Presented by:-Sujit R. Patel,Sujit R. Patel,Dept. of Pharmaceutics,Dept. of Pharmaceutics,Maratha Mandal College Of Pharmacy, Maratha Mandal College Of Pharmacy, Belgaum-590 010.Belgaum-590 010.

Contents:- Anatomy of eye

Introduction

Advantages

Disadvantages

Classification

Evaluation of ocular drug delivery system

Future trends

Conclusion 2April 8, 2023 Dept. Of Pharmaceutics

Anatomy of the Eye:-

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INTRODUCTION:-

Ophthalmic preparationApplied topically to the cornea, or instilled in the

space between the eyeball and lower eyelidSolution

• Dilutes with tear and wash away through lachrymal apparatus

• Administer at frequent intervalsSuspension

• Longer contact time• Irritation potential due to the particle size of drug

Ointment • Longer contact time and greater storage stability• Producing film over the eye and blurring vision

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Contd. . .

Emulsions

• Prolonged release of drug from vehicle but blurred vision, patient non compliance and oil entrapment are the drawbacks.

Gels

• Comfortable, less blurred vision but the drawbacks are matted eyelids and no rate control on diffusion.

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Controlled delivery system

– Release at a constant rate for a long time

– Enhanced corneal absorption

– Drug with not serious side effect or tolerate by the

patient

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ADVANTAGES:-

Increase ocular residence, hence improving bioavailability.

Possibility of providing a prolonged drug release and thus a

better efficacy.

Increased shelf life with respect to aqueous solutions.

Exclusion of preservatives, thus reducing the risk of

sensitivity reactions as compare to aqueous solutions.

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Possibility of targeting internal ocular tissue through non-corneal routes.

Reduction of systemic side effects and thus reduced adverse effects in case of topical application.

Reduction in the number of doses administration and thus better patient compliance.

Administration of an accurate dose in the eye, which is fully retained at the administration site, thus a better therapy.

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Contd...

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DISADVANTAGES:-

It is Expensive.

Insertion technique is difficult & expulsion of shields may occur not individually fit for each patient.

Shields are not fully transparent & thus reduce visual activity.

Occasional inadvertent loss.

Difficult to handle.

Foreign body sensation.

CLASSIFICATION OF COTROLLED RELEASE OCULAR DRUG DELIVERY

SYSTEMS:-

Mucoadhesive/Bioadhesive dosage forms

Ocular inserts

Collagen shield

Drug presoaked hydrogel type lens and pledges

Ocular iontophoresis

Polymeric solutions

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PseudolaticesOcular penetration enhancersPhase transition systemsParticulate system like, microspheres and

nanoparticlesVesicular systems like liposomes, niosomes,

phamacosomes and discomesChemical delivery system for ocular drug

targeting11

Contd…

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EVALUATION OF OCULAR DRUG DELIVERY SYSTEM

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THICKNESS OF THE FILM :-

• Measured by Dial Caliper at different points and the

mean value is calculated.

DRUG CONTENT UNIFORMITY :-

• The cast film cut at different places and tested for drug

as per monograph.

UNIFORMITY OF WEIGHT :-

• Here, three patches are weighed.

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PERCENTAGE MOISTURE ABSORPTION :-

• Here, ocular films are weighed and placed in a dessicator containing 100 ml of saturated solution of Aluminium Chloride and 79.5% humidity was maintained.

• After three days the ocular films are reweighed and the percentage moisture absorbed is calculated using the formula –

% moisture absorbed = 14

Final weight – Initial weight x 100 Initial weight

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PERCENTAGE MOISTURE LOSS:-

• Ocular films are weighed and kept in a dessicator containing anhydrous Calcium Chloride.

• After three days, the films are reweighed and the percentage moisture loss is calculated using formula –

% moisture loss =

15

Initial weight – Final weight x 100 Initial weight

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IN VITRO EVALUATION METHODS:-

BOTTLE METHOD

In this, dosage forms are placed in the bottle containing dissolution medium maintained at specified temperature and pH.

The bottle is then shaken.

A sample of medium is taken out at appropriate intervals and analyzed for drug content.

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DIFFUSION METHOD

Here ocular film is placed between the donor and receptor compartment.

Drug diffused from donor compartment to receptor compartment containing buffer solution is measured at various time intervals.

MODIFIED ROTATING BASKET METHOD

Dosage form is placed in a basket assembly connected to a stirrer.

The assembly is lowered into a jacketed beaker containing buffer medium and temperature 37 °C.

Samples are taken at appropriate time intervals and analyzed for drug content.

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MODIFIED ROTATING PADDLE APPRATUS

Here, dosage form is placed in a diffusion cell which is placed in the flask of rotating paddle apparatus.

The buffer medium is placed in the flask and paddle is rotated at 50 rpm.

The entire unit is maintained at 37 °C.

Aliquots of sample are removed at appropriate time intervals and analyzed for drug content.

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IN VIVO DRUG RELEASE RATE STUDY:-

Here, the dosage form is applied to one eye of animals and the other eye serves as control.

Then the dosage form is removed carefully at regular time interval and are analyzed for drug content.

The drug remaining is subtracted from the initial drug content, which will give the amount of drug absorbed in the eye of animal at particular time.

After one week of washed period, the experiment was repeated for two times as before.

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ACCELERATED STBILITY STUDIES:- These are carried out to predict the breakdown

that may occur over prolonged periods of storage at normal shelf condition.

Here, the dosage form is kept at elevated temperature or humidity or intensity of light, or oxygen.

Then after regular intervals of time sample is taken and analyzed for drug content.

From these results, graphical data treatment is plotted and shelf life and expiry date are determined.

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FUTURE TRENDS

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Carbon nanotube:-

Carbon nanotubes are made up of graphite.

Its name is derived from its size, since the

diameter of a nanotube is in the order of a few

nanometers (approximately 1/50,000th of the

width of a human hair), while they can be up to

several millimeters in length.

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3D structure of Carbon nanotubeApril 8, 2023 Dept. Of Pharmaceutics

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Pseudolatices:-

• Organic solution of polymers is dispersed in an aqueous phase to form O/W emulsion

• The pseudolatex-based ocular formulations of Pilocarpine were prepared using different combinations of Eudragit RS 100 and Polyvinyl Pyrrolidone (PVP)for prolonged and controlled release of the drug.

• Water is removed partially to an extent that residual water is removed sufficient enough to keep polymeric phase discrete & dispersed

• On application leave an intact noninvasive continuous polymer film which reserves drugs

• Drug released slowly over prolonged period of time , better ocular bioavailability patient compliance

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Microspheres & Nanoparticles:-

• The drugs are bound to small particles which are then dispensed in aqueous vehicles

• Nanoparticles of polybutylcyanoacrylate have been used for human being as a drug carrier

• Pilocarpine nitrate loaded egg albumin microspheres were prepared by thermal denaturation process in the size range of 1-12 μm.

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Ocular Iontophoresis:-

It is the process in which the direct current drives ions into cells or tissues

I. Trans-corneal

II. Trans- scleral

Antibiotics, Antifungal(e.g. Natamycin), Anesthetics(e.g. Benoxinate) and Adrenergic(e.g. Timolol) are delivered by this method

Types:-

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• Liposomes : Phospholipid-lipid vesicles

• Niosomes : Vesicles based on some non-ionic surfactants like dialkyl polyoxyethylene ethers

• Phamacosomes : Pharmacosomes are amphiphilic phospholipid complexes of drugs bearing active hydrogen that bind to phospholipids. Pharmacosomes impart better biopharmaceutical properties to the drug, resulting in improved bioavailability. Pharmacosomes have been prepared for various non-steroidal anti-inflammatory drugs, proteins, cardiovascular and antineoplastic drugs. Developing the pharmacosomes of the drugs has been found to improve the absorption and minimize the gastrointestinal toxicity.

• Discosomes : Systems formed by addition of specific amount of surfactant to vesicular dispersions consisting of mixed vesicular and micelle regions

Vesicular System:-

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Continuous delivery system based upon the osmotic property:-

Implantable mini-pump such as Alzet is the example of such system.

Such system is placed beneath the skin of the scalp.

To deliver the drug to the eye, the pump is connected to the upper fornix by means of polyethylene tubing.

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Contd. . .

Delivery of diethyl carbamazine in ocular onchocerciasis

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CONCLUSION:-

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Controlled ocular drug delivery systems increase the efficiency of the drug by reducing its wastage and by enhancing absorption by increasing contact time of drug to the absorbing surface.

They improve patient compliance by reducing the frequency of dosing.

They reduces the dose and thereby reduces the adverse effects of the drug.

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Although controlled release devices could be more useful in the management of many ophthalmic conditions, they are not very much popular because such devices have to be put in place and taken out from under the eyelid periodically.

Moreover, the devices can move around in the precorneal space resulting in discomfort and visual disturbances.

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Contd. . .

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1. Controlled drug delivery – Concepts and Advances, by S.P. Vyas and Roop K. Khar.

2. Ansel’s Pharmaceutical dosage forms and drug delivery systems, by Loyd V. Allen, Nicholas G. Popovich and Howard c. Ansel.

3. Advances in Controlled and Novel drug delivery, edited by N.K. Jain.

4. Textbook of Industrial Pharmacy, edited by Shobharani R. Hiremath.

5. Novel drug delivery systems, by Y.W. Chein, published by Marcel Dekker, volume 50.

6. http://google.co.in

7. http://youtube.com

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References References :-:-

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EndoSerter MDEA Finalist 2012 - YouTube.flv

Crystalsert Crystalens Delivery System - YouTube.flv

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Important Questions:-

1) What are the causes of poor drug availability from conventional ophthalmic preparations? Explain design, mechanism and adv of ocuserts? [2005]

2) Give an account of ocular absorption, Give examples of controlled release products for ocular route?[2002]

3) a) Explain different methods for formulating ocular controlled drug

delivery systems? b) Explain different methods for formulating ocular controlled drug

delivery systems?[2001]

20 Marks

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10 Marks

1)Bring out the specific advantages & disadvantages ocuserts systems for ocular drug delivery? sketch a neat blow up diagram of ocusert diagram of “ocusert”?[2004]

2)Explain the formulation of ocuserts?[2006]

3)Explain the drug release pattern of ophthalmic inserts ?[2006]

4)Giving the disadvantages of ophthalmic formulations .write a note on ocusert?[2007]

5)How do you design and manufacture ocuserts?[2008]

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Thank You

Thank You

April 8, 2023 Dept. Of Pharmaceutics