Ocular drug delivery

presented by Mishra sheetkantha

pharmaceutics

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INTRODUCTION• Ocular drug delivery is a system which involve the

administration of drug in the eye.

• Drug delivery to the eye can be broadly classified into

1) Anterior Segments.

2) Posterior segments.

• The unique structure of the eye restricts the entry of

drug molecules at the required site of action.2

Traditionally used eye drops formulations lacked good

bioavailability and had low patient compliance, hence

most investigations in this field emphasize on the

duration of action and enhancement of corneal

absorption.

Recent developments in ophthalmic drug delivery

systems include use of gelling polymers, prodrugs,

microspheres, nanoparticles, liposomes and hydrophilic

ocular inserts, non-aqueous vehicles are new areas of

interest in ophthalmic drug delivery. 3

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Approaches to improve ocular bioavailability are

Penetration Enhancers.

Liposomes.

Niosomes.

Nanosuspension.

Microemulsion.

Nanoparticles/nanospheres.

In situ-forming gel. 5

OPTHALMIC DISORDERS Periocular diseases:

• Conjuctivitis.

• Keratitis.

• Trachoma.

• Dry Eye.

Intraocular diseases:

• Glaucoma.

• Cataract.

• Macular Degeneration.6

Glaucoma Progressive and Irreversible Disease.

Leads to blindness.

Deterioration of Optic Nerve.

fluid accumulates in eye.

Diameter of cornea changes.

Asymptomatic.

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What Happens To EYE In Glaucoma

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Current Glaucoma Monitoring Systems :

Measures static intraocular pressure

Single Snapshots in Time

taken during the day when pressure is lowest

Monitoring in Overnight Sleep Labs

cumbersome

expensive

Frequent Punctual Measurements

affects intraocular pressure

checks pressure peaks9

Class of drugs used in Glaucoma

•Prostaglandins.

•Beta-blockers.

•Alpha-adrenergic agonists.

•Carbonic anhydrase inhibitors.

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New APPROVED PREPRATION Glaucoma Simbrinza :

Simbrinza is the first combination eye drop containing a carbonic anhydrase inhibitor and an alpha2 agonist for the treatment of glaucoma.

Taptiqom : Taptiqom is a fixed-dose combination of the prostaglandin analogue tafluprost and the beta-blocker timolol, for the treatment of glaucoma.

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Current Clinical Trials STUDY

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Active ingredient Dosage form Target Indication Developmental stage

Latanoprost Puctal plug Glaucoma P2

Bimatoprost Puctal plug Glaucoma P2

Latanoprost Subconjunctival insert

Glaucoma P1

ONGOING Research work on Glaucoma Rho kinase inhibitors :

Rho kinase inhibitors, such as Ripasudil work by inhibition of the actin cytoskeleton,

resulting in the morphological changes in the trabecular meshwork and increased

aqueous outflow. More compounds in this class are being investigated in phase 2 and

phase 3 trials

Dendrimers as tunable vectors of drug delivery systems and biomedical and

ocular applications:

• Dendrimers were examined for the putative use as ophthalmic vehicles for ocular

delivery of pilocarpine nitrate (cholinomimetic). It was observed that the use of

dendrimers with carboxylic or hydroxyl surface groups as drug carriers increased the

bioavailability of pilocarpine nitrate in eyes of albino rabbits and the time of drug

residence .

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DESIGN OF OCULAR CONTROLLED RELEASE OCUSERTS OF

BRINZOLAMIDE:

Ocuserts were formulated using various polymers and plasticizers by film

casting technique.

ENV515 Travoprost Extended Release (XR) in Patients With Open

Angle Glaucoma:

• Envisia Therapeutics Releases ENV515 (travoprost XR) Phase 2 Data

Showing Nine-Month Duration Of Action After A Single Dose in Patients

with Glaucoma showing clinically meaningful reduction in intraocular

pressure.

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Ocular Inserts for Sustained Release of the Angiotensin-Converting

Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma.

• In view of the fact that activation of endogenous ACE2 is a potential strategy

to develop new anti glaucomatous agents, a non-implantable drug delivery

device made of chitosan .

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Gene Therapy For Glaucoma • A gene therapy approach in which a mutated gene is replaced or

inactivated, or in which a new gene is introduced, could provide a novel and more effective way of targeting the disease

• Both viral and non viral vector gene delivery systems have been used to target specific tissues involved in the pathogenesis of glaucoma. These tissues include the trabecular meshwork, ciliary body, ciliary epithelium.

• Given recent laboratory studies utilizing gene therapy techniques to lower intraocular pressure and to provide neuroprotection, and the continued development of tissue-specific vectors, it seems that we are well poised for a new generation of treatments for glaucoma.

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Marketed products

ADVANCED SYSTEMS :

• Design of Punctal Plug :

1. Punctal plugs are placed in the tear duct (punctum) to release

a variety of drugs.

2. Currently targeting the treatment of glaucoma and ocular

hypertension .

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Design of Replenish Mini Pump1. Micro-electromechanical system that delivers continuous or

bolus-targeted drugs to both the anterior and posterior segments.

2. Refillable drug reservoir (via 31 gauge needle) that is capable of storing and delivering up to 12 months.

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Triggerfish System Created by SENSIMED.

First of its Kind on the market constant reading device.

Safety Approval in Europe last year.

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Benefits of Triggerfish System• Improved Understanding of Pressure Change

• pressure during day versus night

• More Efficient

• Personalized Drug Delivery and Treatment

• Adapt Treatment

• dependent on changing conditions

• Sensor is Placed Outside of Vision Field

• Early Diagnosis and Treatment23

ConclusionA considerable amount of research has been carried

out on the development of ocular drug delivery systems.

It is appreciated that the topical route is preferred for delivery of drugs to the eye. 

The primary objective of all the ocular drug delivery systems developed till date is to increase ocular drug residence time which leads to improvement in ocular drug bioavailability, diminish side effects for a therapeutic response in the eye

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References • K. P. Sampath Kumar, Debjit Bhowmik, G.Harish, S.Duraivel, B. Pragathi

kumar,Ocular Inserts: A Novel Controlled Drug Delivery System.• Chrai SS, Makoid MC, Erikson SP, Robinson JR.Drop size and initial

dosing frequency problems of topically applied ophthalmic drugs. J Pharm Sci. 1974;64:333–8.

• Shweta Kaul, G. Kumar and P. Kothiyal AN INSIGHT INTO OCULAR INSERT, IJPSR, 2012; Vol. 3(7): 1905-1912 .

• Sikandar et al.: Ocular Drug Delivery System: An Overview. Int. J. Phar. Sci. Res 2011, 2(5): 1168-1175.

• Robinson J C: Ocular Anatomy and Physiology Relevant to Ocular Drug Delivery Chapter – 2, In: Ophthalmic Drug Delivery Systems. Marcel Dekker, New York, Vol – 58 , 1993: 29.

• Marina Kalomiraki, Kyriaki Thermos, NikosChaniotakis, Dendrimers as tunable vectors of drug delivery systems and biomedical and ocular applications, International Journal of Nanomedicine

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• Kesharwani P, Jain K, Jain NK. Dendrimer as nanocarriers for drug delivery. Prog Polym Sci. 2014;39:268–307.

• Azmat Shaikh , Talat Farheen, Dr. Sadhana Shahi, OPHTHALMIC DRUG DELIVERY SYSTEM WITH RECENT ADVANCES, IJPRD, 2015; Vol 7(05):July-2015 (011 - 022).

• Foureaux G, Franca JR, Nogueira JC,Fulgêncio GdO, Ribeiro TG, Castilho RO, et al. Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma doi:10.13.71/journa l(133 -149).

• Weinreb RN,Tee Khaw P. Primary open-angle glaucoma. Lancet. 2004; 363: 1711–1720. PMID:15158634.

• S K Motwani ; S Chopra ; S Talegaonkar ; K Kohli; F J Ahmad ;R.K.Khar Eur.J.Pharm.Biopharm. 2008; 68:513–525.

• Rekas M, Danielewska ME, Byszewska A, et al. Assessing efficacy of canaloplasty using continuous 24-hour monitoring of ocular dimensionalchanges. Invest Ophthalmol Vis Sci.2016;57:2533–2542. DOI:10.1167/iovs.16-19185.

• Akanksha Tiwari1, Raj Kumar Shukla, Novel ocular drug delivery systems: An overview, J. Chem. Pharm. Res., 2010, 2(3):348-355.

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• Tarek Shaarawy , Shibal Bhartiya, Recent Advances in the Treatment of Glaucoma, European Ophthalmic Review, 2011;5(1):33–7.

• R M Handjani-Vila ; A Rlbier ;B Rondot ; G Vanlerberghe . Int. J. Cosmetic Sci. 1979; 1, 303-314.

• Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262–267.

• V’Ooteghem MM., 1993.,Edman Biopharmaceutics of Ocular Drug Delivery. Boca Raton, CRC Press., 27–41.

• Barbu E, Sarvaiya I, Green KL, Nevell TG and Tsibouklis J., A. 2005. Vinylpyrrolidone-co-(meth) acrylic acid inserts for ocular drug delivery: synthesis and evaluation. J Biomed Mater Res.,74(4):598-606.

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“Sight is the sense which is more valuable

than all the rest.” So Take care of Eyes!!!

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QUERIES…..

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