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.
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
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.
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.
India Clinical Trials Market: Industry Size and Growth Trends [2030] Analyzed...Kumar Satyam
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CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
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M Capital Group (“MCG”) predicts that with, against, despite, and even without the global pandemic, the medical technology (MedTech) industry shows signs of continuous healthy growth, driven by smaller, faster, and cheaper devices, growing demand for home-based applications, technological innovation, strategic acquisitions, investments, and SPAC listings. MCG predicts that this should reflects itself in annual growth of over 6%, well beyond 2028.
According to Chris Mouchabhani, Managing Partner at M Capital Group, “Despite all economic scenarios that one may consider, beyond overall economic shocks, medical technology should remain one of the most promising and robust sectors over the short to medium term and well beyond 2028.”
There is a movement towards home-based care for the elderly, next generation scanning and MRI devices, wearable technology, artificial intelligence incorporation, and online connectivity. Experts also see a focus on predictive, preventive, personalized, participatory, and precision medicine, with rising levels of integration of home care and technological innovation.
The average cost of treatment has been rising across the board, creating additional financial burdens to governments, healthcare providers and insurance companies. According to MCG, cost-per-inpatient-stay in the United States alone rose on average annually by over 13% between 2014 to 2021, leading MedTech to focus research efforts on optimized medical equipment at lower price points, whilst emphasizing portability and ease of use. Namely, 46% of the 1,008 medical technology companies in the 2021 MedTech Innovator (“MTI”) database are focusing on prevention, wellness, detection, or diagnosis, signaling a clear push for preventive care to also tackle costs.
In addition, there has also been a lasting impact on consumer and medical demand for home care, supported by the pandemic. Lockdowns, closure of care facilities, and healthcare systems subjected to capacity pressure, accelerated demand away from traditional inpatient care. Now, outpatient care solutions are driving industry production, with nearly 70% of recent diagnostics start-up companies producing products in areas such as ambulatory clinics, at-home care, and self-administered diagnostics.
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
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Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
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Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
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1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
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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 .
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