The document discusses challenges in ocular drug delivery and formulation approaches to improve ocular bioavailability. It outlines anatomical and physiological barriers like drainage, dilution by tears, and enzymatic metabolism that impede drug delivery. Pharmacokinetic considerations include corneal and conjunctival absorption pathways. Formulation must account for drug properties, pH, tonicity, and preservatives. Polymeric, colloidal, and other delivery systems aim to increase corneal permeability and prolong contact time, through viscosity enhancement, mucoadhesion, in-situ gelling, nanoparticles, liposomes, and prodrugs.
Statistical modeling in pharmaceutical research and development.ANJALI
Statistical modeling in pharmaceutical research and development. This modelling is used in pharmaceutical industries to overcome the challenges related to pharmaceutical formulation, to reduce cost and increase quality and speed of pharmaceutical products.
Statistical modeling in pharmaceutical research and development.ANJALI
Statistical modeling in pharmaceutical research and development. This modelling is used in pharmaceutical industries to overcome the challenges related to pharmaceutical formulation, to reduce cost and increase quality and speed of pharmaceutical products.
DISSOLUTION
Dissolution is a process in which solid substance solubilizes in a given solvent
DISSOLUTION TESTING
A dissolution test uses an apparatus with specific test conditions in combination with acceptance criteria to evaluate the performance of the product. In-vitro test must predict the in-vivo behaviour
Factors in design of dissolution tests:
Factors relating to dissolution apparatus
Factors relation to dissolution fluid
Process parameters
Need of Dissolution Testing:
Development and optimisation of dosage forms
Batch to batch drug release uniformity
Quality, safety, efficacy and stability of the product
IVIV Correlation
Bioequivalence
Assessing pre and post approval changes
DISSOLUTION APPARATUS
Dissolution apparatus evolved to prepare a sample under controlled conditions thereby making the test repeatable.
Principle types of dissolution apparatus-
Close-compartment apparatus
Open-compartment apparatus
Dialysis systems
Ideal features of Dissolution Apparatus:
The fabrication, dimensions, and positioning of all components must be precisely specified and reproducible
Simple in design, easy to operate and useable
Sensitive
Nearly perfect sink conditions
Provide an easy means of introducing the dosage form into the dissolution medium
Provide minimum mechanical abrasion
Easy withdrawal of samples
Elimination of evaporation of solvent medium
DISSOLUTION METHODS
The Standard Dissolution Methods Database has been prepared by the Division of Bioequivalence, Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA).
Official methods:
Rotating Basket
Rotating Paddle
Reciprocating Cylinder
Flow-Through Cell
Paddle Over Disc
Rotating Cylinder
Reciprocating Disc
Non-official methods:
Static Disc Method
Beaker Method
Flask Stirrer Method
Peristalsis Method
Rotating Bottle Method
Dialysis Method
Diffusion Cell Method
Dissolution Apparatus Types and their Applications
Problems associated with dissolution apparatus
USP Performance Verification Test (PVT):
The USP Performance Verification Test (PVT) assesses the suitable performance of apparatus used in dissolution testing.
Responsible for detecting problems associated with the dissolution apparatus that are found to be within mechanical tolerances.
REFERENCES
Osmotic drug delivery uses the osmotic pressure of drug or other solutes (osmogens or osmagents) for controlled delivery of drugs. Osmotic drug delivery has come a long way since Australian physiologists Rose and Nelson developed an implantable pump in 1955.
Computational modeling of drug dispositionPV. Viji
Computational modeling of drug disposition , Modeling techniques , Drug absorption , solubility , intestinal permeation , Drug distribution , Drug excretion , Active Transport , P-gp , BCRP , Nucleoside transporters , hPEPT1 , ASBT , OCT , OATP , BBB-choline transporter
This presentation includes introduction, physiology of GIT, factors affecting GRDDS, Advantages and disadvantages, approaches to GRDDS and their mechanism, some of the marketed products using GRDDS mechanism.
Directly Compresible Vehicle By Mr. Vishal ShelkeVishal Shelke
Directly Compresible Vehicle By Mr. Vishal Shelke
https://youtube.com/vishalshelke99
https://instagram.com/vishal_stagram
Introduction
These are the diluents or fillers designed to make up the required bulk of the tablets.
These are inactive ingredients that are added to tablets in addition to the active drug.
Some very common diluents in tablets include lactose and their derivatives, starch, cellulose derivatives.
Used in the direct compression of the tablets.
Requirements For A Good DCV :
Non-toxic and acceptable to the regulatory agencies.
Low cost.
Physiologically inert.
Must be color-compatible
Stability.
Controlled particle size.
Good flowability.
What is Direct compression ?
Direct compression (DC) is the tabletting of a blend of ingredients i.e. the compression mix, without a preliminary granulation or aggregation process.
The compression mix contains the active pharmaceutical ingredient (API) blended with one or more excipients.
The excipients may include binders, fillers/diluents, disintegrant and lubricants.
Advantages of DC :
More Economic compare to wet granulation since it requires fewer unit operations.
Documentation and validation requirements are reduced.
It requires less equipment, and space, time.
lower power consumpation , and less labor leading to reduce production cost of tablets.
More suitable for moisture and heat sensitive APIs, since it eliminates wetting and drying steps.
Lower microbial contamination
Faster drug release.
Disadvantages of DC :
Segregation because of the difference in the density of the API and excipients.
The dry state of the material during mixing may induce static charge and lead to segregation. due to this problems like weight variation and content uniformity may occur.
APIs that have poor flow properties and low bulk density is difficult to process by direct compression.
DC excipients are costly because these are prepared by spray drying, fluid bed drying, roller drying or co-crystallization.
Classification of DCV:
Disintegrants And Poor Flow:
ex. Microcrystalline cellulose , Starch.
Free-flowing Materials That Do Not Disintegrate :
ex. Dicalcium phosphate dihydrate.
Free-flowing Powders That Disintegrate By Dissolution:
ex. Lactoses,Sucrose, Dextrose Sorbitol , Mannitol
Co-processed exicipients :
ex. Ludipress
REFERENCES -
* Pharmaceutical dosage forms tablet Vol-II second edition lachman leon, lieberman H.A. Page.No 77-160.
* www.authorstream.com
DISSOLUTION
Dissolution is a process in which solid substance solubilizes in a given solvent
DISSOLUTION TESTING
A dissolution test uses an apparatus with specific test conditions in combination with acceptance criteria to evaluate the performance of the product. In-vitro test must predict the in-vivo behaviour
Factors in design of dissolution tests:
Factors relating to dissolution apparatus
Factors relation to dissolution fluid
Process parameters
Need of Dissolution Testing:
Development and optimisation of dosage forms
Batch to batch drug release uniformity
Quality, safety, efficacy and stability of the product
IVIV Correlation
Bioequivalence
Assessing pre and post approval changes
DISSOLUTION APPARATUS
Dissolution apparatus evolved to prepare a sample under controlled conditions thereby making the test repeatable.
Principle types of dissolution apparatus-
Close-compartment apparatus
Open-compartment apparatus
Dialysis systems
Ideal features of Dissolution Apparatus:
The fabrication, dimensions, and positioning of all components must be precisely specified and reproducible
Simple in design, easy to operate and useable
Sensitive
Nearly perfect sink conditions
Provide an easy means of introducing the dosage form into the dissolution medium
Provide minimum mechanical abrasion
Easy withdrawal of samples
Elimination of evaporation of solvent medium
DISSOLUTION METHODS
The Standard Dissolution Methods Database has been prepared by the Division of Bioequivalence, Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA).
Official methods:
Rotating Basket
Rotating Paddle
Reciprocating Cylinder
Flow-Through Cell
Paddle Over Disc
Rotating Cylinder
Reciprocating Disc
Non-official methods:
Static Disc Method
Beaker Method
Flask Stirrer Method
Peristalsis Method
Rotating Bottle Method
Dialysis Method
Diffusion Cell Method
Dissolution Apparatus Types and their Applications
Problems associated with dissolution apparatus
USP Performance Verification Test (PVT):
The USP Performance Verification Test (PVT) assesses the suitable performance of apparatus used in dissolution testing.
Responsible for detecting problems associated with the dissolution apparatus that are found to be within mechanical tolerances.
REFERENCES
Osmotic drug delivery uses the osmotic pressure of drug or other solutes (osmogens or osmagents) for controlled delivery of drugs. Osmotic drug delivery has come a long way since Australian physiologists Rose and Nelson developed an implantable pump in 1955.
Computational modeling of drug dispositionPV. Viji
Computational modeling of drug disposition , Modeling techniques , Drug absorption , solubility , intestinal permeation , Drug distribution , Drug excretion , Active Transport , P-gp , BCRP , Nucleoside transporters , hPEPT1 , ASBT , OCT , OATP , BBB-choline transporter
This presentation includes introduction, physiology of GIT, factors affecting GRDDS, Advantages and disadvantages, approaches to GRDDS and their mechanism, some of the marketed products using GRDDS mechanism.
Directly Compresible Vehicle By Mr. Vishal ShelkeVishal Shelke
Directly Compresible Vehicle By Mr. Vishal Shelke
https://youtube.com/vishalshelke99
https://instagram.com/vishal_stagram
Introduction
These are the diluents or fillers designed to make up the required bulk of the tablets.
These are inactive ingredients that are added to tablets in addition to the active drug.
Some very common diluents in tablets include lactose and their derivatives, starch, cellulose derivatives.
Used in the direct compression of the tablets.
Requirements For A Good DCV :
Non-toxic and acceptable to the regulatory agencies.
Low cost.
Physiologically inert.
Must be color-compatible
Stability.
Controlled particle size.
Good flowability.
What is Direct compression ?
Direct compression (DC) is the tabletting of a blend of ingredients i.e. the compression mix, without a preliminary granulation or aggregation process.
The compression mix contains the active pharmaceutical ingredient (API) blended with one or more excipients.
The excipients may include binders, fillers/diluents, disintegrant and lubricants.
Advantages of DC :
More Economic compare to wet granulation since it requires fewer unit operations.
Documentation and validation requirements are reduced.
It requires less equipment, and space, time.
lower power consumpation , and less labor leading to reduce production cost of tablets.
More suitable for moisture and heat sensitive APIs, since it eliminates wetting and drying steps.
Lower microbial contamination
Faster drug release.
Disadvantages of DC :
Segregation because of the difference in the density of the API and excipients.
The dry state of the material during mixing may induce static charge and lead to segregation. due to this problems like weight variation and content uniformity may occur.
APIs that have poor flow properties and low bulk density is difficult to process by direct compression.
DC excipients are costly because these are prepared by spray drying, fluid bed drying, roller drying or co-crystallization.
Classification of DCV:
Disintegrants And Poor Flow:
ex. Microcrystalline cellulose , Starch.
Free-flowing Materials That Do Not Disintegrate :
ex. Dicalcium phosphate dihydrate.
Free-flowing Powders That Disintegrate By Dissolution:
ex. Lactoses,Sucrose, Dextrose Sorbitol , Mannitol
Co-processed exicipients :
ex. Ludipress
REFERENCES -
* Pharmaceutical dosage forms tablet Vol-II second edition lachman leon, lieberman H.A. Page.No 77-160.
* www.authorstream.com
What is Artificial Intelligence | Artificial Intelligence Tutorial For Beginn...Edureka!
** Machine Learning Engineer Masters Program: https://www.edureka.co/masters-program/machine-learning-engineer-training **
This tutorial on Artificial Intelligence gives you a brief introduction to AI discussing how it can be a threat as well as useful. This tutorial covers the following topics:
1. AI as a threat
2. What is AI?
3. History of AI
4. Machine Learning & Deep Learning examples
5. Dependency on AI
6.Applications of AI
7. AI Course at Edureka - https://goo.gl/VWNeAu
For more information, please write back to us at sales@edureka.co
Call us at IN: 9606058406 / US: 18338555775
Facebook: https://www.facebook.com/edurekaIN/
Twitter: https://twitter.com/edurekain
LinkedIn: https://www.linkedin.com/company/edureka
Introduction
Anatomy and physiology of human eye
Ocular delivery system
Optimum characters of ophthalmic drugs
Routes of ophthalmic drugs
Mechanism of ocular drug absorption
Barriers and fate of ocular drug delivery
Formulation consideration of ocular dosage forms
Evaluation tests
References
Ophthalmic drug delivery system :Challenges and Approaches.Ashish Kumar Mishra
This presentation mainly cover all the challenges which the pharmaceuticals scientist are facing in formulation of an ocular drug delivery system and the method involved to overcomes the problems and provided an more stable and convenient ODDS with increased Bio-availability.
INTRODUCTION :
Ocular administration of drug is primarily associated with the need to treat ophthalmic diseases.
Eye is the most easily accessible site for topical administration of a medication.
Ideal ophthalmic drug delivery must be able to sustain the drug release and to remain in the vicinity of front of the eye for prolong period of time.
The bioavailability of ophthalmic drugs is very poor due to efficient protective mechanisms of the eye.
Blinking, reflex lachrymation, and drainage rapidly remove drugs, from the surface of the eye.
To overcome these, two approaches can be followed.
The first involves using alternate delivery routes to conventional ones allowing for more direct access to intended target sites.
Second approach involves development of novel drug delivery systems providing better permeability, treatability and controlled release at target site.
Combination of both these approaches are being utilized and optimized in order to achieve optimal therapy with minimal adverse effects.
Routes of Ocular Delivery.
COMPOSITION OF EYE.
MECHANISM OF OCULAR ABSORPTION.
Barriers of Drug Permeation.
Anatomical Barrier.
CORNIAL CROSS SECTION.
Physiological Barrier.
Blood-Occular Barriers.
Routes of Ocular Drug Delivery.
Topical Route & Novel Route ocular drug delivery.
Methods to Overcome Barriers.
Bioavailability Improvement & Controlled Ocular Drug Delivery
Contents
Introduction
Objective
Anatomy of the Eye
Routes of drug delivery of the eye
Mechanism of ocular absorption
Factors affecting intra-ocular bioavailability
Barriers of ocular drug absorption
Methods to overcome drug barriers
Evaluation
Conclusion
Reference
Ocular administration of drug is primarily associated with the need to treat ophthalmic diseases.
Applied topically to the cornea, or instilled in the space between the eyeball and lower eyelid
Definition: Ocular DDS are designed to instilled on to topical or intra-ocular or peri-ocular to eye.
Most commonly used ocular dosage forms-
- Solutions
- Suspensions
- ointments
Ideal ophthalmic drug delivery must be able to sustain the drug release and to remain in the vicinity of front of the eye for prolong period of time.
Challenges in trancorneal drug deliveryBibin Mathew
Ophthalmic drug delivery is one of the challenging endeavors which is being faced by the pharmaceutical scientist, owing to the anatomy, physiology, and biochemistry of the eye, that renders it impervious to foreign substances. Topical administration of ophthalmic medications is the most common method for treating conditions that affect the exterior parts of the eye. The unique anatomy and physiology of the eye makes it difficult to achieve an effective drug concentration at the target site. Therefore, the major challenge remains to efficiently deliver a drug past the protective ocular barriers accompanied with a minimization of its systemic side effects.Conventional eye drops currently account for more than 90% of the marketed ophthalmic formulations. However, after instillation of an eye drop, only a small amount of the applied drug penetrates the cornea and reaches the intraocular tissues, which is due to the rapid and extensive precorneal loss caused by drainage and high tear fluid turn-over. Tear drainage leads to absorption of the administered dose by the nasolacrimal duct, leading to side effects. As a consequence of the precorneal loss, the ocular bioavailability is usually less than 10%. Furthermore, rapid elimination of the eye drops administered often results in a short duration of action which leads to increase in frequency of administration.
A medication is applied to the eye to treat the diseases on the surface of the eye such as conjunctivitis, blepharitis, and keratitis sicca, as well as to provide intraocular treatment through the cornea for diseases such as glaucoma and uveitis. Topical administration of antibacterial medication to the conjunctival sac is usually an effective avenue for treating bacterial conjunctivitis.[2]
An ideal topical drug delivery system should possess the following characteristics:
1. Good corneal and conjunctival penetration.
2. Prolonged precorneal residence time.
3. Easy instillation.
4. Appropriate rheological properties.
Eye diseases are commonly encountered in day to day life, which are cured or prevented through the conventionally used dosage forms. Delivery to the internal parts of the eye still remains troublesome due to the anatomical and protective structure of the eye. Drugs may be delivered to the eye through the application of four primary modes of administration: topical, systemic, intravitreal, and periocular.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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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
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
- 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
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
2. OCULAR DRUG DELIVERY
Introduction
Challenges in Ocular Drug Delivery
Anatomical and Physiological Considerations
Pharmacokinetic Considerations
Formulation Considerations
Formulation Approaches to Improve Ocular Bioavailability
Conventional Dosage Forms
Polymeric Delivery Systems
Colloidal Delivery Systems
Other Delivery Approaches
Conclusion
References
3. INTRODUCTION
• Due to the accessibility of the eye surface, topical administration of ophthalmic
medications is the most common method for treating conditions affecting the
exterior eye surface.
• The unique anatomy and physiology of the eye renders it difficult to achieve an
effective drug concentration at the target site. So, efficient delivery of a drug
through the protective ocular barriers with minimization of its systemic side effects
remains a major challenge.
• Ocular delivery systems, such a ointments, suspensions, micro - and nanocarriers,
and liposomes, have been investigated during the past two decades focusing two
main strategies:
– to increase the corneal permeability and
– to prolong the contact time on the ocular surface .
4. Challenges in
Ocular Drug Delivery
Anatomical and Physiological
Considerations
Pharmacokinetic Considerations
Formulation Considerations
5. Anatomical and Physiological Considerations :
a) Spillage of drug by overflow:
• Eye can accommodate 30L without blinking.
• Eye dropper deliver volume of 50L, 70% of administered dose is expelled by over
flow.
• Upon Blinking 10L residual volume is left (i.e 90% of the dose expelled)
b) Dilution of drug by tears turn over:
Normal human tear turnover is approximately 16% per minute. Factors like drug entity,
pH, and tonicity of dosage form cause tears turn over.
c) Enzymatic metabolism
Precorneal and corneal enzymatic metabolism results in the loss of drugs entities
possessing labile bonds.
d) Conjunctival absorption:
The absorption of drug into pulpebral and bulbelar conjunctiva (highly vascular) with
concomitant removal from the ocular tissues by peripheral blood stream.
6. Anatomical and Physiological Considerations (Contd..) :
e) Nasolacrimal Drainage System
• Causes systemic side effect.
• The drainage rate is much faster than the ocular absorption rate. So, ocular
bioavailability of a drug still remains challenge.
Lacrimal gland
secrete
tear fluid in cornea
blinking
creates a suction mechanism, Fluid from the
lacrimal sac into nasolacrimal duct
the inferior nasal passage (highly vascular)
systemic drug absorption
7. Pharmacokinetic Consideration:
• Corneal absorption is considered to be the major penetration
pathway for topically applied drugs.
• There are two mechanisms for absorption across the corneal
epithelium are :
• Transcellular diffusion
• Paracellular diffusion
• Lipophilic drugs prefer the transcellular route.
• Hydrophilic drugs penetrate prefer paracellular route.
•Transport along the transcellular route includes :
Simple diffusion/ Facilitated diffusion / Active transport
/ Endocytosis.
Figure: Cornea structures
8. Pharmacokinetic Consideration (Contd…….) :
•Transport along the paracellular route includes :
Passive diffusion/ Limited by the pore size / Charge of the intracellular spaces.
• Relatively small molecules can permeate through the pores.
•Negatively charged molecules permeate at a slower rate than positively charged and
neutral ones.
•In addition, a positive charge may also decrease the permeation due to the possible
ionic interaction with the negatively charged carboxylic acid residues of the tight
junction proteins.
• Choice of the molecule in ascending order on basis of corneal permeation :
Neutral > positively charged molecules > Negatively charged molecules
9. Challenges in Ocular Drug Delivery
Formulation Consideration:
a) Physicochemical Drug Properties
b) Buffer Capacity and p H
c) Anti-oxidants
d) Instillation Volume
e) Tonicity adjustment
f) Surfactants
g) Preservatives
Note : General safety considerations such as sterility, ocular toxicity and irritation
need to be taken into account when formulating an ocular dosage form.
10. Formulation Consideration:
Physicochemical Drug Properties : It includes the factors that affcect the corneal
permeability of the drug.
• Lipophilicity of the drug as reflected by its n - octanol – water partition coefficient
• Molecular size and shape .
Buffer Capacity and p H: Normal Tear fluid pH 7.4 ,posses some buffering capacity.
• pH should be chosen to optimize drug stability.
• When pH deviates from 7.4 it is important to be aware of buffer capacity to minimize
lacrimation and irritation.
Instillation Volume : The cul - de - sac normally holds 7 – 9 L , & accommodate 30 L
without blinking.
• Upon application of Eye droppers (50 L volume), the excess volume removed by
Spillage (conjunctival sac ) & Nasolacrimal drainage system.
• Formulation target is to , keeping the applied dose constant while decreasing the
instilled volume.
11. Formulation Consideration(Contd…):
Tonicity Adjustment :
• Tonicity needs to be adjusted so that it exerts an osmotic pressure equal to that of
tear fluids (equivalent to 0.9% NaCl ideally) .
• Ophthalmic solutions are hypotonic to enhance absorption and provide concentration of
active ingredient sufficient to achieve efficacy.
• Common tonicity adjusting agents are NaCl , Cl, buffer salt, d-mannitol, propylene
glycol etc.
Anti-oxidants:
• They are commonly added to mitigate oxidation issues.
• Example : Sodium bisulfite or metabisulfite is used in concentrations up to 0.3% in
epinephrine hydrochloride and bitartrate solutions.
12. Formulation Consideration(Contd..):
Surfactants:
• Several nonionic surfactants are used in relatively low concentrations to achieve drug
solubility. Eg: Polysorbate, tyloxapol, polyoxyl 40 stearate etc.
• The order of surfactant toxicity is: Anionic > cationic > nonionic
• Nonionic surfactants preferred for ophthalmic use .
Preservatives :
• Help to prevent contamination of the bottle contents over the course of multiple uses.
• By preventing contamination, preservatives may help ensure product stability.
• Benzalkonium chloride is the most commonly used ophthalmic preservative and is used
in 72% of ophthalmic solutions
13. Formulation Consideration (Articles)
• Article: Kaur , I. P. , and Smitha , R. ( 2002 ), Penetration enhancers and ocular
bioadhesives: Two new avenues for ophthalmic drug delivery , Drug Dev. Ind. Pharm. ,
28 ( 4 ), 353 – 369 .
• Conclusion : According to Kaur and Smitha [36] , the optimum lipophilicity for corneal
absorption is found in drugs with an n - octanol – water partition coefficient between 10
and 100.
• Article: Huang , A. J. W. , Tseng , S. C. G, and Kenyon , K. R. ( 1989 ), Paracellular
permeability of corneal and conjunctival epithelia , Invest. Ophthalmol. Vis. Sci. , 30 ( 4
), 684 – 689 .
• Conclusion : The molecular size of the drug has an effect on the corneal absorption. The
cornea is impermeable to molecules larger than 5000 Da, whereas the conjunctival tissues
allow compounds of up to 20,000 Da to penetrate .
• Article : Chrai , S. S. , and Robinson , J. R. ( 1974 ), Ocular evaluation of methylcellulose
vehicle in albino rabbits , J. Pharm. Sci. , 63 ( 8 ), 1218 – 1223 .
• Conclusion : The drainage process followed first - order kinetics and found that the rate
of solution drainage from the conjunctival sac (as reflected by the elimination rate
constant) was directly proportional to the instilled volume .
15. FORMULATION APPROACHES TO IMPROVE OCULAR
BIOAVAILABILITY
Approaches to improve the ocular bioavailability have been attempted in two
directions: To increase the corneal permeability
To prolong the contact time with the ocular surface
Conventional Dosage Forms Polymeric Delivery System
Solutions Viscosity - Enhancing Polymers
Suspensions Mucoadhesive Polymers
Ointments In Situ Gelling Systems
Colloidal Delivery Systems Other Delivery Approaches
Nanoparticles Prodrugs
Liposomes Penetration Enhancers
Niosomes Cyclodextrins
Microemulsions Ocular Inserts
16. Conventional Dosage Forms
Solutions:
• Addition of viscosity - enhancing agents such as cellulose derivates, which are believed to
increase the viscosity of the preparation .
• Reduce the drainage rate encountered installation
frequency.
Suspensions:
• Micronized drug ( < 10 μ m) in a suitable aqueous vehicle are formulated, where the active
compound is water insoluble.
• Particles greater than 10 μ m cause patient discomfort.
• Achieving a near - solution state with small particles that are easy to resuspend and show
minimal sedimentation.
17. Conventional Dosage Forms(Contd….)
Ointments:
•It remain in the cul - de - sac as a drug depot, reduce dilution of the drug via the tear film.
•Increased precorneal contact time .
•Blurred vision
•Matting of eyelids
Note : Ointments are used in combination with eye drops, which can be administered
during the day, while the ointment is applied at night, when clear vision is not required.
18. Polymeric Delivery Systems
Polymeric Delivery System
Viscosity - Enhancing Polymers:
•Simply increase the formulation viscosity.
•Decreased lacrimal drainage and enhanced bioavailability.
•Example : HPMC, PVA
Article : Trueblood , J. H. , Rossomondo , R. M. , Wilson , L. A. , and Carlton , W. H. (
1975 ), Corneal contact times of ophthalmic vehicles. Evaluation by
microscintigraphy , Arch. Ophthalmol, 93 ( 2 ), 127 – 130 .
Conclusion : Trueblood et al. [183] used lacrimal microscintigraphy to evaluate the
corneal contact time for saline, PVA, and hydroxpropyl methylcellulose (HPMC) and
observed the longest contact time for the formulation with HPMC as a viscosity -
enhancing agent.
19. Polymeric Delivery Systems
Polymeric Delivery System (Contd…)
Mucoadhesive Polymers :
•Mucoadhesive polymers, interact with the ocular mucin, increasing the contact
time with the ocular tissues.
•In order to spread onto the mucus polymers must show
the following features :
a) Strong hydrogen binding group,
b) Strong anionic charge
c) Sufficient chain flexibility
Article :Saettone , M. F. , Chetoni , P. , Tilde Torracca , M. , Burgalassi , S. , and
Giannaccini , B. ( 1989 ),Evaluation of muco - adhesive properties and in vivo activity
of ophthalmic vehicles based on hyaluronic acid , Int. J. Pharm. , 51 ( 3 ), 203 – 212 .
Conclusion :Saettone et al. evaluated a series of bioadhesive dosage forms for ocular
delivery of pilocarpine and tropicamide and found hyaluronic acid to be the most
promising mucoadhesive polymer.
20. Polymeric Delivery Systems
Polymeric Delivery System (Contd....)
In Situ Gelling Systems :
•Polymers undergo sol - to – gel phase transition upon exposure to the physiological
conditions present in the eye.
•Easy, accurate, and reproducible administration of a dose
Article :Shedden , A. H. , Laurence , J. , Barrish , A. , and Olah , T. V. ( 2001 ), Plasma
timolol concentrations of timolol maleate: Timolol gel - forming solution
(TIMOPTIC - XE) once daily versus timolol maleate ophthalmic solution twice daily
, Doc. Ophthalmol. , 103 ( 1 ),73 – 79 .
Conclusion :Shedden et al. [76] compared the plasma concentrations of timolol
following multiple applications of Timoptic - XE and a timolol maleate solution. They
found that a once - daily application of the in situ gelling formulation was
sufficient to reduce the intraocular pressure to levels comparable to a twice - daily
application of the solution, leading to better patient compliance as well as a
reduction in systemic side effects.
21. Polymeric Delivery Systems
Colloidal Delivery System
•Nanoparticles
•Polymeric ranging from 10 to 1000 nm in which the drug can be dissolved,
entrapped, encapsulated, or adsorbed.
•Nanoparticles retain in the cul - de - sac and the entrapped drug released from the
particles at a certain rate.
•Sustained drug release and a prolonged therapeutic activity.
Article : Ding , S. ( 1998 ), Recent developments in ophthalmic drug delivery ,
Pharm. Sci. Technol.Today , 1 ( 8 ), 328 – 335 .
Conclusion :
Betoptic S is obtained by binding of betaxolol to ion exchange resin particles.
Betoptic S 0.25% was found to be bioequivalent to the Betoptic 0.5% solution in
lowering the intraocular pressure.
22. Polymeric Delivery Systems
Colloidal Delivery System(Contd..)
Liposomes :
•Liposome’s are phospholipids-lipid vesicles that can entrap only Lipophilic drugs
.Improve in ocular contact time.
•Provide sustained effect
•Reduce side effects of the drug(s) entrapped.
Niosomes :
•Nisomes entrap both hydrophilic and lipophilic drugs.
•Here surfactants act as penetrations enhancer & remove the mucous layer from the
ocular surface.
23. Polymeric Delivery Systems
Colloidal Delivery System (Contd…)
Discomes :
•Modified version of niosomes (12 – 60 μm)
•Prevents drainage into the nasolacrimal drainage system.
•Disclike shape provides better fit in the cul - de - sac .
Article : Vyas , S . P. , Mysore , N. , Jaitely , V. , and Venkatesan , N. ( 1998 ),
Discoidal niosome based controlled ocular delivery of timolol maleate , Pharmazie ,
53 ( 7 ), 466 – 469 .
Conclusion: Vyas et al. demonstrated that discomes entrapped higher amounts of
timolol maleate than niosomes and that both niosomes and discomes significantly
increased the bioavailability of timolol maleate when compared to a conventional
timolol maleate solution.
24. Colloidal Delivery System (Contd…)
Microemulsions :
• Microemulsions (MEs) are colloidal dispersions composed of an oil phase, an aqueous
phase, and one or more surfactants.
• Presence of surfactants is advantageous due to an increase in cellular membrane
permeability, which facilitates drug absorption and bioavailability.
• They are thermodynamically stable and transparent, possess low viscosity. Thus are
easy to instill, formulate, and sterilize.
• Example : poloxamers, polysorbates, and polyethylene glycol derivatives.
• Article: Gasco , M. R. , Gallarate , M. , Trotta , M. , Bauchiero , L. , Chiappero , O.
et al. ( 1989 ), Microemulsions as topical delivery vehicles: Ocular administration of
timolol , J. Pharm.Biomed. Anal. , 7 ( 4 ), 433 – 439 .
• Conclusion :The ocular bioavailability of the timolol ion pair incorporated into the
ME was compared to that of an ion pair solution as well as a simple timolol solution.
A prolonged absorption was achieved using the ME with detectable amounts of the
drug still present 120 min after instillation.
25. Other Delivery Approaches
Prodrugs :
• Of all enzymes participating in the activation of prodrugs, esterases are present in
all anterior segment tissues.
• So, majority of ophthalmic prodrugs developed from the esterification of the
hydroxyl or carboxylic acid groups present in the parent molecule.
• Article: Tirucherai , G. S. , Dias , C. , and Mitra , A. K. ( 2002 ), Corneal
permeation of ganciclovir: Mechanism of ganciclovir permeation enhancement
by acyl ester prodrug design ,J. Ocul. Pharmacol. Ther. , 18 ( 6 ), 535 – 548 .
• Conclusion : Tirucherai et al. [137] formulated an acylester prodrug of ganciclovir.
The increased permeability was associated with a linear increased
susceptibility of the ganciclovir esters to the esterases present in the cornea.
26. Other Delivery Approaches (Contd…)
Penetration Enhancers :
• It increases the permeability of the corneal cell membrane .
• It looses the tight junctions between the epithelial cells, which restrict the entry of
molecules via the paracellular pathway.
• Example : surfactants, bile salts, calcium chelators, fatty acids, some glycosides such a
saponin.
• Article : Grass , G. M. , Wood , R. W. , and Robinson , J. R. ( 1985 ), Effects of calcium
chelating agents on corneal permeability , Invest. Ophthalmol. Vis. Sci. , 26 ( 1 ), 110
– 113 .
• Conclusion : Grass et al. were among the first to emphasize the enhancing effects of
chelating agents for ocular drug delivery. They found that 0.5% EDTA doubled the
corneal absorption of topically applied glycerol and cromoclycin sodium.
27. Other Delivery Approaches (Contd…)
Cyclodextrins:
• They are a group of homologous cyclic oligosaccharides with a hydrophilic outer surface
and a lipophilic cavity in the center.
• Cyclodextrin complexation generally results in improved wettability, dissolution,
solubility, and stability in solution as well as reduced side effects.
• Article : Nijhawan , R. , and Agarwal , S. P. ( 2003 ), Development of an ophthalmic
formulation containing ciprofl oxacin - hydroxypropyl - β - cyclodextrin complex ,
Boll. Chim. Farm. ,142 ( 5 ), 214 – 219 .
• Conclusion : Nijhawan and Agarwal investigated inclusion complexes of ciprofloxacin
hydrochloride and hydroxy - propyl - β - cyclodextrin and found that the complexes
exhibited better stability, biological activity, and ocular tolerance than the
uncomplexed drug in solution.
28. Other Delivery Approaches (Contd…)
Ocular Inserts :
• It provide a sustained, and continuous drug delivery by maintaining an effective drug
concentration in the target tissues.
• However, this systems is less popular because
– Difficulty of insertion by the patient
– Foreign - body sensation by eye .
29. CONCLUSION :
An ophthalmic delivery system :
• Must be sterile and isotonic.
• Should have corneal permeability characteristic.
• Should have prolong contact time with the ocular surface.
• Should be easy to use for patient’s acceptance .
30. REFERENCES
• Chrai , S. S. , and Robinson , J. R. ( 1974 ), Ocular evaluation of methylcellulose vehicle in albino
rabbits , J. Pharm. Sci. , 63 ( 8 ), 1218 – 1223 .
• Ding , S. ( 1998 ), Recent developments in ophthalmic drug delivery , Pharm. Sci. Technol.Today ,
1 ( 8 ), 328 – 335 .
• Gasco , M. R. , Gallarate , M. , Trotta , M. , Bauchiero , L. , Chiappero , O. et al. ( 1989 ),
Microemulsions as topical delivery vehicles: Ocular administration of timolol , J. Pharm.Biomed.
Anal. , 7 ( 4 ), 433 – 439 .
• Grass , G. M. , Wood , R. W. , and Robinson , J. R. ( 1985 ), Effects of calcium chelating agents on
corneal permeability , Invest. Ophthalmol. Vis. Sci. , 26 ( 1 ), 110 – 113 .
• Greaves , J. L. , Wilson , C. G. , and Birmingham , A. T. ( 1993 ), Assessment of the precorneal
residence of an ophthalmic ointment in healthy subjects , Br. J. Clin. Pharmacol. , 35 ( 2 ), 188 –
192 .
• Huang , A. J. W. , Tseng , S. C. G, and Kenyon , K. R. ( 1989 ), Paracellular permeability of corneal
and conjunctival epithelia , Invest. Ophthalmol. Vis. Sci. , 30 ( 4 ), 684 – 689 .
• Jarvinen , K. , Jarvinen , T. , and Urtti , A. ( 1995 ), Ocular absorption following topical delivery,
Adv. Drug Deliv. Rev. , 16 ( 1 ), 3 – 19 .
• Kaur , I. P. , and Smitha , R. ( 2002 ), Penetration enhancers and ocular bioadhesives: Two new
avenues for ophthalmic drug delivery , Drug Dev. Ind. Pharm. , 28 ( 4 ), 353 – 369 .
• Nijhawan , R. , and Agarwal , S. P. ( 2003 ), Development of an ophthalmic formulation containing
ciprofl oxacin - hydroxypropyl - β - cyclodextrin complex , Boll. Chim. Farm. ,142 ( 5 ), 214 – 219
• Olejnik , O. ( 1993 ), Conventional systems in ophthalmic drug delivery , in Mitra , A . K. ,Ed.,
Ophthalmic Drug Delivery Systems , Marcel Dekker , New York , pp. 177 – 198 .
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rabbits , J. Pharm. Sci. , 64 ( 8 ), 1312 – 1316 .
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International Journal of Pharma Research & Review, August 2014; 3(8):29-41 ISSN: 2278-6074 .
• Saettone , M. F. , Chetoni , P. , Tilde Torracca , M. , Burgalassi , S. , and Giannaccini , B. ( 1989
),Evaluation of muco - adhesive properties and in vivo activity of ophthalmic vehicles based on
hyaluronic acid , Int. J. Pharm. , 51 ( 3 ), 203 – 212 .
• Shedden , A. H. , Laurence , J. , Barrish , A. , and Olah , T. V. ( 2001 ), Plasma timolol
concentrations of timolol maleate: Timolol gel - forming solution (TIMOPTIC - XE) once daily
versus timolol maleate ophthalmic solution twice daily , Doc. Ophthalmol. , 103 ( 1 ),73 – 79 .
• Sieg , J. W. , and Robinson , J. R. ( 1977 ), Vehicle effects on ocular drug bioavailability II:
Evaluation of pilocarpine , J. Pharm. Sci. , 66 ( 9 ), 1222 – 1228 .
• Tirucherai , G. S. , Dias , C. , and M itra , A. K. ( 2002 ), Corneal permeation of ganciclovir:
Mechanism of ganciclovir permeation enhancement by acyl ester prodrug design ,J. Ocul.
Pharmacol. Ther. , 18 ( 6 ), 535 – 548 .
• Trueblood , J. H. , Rossomondo , R. M. , Wilson , L. A. , and Carlton , W. H. ( 1975 ), Corneal
contact times of ophthalmic vehicles. Evaluation by microscintigraphy , Arch. Ophthalmol, 93 ( 2 ),
127 – 130 .
• Vyas , S . P. , Mysore , N. , Jaitely , V. , and Venkatesan , N. ( 1998 ), Discoidal niosome based
controlled ocular delivery of timolol maleate , Pharmazie , 53 ( 7 ), 466 – 469 .