pradesh, India *Corresponding author: debjit_cr@yahoo.com ABSTRACT Disintegrants are an essential component to tablet formulations. While rapidly disintegrating tablets do not necessarily ensure fast bioavailability, slowly disintegrating tablets almost always assure slow bioavailability. The ability to interact strongly with water is essential to disintegrant function. Combinations of swelling and/or wicking and/or deformation are the mechanisms of disintegrant action. Super disintegrants offer significant improvements over starch. But hygroscopicity may be a problem in some formulations. Tablet disintegration has received considerable attention as an essential step in obtaining fast drug release. Disintegration remains a powerful influence and precursor for drug absorption. Disintegration of tablet or capsule is depending upon the type and quantity of disintegrants. The development of Orodispersible tablets provides an opportunity to take an account of tablet disintegrants. Therefore, there is a huge potential for the evaluation of new disintegrants or modification of an existing disintegrants into superdisintegrants, so as to formulate Orodispersible tablets. The present study comprises the various kinds of disintegrants and superdisintegrants, which are being used in the formulation to provide the safer, effective drug delivery with patient's compliance. Key words: Super disintegrants, Polysorbate, Modified starches, Modified cellulose, Crospovidone 1. INTRODUCTION Bioavailability of a drug depends in absorption of the drug, which is affected by solubility of the drug in gastrointestinal fluid and permeability of the drug across gastrointestinal membrane. The drugs solubility mainly depends on physical – chemical characteristics of the drug. However, the rate of drug dissolution is greatly influenced by disintegration of the tablet. The drug will dissolve at a slower rate from a non-disintegrating tablet due to exposure of limited surface area to the fluid. The disintegration test is an official test and hence a batch of tablet must meet the stated requirements of disintegration. Disintegrants are substances or mixture of substances added the drug formulation that facilitates the breakup or disintegration of tablet or capsule content into smaller particles that dissolve more rapidly than in the absence of disintegrants. Superdisintegrants are generally used at a low level in the solid dosage form, typically 1 to 10 % by weight relative to the total weight of the dosage unit. Examples of Superdisintegrants are crosscarmelose, crosspovidone, sodium starch glycolate which represent example of a crosslinked cellulose, crosslinked polymer and a crosslinked starch respectively. Superdisintegrants -an economical alternative: Orally disintegrating tablets are an emerging trend in formulation, gaining popularity due to ease of administration and better patient compliance for geriatric and pediatric patients. Disintegrating agents are substances routinely included in tablet formulations and in some hard shell capsule formulations to promote moisture penetration and dispersion of the matrix of the dosage form in dissolution fluids. An oral solid dosage form should ideally disperse into the primary particles from which it was prepared. Although various compounds have been proposed and evaluated as disintegrants, relatively few are in common usage today. Traditionally, starch has been the disintegrant of choice in tablet formulations, and it is still widely used. However, starch is far from ideal. For instance, starch generally has to be present at levels greater than 5% to adversely affect compactibility, especially in direct compression. Moreover, intragranular starch in wet granulations is not as effective as dry starch. In more recent years, several newer disintegrants have been developed. Often called “super disintegrants,” these newer substances can be used at lower levels than starch. Because they can be a smaller part of the overall formulation than starch, any possible adverse effect on fluidity or compactibility would be minimized. These newer disintegrants may be organized into three classes based on their chemical structure (Table 1). Method of addition of disintegrants: The requirement placed on the tablet disintegrant should be clearly defined. The ideal disintegrant has- 1. Poor solubility 2. Poor gel formation 3. Good hydration capacity 4. Good molding and flow properties 5. No tendency to form complexes with the drugs
  22. 22. ISSN: 2320 – 3471(Online) J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 170 Disintegrants are essentially added to tablet granulation for causing the compressed tablet to break or disintegrate when placed in aqueous environment. There are two methods of incorporating disintegrating agents into the tablet: I. Internal Addition (Intragranular) II.External Addition (Extragranular) III.Partly Internal and External In external addition method, the disintegrant is added to the sized granulation with mixing prior to compression. In Internal addition method, the disintegrant is mixed with other powders before wetting the powder mixtures with the granulating fluid. Thus the disintegrant is incorporated within the granules. When these methods are used, part of disintegrant can be added internally and part externally. This provides immediate disruption of the tablet into previously compressed granules while the disintegrating agent within the granules produces further erosion of the granules to the original powder particles. The two step method usually produces better and more complete disintegration than the usual method of adding the disintegrant to the granulation surface only. Table 1 Classification of “super disintegrants” (partial listing) Structural type (NF name) Description Trade name (manufacturer) Modified starches (Sodium starch glycolate, NF) Sodium carboxymethyl starch; the carboxymethyl groups induces hydrophilicity and cross-linking reduces solubility. Explotab®(Edward Mendell Co.) Primojel® (Generichem Corp.) Tablo® (Blanver, Brazil) Modified cellulose (Croscarmellose, NF) Sodium carboxymethyl cellulose which has been cross-linked to render the material insoluble. AcDiSol® (FMC Corp.) Nymcel ZSX® (Nyma, Netherlands) Primellose® (Avebe, Netherlands) Solutab® (Blanver, Brazil) Cross-linked poly- vinylpyrrolidone (Crospovidone, NF) Cross-linked polyvinylpyrrolidone; the high molecular weight and cross- linking render the material insoluble in water. Crospovidone M® (BASF Corp.) Kollidon CL® (BASF Corp.) Polyplasdone XL (ISP Corp.) Factors affecting action of disintegrants: 1. Percentage of disintegrants present in the tablets. 2. Types of substances present in the tablets. 3. Combination of disintegrants. 4. Presence of surfactants. 5. Hardness of the tablets. 6. Nature of Drug substances. 7. Mixing and Screening. Effect of fillers:The solubility and compression characteristics of fillers affect both rate and mechanism of disintegration of tablet. If soluble fillers are used then it may cause increase in viscosity of the penetrating fluid which tends to reduce effectiveness of strongly swelling disintegrating agents and as they are water soluble, they are likely to dissolve rather than disintegrate. Insoluble diluents produce rapid disintegration with adequate amount of disintegrants. Chebli and cartilier proved that tablets made with spray dried lactose (water soluble filler) disintegrate more slowly due to its amorphous character and has no solid planes on which the disintegrating forces can be exerted than the tablet made with crystalline lactose monohydrate. Effect of binder: As binding capacity of the binder increases, disintegrating time of tablet increases and this counteract the rapid disintegration. Even the concentration of the binder can also affect the disintegration time of tablet. Effect of lubricants: Mostly lubricants are hydrophobic and they are usually used in smaller size than any other ingredient in the tablet formulation. When the mixture is mixed, lubricant particles may adhere to the surface of the other particles. This hydrophobic coating inhibits the wetting and consequently tablet disintegration. Lubricant has a strong negative effect on the water uptake if tablet contains no disintegrants or even high concentration of slightly swelling disintegrants. On the contrary, the disintegration time is hardly affected if there is some strongly swelling disintegrants are present in the tablet. But there is one exception like sodium starch glycolate whose effect remains unaffected in the presence of hydrophobic lubricant unlike other disintegrants.
  23. 23. ISSN: 2320 – 3471(Online) J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 171 Effect of surfactants: Sodium lauryl sulphate increases absorption of water by starch. Surfactants are only effective within certain concentration ranges. Surfactants are recommended to decrease the hydrophobicity of the drugs because the more hydrophobic the tablet the greater the disintegration time. Table.2. Effects of various surfactants on the disintegration of tablets containing various drugs SURFACTANT REMARKS Sodium lauryl sulfate Good-various drugs Poor - various drugs Polysorbate 20 Good Polysorbate 40 & 60 Poor Polysorbate 80 Good Tweens Poor Poly ethylene glycol Poor (Good – decrease in disintegration time, Poor – increase in disintegration time) Superdisintegrants used in formulation of orodispersible tablets: Disintegrating agents are substances routinely included in the tablet formulations to aid in the breakup of the compacted mass when it is put into a fluid environment. They promote moisture penetration and dispersion of the tablet matrix. In recent years, several newer agents have been developed known as “Superdisintegrants”. These newer substances are more effective at lower concentrations with greater disintegrating efficiency and mechanical strength. On contact with water the superdisintegrants swell, hydrate, change volume or form and produce a disruptive change in the tablet. Effective superdisintegrants provide improved compressibility, compatibility and have no negative impact on the mechanical strength of formulations containing high-dose drugs. The commonly available superdisintegrants along with their commercial trade names are briefly described herewith. Modified starches: Sodium starch glycolate is the sodium salt of a carboxymethyl ether of starch. It is effective at a concentration of 2-8%. It can take up more than 20 times its weight in water and the resulting high swelling capacity combined with rapid uptake of water accounts for its high disintegration rate and efficiency. It is available in various grades i.e. Type A, B and C, which differ in pH, viscosity and sodium content. Other special grades are available which are prepared with different solvents and thus the product has a low moisture (<2%) and solvent content (<1%), thereby being useful for improving the stability of certain drugs. Modified celluloses Carboxymethylcellulose and its derivative (Croscarmellose Sodium): Cross-linked sodium carboxymethylcellulose is a white, free flowing powder with high absorption capacity. It has a high swelling capacity and thus provides rapid disintegration and drug dissolution at lower levels. It also has an outstanding water wicking capability and its cross-linked chemical structure creates an insoluble hydrophilic, highly absorbent material resulting in excellent swelling properties. Its recommended concentration is 0.5–2.0%, which can be used up to 5.0% L-HPC (Low substituted Hydroxy propyl cellulose) It is insoluble in water, swells rapidly and is used in the range of 1-5%. The grades LH- 11 and LH-21 exhibit the greatest degree of swelling. Cross-linked polyvinylpyrrolidone: It is a completely water insoluble polymer. It rapidly disperses and swells in water but does not gel even after prolonged exposure. The rate of swelling is highest among all the superdisintegrants and is effective at 1-3%. It acts by wicking, swelling and possibly some deformation recovery. The polymer has a small particle size distribution that imparts a smooth mouth feel to dissolve quickly. Varieties of grades are available commercially as per their particle size in order to achieve a uniform dispersion for direct compression with the formulation. Soy polysaccharide: It is a natural super disintegrant that does not contain any starch or sugar so can be used in nutritional products. Cross-linked alginic acid: It is insoluble in water and disintegrates by swelling or wicking action. It is a hydrophilic colloidal substance, which has high sorption capacity. It is also available as salts of sodium and potassium. Gellan gum: It is an anionic polysaccharide of linear tetrasaccharides, derived from Pseudomonas elodea having good superdisintegrant property similar to the modified starch and celluloses. Xanthan gum: Xanthan Gum derived form Xanthomonas campestris is official in USP with high hydrophilicity and low gelling tendency. It has low water solubility and extensive swelling properties for faster disintegration. Calcium Silicate: It is a highly porous, lightweight superdisintegrant, which acts by wicking action. Its optimum concentration range is 20-40%
  24. 24. ISSN: 2320 – 3471(Online) J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 172 Ion exchange resins: The INDION 414 has been used as a superdisintegrant for ODT. It is chemically cross-linked polyacrylic, with a functional group of – COO – and the standard ionic form is K+. It has a high water uptake capacity. Others: Although there are many superdisintegrants, which show superior disintegration, the search for newer disintegrants is ongoing and researchers are experimenting with modified natural products, like formalincasein, chitin, chitosan, polymerized agar acrylamide, xylan, smecta, key-jo-clay, crosslinked carboxymethylguar and modified tapioca starch. Mechanism of action of superdisintegrating agent: Disintegrants are agents added to tablet (and some encapsulated) formulations to promote the breakup of the tablet (and capsule “slugs’) into smaller fragments in an aqueous environment thereby increasing the available surface area and promoting a more rapid release of the drug substance. There are three major mechanisms and factors affecting tablet disintegration as follows: A: Swelling: Although not all effective disintegrants swell in contact with water, swelling is believed to be a mechanism in which certain disintegrating agents (such as starch) impart the disintegrating effect. By swelling in contact with water, the adhesiveness of other ingredients in a tablet is overcome causing the tablet to fall apart. B: Porosity and Capillary Action (Wicking): Effective disintegrants that do not swell are believed to impart their disintegrating action through porosity and capillary action. Tablet porosity provides pathways for the penetration of fluid into tablets. The disintegrant particles (with low cohesiveness & compressibility) themselves act to enhance porosity and provide these pathways into the tablet. Liquid is drawn up or “wicked” into these pathways through capillary action and rupture the interparticulate bonds causing the tablet to break apart. C: Deformation: Starch grains are generally thought to be “elastic” in nature meaning that grains that are deformed under pressure will return to their original shape when that pressure is removed. But, with the compression forces involved in tableting, these grains are believed to be deformed more permanently and are said to be “energy rich” with this energy being released upon exposure to water. In other words, the ability for starch to swell is higher in “energy rich” starch grains than it is for starch grains that have not been deformed under pressure. It is believed that no single mechanism is responsible for the action of most disintegrants. But rather, it is more likely the result of inter-relationships between these major mechanisms. The classical example of the earliest known disintegrant is Starch. Corn Starch or Potato Starch was recognized as being the ingredient in tablet formulations responsible for disintegration as early as 1906 (even though tablet disintegration was itself not given much importance in tablet formulations until much later). Until fairly recently, starch was the only excipient used as a disintegrant. To be effective, corn starch has to be used in concentrations of between 5-10%. Below 5%, there is insufficient “channels” available for wicking (and subsequent swelling) to take place. Above 10%, the incompressibility of starch makes it difficult to compress tablets of sufficient hardness. Although the connection between bioavailability of drug and tablet disintegration took some time to become appreciated, it is now accepted that the role of the disintegrant is extremely important. In a direct compression process, drug is blended with a variety of excipients, subsequently lubricated and directly compressed into a tablet. A disintegrant used in this type of formulation, simply has to break the tablet apart to expose the drug substance for dissolution. Pregelatinized Starch (Starch 1500): Pregelatinized starch is a directly compressible form of starch consisting of intact and partially hydrolyzed ruptured starch grains. Pregelatinized starch has multiple uses in formulations as a binder, filler and disintegrant. As a disintegrant, its effective use concentration is between 5-10%. It’s major mechanism of action as a disintegrant is thought to be through swelling. Microcrystalline Cellulose (Avicel): Like pregelatinized starch, microcrystalline cellulose is widely used in formulations because of its excellent flow and binding properties. It is also an effective tablet disintegrant when used in a concentration of between 10-20%. Others: Sodium Bicarbonate in combination with citric or tartaric acids is used as an “effervescent” disintegrant.Alginic Acid at a concentration of between 5-10% is an effective, but very expensive disintegrant.Ion Exchange Resins (Amberlite 88) has disintegrant properties at a concentration of between 1-5%. But this type of disintegrant is rarely used. Super disintegrants: Because of the increased demands for faster dissolution requirements, there are now available, a new generation of “Super Disintegrants” in addition to the disintegrants discussed earlier. Three major groups of compounds have been developed which swell to many times their original size when placed in water while producing minimal viscosity effects:
  25. 25. ISSN: 2320 – 3471(Online) J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 173 1. Modified Starches: Sodium Carboxymethyl Starch (Chemically treated Potato Starch) i.e. Sodium Starch Glycolate (Explotab, Primogel) Mechanism of Action: Rapid and extensive swelling with minimal gelling. Effective Concentration: 4-6%. Above 8%, disintegration times may actually increase due to gelling and its subsequent viscosity producing effects. 2. Cross-linked polyvinylpyrrolidone: water insoluble and strongly hydrophilic. i.e. crospovidone (Polyplasdone XL, Kollidon CL) Mechanism of Action: Water wicking, swelling and possibly some deformation recovery. Effective concentration: 2-4% dified Cellulose: Internally cross-linked form of Sodium carboxymethyl cellulose. i.e. Ac-Di-Sol (Accelerates Dissolution), Nymcel Mechanism of Action: Wicking due to fibrous structure, swelling with minimal gelling. Effective Concentrations: 1-3% (Direct Compression), 2-4% (Wet Granulation) ADVANTAGES:  Effective in lower concentrations than starch  Less effect on compressibility and flow ability  More effective intragranularly DISADVANTAGES:  More hygroscopic (may be a problem with moisture sensitive drugs)  Some are anionic and may cause some slight in-vitro binding with cationic drugs (not a problem in-vivo). Table.3. List of disintegrants Disintegrants Concentration in granules (%w/w) Special comments Starch USP 5-20 Higher amount is required, poorly compressible Starch 1500 5-15 - Avicel® (PH 101, PH 102) 10-20 Lubricant properties and directly compressible Solka floc® 5-15 Purified wood cellulose Alginic acid 1-5 Acts by swelling Na alginate 2.5-10 Acts by swelling Explotab® 2-8 Sodium starch glycolate, superdisintegrant. Polyplasdone® (XL) 0.5-5 Crosslinked PVP Amberlite® (IPR 88) 0.5-5 Ion exchange resin Methyl cellulose, Na CMC, HPMC 5-10 - AC-Di-Sol® 1-3 Direct compression 2-4 Wet granulation CONCLUSION: Disintegrants, an important excipient of the tablet formulation, are always added to tablet to induce breakup of tablet when it comes in contact with aqueous fluid and this process of desegregation of constituent particles before the drug dissolution occurs, is known as disintegration process and excipients which induce this process are known as disintegrants.The objectives behind addition of disintegrants are to increase surface area of the tablet fragments and to overcome cohesive forces that keep particles together in a tablet. One of the challenges every formulator of oral solid dosage forms must address is drug solubility. Drugs must dissolve efficiently to be absorbed by the body, but this is a special challenge fo rpoorly soluble drugs. The choice of formulation ingredients can have a significant effect on the rate and extent of drug dissolution. Superdisintegrants used as enhance solubililty of poorly water soluble drugs.
  26. 26. ISSN: 2320 – 3471(Online) J Preethi et.al Indian Journal of Research in Pharmacy and Biotechnology Volume 1(2) March-April 2013 Page 174 Table.4. List of superdisintegrants SUPERDISINTEGRANTS EXAMPLE OF MECHANISM OF ACTION SPECIAL COMMENT Crosscarmellose® , Ac-Di-Sol® , Nymce ZSX® , Primellose® , Solutab® , Vivasol® Crosslinked cellulose Swells 4-8 folds in < 10 seconds. Swelling and wicking both. Swells in two dimensions, Direct compression or granulation, Starch free Crosspovidone, Crosspovidon M® , Kollidon® , Polyplasdone® Crosslinked PVP Swells very little and returns to original size after ompression but act by capillary action Water insoluble and spongy in nature so get porous tablet Sodium starch glycolate Explotab® , Primogel® Crosslinked starch Swells 7-12 folds in <30 seconds Swells in three dimensions and high level serve as sustain release matrix Alginic acid NF Satialgine® Crosslinked alginic acid Rapid swelling in aqueous medium or wicking action Promote disintegration in both dry or wet granulation Soy polysaccharides Emcosoy® Natural super disintegrant Does not contain any starch or sugar. Used in nutritional products. Calcium silicate Wicking action Highly porous, light weight optimum concentration is between 20-40% REFERENCES Bi Y, Sunada H, Yonezawa Y, Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity, Chem Pharm Bull (Tokyo), 44, 1996, 2121-2127. Bi YX, Sunada H, Yonezawa Y, Danjo K.Evaluation of rapidly disintegrating tablets prepared by a direct compression method, Drug Dev Ind Pharm, 25, 1999, 571-581. Chaudhari K.P.R, and Rao Rama N, Indian Drugs, 35 (6), 1988, 368 to 371, Chudhari K. P.R, and Radhika, Int. J. Pharm. Excipts, 2000 (4), 181-184 Grasono Alesandro et al, US Patent 6, 1997, 336 2001 Grasono, Alessandro et al, U S Patent 6,197,336 2001 Ihang J. A., & Christensen J. M., Drug Dev Ind Pharn, 22 (8), 1996, 833-839 Korunubhum S. S., Batopak S. B., J. Pharm Sci, 62 (1), 1973, 43-49 Liberman H.A., Lachman L. and Schawstr J.B., Pharmaceutical Dosage forms, tablets, vol 2, 1989, 173-177 Sallam E, Ibrahim H, Abu Dahab R, Shubair M, Khalil E.Evaluation of fast disintegrants in terfenadine tablets containing a gas-evolving disintegrant, Drug Dev Ind Pharm, 24, 1998,501-507. Sallem E, Ibrahim H, Dahab R. A, Drug Dev. Ind. Pharm, 24 (6), 1998, 501-507 Schimidt P.C and Brogramann B, Acta. Pharm. Technol, 1988, 34, 22.

×