Ocular drug delivery system rucha

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Ocular drug delivery system rucha

  1. 1. Ocular Drug Delivery System Presented by, R.V.Deshmukh 1 st year M-Pharm Dept of Pharmaceutics
  2. 2. <ul><li>Eye is the most easily accessible site for topical administration of a medication. </li></ul><ul><li>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. </li></ul>
  3. 3. Composition of eye <ul><li>Water - 98% </li></ul><ul><li>Solid -1.8% </li></ul><ul><li>Organic element – </li></ul><ul><li>Protein - 0.67%, sugar - 0.65%, Nacl - 0.66% </li></ul><ul><li>Other mineral element sodium, potassium and ammonia - 0.79% </li></ul>
  4. 4.
  5. 5. Anatomy and Physiology
  6. 6. characteristics required to optimize ocular drug delivery system <ul><li>Good corneal penetration. </li></ul><ul><li>Prolong contact time with corneal tissue. </li></ul><ul><li>Simplicity of instillation for the patient. </li></ul><ul><li>Non irritative and comfortable form (viscous solution should not provoke lachrymal secretion and  reflex blinking) </li></ul><ul><li>Appropriate rheological properties concentrations of the viscous system. </li></ul>
  7. 7. Advantages <ul><li>Increase ocular residence….. Improving bioavailability </li></ul><ul><li>Prolonged drug release….. better efficacy </li></ul><ul><li>Less visual & systemic side effects </li></ul><ul><li>Increased shelf life </li></ul><ul><li>Exclusion of preservatives </li></ul><ul><li>Reduction of systemic side effects </li></ul><ul><li>Reduction of the number of administration </li></ul><ul><li>Better patient compliance </li></ul><ul><li>Accurate dose in the eye…. a better therapy </li></ul>
  8. 8. Ideal characteristics of OCDDS <ul><li>Sterility </li></ul><ul><li>Isotonicity - e.g.: 1.9% boric acid,0.9% Nacl </li></ul><ul><li>Buffer / P H adjustment </li></ul><ul><li>Less drainage tendency </li></ul><ul><li>Minimum protein binding </li></ul>
  9. 9. Blood Ocular Barrier <ul><li>BLOOD AQUEOUS BARRIER </li></ul><ul><li>Capillary epithelium & capillaries of iris </li></ul><ul><li>BLOOD RETINAL BARRIER </li></ul><ul><li>prevents the passage of large molecules </li></ul>
  10. 10. Role Of Polymers <ul><li>Improving the ocular contact time. </li></ul><ul><li>Increase solution viscosity </li></ul><ul><li>reduces solution drainage. </li></ul><ul><li>Hydrophilic polymer - Ethyl acetate ,Polyvinyl acetate, Polyacrylic acid. </li></ul><ul><li>Hydrophobic polymer - Glycerin monostearate, Nylon , Polyvinyl chloride. </li></ul>
  11. 11. Factors influencing corneal absorption of drugs <ul><li>Partition coefficient </li></ul><ul><li>Molecular size </li></ul><ul><li>Charge </li></ul><ul><li>pka of the drug </li></ul>
  12. 12. Formulation of ocular drug delivery system Dosage form Advantages Disadvantages Solutions Convenience Rapid precorneal elimination, Loss of drug by drainage, Non sustained action Suspension Patient compliance, Best for drug with slow dissolution Drug properties decide performance loss of both solution and suspended solid Emulsion Prolonged release of drug from vehicle Blurred vision, patient non compliance, possible oil entrapment Ointment Flexibility in drug choice, Improved drug stability Sticking of eye lids, Blurred vision poor patient compliance, Drug choice limited by partition coefficient
  13. 13. Recent formulation trends in OCDDS <ul><li>Polymeric solutions </li></ul><ul><li>Phase transition system </li></ul><ul><li>Mucoadesive / Bioadhesive Dosage forms </li></ul><ul><li>Collagen shields </li></ul><ul><li>Pseudolatices </li></ul><ul><li>Ocular Penetration Enhancers </li></ul><ul><li>Ocular Iontophoresis </li></ul><ul><li>Particulate system : Microspheres, Nanoparticles </li></ul><ul><li>Vesicular system : Liposomes, Niosomes, Pharmacosomes, Discomes </li></ul>
  14. 14. 1. Polymeric Solutions <ul><li>Increases tear viscosity </li></ul><ul><li>Decreases rapid initial drainage rate </li></ul><ul><li>Increases corneal contact time </li></ul><ul><li>Increases the corneal penetration of drug </li></ul><ul><li>Enhanced drug bioavailability </li></ul><ul><li>Optimal viscosity - 12 to 15 cps </li></ul>
  15. 15. <ul><li>Polyvinyl alcohol </li></ul><ul><li>Polyvinyl pyrollidone </li></ul><ul><li>Cellulose acetate pthalate </li></ul><ul><li>Methyl cellulose </li></ul><ul><li>Hydroxy ethyl cellulose </li></ul><ul><li>Polyacrylic acid </li></ul><ul><li>Gallan gum </li></ul><ul><li>Chitosan </li></ul><ul><li>HPMC </li></ul>Polymers used
  16. 16. Phase transition System <ul><li>Temperature dependent phase transition system e.g. Lutrol FC 127 and Poloxamer 407 </li></ul><ul><li>triggered transition system P H e.g. Cellulose acetate phthalate, Carbopol </li></ul><ul><li>Ion activated system gelrite - An ion activated in situ gelling polymer forms a clear gel in the presence of cation. e.g. Calcium or sodium ions present in the tears increase the corneal residence time & bioavailability of drugs. </li></ul>
  17. 17. Bioadhesive / Mucoadhesive dosage form <ul><li>Any polymer solution or suspension placed in the eye first encounters mucin at the cornea & conjunctival surface </li></ul><ul><li>If polymers adheres to the mucin, the interaction is referred as Mucoadhesion </li></ul><ul><li>Should exhibit a zero contact angle to allow maximum contact with mucin coat </li></ul><ul><li>The capacity of polymer to adhere to the mucin coat covering the conjunctiva and corneal surface of the eye non covalent bond forms the basis of ocular mucoadhesion </li></ul>
  18. 18. Collagen Shields <ul><li>Collagen is the structural protein of bones, tendons, ligaments, & skin and comprises more than 25% of the total body weight. </li></ul><ul><li>Collagen shields belong to soluble ophthalmic inserts manufactured from Procine scleral tissue. </li></ul><ul><li>Cross linked collagen shields might be useful in ocular drug delivery devices because they can allow drug concentrations to achieve higher levels in cornea & aqueous humor. </li></ul>
  19. 19. Advantages <ul><li>Appropriate delivery system for both hydrophilic and hydrophobic drugs with poor penetration properties </li></ul><ul><li>Biological inertness, structural stability, good biocompatibility and low cost of production. </li></ul><ul><li>Insertion technique is difficult & expulsion of shields may occur </li></ul><ul><li>Not individually fit for each patient </li></ul><ul><li>Shields are not fully transparent & thus reduce visual activity. </li></ul>Disadvantages
  20. 20. Pseudolatices <ul><li>Organic solution of polymers is dispersed in an aqueous phase to form O/W emulsion </li></ul><ul><li>Water is removed partially to an extent that residual water is removed sufficient enough to keep polymeric phase discrete & dispersed </li></ul><ul><li>On application leave an intact noninvasive continuous polymer film which reserves drugs </li></ul><ul><li>Drug released slowly over prolonged period of time , better ocular bioavailability patient compliance </li></ul>
  21. 21. Ocular Penetration Enhancers <ul><li>Substance which increase the permeability characteristics of the cornea modifying the integrity of corneal epithelium are known as penetration enhancer </li></ul><ul><li>1.Calcium chelators – They act by loosening the tight junction between superficial epithelial cells and thus facilitating paracellular transport. e.g. EDTA. </li></ul><ul><li>2.Surfactants – e.g. Palmiloyl carnitine, sodium caprate </li></ul><ul><li>3.Bile acid and salts - e.g. Sodium deoxycholate. </li></ul><ul><li>4.Preservative – e.g. Benzalkonium chloride. </li></ul><ul><li>5.Glycoside – e.g. Saponin and digitonin. </li></ul><ul><li>6.Fatty acid - e.g. Caprylic acid </li></ul>Classification
  22. 22. Particulate System <ul><li>The drugs are bound to small particles which are then dispensed in aqueous vehicles </li></ul><ul><li>They are akin to colloidal solutions </li></ul><ul><li>Nanoparticles of polybutylcyanoacrylate have been used for human being as a drug carrier </li></ul>Microspheres & Nanoparticles
  23. 23. Ocular Iontophoresis <ul><li>It is the process in which the direct current drives ions into cells or tissues </li></ul><ul><li>Trans-corneal </li></ul><ul><li>Trans-scleral </li></ul><ul><li>Antibiotics, antifungal, anesthetics and adrenergic are delivered by this method </li></ul>Types
  24. 24. <ul><li>Liposomes : Phospholipid-lipid vesicles </li></ul><ul><li>Niosomes : Vesicles based on some non-ionic surfactants like dialkyl polyoxyethylene ethers </li></ul><ul><li>Phamacosomes : Colloidal dispersions of drugs co-valently bound to liquids </li></ul><ul><li>Discosomes : Systems formed by addition of specific amount of surfactant to vesicular dispersions consisting of mixed vesicular and micelle regions </li></ul>Vesicular System
  25. 25. Ophthalmic Inserts <ul><li>sterile solid devices delivering the drugs to the anterior segment of the eye. </li></ul><ul><li>Desired criterias </li></ul><ul><li>a) Comfort </li></ul><ul><li>b) Ease of handling and insertion </li></ul><ul><li>c) Non interference with vision and oxygen </li></ul><ul><li>permeability </li></ul><ul><li>d) Reproducibility of release kinetics </li></ul><ul><li>e) Sterility </li></ul><ul><li>f) Stability </li></ul><ul><li>g) Ease of manufacture </li></ul>
  26. 26. Advantages <ul><ul><li>Increased ocular residence </li></ul></ul><ul><ul><li>Reduced systemic absorption </li></ul></ul><ul><ul><li>Better patient compliance </li></ul></ul><ul><ul><li>Exclusion of preservatives </li></ul></ul><ul><ul><li>Accurate dosing </li></ul></ul><ul><ul><li>Increased shelf life </li></ul></ul><ul><ul><li>Targeting of internal ocular tissues </li></ul></ul><ul><ul><li>Releasing of drug at a slow constant rate </li></ul></ul><ul><ul><li>Fewer ocular & systemic side effects </li></ul></ul>
  27. 27. Disadvantages <ul><ul><li>Expensive </li></ul></ul><ul><ul><li>Occasional inadvertent loss </li></ul></ul><ul><ul><li>Difficult to handle </li></ul></ul><ul><ul><li>Foreign body sensation </li></ul></ul>
  28. 28. Classification <ul><li>Non erodible inserts. </li></ul><ul><li>Ocusert </li></ul><ul><li>Contact lens </li></ul><ul><li>Erodible inserts </li></ul><ul><li>Lacriserts </li></ul><ul><li>SODI </li></ul><ul><li>Minidisc </li></ul>
  29. 29. GLAUCOMA AND ITS MANAGEMENT <ul><li>Increase in an intraocular tension </li></ul><ul><li>Irreversible loss of vision </li></ul><ul><li>Glaucoma can be classified in to three types </li></ul><ul><li>1…P rimary glaucoma </li></ul><ul><ul><ul><li>2 …Secondary glaucoma </li></ul></ul></ul><ul><li>3 ....Congenital glaucoma </li></ul>
  30. 30. 1) Non erodible inserts <ul><li>The Ocusert therapeutic system is a flat, flexible, elliptical device designed to be placed in the inferior cul-de-sac between the sclera and the eyelid and to release Pilocarpine continuously at a steady rate for 7 days . </li></ul><ul><li>The device consists of 3 layers….. </li></ul><ul><li>1. Outer layer – ethylene vinyl acetate copolymer layer. </li></ul><ul><ul><ul><ul><li>2 . Inner Core – Pilocarpine gelled with alginate main polymer. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>3 . A retaining ring - of EVA impregnated with titanium dioxide </li></ul></ul></ul></ul>
  31. 31.
  32. 32. <ul><li>The ocuserts available in two forms. </li></ul><ul><li>Pilo – 20  20 microgram / hour </li></ul><ul><li>Pilo – 40  40 microgram / hour </li></ul><ul><li>Use : Chronic glaucoma </li></ul><ul><li>ADVANTAGES : </li></ul><ul><ul><ul><li>Reduced local side effects and toxicity. </li></ul></ul></ul><ul><ul><ul><li>Around the clock control of IOP. </li></ul></ul></ul><ul><ul><ul><li>Improved compliance. </li></ul></ul></ul><ul><li>DIS-ADVANTAGES : </li></ul><ul><ul><ul><li>Retention in the eye for the full 7 days. </li></ul></ul></ul><ul><ul><ul><li>Periodical check of unit. </li></ul></ul></ul><ul><ul><ul><li>Replacement of contaminated unit </li></ul></ul></ul><ul><ul><ul><li>Expensive. </li></ul></ul></ul>
  33. 33. CONTACT LENSES <ul><li>These are circular shaped structures </li></ul><ul><li>The coherent system is covalently cross linked hydrophilic or hydrophobic polymers that form three dimensional network or matrix capable of retaining water </li></ul><ul><li>Dyes may be added during polymerization </li></ul><ul><li>Drug incorporation depends on whether their structure is hydrophilic or hydrophobic. </li></ul><ul><li>Drug release depends upon </li></ul><ul><ul><li>Amount of drug </li></ul></ul><ul><ul><li>Soaking time. </li></ul></ul><ul><ul><li>Drug concentration in soaking solution. </li></ul></ul>
  34. 34. <ul><li>Advantages </li></ul><ul><ul><li>1.No preservation. </li></ul></ul><ul><ul><li>2.Size & shape </li></ul></ul><ul><li>Disadvantages </li></ul><ul><li>1.Handling & cleaning </li></ul><ul><ul><li>2.Expensive </li></ul></ul>
  35. 35. ERODIBLE INSERTS <ul><li>The solid inserts absorb the aqueous tear fluid and gradually erode or disintegrate. The drug is slowly leached from the hydrophilic matrix </li></ul><ul><li>They quickly lose their solid integrity and are squeezed out of the eye with eye movement and blinking </li></ul><ul><li>Do not have to be removed at the end of their use </li></ul><ul><li>Three types </li></ul><ul><li>LACRISERTS </li></ul><ul><li>SODI </li></ul><ul><li>MINIDISC </li></ul>
  36. 36. LACRISERTS <ul><li>Sterile rod shaped device made up of hydroxy propyl cellulose without any preservative </li></ul><ul><li>For the treatment of dry eye syndromes </li></ul><ul><li>It weighs 5 mg & measures 1.27 mm in diameter with a length of 3.5 mm </li></ul><ul><li>It is inserted into the inferior fornix </li></ul>
  37. 37. SODI <ul><li>Soluble Ocular Drug Inserts </li></ul><ul><li>Small oval wafer </li></ul><ul><li>Sterile thin film of oval shape </li></ul><ul><li>Weighs 15-16 mg </li></ul><ul><li>Introduced into the inferior cul-de-sac. </li></ul><ul><li>Use – glaucoma </li></ul><ul><li>Advantage – single application </li></ul>
  38. 38. MINIDISC <ul><li>Countered disc with a convex front and a concave back surface </li></ul><ul><li>Diameter – 4 to 5 mm </li></ul><ul><li>Composition </li></ul><ul><li>Silicone based prepolymer-alpha-w-dis(4-methacryloxy)- butyl polydimethyl siloxane. (M2DX ) </li></ul><ul><li>M  Methyl a cryloxy butyl functionalities. </li></ul><ul><li>D  Dimethyl siloxane functionalities. </li></ul><ul><li>Pilocarpine, chloramphenicol </li></ul>
  39. 39. Evaluation of OCDDS
  40. 40. Evaluation of OCDDS <ul><li>THICKNESS OF THE FILM : </li></ul><ul><li>Measured by dial caliper at different points and the mean value is calculated. </li></ul><ul><li>DRUG CONTENT UNIFORMITY : </li></ul><ul><li>The cast film cut at different places and tested for drug as per monograph. </li></ul><ul><li>UNIFORMITY OF WEIGHT : </li></ul><ul><li>Here, three patches are weighed. </li></ul>
  41. 41. <ul><li>PERCENTAGE MOISTURE ABSORPTION : </li></ul><ul><li>Here, ocular films are weighed and placed in a dessicator containing 100 ml of saturated solution of aluminiumchloride and 79.5% humidity was maintained. </li></ul><ul><li>After three days the ocular films are reweighed and the percentage moisture absorbed is calculated using the formula – </li></ul><ul><li>% moisture absorbed = Final weight – initial weight x 100 </li></ul><ul><li>Initial weight </li></ul>
  42. 42. <ul><li>Ocular films are weighed and kept in a dessicator containing anhydrous calcium chloride. </li></ul><ul><li>After three days, the films are reweighed and the percentage moisture loss is calculated using formula – </li></ul><ul><li>% moisture loss = </li></ul><ul><li>Initial weight – Final weight x 100 </li></ul><ul><li>Initial weight </li></ul>PERCENTAGE MOISTURE LOSS
  43. 43. In-Vitro Evaluation Methods <ul><li>In this, dosage forms are placed in the bottle containing dissolution medium maintained at specified temperature and pH. </li></ul><ul><li>The bottle is then shaken. </li></ul><ul><li>A sample of medium is taken out at appropriate intervals and analyzed for drug content. </li></ul>Bottle Method
  44. 44. Diffusion Method <ul><li>Drug solution is placed in the donor compartment and buffer medium is placed in between donor and receptor compartment. </li></ul><ul><li>Drug diffused in receptor compartment is measured at various time intervals </li></ul><ul><li>Dosage form is placed in a basket assembly connected to a stirrer. </li></ul><ul><li>The assembly is lowered into a jacketed beaker containing buffer medium and temperature 37 °C. </li></ul><ul><li>Samples are taken at appropriate time intervals and analyzed for drug content . </li></ul>Modified Rotating Basket Method
  45. 45. Modified Rotating Paddle Apparatus <ul><li>Here, dosage form is placed in a diffusion cell which is placed in the flask of rotating paddle apparatus. </li></ul><ul><li>The buffer medium is placed in the flask and paddle is rotated at 50 rpm. </li></ul><ul><li>The entire unit is maintained at 37 °C. </li></ul><ul><li>Aliquots of sample are removed at appropriate time intervals and analyzed for drug content </li></ul>
  46. 46. In-Vivo Study <ul><li>Here, the dosage form is applied to one eye of animals and the other eye serves as control. </li></ul><ul><li>Then the dosage form is removed carefully at regular time interval and are analyzed for drug content </li></ul><ul><li>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 </li></ul><ul><li>After one week of washed period, the experiment was repeated for two times as before </li></ul>
  47. 47. Accelerated Stability Studies <ul><li>These are carried out to predict the breakdown that may occur over prolonged periods of storage at normal shelf condition </li></ul><ul><li>Here, the dosage form is kept at elevated temperature or humidity or intensity of light, or oxygen </li></ul><ul><li>Then after regular intervals of time sample is taken and analyzed for drug content </li></ul><ul><li>From these results, graphical data treatment is plotted and shelf life and expiry date are determined </li></ul>
  48. 48. Conclusion <ul><li>All approaches improve ocular drug bioavailability by increasing ocular drug residence time, diminishe side effects due to systemic absorption and diminishing the necessary therapeutic amount of drug for therapeutic response in anterior chamber </li></ul><ul><li>They improve patient compliance by reducing the frequency of dosing </li></ul><ul><li>They reduce the dose and thereby reduce the adverse effects of the drug </li></ul>
  49. 49. References <ul><li>Controlled drug delivery – Concepts and Advances, by S.P. Vyas and Roop K. Khar, page no.: 383 – 410’ </li></ul><ul><li>Ansel’s Pharmaceutical dosage forms and drug delivery systems, by Loyd V. Allen, Nicholas G. Popovich and Howard c. Ansel page no.: 661 – 663 </li></ul><ul><li>Advances in Controlled and Novel drug delivery, edited by N.K. Jain, page no.: 219 – 223 </li></ul><ul><li>The Eastern Pharmacist, “Ophthalmic Inserts – An overview”, Issue: February 1996, page no.: 41 – 44 </li></ul><ul><li>Textbook of Industrial Pharmacy, edited by Shobharani R. Hiremath, page no.: 57 – 58. </li></ul><ul><li>Novel drug delivery systems, by Y.W. Chein, published by Marcel Dekker, vol.-50, page no.: 269 – 301 </li></ul><ul><li>www.google.com </li></ul>
  50. 50. Thank you

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