OCULAR DRUG DELIVERY SYSTEM By M. Priyanka M. Pharmacy JNTUK
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OCULAR DRUG DELIVERY SYSTEMByM. PriyankaM. PharmacyJNTUK
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CONTENTS:-Introduction to ocular drug delivery systemAnatomy of eyeAbsorption of drugs in eyeDrug elimination from eyePharmacokinetics of ocular drug administrationFactors affecting intraocular bioavailabilityConventional ocular formulations for ocular dug deliveryControlled ocular drug delivery systemsOcular drug delivery devicesRetrometabolic drug design concepts in ophthalmic specific drug deliveryEvaluation of [email protected]
INTRODUCTIONOcular administration of drug is primarily associated with the need to treat ophthalmic diseases. Major classes of drugs used areMiotics Cholinergic agentsMydriatics Anticholinergics(atropine) Anti- inflammatories Anti- infectives Surgical adjuvants
These drugs are meant for local therapy & not for systemic [email protected]
ANATOMY OF EYE
Diameter of 23mmStructure comprises of 3 layersOutermost coat:-The clear, transparent cornea & the white, opaque scleraMiddle layer:-the iris anteriorly, the choroid posteriorly & the ciliary body at the intermediate part Inner layer:-RetinaCORNEA:-Epithelium-stroma-endothelium(fat-water-fat structure)Penetration of the drug depends on oil-water [email protected]
FLUID SYSTEMS IN EYE:- Aqueous humor:-Secreted from blood through epithelium of the ciliary bodySecreted in posterior chamber Vitreous humor:- Secreted from blood through epithelium of the ciliary body Diffuse through the vitreous bodyLacrimal glands:- Secrete tears and wash foreign bodies Moistens the cornea from drying [email protected]
ABSORPTION OF DRUGS IN EYE [email protected]
DRUG ELIMINATIONDRUG ELIMINATION FROM LACRIMAL FLUIDS:-Drugs are mainly eliminated from the pre corneal lacrimal fluid by solution drainage, lacrimation & non productive absorption to the conjunctiva of the eye.Spillage of drug by overflow:-With an estimated drop volume of 50 ml, 70% of administered dose is expelled from the eye by overflowIf blinking occurs only the residual volume 10ml is left indicating that 90% of the dose is expelledDilution of drug by tears turnover:-Tears turnout to have a major share in removing drug solution from conjuctival cul-de-sac.Normal human tear turnover is approximately 16% per minute, which is stimulated by many factors like drug entity, pH, tonicity of dosage form and formulation [email protected]
Nasolacrimal drainage or systemic drug absorption:- Most of the administered drug is lost through nasolacrimal drainage immediately after dosing. The drainage allows drug to be systemically absorbed across the nasal mucosa and the gastrointestinal tract leading to multifarious effects. e.g. Timolol & mixed 1 & 2 antagonist used in glaucomaConjunctival absorption:-Another mechanism that competes for the drug absorption into the eye is the superficial absorption of drug into palpebral and bulbar conjunctiva with concomitant removal from the ocular tissues by peripheral blood streamEnzymatic metabolism:-Enzymatic metabolism may operate in the pre-corneal space or in the cornea which results in the further loss of those drug entities possessing labile bonds. [email protected]
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Factors & corneal barrier limitations for penetration of topically administered [email protected]
ELIMINATION OF INSTILLED DRUG VIA DIFFERENT ROUTESPre-corneal area
Instilled doseDrug protein interactionDrug metabolismDrainageInduced lacrimationNormal tear turnoverEvaporation of tearsCorneal absorptionConjuctival [email protected]
Elimination of drug after instillation in cul-de-sacPRECORNEAL DRUG POOLNASOLACRIMAL DRAINAGE SYSTEMSTROMA EPITHELIUMCORNEAL EPITHELIUMEPITHETICAL SURFACETEAR FLUIDELIMINATIONCONJUCTIVAMETABOLISMAQUEOUS [email protected]
PHARMACOKINETICS OF OCULAR DRUG [email protected]
FACTORS AFFECTING INTRAOCULAR BIOAVAILABILITYIncludesPre-cornealCornealInterior of the eyeInflow & outflow of lacrimal fluidsEfficient naso-lacrimal drainageInteraction of drug with proteins of lacrimal fluidDilution with tearsCorneal barriersPhysico-chemical properties of drugActive ion transport at [email protected]
CONVENTIONAL OCULAR FORMULATIONS FOR OCULAR DRUG DELIVERYDOSAGE FORMADVANTAGESDISADVANTAGESSolutionsConvenienceRapid pre-corneal eliminationLoss of drug by drainageNo sustained actionSuspensionsPatient complianceBest for drugs with slow dissolutionDrug properties decide performanceLoss of both solution & suspended solidEmulsionsProlonged release of drug from vehicleEnhanced pulsed entryPatient non complianceBlurred visionPossible oil entrapmentOintmentsFlexibility in drug choiceImproved drug stabilityIncreased tissue contact timeInhibition of dilution by tearsResistance to nasolacrimal drainageSticking of eye lidsPoor patient complianceBlurred visionNo true sustained effectDrug choice limited by partition coefficientErodible insertsSophisticated & effective delivery systemFlexibility in drug type & dissolution rateNeed only be introduced into eye & not removedPatient discomfortRequires patient insertionMovement of system around eye can cause abrasionOccasional product
GelsComfortableLess blurred vision than ointmentsNo rate control on diffusionMatted eye lids after useNon erodible insertsControlled rate of releaseProlonged deliveryFlexibility for type of drug selectedSustained releasePatient discomfortIrritation to eyePatient placement & removalInadvertent loss of system from eyeTissue fibrosis
CONTROLLED OCULAR DELIVERY SYSTEMS:-Polymeric solutionsPhase transition systemsMuco-adhesive or bio-adhesive dosage formsCollagen [email protected]
POLYMERIC SOLUTIONS:-Addition of polymers to the eye drop solution increases the corneal penetration of drugThis is due to on increases tear viscosity, which decreases the rapid initial drainage rate, increases the corneal contact time & thus sustains to some extent the initial tear concentration of the drugE.g. of polymers are methyl cellulose, polyvinyl alcohol, hydroxyl propyl cellulose & polyvinyl pyrrolidonePHASE TRANSITION SYSTEMS:-These are liquid dosage forms which shift to the gel or solid phase when instilled in the cul-de-sacPolymers used are cellulose acetate phthalate, Lutrol FC-127 & poloxamer 407 whose viscosity increases when its temperature raised to [email protected]
MUCOADHESIVE OR BIOADHESIVE DOSAGE FORMS:-They can be either polymeric solutions or micro particle suspensionsThey retained in the cul-de-sac through adhesive bonds established with the mucins or epitheliumThus, corneal contact time will be increasedFactors affecting bio adhesion are chain flexibility, molecular weight, pH, ionic strength of dosage formCOLLAGEN SHIELDS:-Initially Collagen inserts were used as tear substitute & as delivery system for gentamycin.For drug delivery, the shields are rehydrated in a water solution of the drug, whereby the drug is absorbed by the protein matrix & is released once the shield dissolves in the eye. Water soluble drug is incorporated at the time of manufacture.New preparation under the category of collagen shields is collasomes
PSEUDOLATICES:-They are polymeric colloidal dispersions & film forming agents which on application leave an intact non-invasive continuous polymer film which reserves drug.These systems slowly releases the drug over a prolonged period of time.
ROLE OF POLYMERS IN ODDS:-Polymers increases the viscosity of drug hence it leads to decreased drainagePolymer muco-adhesive vehicle will retain in the eye due to non covalent bonding wit conjunctival mucinMucin is capable of picking of 40-80 times of weight of water
OCCULAR DRUG DELIVERY DEVICES:-TYPEEXAMPLEMatrix type ODDSHydrophilic soft contact lensesSoluble ocular insertsCapsular type ODDSOcusert & related devicesImplantable silicone rubber deviceImplantable drug delivery pumpsOsmotic minipumpsImplantable infusion systemOther devicesOcufit & lacrisertMinidisk ocular therapeutic systemsThe new ophthalmic delivery system(NODS)Particulate systemsMicrospheresNanoparticlesVesicular systemLiposomesNiosomesPharmacosomesDiscomes
MATRIX TYPE DRUG DELIVERY SYSTEM:-HYDROPHILIC SOFT CONTACT LENSES:-Polymers are used for the preparation of these lensesThey made up of hydrogels that absorb certain amounts of aqueous solutionsDisposable soft contact lenses can absorb various ocular therapeutic agents & release them.SOLUBLE OCULAR INSERTS:-SODIs are polypeptide devices & are also called as polyvinyl alcohol inserts(PVAI).They are characteristically thin, elastic, oval shaped plates & impregnated with ophthalmic drugsPolyvinyl alcohol & hydroxyl propyl cellulose inserts were studied to develop prolonged release pattern of pilocarpine.
CAPSULAR TYPE DRUG DELIVERY SYSTEMS:-These are the devices that have a therapeutic agent encapsulated within a closed compartment surrounded by a polymeric membrane
OCUSERT:-This is a system for hydrophilic drugs consists of a pilocarpine alginate core sandwiched between two transparent, rate controlling ethylene vinyl acetate copolymer membranes.A retaining ring of the same material impregnated with titanium dioxide encloses the drug reservoir. When this is placed under the upper or lower eye lid, the pilocarpine molecules dissolves in the lacrimal fluid & releases at predefined rates.
IMPLANTABLE SILICONE RUBBER DEVICE:-this is a system for hydrophobic drugs, consists of a constant release rate implantable silicone rubber device & the drug used is BCNU[1,3-bis (2-chloroethyl) -1- nitrosourea].This device consists of two sheets of silicone rubber glued together. A tube of same material extends from device. The device releases BCNU at a nearly constant rate for a time determined by amount of drug in the device.
IMPLANTABLE DRUG DELIVERY PUMPS:-OSMOTIC MINIPUMP:-This is a useful implantable drug delivery system with a constant drug delivery rate with a pumping duration of up to 2 weeks.IMPLANTABLE INFUSION SYSTEM:-This is also known as infusaid, which is an implantable infusion system. The device permits long term infusion via refilling.OTHER DELIVERY DEVICES:-OCUFIT & LACRISERT:-Ocufit is a sustained release, rod shaped device made up of silicone elastomer. It was designed to fit the shape & size of the human conjunctival fornix.lacrisert is another cylindrical device, which is made of cellulose & used to treat dry-eye [email protected]
A VIDEO ON LACRISERT
MINIDISC OCULAR THERAPEUTIC SYSTEMS:-This is a monolithic polymeric device, shaped like miniature contact lense, with a convex & a concave faceThe device can be easily placed under the upper or lower eye lid without compromising comfort, vision or oxygen permeability because of its particular size & shape.THE NEW OPTHALMIC DELIVERY SYSTEM:-The device consists of a medicated flag which is attached to a short & thin membrane. All components are made of the same grade of water soluble polyvinyl alcoholFor use, the flag is touched onto the surface of lower conjunctival sac. The membrane proceeds to dissolve in the lacrimal fluid, delivering the [email protected]
PARTICULATE SYSTEMS:-MICROSPERES & NANOPARTICLES:-By using these systems, the drug absorption in the eye is enhanced significantly in comparison to eye drop solutions owing to the much slower ocular elimination rate of particles.Smaller particles are better tolerated by the patients than larger particles therefore nanoparticles may represent very comfortable ophthalmic prolonged action delivery systems.VESICULAR SYSTEMS:-LIPOSOMES:-Liposomes can enhance or reduce the ocular absorption of encapsulated agents applied to the eye.The first study to utilize liposomes for ophthalmic therapy reported that Idoxuridine entrapped in liposomes was superior to the solution form in treating herpes simplex keratitis in rabbit [email protected]
NIOSOMES:-They are osmotically active & relatively stable.They behave invivo like liposomes.PHARMACOSOMES:-When they were administered into the eye, the lysosomal enzymes cause cleavage of drug from the glyceride moiety.DISCOMES:-They are large structures formed by solubilisation of niosomes with a non-ionic surfactant solulan C24.They act as drug reservoirs, as they are capable of entrapping water soluble solutes.
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RETROMETABOLIC DRUG DESIGN CONCEPTS IN OPTHALMIC SPECIFIC DRUG DELIVERYBy understanding drug metabolism behaviour & various enzymes involved in metabolic transformations, newer drugs can be designed.For drug metabolism based drug designing structure activity relationship(SARs) & structural metabolic relationships(SMRs) are used in combination.This approach of drug design is termed as Retrometabolic drug design(RMDD) approachesSuccessful eye-specific therapeutic agents can be obtained only by a drug-design process that thoroughly integrates the specific pharmacological, metabolic, and targeting requirements of ophthalmic drugs.Retrometabolic approach is particularly well suited for this purpose, can provide flexible, generally applicable solutions. Their potential is well illustrated by the results obtained with several new chemical entities designed within this framework, such as betaxoxime, adaprolol, loteprednol etabonate, and etiprednol [email protected]
EVALUATION OF OCDDS
Thickness of the filmDrug content uniformityUniformity of weightPercentage moisture absorptionPercentage moisture loss
INVITRO EVALUATION METHODSBottle methodDiffusion methodmodified rotating basket methodmodified rotating paddle [email protected]
CONCLUSIONOcular drug delivery has to overcome unique barriersHowever, several approaches have been shown experimentally to improve ocular drug absorptionConstantly increasing understanding of the absorption processes offers new possibilities in the future.It seems that new tendency of research in ophthalmic drug delivery systems is directed towards a combination of several drug delivery [email protected]
REFERENCESConcepts and advances in controlled drug delivery by Suresh.P.Vyas & Roop.K.KharAdvances in controlled & novel drug delivery by N.K.JainNovel drug delivery system by Y.W.Cheinwww.slideshare.netwww.Wikipedia.comwww.ncbi.nlm.nih.govpriyankamodugu@outlook.com32
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