Aim: This diploma thesis focused on the study of the influence of two types of high-shear
mixers as well as the effect of poly(meth)acrylate concentrations on the properties of
prepared granules and consequently matrix tablets.
Methods: Caffeine was employed as the model drug and matrix tablets were prepared via
the wet granulation process using two different high-shear mixers either Stephan UMC5 or
Rotolab mixer. Eudragit® NM 30D was used in various concentrations as a wet granulation
agent for time controlled drug release with low permeability and pH independent swelling.
In addition, lactose monohydrate was added as indifferent soluble filler, magnesium
stearate served as the antiadhesive excipient and colloidal silica was added for flowability
improvement. Matrix tablets were evaluated for mass, content and dosage uniformity,
uniformity of dosage units, friability, hardness and dissolution according to Ph. Eur.
Results - Conclusions: All prepared tablets exhibited sustained drug release. The
employment of different mixers for sustained matrix tablets preparation did not
significantly influence the release profile of caffeine (Eudragit® NM concentrations 9-
14%), except when the lower Eudragit® NM concentration (7%) was used for granulation.
Furthermore, Eudragit® NM concentrations (7 – 14% per tablet) did not significantly affect
the release profile of caffeine from matrix tablets, neither in the Stephan UMC5 nor the
Rotolab mixer.
Development and Evaluation of Enteric Coated Herbal Drug Delivery System for ...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Aim: This diploma thesis focused on the study of the influence of two types of high-shear
mixers as well as the effect of poly(meth)acrylate concentrations on the properties of
prepared granules and consequently matrix tablets.
Methods: Caffeine was employed as the model drug and matrix tablets were prepared via
the wet granulation process using two different high-shear mixers either Stephan UMC5 or
Rotolab mixer. Eudragit® NM 30D was used in various concentrations as a wet granulation
agent for time controlled drug release with low permeability and pH independent swelling.
In addition, lactose monohydrate was added as indifferent soluble filler, magnesium
stearate served as the antiadhesive excipient and colloidal silica was added for flowability
improvement. Matrix tablets were evaluated for mass, content and dosage uniformity,
uniformity of dosage units, friability, hardness and dissolution according to Ph. Eur.
Results - Conclusions: All prepared tablets exhibited sustained drug release. The
employment of different mixers for sustained matrix tablets preparation did not
significantly influence the release profile of caffeine (Eudragit® NM concentrations 9-
14%), except when the lower Eudragit® NM concentration (7%) was used for granulation.
Furthermore, Eudragit® NM concentrations (7 – 14% per tablet) did not significantly affect
the release profile of caffeine from matrix tablets, neither in the Stephan UMC5 nor the
Rotolab mixer.
Development and Evaluation of Enteric Coated Herbal Drug Delivery System for ...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Formulation and evaluation of omeprazole floating tabletsmedicinefda
formulation and evaluation of omeprazole floating tablets, literature review and plan of work ,methods results and discussion,conclusion sample ppt http://www.medicinefda.com/
Bilayer tablet is suitable for sequential release of two drugs in combination and also for controlled release tablet in which one layer is for immediate release as initial dose and the second layer is for controlled release or maintenance dose. Bilayer tablet is an improved beneficial technology to overcome the shortcoming of the monolayer tablet. This technology avoids frequent administration of dosage form. Now a days such technology is used for co-administration of two drugs like anti-diabetic, anti-hypertensive, anti-inflammatory to the patients. Conventional solid oral dosage forms are a traditional approach, but bilayer tablet is a novel approach that requires new machinery for manufacturing. The technique is cost effective, safe and reproducible.
Preparation and evaluation of kollidon sr matrix tablets of tinidazole for co...IJSIT Editor
Amoebiasis is an infection of the large intestine caused by Entamoeba histolytica, and it is mainly
present in the intra-intestinal lumen. The efficient treatment of amoebiasis and other colonic infections could
be achieved by targeting the drug to the colon. Tinidazole is the drug of choice for intestinal amoebiasis and
other colonic infections and the best approach for this drug is to target the drug to the colon which would
make the drug effective with low dose and prevent the potential hazards observed in conventional dose.
Moreover, addition of suitable polymers in the formulation could enhance the drug solubility. The aim of the
present investigation was to formulate matrix formulations using different concentrations of Kollidon SR and
PVP K-30, Eudragit S100 to prevent the premature drug release in the GI tract, the matrix formulations
further taken for compression to test the suitability for targeted drug delivery to the colon. The release
kinetics of the formulations was calculated. All the Matrix, compression coated formulations showed the
desired physicochemical properties as per the official limits. Based on the drug release study in pH 1.2 (0.1N
HCl), Phosphate buffer pH 6.8 and the results showed that among the 9 formulations FE2 and FL3 showed
good dissolution profile to control the drug release respectively.
ABSTRACT
Hyperglycemia is the technical term for high blood glucose (sugar). It
happens when the body has too little or not enough insulin or when the
body can‘t use insulin properly. The main objective of the present
research work was to develop a bilayer tablet of immediate release
Pioglitazone and controlled release Metformin Hydrochloride, which is
used as an Anti-hyperglycemic agent. Metformin Hydrochloride has
biological half-life nearly about 6 hours, so, an attempt was made in
the direction of preparation and optimization of a combination of
sustained release and immediate release in a single tablet. In controlled
release layer natural gums like xanthum gum, gum trgacanth and guar
gum were used as retarding materials and in immediate release laye
croscarmellose sodium was used as a superdisintegrent to give the faster release of
pioglitazone. The tablets were prepared by wet granulation method and by direct
compression. Granules were evaluated for precompression parameters and the tablets were
evaluated for post compression parameters.
Key Words: Bilayer tablets, Metformin Hydrochloride, pioglitazone, xanthum gum, guar
gum, gum tragacanth and crosscarmellose sodium.
Matrix dosage forms in pharmaceutics (pharmaceutical dosage forms)YashYuvaraj
various sources from#detail of matrix dosage forms!!
1formulative pharmacy and biopharmaceutics
@pharmaceutical dosage forms
department of pharmaceutics
Design and in vitro evaluation of bilayer tablets of Tramadol hydrochloride f...ijperSS
ABSTRACT
The aim of the present work was to design bilayer tablet of Tramadol hydrochloride for biphasic release and its in vitro evaluation. Bilayer tablets comprises of two layers, i.e., immediate release and sustained release layer. The immediate release layer comprised of various superdisintegrants and the sustained release layer comprised HPMC K4M, HPMC K15M, and HPMC K100M as the release retarding polymers. The bilayer tablets were prepared by direct compression method. The seven different formulations (F1-F7) were evaluated for pre- and post-compression parameters. In vitro dissolution studies were carried out for the optimized formulation (F6). It has found that the release of drug from the sustained release layer by 99.5% in 12 h. FT-IR studies revealed that there was no interaction between the drug and polymers used in the study. The release of Tramadol hydrochloride was found to follow a pattern of Korsmeyer-Peppas, with Quasi-Fickian diffusion. Accelerated stability studies were carried out on the prepared tablets in accordance with ICH guidelines. There were no changes observed in physicochemical properties and drug release pattern of tablets. Biphasic drug release pattern was successfully achieved through the formulation of bilayer tablets in this study.
Key words: Tramadol hydrochloride, bilayer tablet, direct compression, carmellose sodium, cross povidone, HPMC K4M.
Formulation and evaluation of omeprazole floating tabletsmedicinefda
formulation and evaluation of omeprazole floating tablets, literature review and plan of work ,methods results and discussion,conclusion sample ppt http://www.medicinefda.com/
Bilayer tablet is suitable for sequential release of two drugs in combination and also for controlled release tablet in which one layer is for immediate release as initial dose and the second layer is for controlled release or maintenance dose. Bilayer tablet is an improved beneficial technology to overcome the shortcoming of the monolayer tablet. This technology avoids frequent administration of dosage form. Now a days such technology is used for co-administration of two drugs like anti-diabetic, anti-hypertensive, anti-inflammatory to the patients. Conventional solid oral dosage forms are a traditional approach, but bilayer tablet is a novel approach that requires new machinery for manufacturing. The technique is cost effective, safe and reproducible.
Preparation and evaluation of kollidon sr matrix tablets of tinidazole for co...IJSIT Editor
Amoebiasis is an infection of the large intestine caused by Entamoeba histolytica, and it is mainly
present in the intra-intestinal lumen. The efficient treatment of amoebiasis and other colonic infections could
be achieved by targeting the drug to the colon. Tinidazole is the drug of choice for intestinal amoebiasis and
other colonic infections and the best approach for this drug is to target the drug to the colon which would
make the drug effective with low dose and prevent the potential hazards observed in conventional dose.
Moreover, addition of suitable polymers in the formulation could enhance the drug solubility. The aim of the
present investigation was to formulate matrix formulations using different concentrations of Kollidon SR and
PVP K-30, Eudragit S100 to prevent the premature drug release in the GI tract, the matrix formulations
further taken for compression to test the suitability for targeted drug delivery to the colon. The release
kinetics of the formulations was calculated. All the Matrix, compression coated formulations showed the
desired physicochemical properties as per the official limits. Based on the drug release study in pH 1.2 (0.1N
HCl), Phosphate buffer pH 6.8 and the results showed that among the 9 formulations FE2 and FL3 showed
good dissolution profile to control the drug release respectively.
ABSTRACT
Hyperglycemia is the technical term for high blood glucose (sugar). It
happens when the body has too little or not enough insulin or when the
body can‘t use insulin properly. The main objective of the present
research work was to develop a bilayer tablet of immediate release
Pioglitazone and controlled release Metformin Hydrochloride, which is
used as an Anti-hyperglycemic agent. Metformin Hydrochloride has
biological half-life nearly about 6 hours, so, an attempt was made in
the direction of preparation and optimization of a combination of
sustained release and immediate release in a single tablet. In controlled
release layer natural gums like xanthum gum, gum trgacanth and guar
gum were used as retarding materials and in immediate release laye
croscarmellose sodium was used as a superdisintegrent to give the faster release of
pioglitazone. The tablets were prepared by wet granulation method and by direct
compression. Granules were evaluated for precompression parameters and the tablets were
evaluated for post compression parameters.
Key Words: Bilayer tablets, Metformin Hydrochloride, pioglitazone, xanthum gum, guar
gum, gum tragacanth and crosscarmellose sodium.
Matrix dosage forms in pharmaceutics (pharmaceutical dosage forms)YashYuvaraj
various sources from#detail of matrix dosage forms!!
1formulative pharmacy and biopharmaceutics
@pharmaceutical dosage forms
department of pharmaceutics
Design and in vitro evaluation of bilayer tablets of Tramadol hydrochloride f...ijperSS
ABSTRACT
The aim of the present work was to design bilayer tablet of Tramadol hydrochloride for biphasic release and its in vitro evaluation. Bilayer tablets comprises of two layers, i.e., immediate release and sustained release layer. The immediate release layer comprised of various superdisintegrants and the sustained release layer comprised HPMC K4M, HPMC K15M, and HPMC K100M as the release retarding polymers. The bilayer tablets were prepared by direct compression method. The seven different formulations (F1-F7) were evaluated for pre- and post-compression parameters. In vitro dissolution studies were carried out for the optimized formulation (F6). It has found that the release of drug from the sustained release layer by 99.5% in 12 h. FT-IR studies revealed that there was no interaction between the drug and polymers used in the study. The release of Tramadol hydrochloride was found to follow a pattern of Korsmeyer-Peppas, with Quasi-Fickian diffusion. Accelerated stability studies were carried out on the prepared tablets in accordance with ICH guidelines. There were no changes observed in physicochemical properties and drug release pattern of tablets. Biphasic drug release pattern was successfully achieved through the formulation of bilayer tablets in this study.
Key words: Tramadol hydrochloride, bilayer tablet, direct compression, carmellose sodium, cross povidone, HPMC K4M.
Formulation development and invitro evaluation of lamotrigine fast dissolving...SriramNagarajan19
The present study was to formulate and evaluate oral fast dissolving Oral tablet containing Lamotrigine. Present study reveals that all the nine formulated tablet showed satisfactory tablet parameters. It can be concluded that, Oral fast dissolving tablet -containing Lamotrigine can be prepared by direct compression method. 10% CCS (FV) tablet exhibited required disintegration time and dissolution time. The drug release was about 98.7 % in 15min. The accelerated stability studies of the optimized F5 formulation indicates that the formulated oral fast dissolving tablet were unaffected after 3 months storage under accelerated conditions as there were no signs of visually distinguishable changes in appearance, disintegration time and cumulative percentage of drug release. From the present investigation it can be concluded that oral fast dissolving tablet formulation can be a potential novel drug dosage form for pediatric, geriatric and also for general population.
ABSTRACT
Overactive bladder (OAB) is a prevalent condition which has an adverse effect on quality of life. The presence
of urgency incontinence confers significant morbidity above and beyond that of OAB sufferers who are
continent. The primary treatment for OAB and urgency incontinence is a combination of behavioral measures
and antimuscarinic drug therapy. The ideal antimuscarinic agent should effectively relieve the symptoms of
OAB, with the minimum of side effects; it should be available as a once-daily sustained release formulation
and in dosage strength that allows easy dose titration for the majority of sufferers. Solifenacin succinate was
launched in 2005 and has been shown in both short and long term clinical trials to fulfill these requirements.
Solifenacin is a competitive M3 receptor antagonist with a long half-life (45-68 hours). It is available in two
dosage strengths namely a 5 or 10 mg once-daily tablet. The efficacy and tolerability of solifenacin for the
treatment of all symptoms of OAB has been evaluated in a number of large, placebo controlled, randomized
trials. Long-term safety, efficacy, tolerability and persistence with treatment have been established in an open
label 40 week continuation study.
KEYWORDS
Solifenacin, Urinary incontinence, Overactive bladder and Wet granulation method.
The main objective of present investigation is to formulate the floating tablets of
Ranitidine.HCl using 32 factorial design. Ranitidine.HCl, H2-receptor antagonist belongs to
BCS Class-III. The Floating tablets of Ranitidine.HCl were prepared employing different
concentrations of HPMCK4M and Guar Gum in different combinations as a release rate
modifiers by Direct Compression technique using 32 factorial design. The concentration of
Polymers , HPMCK4M and Guar Gum required to achieve desired drug release was selected
as independent variables, X1 and X2 respectively whereas, time required for 10% of drug
dissolution (t10%), 50% (t50%), 75% (t75%) and 90% (t90%) were selected as dependent variables.
Totally nine formulations were designed and are evaluated for hardness, friability, thickness,
% drug content, Floating Lag time, In-vitro drug release. From the Results concluded that all
the formulation were found to be within the Pharmacopoeial limits and the In-vitro
dissolution profiles of all formulations were fitted in to different Kinetic models, the
statistical parameters like intercept (a), slope (b) & regression coefficient (r) were calculated.
Polynomial equations were developed for t10%, t50%, t75%, t90%. Validity of developed
polynomial equations were verified by designing 2 check point formulations(C1, C2).
According to SUPAC guidelines the formulation (F5) containing combination of 22.5%
HPMCK4M and 22.5% Guar Gum, is the most similar formulation (similarity factor f2=85.01,
dissimilarity factor f1= 15.358 & No significant difference, t= 0.169) to marketed product
(ZANTAC). The selected formulation (F5) follows Higuchi’s kinetics, and the mechanism of
drug release was found to be Non-Fickian Diffusion (n= 0.922).
MICROBALLOONS: A NOVEL APPROACH IN GASTRO-RETENTION FLOATING DRUG DELIVERY SY...Snehal Patel
ABSTRACT
Oral controlled release dosage forms face several physiological restriction like inability to retain
and position the controlled drug delivery system within the targeted region of the gastrointestinal
tract (GIT) due to fluctuation in gastric emptying. This results in non uniform absorption
pattern, inadequate medication release and shorter residence time of the dosage form in the
stomach. As the fallout of this episode there is inadequate absorption of the drug having
absorption window predominantly, in the upper area of GIT. These contemplations have
provoked to the development of oral controlled release dosage forms with gastroretentive
properties. Microballoons (Hollow microspheres) hold certification as one of the potential
approaches for gastric retention. Microballoons are spherical empty particles without core and
can remain in the gastric region for delayed periods. They significantly increase the gastric
residence time of medication, thereby enhance bioavailability, improves patient compliance by
reducing dosing frequency, lessen the medication waste, enhance retention of medication which
solubilize only in stomach, enhance solubility for medications that are less soluble at a higher pH
environment. The present review preparation methods, characterization, advantages,
disadvantages, mechanism of drug release from microballoons, applications and list of the drugs
formulated as microballoons are discussed.
KEYWORDS: Microballoons, Gastro-retention, Floating drug delivery system (FDDS).
Stability indicating method and validation for the simultaneous estimation of...SriramNagarajan18
Stability indicating method and validation for the simultaneous estimation of metformin and empagliflozin by using RP-HPLC in a bulk and pharmaceutical dosage forms
Stability indicating method development and validation for the estimation of ...SriramNagarajan18
Stability indicating method development and validation for the estimation of Doxorubicin by using RP-HPLC method in a bulk and pharmaceutical dosage form
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Development, optimization and invitro characterization of Losartan potassium gastroretentive bioadhesive tablets
1. Sandhya P et al / Int. J. of Farmacia, 2016; Vol-(2) 2: 106-117
106
International Journal of Farmacia
Journal Home page: www.ijfjournal.com
Development, optimization and invitro characterization of Losartan
potassium gastroretentive bioadhesive tablets
Pamu Sandhya*1, 2
, Shireen Begum 2
1
University College of Technology, Department of Pharmacy, Osmania University,
Hyderabad 500 007, Telangana State, India
2
Shadan Women’s College of Pharmacy, Department of Pharmaceutics, Khairatabad,
Hyderabad, 500 004, Telangana State, India
Corresponding Author: Pamu Sandhya
*
E-mail: sandhyapasikanti@gmail.com
ABSTRACT
Losartan bioadhesive tablets were prepared by direct compression method. The tablets were evaluated for pre
compression and post compression parameters, swelling studies and in-vitro drug release. The formulation with
desired drug release was tested for stability. The formulation F8 was selected as the best formulation, as the release
of Losartan from the formulation was found to be zero order kinetics and Korsmeyer-Peppas model. The optimized
formulation was found to have good mucoadhesive strength in sheep gastric mucosa and showed drug release up to
12 hours (99.8 %).Therefore, bimodal drug release pattern was successfully achieved through the formulation of
bioadhesive tablets in this study. Formulating bioadhesive tablets of losartan increased the bioavailability to 99.8 %
with the use of polymer carbopol.
Keywords: Gastro retentive, Bioadhesive, HPMC K4M, Carbopol 974 P, Losartan, zero order kinetics and
Korsmeyer-Peppas model.
INTRODUCTION
Historically, oral drug administration has been the
predominant route for drug delivery due to the ease of
administration, patient convenience and flexibility in
formulations [3]. However, it is a well-accepted fact
today that drug absorption throughout the GI tract is
not uniform. Using currently utilized release
technology, oral drug delivery for 12 or even 24 hours
is possible for many drugs that are absorbed uniformly
from GI tract [5]. Nevertheless this approach is not
suitable for a variety of important drugs characterized
by narrow absorption window in the upper part of GI
tract i.e., stomach and small intestine [1]. The design
of oral controlled drug delivery systems (OCDDS)
should be primarily aimed to achieve the more
predictability and reproducibility to control the drug
release [6], drug concentration in the target tissue and
optimization of the therapeutic effect of a drug by
controlling its release in the body with lower and less
frequent dose [2].
Controlled release system
Controlled release dosage forms cover a wide
range of prolonged action formulations which provide
continuous release of their active ingredients at a
predetermined rate and predetermined time [7]. The
most important objective for the development of these
systems is to furnish an extended duration of action
and thus assure greater patient compliance [8]. Ideally,
2. Sandhya P et al / Int. J. of Farmacia, 2016; Vol-(2) 2: 106-117
107
the optimization of therapeutic efficacy and safety
may be attained as a result of providing nearly a
constant pharmacological response [9], thereby
avoiding the normal peak and valley pattern associated
with multiple dosing of conventional drug products
[4]. To improve the efficacy of oral administration,
some recent studies have reported that controlled oral
drug delivery system with prolonged gastric residence
time [10], such as bioadhesive dosage system have
been proved to be advantages. Approaches to gastric
retention [11].
1. Floating Systems
2. Bio/Muco-adhesive Systems
3. Swelling and Expanding Systems
4. High Density Systems
5. Incorporation of Passage Delaying Food Agents
6. Ion Exchange Resins
7. Osmotic Regulated Systems
Losartan is a selective, competitive angiotensin II
receptor type 1 (AT1) receptor antagonist [12],
reducing the end organ responses to angiotensin II.
Losartan administration results in a decrease in total
peripheral resistance (afterload) and cardiac venous
return (preload) [13]. All of the physiological effects
of angiotensin II, including release of aldosterone, are
antagonized in the presence of losartan [14].
Reduction in blood pressure occurs independently of
the status of the renin-angiotensin system [15]. As a
result of losartan dosing, plasma renin activity
increases due to removal of the angiotensin II
feedback [16].
MATERIALS AND METHODS
Losartan USP grade, Lactose monohydrate, Micro
crystalline cellulose, HPMC K4M, ethyl cellulose,
Carbopol 974 P and Magnesium stearate [17].
Formulation of bioadhesive tablet of Losartan
Potassium
The bioadhesive tablets of losartan potassium was
prepared by blending the drug with different
concentrations of polymers [18], physical mixture was
then compressed by direct compression method. Nine
formulations were prepared [19].
FTIR studies of losartan with excipients
Infrared spectrum of losartan, excipients was
determined by Fourier transform infrared
spectrophotometer using KBr pellet method [20].
Table 1: Formulation of Losartan Bioadhesive tablets
Ingredients
(mg)
Losartan Lactose
monohydrate
Micro
crystalline
cellulose
HPMCK4
M
Ethyl
cellulose
Carbopol Mg.
stearate
Total
F1 25 86.25 86.25 50 - - 2.5 250
F2 25 61.25 61.25 100 - - 2.5 250
F3 25 36.25 36.25 150 - - 2.5 250
F4 25 86.25 86.25 - 50 - 2.5 250
F5 25 61.25 61.25 - 100 - 2.5 250
F6 25 36.25 36.25 - 150 - 2.5 250
F7 25 86.25 86.25 - - 50 2.5 250
F8 25 61.25 61.25 - - 100 2.5 250
F9 25 36.25 36.25 - - 150 2.5 250
Post formulation studies
The tablets of the proposed formulations F1 to F9
were evaluated for hardness by using Monsanto
hardness tester [21], weight variation, and thickness by
using Vernier calipers, friability by using Roche
friabilator and drug content. Losartan tablets should
contain not less than 90.0 percent and not more than
110.0 percent [22, 23].
In-vitro drug release studies
The USP II dissolution test apparatus is used. The
whole assembly is kept in a jacketed vessel of water
maintained at 37± 10
C. Bio adhesive tablet is stuck on
to the bottom of the flask (so as to allow one sided
release from the tablet).The beaker is filled with
900ml of phosphate buffer. The vessel is maintained at
100 rpm under stirring conditions by means of a
3. Sandhya P et al / Int. J. of Farmacia, 2016; Vol-(2) 2: 106-117
108
paddle fabricated for the purpose in a dissolution
apparatus [24, 25]. At various time intervals samples
of dissolution medium are withdrawn and filtered
through whatman filter paper. It is replaced
immediately with an equal amount of fresh buffer. The
samples are then analyzed in UV spectrophotometer at
234 nm. Absorbance measured and % drug release is
determined.
Swelling studies
The tablets of each formulation were weighed
individually (designated as W1) and placed separately
in petri dishes containing 2 % agar gel. At regular
intervals of 1, 2, 3, 4, 5, 6, 7 and 8 hours, the tablets
were removed from the petri dishes and excess water
was removed carefully by using filter paper. The
swollen tablets were reweighed (W2), the swelling
index of each formulation was calculated using the
formula,
Evaluation of bioadhesive strength
Detachment force measurement
Method
Immediately after slaughter, the intestines was
removed from the goat and transported to laboratory in
tyrode solution is (g/litre); (sodium chloride 8 gm;
potassium chloride 0.2 gm; calcium chloride 2H2O
0.134 gm; sodium bicarbonate 1.0 gm; sodium
dihydrogen phosphate 0.05 gm and glucose H2O 1gm).
During this experiment take the intestine in a specified
area and place it on one glass slide and tie it. The glass
slide with the intestine was affixed on one side floor
below the modified physical balance. Already
prepared 200 mg plain polymer tablet was pasted in
another glass slide and it balanced in the assembled
physical balance with a beaker in other side which is
used to hold the water. Now the balance was
calibrated.
RESULTS AND DISCUSSION
Pre-formulation studies
The loose bulk density and tapped bulk density of
all the batches varied from 0.343±0.030 to
0.446±0.006g/ml and 0.372±0.012 to 0.507±0.010
g/ml. Carr’s consolidation index ranged from
4.76±0.001to 13.63±0.005. Results clearly showed
that flow- ability of all the formulations is good and
has good compressibility (Table 2).
Pre-compression parameters of Losartan tablets blend
Table 3: Pre-compression parameters of Losartan tablets blend F1-F9
F.
code
Angle of Repose
(0
)
Bulk
Density
(gm / ml )
Tapped
Density
(gm / ml )
Compressbility Index
(%)
Hausner
Ratio
F1 19.77±1.04 0.394±0.00 0.416±0.01 5.263±3.29 1.055±0.03
F2 20.01±0.87 0.399±0.00 0.446±0.00 10.526±0.42 1.117±0.00
F3 20.54±0.41 0.357±0.02 0.375±0.04 4.761±3.65 1.050±0.04
F4 19.35±1.34 0.375±0.01 0.416±0.01 10.000±0.05 1.111±0.00
F5 22.86±1.13 0.340±0.03 0.394±0.03 13.636±2.62 1.157±0.03
F6 21.53±0.19 0.441±0.03 0.500±0.04 11.764±1.29 1.133±0.01
F7 21.37±0.08 0.416±0.01 0.468±0.02 11.111±0.83 1.125±0.00
F8 22.53±0.73 0.441±0.03 0.500±0.04 11.764±1.29 1.133±0.015
F9 23.32±1.46 0.394±0.00 0.441±0.00 10.526±0.42 1.117±0.00
4. Sandhya P et al / Int. J. of Farmacia, 2016; Vol-(2) 2: 106-117
109
Standard curve of losartan potassium in 0.1 N HCL
Table 4: Standard curve of Losartan
Concentration (µg/ml) Absorbance at 234 nm
0 0
10 0.1414
20 0.2968
30 0.4539
40 0.6085
50 0.7686
Fig. 1: Standard calibration curve of Losartan
Post formulation studies
The tablets of the proposed formulations F1 to F9
were evaluated for hardness, weight variation,
thickness, friability and drug content. The thickness
for tablets (n=3, mean ± SD) ranged from 4.0 ± 0.04 to
4.10 ± 0.02 mm. The hardness and friability (n=3,
mean ± SD) of the tablets was found to be ranging
from 4.7±0.20 to 6.5±0.20 kg/cm2
respectively. All the
tablets passed the weight variation test i.e., they were
within the Pharmacopoeia limits of ±5%. Content
uniformity ranged from 99.0±0.54to 100.47±0.34,
meets the USP specification of 90-100 %. All the
batches of the fabricated tablets were of good quality
with regard to hardness, friability and drug content
(Table 5).
Table 5: Post formulation studies of F1-F9
Form. Weight variation
(mg)
Thickness
(mm)
Hardness
(Kg/cm2
)
Friability
(%)
Drug content
(%)
Muco adhesion
force
F1 248±0.02 4.1±0.10 4.7±0.06 0.17±0.0001 99±0.157 1.867±0.022
F2 249±0.74 4.2±0.03 5.4±0.47 0.20±0.0003 100±0.549 2.060±0.114
F3 248±0.96 4.2±0.17 6.5±0.58 0.14±0.0001 99±0.157 2.142±0.172
F4 251±0.14 4.1±0.17 5.5±0.12 0.14±0.0001 100±0.549 1.968±0.048
F5 250±0.46 4.3±0.10 6.2±0.22 0.36±0.0014 99±0.157 2.130±0.183
F6 250±0.72 4.4±0.25 5.1±0.47 0.21±0.0009 99±0.157 2.158±0.183
F7 250±0.51 4.2±0.39 6.1±0.72 0.19±0.0002 98±0.864 1.569±0.233
0
0.1414
0.2968
0.4539
0.6085
0.7686y = 0.0154x - 0.0076
R² = 0.9997
-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
0 10 20 30 40 50 60
Absorbance
Concentration (µg/ml)
Standard calibration curve of Losartan
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110
F8 251±0.12 4.1±0.10 5.2±0.01 0.18±0.0005 100±0.549 1.573±0.230
F9 251±0.71 4.1±0.10 6.2±0.22 0.19±0.0004 99±0.157 1.621±0.196
In vitro drug release study
F8 was selected as optimized formulation since it
released maximum amount of the drug in 12 hours
compared to other batch formulations. The mechanism
of drug release of F8 was found to be non Fickian
diffusion, zero order as evident from release exponent
(n) value (Table 6, fig.2).
Table 6: In vitro drug release study of Formulations F1-F9
Time
(hrs.)
F1 F2 F3 F4 F5 F6 F7 F8 F9
0 0±23.03 0±32.2 0±30.9 0±35.0 0±32.3 0±33.9 0±35.35 0±34.64 0±34.04
2 10±15.9 21±17.3 19±17.4 24±18.0 13±23.1 23±17.6 28±15.55 20±20.50 21±19.19
4 17±11.0 27±13.1 29±10.4 31±13.1 33±8.99 44±2.82 34±11.31 38±7.77 36±8.58
6 22±7.47 51±3.8 45±0.90 53±2.42 50±3.03 48±0.98 52±1.41 54±3.53 55±4.84
8 39±4.54 61±10.9 59±10.8 72±15.85 65±13.6 63±10.60 66±11.31 62±9.19 60±8.38
10 66±23.63 73±19.3 71±19.2 78±20.1 72±18.5 70±15.55 77±19.09 84±17.67 75±18.9
12 74±29.29 86±28.5 83±27.7 89±27.8 87±29.1 88±28.28 93±30.40 99±32.52 90±29.59
Fig 2: In vitro drug release study of formulations F1-F9
0
20
40
60
80
100
120
Time
(hrs.)
F1 F2 F3 F4 F5 F6 F7 F8 F9
%ofdrugrelease
Formulations
In vitro drug release study of formulations F1-F9
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111
Swelling studies
The swelling index of bioadhesive tablets for a
period of 8 hours was studied. The values obtained
are shown in table. It is evident that an increase
amount of HPMC K 4 M , Carbopol causes increase in
swelling index and depending on the concentration the
drug release will vary. Among all the formulation
carbapol showed highest and HPMC K 4 M and ethyl
cellulose showed lowest swelling index value (Table
7).
Table 7: Swelling studies of formulations F1-F9
Time
(hrs.)
F1 F2 F3 F4 F5 F6 F7 F8 F9
1 51.38±
6.3
30.14±13
.92
24.54±11
.16
49.27±7.
32
30.06±1
3.6
32.55±19
.0
43.15±1
1.8
29.06±14
.9
31.15±19.7
2 61.77±
0.9
47.33±1.
76
32.51±5.
52
60.51±0.
62
44.18±3.
69
49.92±6.
71
62.30±1.
65
45.12±3.
61
48.21±7.70
3 79.56±
13.5
54.83±3.
53
39.83±0.
35
76.81±1
2.1
51.34±1.
37
67.37±5.
62
77.74±1
2.5
52.39±1.
52
66.72±5.38
4 89.92±
20.8
65.44±11
.03
46.41±4.
30
88.56±2
0.4
64.29±1
0.5
77.11±12
.0
89.28±2
0.7
66.30±11
.35
78.29±13.5
5 88.21±
19.6
78.33±20
.15
50.10±6.
911
88.17±2
0.1
76.14±1
8.9
82.54±16
.3
88.41±2
0.1
78.52±19
.9
83.45±17.2
1
6 63.11±
1.90
55.42±3.
95
48.23±5.
58
63.43±2.
6
57.55±5.
7
76.44±12
.03
66.40±4.
55
59.21±6.
34
71.30±8.62
7 32.15±
19.98
39.22±7.
50
41.11±0.
55
32.98±1
8.8
42.18±5.
10
59.15±0.
19
34.12±1
8.2
43.15±5.
01
62.26±2.23
8 17.18±
30.5
27.93±15
.4
39.87±0.
32
17.26±2
9.9
29.46±1
4.0
30.29±20
.5
18.31±2
9.4
28.16±15
.6
31.42±19.5
Fig 3: Swelling studies of formulations F1-F9
Swelling studies of formulations F1-F9
Time (hrs.)
F1
F2
F3
F4
F5
F6
F7
F8
F9
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113
Fig 6: FTIR spectra of Drug + Carbopol
Fig 7: FTIR spectra of drug + HPMC K4M
The FTIR spectra of pure losartan and optimized
formulation does not show any significant changes in
peaks, indicating no incompatibility. Thus, confirms
the structure of Losartan drug.
Stability study
It was done only for selected formulation F8. The
storage conditions were at 40O
C2 O
C / 75% RH5%
for 30 days. The friability was 0.09% and hardness 4.5
± 0.1 Kg/cm2
after 30 days, indicating no significant
changes. Dissolution study also showed no significant
changes in drug release (Table 8).
Table 8: Dissolution studies after stability studies for F8
Time in Hours % of drug release of F8
Day 1 After 30 days
3897.143736.96
3643.75
3478.44
2975.68
2877.38
2312.53 1481.57
1449.841376.03
1311.98
1270.72
1054.79
918.70
879.92
100015002000250030003500
Wavenumber cm-1
84
86
88
90
92
94
96
Transmittance [%]
3896.
93
3795.
71
3726.
93
3667.
23
3643.
11
3417.
72 2976.
87
2887.
09
2832.
94
2312.
37
1643.
95
1453.
151375.
76
1337.
51
1313.
95
1049.
66
943.6
2
100015002000250030003500
Wavenumber cm-1
84
86
88
90
92
94
Transmittance [%]
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114
2 23 22
4 30 28
6 48 45
8 56 59
10 77 82
12 94 92
Drug release kinetics
To investigate the mechanism of drug release from
tablets, various kinetic models like zero order, first
order, Higuchi, Korsmeyer- Peppas equations were
applied to the in vitro release data obtained from
different formulations. Diffusion exponents (n) were
determined for all the formulations. From the
observations it was concluded that the optimized
formulation F8 was best explained by zero order
(R2
=0.990) and Korsmeyer - Peppas (R2
=0.995). The
drug release was proportional to the square root of
time indicating that the drug release was diffusion
controlled. The kinetic release data also suggest the
diffusion mechanism to be non Fickian diffusion since
it indicates a good linearity (Table 9 and fig. 8, 9, 10
and 11).
Table 9: Kinetics of drug release for F8
Time Log
Time
Square
root of
Time
Cumulative %
Drug Released
Log Cumulative
%Drug Released
Cumulative
%Drug
Remained
Log Cumulative
%Drug Remained
0 0 1 - 1 100 2
2 1.414214 0.30103 20 1.30103 80 1.903089987
4 2 0.60206 38 1.5797836 62 1.792391689
6 2.44949 0.778151 50 1.69897 50 1.698970004
8 2.828427 0.90309 72 1.8573325 28 1.447158031
10 3.162278 1 80 1.90309 20 1.301029996
12 3.464102 1.079181 95 1.9777236 5 0.698970004
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115
Fig 8: Zero order plot for F8
Fig 9: First order plot for F8
R² = 0.9904
0
20
40
60
80
100
120
0 5 10 15
%drugrelease
time (hrs)
Zero order plot
R² = 0.8812
0
0.5
1
1.5
2
0 5 10 15
Log%drugremeaining
Time (hrs)
First order plot
R² = 0.9868
0
20
40
60
80
100
0 1 2 3 4
%drugrelease
Square root time
Higuchi plot
11. Sandhya P et al / Int. J. of Farmacia, 2016; Vol-(2) 2: 106-117
116
Fig 10: Higuchi plot for F8
Fig 11: Korsmeyer - Peppa's plot for F8
CONCLUSION
The present study was conducted to develop gastro
retentive bioadhesive tablets of Losartan containing
HPMC K4M, ethyl cellulose, Carbopol polymers in
different concentrations along with the excepients
lactose monohydrate and magnesium stearate. The
polymers were used in the ratio of 2:4:6. Formulation
noF8 sowed optimum release upto 12 hours (99%)
with the polymer cabopol. Optimized formulation F8
showed an excellent bimodal drug release pattern. This
could be advantageous in terms of increased
bioavailability. The drug release from the formulation
followed both zero order and kormeyer peppas model
which indicates anamolous fickian diffusion. Stability
studies were conducted which revelead that no
significant changes occurred in the formulation.
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