This document summarizes ocular drug delivery systems. It discusses barriers to drug permeation through the eye such as anatomical barriers like the cornea and physiological barriers like tear turnover. It also discusses strategies to overcome these barriers, including using viscosity enhancers to prolong precorneal residence time, penetration enhancers to increase corneal permeability, and various drug delivery vehicles like ointments, gels, liposomes, nanoparticles, microemulsions, and in-situ forming gels that can enhance ocular absorption and bioavailability. The ideal ocular delivery system maximizes precorneal residence time and drug absorption while minimizing systemic exposure and side effects.
The eye is the most interesting organ due to its drug
disposition characteristics.
▪ The Novel approach of drug delivery system in which
the drug that can be Instilled on the cull de sac cavity of the eye is
known as the Ocular drug delivery system.
(cull de sac cavity: the space between eyelids and eye
balls)
▪Ocular drug delivery is one of the most challenging
tasks faced by Pharmaceutical researchers.
▪One of the major barriers of ocular medication is to
obtain and maintain a therapeutic level at the site of
action for a prolonged period of time.
▪The bioavailability of ophthalmic drugs is very poor
due to efficient protective mechanisms of the eye.
The presentation includes Introduction to Ocular Drug Delivery System, Anatomy of Human eye, Mechanism of Ocular Drug Absorption, Barriers for Ocular Delivery, Factors affecting Intraocular bioavailability, Drawbacks of traditional ophthalmic formulations, Classification of Ocular Drug Delivery System, Formulations of Ocular Drug Delivery System and Evaluation parameters of Ocular Drug Delivery System.
Barrier of drugs permeation through ocular route by Sushil Kumar SinghSushil Singh
Barriers of Drugs Permeation Through Ocular Route. this topic explain about ocular route and barriers system. and classification of different injection routes takes the ocular drugs.
The eye is the most interesting organ due to its drug
disposition characteristics.
▪ The Novel approach of drug delivery system in which
the drug that can be Instilled on the cull de sac cavity of the eye is
known as the Ocular drug delivery system.
(cull de sac cavity: the space between eyelids and eye
balls)
▪Ocular drug delivery is one of the most challenging
tasks faced by Pharmaceutical researchers.
▪One of the major barriers of ocular medication is to
obtain and maintain a therapeutic level at the site of
action for a prolonged period of time.
▪The bioavailability of ophthalmic drugs is very poor
due to efficient protective mechanisms of the eye.
The presentation includes Introduction to Ocular Drug Delivery System, Anatomy of Human eye, Mechanism of Ocular Drug Absorption, Barriers for Ocular Delivery, Factors affecting Intraocular bioavailability, Drawbacks of traditional ophthalmic formulations, Classification of Ocular Drug Delivery System, Formulations of Ocular Drug Delivery System and Evaluation parameters of Ocular Drug Delivery System.
Barrier of drugs permeation through ocular route by Sushil Kumar SinghSushil Singh
Barriers of Drugs Permeation Through Ocular Route. this topic explain about ocular route and barriers system. and classification of different injection routes takes the ocular drugs.
M.pharm (Pharmaceutics) Molecular Pharmaceutics (NTDS) unit 1 part 1 Targeted Drug Delivery Systems: Concepts, Events and biological process involved in drug targeting.
Mucoadhesive drug delivery system interact with the mucus layer covering the mucosal epithelial surface, & mucin molecules & increase the residence time of the dosage form at the site of the absorption.
Mucoadhesive drug delivery system is a part of controlled delivery system.
Since the early 1980,the concept of Mucoadhesion has gained considerable interest in pharmaceutical technology.
combine mucoadhesive with enzyme inhibitory & penetration enhancer properties & improve the patient complaince.
MDDS have been devloped for buccal ,nasal,rectal &vaginal routes for both systemic & local effects.
Hydrophilic high mol. wt. such as peptides that cannot be administered & poor absorption ,then MDDS is best choice.
Mucoadhesiveinner layers called mucosa inner epithelial cell lining is covered with viscoelasticfluid
Composed of water and mucin.
Thickness varies from 40 μm to 300 μm
General composition of mucus
Water…………………………………..95%
Glycoproteinsand lipids……………..0.5-5%
Mineral salts……………………………1%
Free proteins…………………………..0.5-1%
The mechanism responsible in the formation of mucoadhesive bond
Step 1 : Wetting and swelling of the polymer(contact stage)
Step 2 : Interpenetration between the polymer chains and the mucosal membrane
Step 3 : Formation of bonds between the entangled chains (both known as consolidation stage)
Electronic theory
Wetting theory
Adsorption theory
Diffusion theory
Fracture theory
Advantages over other controlled oral controlled release systems by virtue of prolongation of residence of drug in GIT.
Targeting & localization of the dosage form at a specific site
-Painless administration.
-Low enzymatic activity & avoid of first pass metabolism
If MDDS are adhere too tightlgy because it is undesirable to exert too much force to remove the formulation after use,otherwise the mucosa could be injured.
-Some patient suffers unpleasent feeling.
-Unfortunately ,the lack of standardized techniques often leads to unclear results.
-costly drug delivery system
1. Structure of skin.
2. Skin relating problems :
a. Dry skin
b. Acne
c. Pigmentation
d. Prickly heat
e. Wrinkles
f. Body odour
3. Structure of hair.
4. Hair growth cycle.
M.pharm (Pharmaceutics) Molecular Pharmaceutics (NTDS) unit 1 part 1 Targeted Drug Delivery Systems: Concepts, Events and biological process involved in drug targeting.
Mucoadhesive drug delivery system interact with the mucus layer covering the mucosal epithelial surface, & mucin molecules & increase the residence time of the dosage form at the site of the absorption.
Mucoadhesive drug delivery system is a part of controlled delivery system.
Since the early 1980,the concept of Mucoadhesion has gained considerable interest in pharmaceutical technology.
combine mucoadhesive with enzyme inhibitory & penetration enhancer properties & improve the patient complaince.
MDDS have been devloped for buccal ,nasal,rectal &vaginal routes for both systemic & local effects.
Hydrophilic high mol. wt. such as peptides that cannot be administered & poor absorption ,then MDDS is best choice.
Mucoadhesiveinner layers called mucosa inner epithelial cell lining is covered with viscoelasticfluid
Composed of water and mucin.
Thickness varies from 40 μm to 300 μm
General composition of mucus
Water…………………………………..95%
Glycoproteinsand lipids……………..0.5-5%
Mineral salts……………………………1%
Free proteins…………………………..0.5-1%
The mechanism responsible in the formation of mucoadhesive bond
Step 1 : Wetting and swelling of the polymer(contact stage)
Step 2 : Interpenetration between the polymer chains and the mucosal membrane
Step 3 : Formation of bonds between the entangled chains (both known as consolidation stage)
Electronic theory
Wetting theory
Adsorption theory
Diffusion theory
Fracture theory
Advantages over other controlled oral controlled release systems by virtue of prolongation of residence of drug in GIT.
Targeting & localization of the dosage form at a specific site
-Painless administration.
-Low enzymatic activity & avoid of first pass metabolism
If MDDS are adhere too tightlgy because it is undesirable to exert too much force to remove the formulation after use,otherwise the mucosa could be injured.
-Some patient suffers unpleasent feeling.
-Unfortunately ,the lack of standardized techniques often leads to unclear results.
-costly drug delivery system
1. Structure of skin.
2. Skin relating problems :
a. Dry skin
b. Acne
c. Pigmentation
d. Prickly heat
e. Wrinkles
f. Body odour
3. Structure of hair.
4. Hair growth cycle.
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.
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
Slide 1: Title Slide
- Title: Ocular Drug Delivery Systems:
- Presenter Name and Affiliation
Slide 2: Introduction
- Importance of efficient drug delivery to the eye for the treatment of ocular diseases.
- Challenges with conventional eye drops and the need for improved drug absorption and residence time.
- Objectives of ocular drug delivery systems: enhancing drug bioavailability, prolonging drug release, and providing targeted delivery.
Slide 3: Overview of Ocular Drug Delivery Systems
- Definition of ocular drug delivery systems as specialized techniques and formulations for drug administration to the eye.
- Importance of improving drug delivery to achieve therapeutic efficacy.
- Goals: enhancing drug bioavailability, prolonging drug release, and providing targeted delivery.
Slide 4: Types of Ocular Drug Delivery Systems
- Topical Formulations:
- Eye Drops: Traditional method with limited drug absorption.
- Ointments and Gels: Improved residence time but may cause blurred vision.
- Sprays and Aerosols: Effective for certain medications but challenging for accurate administration.
Slide 5: Types of Ocular Drug Delivery Systems (continued)
- Solid Drug Delivery Systems:
- Inserts and Implants: Sustained release of drugs over an extended period.
- Microparticles and Nanoparticles: Enhanced drug stability, bioavailability, and targeted delivery.
Slide 6: Types of Ocular Drug Delivery Systems (continued)
- Contact Lenses:
- Drug-Eluting Lenses: Act as reservoirs to release drugs gradually.
- Mucoadhesive Lenses: Improve drug retention and bioavailability.
Slide 7-45: Advantages of Ocular Drug Delivery Systems
- Increased Bioavailability: Enhanced drug absorption and residence time for improved therapeutic efficacy.
- Targeted Delivery: Localized treatment of ocular tissues, minimizing systemic side effects.
- Prolonged Drug Release: Controlled release systems reduce the frequency of administration.
- Patient Compliance: Convenience and ease of use improve patient adherence to treatment regimens.
Slide 46: Challenges and Future Perspectives
- Barrier Properties: Overcoming the ocular barriers for effective drug penetration.
- Biocompatibility: Ensuring the drug delivery system is well-tolerated by ocular tissues.
- Manufacturing and Regulatory Considerations: Meeting quality standards and regulatory requirements for commercial production.
- Future Developments: Nanotechnology, biomaterials, and gene therapy for advancing ocular drug delivery systems.
Slide 47: Conclusion
- Recap of the importance of ocular drug delivery systems for improving treatment outcomes.
- Potential benefits of enhanced drug bioavailability, targeted delivery, and prolonged drug release.
- Acknowledgment of challenges and the promising future of ocular drug delivery systems.
Slide 48: Thank You
- Contact
ocular drug delivery systems in drug delivery systemsArun Pandiyan
DEFENITION:
Drug delivery systems are designed to enhance the targeted delivery of medications, improving their effectiveness while minimizing side effects. Various approaches include nanoparticles, liposomes, and implantable devices, offering controlled release or targeted delivery to specific tissues. These systems aim to optimize therapeutic outcomes and patient compliance.
CLASSIFICATION OF DRUG DELIVERY SYSTEM
Oral Drug Delivery:- Tablets, capsules, and liquids are commonly used for systemic drug delivery. Controlled-release formulations provide sustained drug release over time
Injectable Drug Delivery:- Intravenous, intramuscular, and subcutaneous injections allow rapid drug delivery into the bloodstream. Depo injections provide sustained release over weeks or months.
Transdermal Drug Delivery:- Patches and topical formulations deliver drugs through the skin. Ensures a controlled and prolonged release of medication.
Inhalation Drug Delivery:- Aerosolized medications for respiratory conditions. Rapid absorption through the lung's extensive surface area.
Implantable Drug Delivery:- Devices like pumps or reservoirs placed under the skin for continuous drug release. Common for long-term conditions requiring a steady dosage.
Nanoparticle-based Drug Delivery:- Nanocarriers (liposomes, micelles, nanoparticles) enhance drug solubility and improve targeted delivery. Effective for delivering drugs to specific cells or tissues.
Targeted Drug Delivery:- Ligand-based systems use specific molecules to target drugs to particular cells or tissues. Minimizes side effects by focusing on diseased areas.
Gastrointestinal Drug Delivery:- Drug formulations designed for specific release in different parts of the gastrointestinal tract. Examples include enteric-coated capsules.
Intrathecal Drug Delivery:- Direct delivery of drugs into the spinal canal. Often used for pain management or neurological conditions.
Ocular Drug Delivery:- Eye drops, ointments, or implants for treating ocular conditions. Ensures targeted drug delivery to the eyes.
These systems cater to diverse medical needs, offering tailored solutions for optimal therapeutic outcomes.
COMPRESSION AND COMPACTION , physics of tablet compression, compression, consolidation, effects of friction, distribution of forces, compaction profiles, solubility.
Paper electrophoresis
gel electrophoresis
capillary electrophoresis
zone electrophoresis
moving boundary electrophoresis
iso electric focusing electrophoresis
GASTRO RETENTIVE DRUG DELIVERY SYSTEM (GRDDS)JayeshRajput7
Gastro retentive drug delivery system which includes, principles concepts, advantages and disadvantages of GRDDS, Modulation of GI transit time, Approaches to extend GI transit, Buccal drug delivery systems, Principle of muco adhesion, advantages and disadvantages of GRDDS, Mechanism of drug permeation, Methods of formulation and its evaluations.
Documentation in pharaceutical industryJayeshRajput7
documentation in pharmaceutical industry, master formula record (MFR), DMF (drug master file), distribution records, generic drugs product development, hatch waxman act, CFR (code of federal regulation), drug product performance, in vitro ANDA regulatory approval process, NDA approval process, BE and drug product assessment, in-vivo scale up process approval changes, post marketing surveillance, outsourcing BA and BE to CRO (contract research organisation), Regulatory requireents for product approval, API, Biologics, Novel therapies obtaining NDA, ANDA for generic drug ways and means of US registration for foreign drugs.
CMC, post approval regulatory affairs, etcJayeshRajput7
this document covers points such as CMC, post approval regulatory affairs, regulation for combination products, and medical devices, common technical document (CTD) and electronic common technical document (eCTD) format, industry and FDA liasion, ICH guidelines of ICH Q,S,E,M, regulatory requirements of EU, MHRA, TGA and ROW countries.
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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
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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!
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...
ocular drug delivery
1. Masters of pharmacy, Pharmaceutical technology (Pharmaceutics)
Subject- Advances in drug delivery (MPT-103T)
Lesion no- 4, Ocular drug delivery systems By- Drx JAYESH M RAJPUT
Points: -
1) Ocular drug delivery system.
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. Due to
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 as a ointment, 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
They are specialized dosage form designed to be instilled onto the external surface of the eye (topical),
administered inside (intraocular) or adjacent (periocular) to the eye or used in conjunction with an
ophthalmic device
The novel approach of drug delivery system in which drug can instilled on the cul-de-sac cavity of eye is
known as ocular drug delivery system
Cul-de-sac cavity is the space between eye lids and eye balls
The most commonly employed ophthalmic dosage forms are solutions, suspensions, and ointments
But these preparations when instilled into the eye are rapidly drained away from the ocular cavity due to
tear flow and lacrimal nasal drainage
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 newest dosage forms for ophthalmic drug delivery are gels, gel-forming solutions, ocular inserts,
intravitreal injections and implants.
Difference between ophthalmic and ocular drug delivery system
Sr.no Ophthalmic DDS Ocular DDS
1 Conventional system Novel system
2 Old concept New concept
3 Addition of preservatives Do not add preservatives
2. 4 High dosing frequency Low dosing frequency
5 Minimum release rate of drug Maximum release rate of drug
6 Limited flexibility Extreme flexibility
7 Minimum absorption rate Maximum absorption rate
8 Minimum bioavailability Maximum bioavailability
Major classes of drugs used are
Miotics- e.g. Pilocarpine HCL
Mydriatics- e.g. Atropine
Cycloplegics- e.g. Atropine
Anti-inflammatory- e.g. Corticosteroids
Anti-infective (antibiotics, antiviral and antibacterial)
Anti-glaucoma drugs- e.g. Pilocarpine HCL
Surgical adjuncts- e.g. Irrigating solutions
Diagnostic drugs-e.g. Sodium fluorescin
Anesthetics- e.g. Tetracaine
Composition of eye
Water- 98%
Solid-1.8%
Organic elements
Protein-0.67%
Sugar-0.65%
NaCL-0.66%
Other mineral element- sodium, potassium and ammonia- 0.79%
Artificial tear- the solution intended to rewet hard lenses in situ are referred has rewetting solutions or
artificial tear.
Lacrimal nasal drainage
3. Anatomy of the human eye
Mechanism of ocular drug absorption
Topically applied drug can be absorbed from, two routes: -
Corneal absorption
The outermost layer, the epithelium is the rate-limiting barrier
Transcellular transport is the major mechanism of ocular absorption for lipophilic drugs
Small ionic and hydrophilic molecules appear to gain access to the anterior chamber through paracellular
pathway.
Non-corneal absorption
It involves penetration across the sclera and conjunctiva into the intraocular tissues
This mechanism of absorption is usually non-productive, as drug penetrating is taken up by the local capillary
beds and removed to the general circulation
Significant for drug molecules with poor corneal permeability
2) Barriers of drug permeation
Drug loss from the ocular surface: - after instillation, the flow of lacrimal fluid removes instilled
compounds from the surface of the eye. Even though the lacrimal turnover rate is only about 1µl/min the
excess volume of the instilled fluid is flown to the nasolacrimal duct rapidly in a couple of minutes
Lacrimal fluid-eye barriers: - corneal epithelium limits drug absorption from the lacrimal fluid into the
eye. The corneal epithelial cells form tight junctions that limit the paracellular drug permeation. Therefore,
lipophilic drugs have typically atleast an order of magnitude higher permeability in the cornea than the
hydrophilic drugs. In general, the conjunctiva is leakier epithelium than the cornea and its surface area is
also nearly 20 times greater than that of the cornea.
Blood-ocular barriers: - the eye is protected from the xenobiotics in the blood stream by blood ocular
barriers. These barriers have two parts: blood-aqueous barrier and blood-retina barrier. The anterior
blood-eye barrier is composed of the endothelial cells in the uvea. This barrier prevents the access of
plasma albumin into the aqueous humour, and also limits the access of plasma albumin into the aqueous
humor. The posterior barrier between blood stream and eye is comprised of retinal pigment epithelium
(RPE) and the tight walls of retinal capillaries.
4. Or
Barriers are broadly classified as: -
1) Anatomical barriers
When a dosage form is topically administered there are two routes of entry, either through the cornea or via
the non-corneal route. The cornea is very tight multilayered tissue that is mainly composed of five sections
Epithelium, bowman’s membrane, stroma, descent’s membrane and endothelium.
Corneal cross section
Out of these it is the epithelium which acts as the principal barrier. These 5-6 layers of columnar epithelial
cells with very tight junctions create high Para cellular resistance of 12-16 KΩ.cm. it acts as a major barrier
to hydrophilic drug transport through intercellular spaces. On the other hand stroma, which consists of
multiple layers of hexagonally, arranged collagen fibers containing aqueous pores or channels allow
hydrophilic drugs to easily pass through but it acts as a significant barrier for lipophilic drugs. Thus for a
drug to have optimum bioavailability, it should have the right balance between lipophilicity and
hydrophilicity. The remaining layers are leaky and do not act as significant barriers. Non-corneal route by
passes the cornea and involves movement across conjunctiva and sclera. This route is important for large
especially and hydrophilic molecules such as peptides, proteins and siRNA (small or short interfering RNA).
The conjunctiva is more permeable than cornea especially for hydrophilic molecules due to much lower
expression of tight junction proteins relative to corneal epithelium. High vascularity of the limbal area
renders this route not suitable for drug delivery as the blood vessels remove a large fraction of absorbed
dose. Only a small fration of the dose reaches the vitreous.
2) Physiological barriers
o The eye’s primary line of defense is its tear film
o Bioavailability of topical administered drugs is further reduced by precorneal factors such as
solution drainage, tears dilution, tear turnover, and increased lacrimation.
o The lacrimal fluid is an isotonic aqueous solution containing a mixture of proteins (such as lysozyme)
as well as lipids
o Following topical application, lacrimation is significantly increased leading to dilution of
administered dose
o This in turn lowers drug concentration leading to diminished drug absorption
o Rapid clearance from the precorneal area by lacrimation and through nasolacrimal drainage and
spillage further reduces contact time between the tissue and drug molecules
o This in turn lowers the exact time for absorption leading to reduced bioavailability
5. o The average tear volume is 7-9 µL with a turnover rate of 16% per minute
o Thus drugs administered as eye drops need to be isotonic and non irritating to prevent significant
precorneal loss
3) Blood-ocular barrier
o The blood-ocular barrier normally keeps most drugs out of the eye. However inflammation breaks
down this barrier allowing drugs and large molecules to penetrate into the eye
4) Blood- aqueous barrier
o The ciliary epithelium and capillaries of the iris
5) Blood- retinal barrier
o Non-fenestrated capillaries of the retinal circulation and the tight junctions between retinal
epithelial cells preventing passage of large molecules from chorio-capillaries into the retina
Drug and dosage form related factors: -
The physicochemical properties of drug molecule become even more important in the case of ocular drug
delivery because of the complex anatomical and physiological constrains
The rate of absorption from the administered site depends highly on the physical properties of drug molecule
(solubility, lipophilicity, degree of ionization and molecular weight) and ocular tissue structure
Solubility: - solubility is dependent on the pKa of the drug and pH of the solution. With these parameters one can
determine the ratio of ionized to unionized molecules
Usually unionized molecules can readily permeate biological membranes example: - the permeability of
unionized Pilocarpine is almost two fold greater than that of its ionized form.
6. The corneal epithelium bears a negative charge at the pH of lachrymal fluid and hence cationic species tend to
penetrate at a faster ratio their anionic counterparts.
Lipophilicity: - lipophilicity and corneal permeability display sigmoidal relationship
This is because of the diffential permeability of the different layers of cornea towards lipophilic drugs. As
previously mentioned, lipophilic drug tend to permeate easily through the epithelial layers of cornea
But the hydrophilicity of the inner layer of cornea (stroma) requires higher hydrophilicity for optimal permeation
Partition coefficient (Log P) value ranging from 2-4 is found to result in optimum corneal permeation.
Molecular weight and size: - the weight and size of a molecules play a critical role in deciding its overall
permeability through paracellular route
The diameter of the tight junctions present on corneal epithelium is less than 2 nm
Molecules having molecular weight less than 500 Dalton are able to permeate readily
The paracellular permeability is further limited by the pore density of corneal epithelium.
Molecular weight and size
The conjunctiva has larger paracellular pore diameter thus allowing permeation of larger molecules such as
small and medium size peptides (5000-10000 Daltons)
Permeation across sclera occurs through the aqueous pores and molecular size of the solute can be the
determining factor
Example: - sucrose (molecular weight- 342 Daltons) permeates 16 times faster than inulin (molecular weight
5000 Daltons)
Sclera permeability is approximately half of conjunctiva but much higher than cornea.
3) Methods to overcome barriers
I. Viscosity enhancers
Viscosity increasing polymers are usually added to ophthalmic drug solutions on the premise that an
increased vehicle viscosity should correspond to a slower elimination from the preocular area, which lead
to improved precorneal residence time and hence a greater transcorneal penetration of the drug into the
anterior chamber
The polymers used include polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), methylcellulose (MC),
hydroxyl ethyl cellulose, hydroxyl propyl methyl cellulose (HPMC), and hydroxyl propyl cellulose.
II. Penetration enhancers
The transport characteristics across the cornea can be maximized by increasing the permeability of the
corneal epithelial membrane
So, one of the approaches used to improve ophthalmic drug bioavailability lies in increasing transiently
the permeability characteristics of the cornea with appropriate substances known as penetration
enhancers or absorption promoters
It has disadvantages like ocular irritation and toxicity. The transport process from the cornea to the
receptor site is a rate-limiting step, and permeation enhancers increase corneal uptake by modifying the
integrity of the corneal epithelium
E.g., cetyl pyridinium chloride, benzalkonium chloride, parabens, tween 20, saponins
7. Classified as:-
Calcium chelators, surfactants, bile acid and salts, preservative, glycoside, fatty acids
III. Eye ointments
The medical agent is added to the base either as a solution or as a finely micronized powder
Upon instillation in the eye, ointments break up into the small droplets and remain as a depot of drug in
the cul-de-sac for extended periods
Ointments are therefore useful in improving drug bioavailability and in sustaining drug release
Although safe and well-tolerated by the eye, ointments suffer with relatively poor patient compliance due
to blurring of vision and occasional irritation.
IV. Gel
It has advantage like reduced systemic exposure. Despite the extremely high viscosity, gel achieves only a
limited improvement in bioavailability, and the dosing frequency can be decreased to once a day at most
The high viscosity, however, results in blurred vision and matted eyelids which substantially reduce
patient acceptability
The aqueous gel typically utilizes such polymers as PVA, polyacrylamide, poloxamer, HPMC, carbomer,
poly methyl vinyl ether maleic anhydride, and hydroxyl propyl ethyl cellulose
The release of a drug from these systems occurs via the transport of the solvent into the polymer matrix,
leading to its swelling. The final step involves the diffusion of the solute through the swollen polymer,
leading to erosion/dissolution
V. Liposomes
Liposomes are the microscopic vesicles composed of one or more concentric lipid bilayers, separated by
water or aqueous buffer compartments
Liposomes possess the ability to have an intimate contact with the corneal and conjunctival surfaces,
which increases the probability of ocular drug absorption
This ability is especially provides the sustained release and site specific delivery. Liposomes are difficult to
manufacture in sterile preparation
It has limitation like low drug load and inadequate aqueous stability and is undesirable for drugs that are
poorly absorbed, the drugs with low partition coefficient.
VI. Niosomes
Niosomes are bilayered structural vesicles made up of non-ionic surfactant which are capable of
encapsulating both lipophilic and hydrophilic compounds
Niosomes reduce the systemic drainage and improve the residence time, which leads to increase ocular
bioavailability
They are non biodegradable and non biocompatible in nature.
VII. Nanoparticles/ Nanospheres
These are polymeric colloidal particles, ranging from 10 nm to 1 mm, in which the drug is dissolved,
entrapped, encapsulated, or adsorbed
Encapsulation of the drug leads to stabilization of the drug. They represent promising drug carriers for
ophthalmic application
They are further classified into nanospheres (small capsules with a central cavity surrounded by a
polymeric membrane) or nanocapsules (solid matricial spheres)
VIII. Microemulsion
8. Microemulsion is stable dispersions of water and oil, facilitated by a combination of surfactant and co-
surfactant in a manner to reduce interfacial tension
Microemulsion improves the ocular bioavailability of the drug and reduces frequency of the
administration
These systems are usually characterized by higher thermodynamic stability, small droplet size (῀100 nm),
and clear appearance
IX. In situ-forming gel
The droppable gels are liquid upon instillation, and they undergo a phase transition in the ocular cul-de-
sac to form a viscoelastic gel, and this provides a response to environmental changes
It improves the patient acceptance. It prolongs the residence time and improves the ocular bioavailability
of the drug
Parameters that can change and trigger the phase transition of droppable gels include pH, temperature,
and ionic strength
Examples of potential ophthalmic droppable gels reported in the literature include gelling triggered by a
change in pH- CAP latex cross linked polyacrylic acid and derivatives such as carbomers and polycarbophil,
gelling triggered by temperature change- poloxamers methyl cellulose and smart hydrogel, gelling
triggered by ionic strength change- gelrite and alginate.
X. Ocular inserts
The ocular inserts overcome this disadvantage by providing with more controlled, sustained and
continuous drug delivery by maintaining an effective drug concentration in the target tissues and yet
minimizing the number of applications
It reduces systemic adsorption of the drug. It causes accurate dosing of the drug
It has disadvantages like patient incompliance, difficulty with self-insertion, foreign body sensation, and
inadvertent loss from the eye.
9. XI. Implants
The goal of the intraocular implant design is to provide prolonged activity with controlled drug release
from the polymeric implant material
Intraocular administration of the implants always requires minor surgery. In general, they are placed
intravitrally, at the pars plana of the eye (posterior to the lens and anterior to the retina)
Although this is an invasive technique, the implants have the benefit of: -
By-passing the blood-ocular barriers to deliver constant therapeutic levels of drug directly to the
site of action
Avoidance of the side effects associated with frequent systemic and intravitreal injections, and
Smaller quantity of drug needed during the treatment
The ocular implants are classified as non biodegradable devices. Non-biodegradable implants can provide
more accurate control of drug release and longer release periods that the biodegradable polymers do, but
the non biodegradable systems require surgical implant removal with the associated risks
XII. Iontophoresis
Ocular Iontophoresis has gained significant interest recently due to its non invasive nature of delivery to
both anterior and posterior segment
Iontophoresis is a non invasive method of transferring ionized drugs through membranes with low
electrical current
The drugs are moved across the membranes by two mechanisms: migration and electro-osmosis, ocular
Iontophoresis is classified into transcorneal, corneosceral, or trans-scleral Iontophoresis
It has ability to modulate dosages (less risk of toxicity), a broad applicability to deliver a broad range of
drugs or genes to treat several ophthalmic diseases in the posterior segment of the eye, and good
acceptance by patients. It may combined with other drug delivery systems
It has disadvantage like no sustained half-life, requires repeated administrations, side effects include mild
pain in some cases, but no risk of infections or ulcerations, risk of low patient compliance because the
frequent administrations that may be needed
Ocuphor™ system has been designed with an applicator, dispersive electrode, and a dose controller for
transscleral Iontophoresis (DDT), this device releases the active drug into retina-choroid as well
A similar device has been designed called visulex ™ to allow selective transport of ionized molecules
through sclera
Examples of antibiotics successfully employed are gentamicin, tobramycin, and ciprofloxacin, but not
vancomycin because of its high molecular weight
10. Approaches for the enhancement of ocular bioavailability
Based on the use of the drug delivery system, which provide the controlled and continuous delivery of opthalmic drugs.
Based on maximizing corneal drug absorption and minimizing precorneal drug loss, these are summarized as: -
Approach Advantages Limitations
Penetration enhancers Ease of formulation due to
compatibility with wide range of
excipients
Accumulation in cornea affecting clear
Vision. Alteration of permeability of
Blood vessels in the uveal tract.
Irritation of eye and nasal mucosa.
Suspension Retention in lower cul-de-sac for
prolonged period
Non-uniformity of dosing formulation
Of non-dispersible cake. Polymorphic
Changes of drug.
Ointments Retention in lower cul-de-sac for
prolonged period, slower diffusion of
drug
Blurred vision
Non esthetic
Gels Retention in lower cul-de-sac for
prolonged period, slower diffusion of
drug
Difficulty in administration
Blurred vision
Mucoadhesive dosage forms Retention in lower cul-de-sac for
prolonged period
Poor compliance
Blurred vision
Liposomes Biodegradable, non-toxic, available in
more than one dosage form
Limited stability, limited drug loading
Capacity, expensive.
Niosomes Non-toxic
Available in more than one dosage
Form
Limited stability, limited drug loading
Capacity, expensive
Micro and Nanoparticles Enhance bioavailability, available in
More than one dosage forms,
Retention in lower cul-de-sac for
Prolonged period
Suitability for only small dose
drugs, difficulty in formulation,
expensive
Micro emulsion Enhanced patient compliance, best of
Drugs with slow dissolution, good
Stability
Rapid precorneal elimination
Ocular inserts Controlled rate of release, prolonged
Delivery
Irritation, need of skilled personnel for
Administration, abrasion of cornea,
expensive
Contact lenses Correction of vision, sustained
Delivery of drugs
Low precision of dosing, expensive
Iontophoresis Fast delivery, painless and safe
drug delivery system, delivery at
the desired ocular tissue,
increased ocular retention time
Difficulty in insertion, patient
non-compliance
11. Formulation considerations in ophthalmics
A. Sterility
Probably the most important property of ophthalmic formulations is that they must be sterile. The USP XXII-NF
xvII (2003) lists five methods of achieving sterility: -
Steam sterilization at 121 degree, dry-heat sterilization, gas sterilization using ethylene oxide (due to
environmental concerns the use of ethylene oxide is being phased out wherever possible), sterilization using
ionizing radiation e.g., radioisotope decay (gamma radiation) and electron beam radiation, sterilization by
filtration.
B. Preservatives
The selection of a preservative for ophthalmic solutions is not an easy task, with very few candidates to choose
from: -
Sr no Preservatives Conc. range
1 Quaternary ammonium compounds 0.004-0.02
2 Organic mercurial’s 0.01- most common
3 Parahydroxy benzoates 0.001- 0.01
4 Chlorobutanol 0.5
The following criteria are important for selection of preservative: -
Bard spectrum of activity against both gram-positive and gram-negative organisms and fungi
The agent should rapidly kill virulent organisms
Satisfactory chemical and physical stability over a wide range of pH and temperature
Compatibility with formulation components and container materials
Non-toxic and non-irritating during use
C. Clarity
o The official definition of ophthalmic solutions requires that they be free of particulate matter
o Solution clarity is usually achieved by filtration, either with a clarifying filter or as part of a sterile filtration
procedure
o The degree of clarity of the finished product can be monitored by means of various instruments capable
of detecting any light scattering or blockage resulting from the presence of particulate matter.
Sr no Particle size (µm) Proposed limit (particles per ml)
1 ≥10 ≤50
2 ≥25 ≤5
3 ˃50 Not allowed
12. D. Stability
The stability of the active ingredient in an ophthalmic solution depends upon the chemical nature of the active
ingredient, pH manufacturing procedure, type of additives, and type of container. The maintenance of a pH that
is consistent with acceptable stability is often in conflict with a pH that would provide optimum corneal
penetration of the drug in question and optimum patient acceptance of the product.
E. pH adjustment and buffers
o the adjustment of ophthalmic solution pH by the appropriate choice of a buffer is one of the most
important formulation considerations
o buffers may be used in an ophthalmic solution for one or more of the following reasons; to maintain the
physiologic pH of the tears upon administration of formulation in order to minimize tearing and patient
discomfort, to optimize the therapeutic activity of the active ingredient by altering the corneal
penetration through changes in the degree of ionization; and to optimize product stability
o the tear fluid pH is reported to be vary between 6.9 and 7.5
F. Tonicity
o The hypertonic solution placed in the eye tends to draw solvent (water) from its surroundings in order to
dilute the instilled solution
o In this case, water flows from the aqueous layer through the cornea to the eye surface
o Conversely, a hypotonic solution could result in the passage of water from the site of application through
the eye tissues
o In this case, the epithelial permeability is increased; allowing water to flow into the cornea, the corneal
tissues swells, and drug concentration on the ocular surface is temporarily increased.
G. Viscosity modifiers
o The viscosity of ophthalmic solutions is often increase in order to prolong the corneal contact time,
decrease the drainage rate, and increase the bioavailability of the active ingredient
o The polymers used to increase viscosity may also lower the frictional resistance between the cornea and
the eyelid which occurs with each blink, thereby exerting a lubricating effect that may be of benefit for
some patients.
H. Additives
o Stabilizers
o The use of stabilizers is permitted in ophthalmic solutions when necessary. Epinephrine hydrochloride
undergoes oxidative degradation and an oxidant such as sodium bisulphate or metabisulfite is commonly
added up to a 0.3% concentration. Epinephrine borate stabilization requires special consideration, and
mixtures of ascorbic acid and acetyl-cysteine or sodium bisulphite and 8-hydroxyquinoline have been
used for this purpose
o Surfactant
o The addition of surfactants to ophthalmic solutions is permitted; even through their use is greatly
restricted. The toxicity of surfactants is on the order:
Anionic ˃ cationic ˃ non-ionic
Non-Ionics are used in low concentration to increase the dispersion of suspended drugs, such as steroids,
and thereby improve solution clarity. The ability of these compounds to bind and thereby inactivate
certain preservatives coupled with their irrational potentials, limits their use to low concentrations.
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