Formulation and evaluation of

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Formulation and evaluation of

  1. 1. ““FORMULATION ANDEVALUATIONFORMULATION ANDEVALUATION OFOF FASTDISSOLVING TABLETDOSAGEFASTDISSOLVING TABLETDOSAGE FORM”FORM” PREPARED BY: Gajanan S. Ingole GUIDED BY : K. B. Charhate DEPARTMENT OF PHARMACEUTICS ANURADHA COLLEGE OF PHARMACY, CHIKHLI. 2012-2013.
  2. 2. Introduction. Review of literature. Drug profile. Excipients. Aim & objectives. Plan of work. Materials & Equipments Experimental work. Result & Discussion. Conclusion. References. CONTENTS :
  3. 3. US FDA defined ODT as “A solid dosage form containing medicinal substances which disintegrates rapidly usually within a matter of seconds, when placed upon the tongue”. Recently, ODT have started gaining popularity and acceptance as new drug delivery systems, because they are easy to administer and better patient compliance, especially in elderly and children. Orodispersible tablets are also known as Mouth dissolving tablets, Orally disintegrating tablets, Melt in mouth, Fast‐ ‐ dissolving drug delivery, Rapimelts tablets, Porous tablets, Quick dissolving tablets etc. Defination :
  4. 4. Orodispersible tablets (ODT) are oral solid dosage forms that disintegrate in the oral cavity in easy swallow residue. faster the drug goes into solution, quicker the absorption and onset of clinical effect, as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablets dosage form. Recently ODT terminology has been approved by United States Pharmacopoeia, British Pharmacopoeia and Centre for Drug Evaluation and Research (CDER).
  5. 5. Advantages of fast dissolving drug delivery system Ease administration for patients who are mentally ill, disabled and uncooperative. No water needed. Can be designed to leave minimal or no residue in mouth It provide a pleasant mouth feel. No chewing needed. Better taste obtained by taste masking. Improved stability, low sensitivity to environmental condition
  6. 6. Disadvantage of Mouth Dissolving Tablets: Drugs with relatively larger doses are difficult to formulate into FDT e.g. antibiotics Patients who concurrently take anticholinergic medications may not be the best candidates for FDT. patients with Sjogren's syndrome or dryness of the mouth due to decreased saliva production may not be good candidates for these tablet formulations.
  7. 7. Need to formulate fast dissolving tablets Geriatric patients mainly suffering from conditions like hand tremors and dysphasia. Pediatric patients who are unable to swallow easily because their central nervous system and internal muscles are not developed completely. Traveling patients suffering from BP and angina pectoris that do not have easy access to water. Mentally challenged patients, bedridden patients and psychiatric patients.
  8. 8. The ideal characteristics of a drug for fast dissolving tablet 1. Ability to permeate the oral mucosa. 2. Have the ability to diffuse and partition into the epithelium of the upper GIT. 3. Small to moderate molecular weight. 4. Low dose drugs preferably less than 50 mg. 5. Short half life and frequent dosing drugs are unsuitable for ODT. 6. Very bitter or unacceptable taste and odour drugs are unsuitable for ODT.
  9. 9. TECHNIQUES FOR SOLUBILITY ENHANCEMENT Inclusion Complex Formation Techniques Grinding method: Drug and carriers were blended in desired proportions using spatula for 10 minutes and then ground in mortar with pestle. The co-grinding mixture was then passed through sieve #40 and stored in desiccator until further use. eg. Cyclodextrine Advantages of cyclodextrin complexes It improves bioavailability from solid formulations. Stability and shelf life can be increased. Gastrointestinal irritation may be reduced. Complexation prevents drug-drug or drug-additive interaction. It can be used to mask unpleasant odor and taste.
  10. 10. 2. REVIEW OF LITERATURE:- 1) Vikas Agarwal et al: Encyclopedia of pharmaceutical technology, Third edition, Volume 2;stated that A large number of companies are in the ODT drug.As pharmaceutical companies are now starting to recognize the need for more technological advances to meet the new challenges in the future, DDT continues to have a significant impact and contribution in meeting those demands and challenges. 2)Abu-Izza et al: Patent on Fast dissolving tablet; shows the present invention relate to the process for preparation of tablet which dissolve rapidly in the mouth and provide an excellent mouthfeel. The tablet of the invention comprise a compound which melt at about 370 C.or lower, have a low hardness, high stability and generally comprise a few insoluble disintegrant which may cause a gritty or chalky sensation in the mouth
  11. 11. Convenient and economically feasible processes by which the tablet of the invention may be produced are also provided.(United States Patent, Patent No. US 6,733,781 B2) . 3) Jain et al: Patent on Rapidly disintegrating solid dosage form; stated that the rapidly disintegrating solid dosage form of poorly soluble active ingredient and at least one pharmaceutically acceptable water- soluble or water-dispersible excipient, where in poorly soluble active ingredient particles have an average diameter, prior to inclusion in the dosage form, of less than about 2000nm.the dosage form of the invention has the advantage of combining rapid presentation and rapid dissolution of the active ingredient in oral cavity(.(United States Patent, Patent No. US 6,316,029 B1) 4) Sahu Chandra Mohan et al: Recent advances in orodispersible tablets: A Review; studied on The techniques and technologies described in this article represent how recent advances in formulation development and processing technologies make the efforts to achieve orodispersible tablets, conclude that the basic approach followed by all
  12. 12. Felodipine (Calcium channel blocker) Category : Antihypertensive and antianginal. Structural formula : Molecular formula : C18H19Cl2NO4 DRUG PROFILE
  13. 13. 13 Molecular weight : 384.25 Description : Slightly yellowish & Crystalline powder. Solubility : It is insoluble in water & freely soluble in ethanol & dichloromethane. Melting point : 142-1450 c Dose : 5mg ones a day Bioavailibility : 15% Absorption : Completely absorbed from g.i.t Metabolism : Metabolised in gut & liver.
  14. 14. Excipients 14
  15. 15. AIM : Formulation of fast dissolving tablet and evaluate them to get optimized result. OBJECTIVES : 1.For rapid dissolution of drug and absorption which may produce rapid onset of action. 2. To avoid first pass metabolism 3.To Improved patient compliance. 4. It can be designed to leave minimal or no residue in mouth . 5. To improved biopharmaceutical properties and better safety compared with conventional oral dosage forms.
  16. 16. PLAN OF WORK: 1. Literature survey. 2. Procurment of drug, polymer & other excipients for the study. 3. Selection of material of required standard & qualitative analysis of raw material 4. Pre-formulation studies. 5. Preparation of various formulae for study.
  17. 17. 6) Evaluation of tablet. a)Tablet appearance. b)Thickness. c)Diameter. d)Hardness. e)Friability. f)Weight variation. g)Assay of tablet. h)Disintegration study i)Dissolution study
  18. 18. Sr. no Ingredients Grade Suppliers 1 Felodipine Pharma Ajanta pharma Ltd,Mumbai 2 Cross carmellose sodium Pharma FDC Ltd, Mumbai 3 Crosspovidone Pharma Leben Laboratories Pvt. Akola 4 Sodium starch glycolate Pharma Leben Laboratories Pvt. Akola 5 Microcrystalline cellulose Pharma Leben Laboratories Pvt. Akola 6 Magnesium stearate Pharma Leben Laboratories Pvt. Akola 7 Talc Pharma Leben Laboratories Pvt. Akola 8 Mannitol AR Rajesh chemicals Materials & Equipments Table : List of Excipients
  19. 19. Sr. No Instruments Manufacturer 1 Electronic Balance Dolphin,Mumbai. 2 Tablet compression machine Cadmach, Ahemadabad. 3 Electronic balance Dolphin,Mumbai. 4 Friability Test Apparatus Roche Friabilator 5 Vernier Caliper Mitutoyo,Japan 6 Tablet Dissolution Tester Electro Lab.(USP XX III) (DTD- 06P) 7 Ultra violet Spectrophotometer UVvisible Double Beam, Elico. (SL218). 8 Fourier Transform Infra Red IR affinity-1,FTIR- 8001:Shimadzu,Japan 9 Digital pH meter Equip-Tronics,EQ-610. 10 Hot Air Oven Shreeji pharmaceuticals,scientific lab Mumbai,India. Table: List of Equipments Equipments
  20. 20. EXPERIMENTAL WORK : SPECTRAL ANALYSIS OF FELODIPINE Differential Scanning Colorimery DRUG –POLYMER INTERACTONS Fourier transform infrared spectroscopy PREPARATION OF BUFFERS AND REAGENTS 1 Sodium hydroxide solution (0.1 N) 2 Monobasic sodium phosphate monohydrate(1 M) 3 Dibasic sodium Phosphate anhydrous(0.5M) 4 Phosphate buffer solution (pH 6.5)
  21. 21. FTIR Spectra of Felodipine DSC of Felodipine FTIR spectra of Felodipine physical mixture.
  22. 22. DETERMINATION OF λ MAX It shows maximum absorbance (λ max) : 312.2 nm
  23. 23. Standard Calibration Curve In phosphate buffer pH 6.5 Concentration(µg/ ml) Absorbance 0 0 10 0.09 20 0.1811 30 0.2737 40 0.3448 50 0.4235 Table : Conc. And absorbance From the standard curve of Felidipine, it was observed that the drug obeys beer’s law in concentration range of 10 to 50 µg/ml against absorbance at 312 nm. in 6.5 phosphate buffer. The linear regression equation generated was used for the calculation of amount of drug release. The value of R2 is 0.997.
  24. 24. FORMULATION DESIGN Direct Compression Method Sr.No Ingredients F1 F2 F3 F4 F5 F6 F7 F8 F9 1 FD+β-CDN complex 10 10 10 10 10 10 10 10 10 2 CP 3 6 9 - - - - - - 3 CCS - - - 3 6 9 - - - 4 SSG - - - - - - 3 6 9 5 Avicel pH101 10 10 10 10 10 10 10 10 10 6 Talc 6 6 6 6 6 6 6 6 6 7 Mg.streate 2 2 2 2 2 2 2 2 2 8 Mannitol 89 86 83 89 86 83 89 86 83 Total 120 120 120 120 120 120 120 120 120 Table : Composition of Fast dissolving tablet formulation containing Felodipine The ingredients used in the manufacture of tablets for the batches F1 to F9 are shown in the Table *FD-Felodipine,*CP-crospovidone,*CCS-crosscarmellose sodium,*SSG-sodium starch glycolate
  25. 25. Physical properties Bulk density. Tapped density. Carr´s Compressibility index. Hausner’s ratio. Angle of repose. Table : Physical properties of the powder-blends of the batches F1 to F3 Parameter F1 F2 F3 Bulk density (gm/cc) Tapped density (gm/cc) Angle of repose, Compressibility index (%) Hausner’s ratio 0.57 0.68 43.15 16.17 1.19 0.47 0.73 41.81 35.61 1.55 0.54 0.72 28.60 18.51 1.29
  26. 26. Parameter F4 F5 F6 Bulk density (gm/cc) Tapped density (gm/cc) Angle of repose, Compressibility index (%) Hausner’s ratio 0.58 0.78 27.34 10.00 1.34 0.56 0.78 40.10 28.20 1.39 0.58 0.77 48.23 24.67 1.32 Table : Physical properties of the powder-blends of the batches F4 to F6 Parameter F7 F8 F9 Bulk density (gm/cc) Tapped density (gm/cc) Angle of repose, Compressibility index (%) Hausner’s ratio 0.58 0.70 26.56 17.14 1.20 0.61 0.72 32.46 15.20 1.18 0.59 0.70 36.32 15.71 1.18 Table : Physical properties of the powder-blends of the batches F7 to F9
  27. 27. 1. Thickness. 2. Diameter. 3. Hardness. 4. Friability. 5. Weight variation. 6. Assay of tablet. 7. Disintegration study 8. Dissolution study Evaluation parameter of tablet.
  28. 28. Sr.No. Parameters F1 F2 F3 1. Thickness (mm 2.5 2.6 2.5 2 Diameter (mm) 6 6 6.1 3 Hardness (kg/cm2. ) 2.86 3.3 2.8 4 Friability (%) 0.81 0.40 0.48 5 Uniformity of weight (mg) 121±10% 116±10 121±10 6 Drug content (%) 96.35 95.87 99.20 7 Disintegration time(sec) 137 129 116 Table: Post compression parameter of fast dissolving tablets for the batches F1 to F3 Sr.No. Parameters F4 F5 F6 1 Thickness (mm) 2.9 2.8 2.7 2 Diameter (mm) 6.1 6 6 3 Hardness (kg/cm2) 3.6 3.8 2.6 4 Friability (%) 0.97 0.48 0.97 5 Uniformity of weight (mg) 122±10 122 ±10 127±10 6 Drug content (%) 96.72 94.5 92.26 7 Disintegration time(Sec) 140 132 126 Table : Post compression parameter of fast dissolving tablets for the batches F4 to F6
  29. 29. Sr. No. Parameters F7 F8 F9 1 Thickness (mm) 2.6 2.6 2.6 2 Diameter (mm) 6.1 6 6.1 3 Hardness (kg/cm2. 4.2 3.5 3.7 4 Friability (%) 1.1 0.40 0.88 5 Uniformity of weight (mg) 125±10 122±10 124±10 6 Drug content (%) 96.72 94.74 97.03 7 Disintegration time(Sec) 138 141 134 Table : Post compression parameter of fast dissolving tablets for the batches F7 to F9
  30. 30. Sr.No. Time (Min) % Drug Release F1 F2 F3 1 1 38.55 15.72 18.28 2 3 54.55 24.60 28.6 3 5 72.47 33.90 39.42 4 10 76.89 52.81 61.41 5 15 73.09 66.60 77.89 6 30 89.07 77.89 90.58 7 45 94.92 84.44 98.18 0 20 40 60 80 100 120 0 10 20 30 40 50 F1 F2 F3 Time(min) %DrugRelease Comparative dissolution profile of F1, F2,F3 Table : In vitro release of felodipine from tablets for the batches F-1 to F-3 Figure : In vitro release of felodipine from the tablets for the batches F1, F2 and F3.
  31. 31. Sr.No. Time (Min) % Drug Release F4 F5 F6 1 1 24.42 36.87 39.64 2 3 28.60 40.48 39.64 3 5 31.65 46.69 54.20 4 10 43.20 53.02 57.08 5 15 51.42 66.39 64.16 6 30 66.93 78.95 80.64 7 45 81.19 88.63 93.76 0 10 20 30 40 50 60 70 80 90 100 0 10 20 30 40 50 F4 F5 F6 Time (Min) Comparative dissolution profile of F4, F5,F6 %DrugRelease Figure: In vitro release of felodipine from the tablets for the batches F4, F5 and F6. Table : In vitro release of felodipine from tablets for the batches F-4 to F-6
  32. 32. Sr. No. Time (Min) % Drug Release F7 F8 F9 1 1 19.75 24.75 28.33 2 3 26.98 30.11 35.19 3 5 37.13 36.70 41.10 4 10 50.35 48.75 48.75 5 15 53.86 63.41 61.93 6 30 70.3 76.73 78.95 7 45 80.14 88.21 92.09 Figure : In vitro release of felodipine from the tablets for the batches F7, F8 and F9 Table : In vitro release of felodipine from tablets for the batches F-7 to F-9
  33. 33. 1. Suitable analytical method based on UV-Visible spectrophotometer was developed for felodipine. λmax of 312.2 nm was identified in methanol and 311 nm in phosphate buffer solution, pH 6.5. 2. From the FT-IR spectra the interference was verified and found that felodipine did not interfere with the excipients used. 3. Direct compression method was established to manufacture fast dissolving tablets of felodipine. 4. Fast dissolving tablets of felodipine were successfully prepared using croscarmellose sodium, sodium starch glycolate, crospovidone. SUMMARY AND CONCLUSION SUMMARY
  34. 34. 5. In the present study, fast dissolving tablets were prepared using single superdisintegrant in each formulation 6. Evaluation parameters like hardness, friability, weight variation and drug content indicate that values were within permissible limit for all formulations. 7. In vitro drug release study was carried out and based on the results; F-3 was identified as the best formulation among all the other formulations and In vitro release profiles was more than 98% within 45 minutes. 8. The formulation F-3 contains croscarmelose a polymer which causes the disintegration by capillary action. It causes the in vitro dispersion within 45 min. and hence the formulation F3 was optimized after conducting the reproducibility study.
  35. 35. CONCLUSION The conclusions arrived in this thesis indicated that the Fast dissolving tablet of felodipine developed in this investigation releases drug batter than conventional tablet drug release, based on in vitro release studies. Further studies are needed to investigate these formulations for its performance in vivo. Thus the objectives of the present thesis are achieved. The result of the study indicates that fast dissolving tablet of felodipine that can be successfully prepared.
  36. 36. REFERENCES:- Mudgal Vinod Kumar, Sethi Pooja, Kheri Rajat, Saraogi G.K., Singhai A.K. Orally Disintegrating Tablets:International Research Journal Of Pharmacy.2011,2(2230 – 8407) 16-22 http://www.pharmainfo.net/tablet-ruling-dosage-form-years/types-tabl . http://4my3939.blogspot.in/ Chein YW. Oral drug delivery and delivery system, 2nd Edition, New York; marcel Dekkar,1992 Harmon TM. Orally Disintegrating Tablet: A Valuable Life cycle management strategy, pharmaceutical commerce march 2007, available online www.pharmaceuticalcommerce.com
  37. 37. Tanmoy Ghosh, Amitava Ghosh And Devi Prasad; A Review On new Generation Orodispersible Tablets And Its Future Prospective (International Journal Of Pharmacy And Pharmaceutical Sciences; Vol 3, Issue 1, (2011) Pebley, W.S., Jager, N.E., Thompson, S.J., Rapidly disintegrating tablets, US Patent No. 5,298,261, 1994. Bhandari S, Kumar R, Mittapalli R, Madhusudan R, Orodispersible tablet: An overview. Asian Journal of Pharmaceutics, 2 10, (2008).‐ Kumaresan C, Orally Disintegrating Tablet - Rapid Disintegration, Sweet Taste, and Target Release Profile, Pharmainfo.Net Sep9 2008.
  38. 38. Agrawal V.A, Rajurkar R.M Thonte S.S, Ingale R.G. Fast Disintegrating Tablet As A New Drug Delivary System:A Review; Pharmacophore (An International Research Journal).2011; Vol. 2 (1), (2229 – 5402) 1. Abu-Izza et al: Patent on Fast dissolving tablet; United States Patent, Patent No. US 6,733,781 B2 Jain et al: Patent on Rapidly disintegrating solid dosage form; United States Patent, Patent No. US 6,316,029 B1 Sahu Chandra Mohan, Chandira R. Margret, Recent advances in orodispersible tablets: A Review. International Journal Of drug discovery And Herbal Research -(IJDDHR).2011, 32(2):78-83
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