Opthalmic products

definition, formulation, evaluation, packaging.

1. Ophthalmic Products Prepared by: K. ARSHAD AHMED KHAN M.Pharm , ( Ph.D ) Dept. of Pharmaceutics RIPER.

2. Ophthalmic Products Definition A sterile solution, suspension or ointment for instillation into the eye in the form of drops, sprays and ointments. Types Eye drops Eye lotions Eye suspensions Eye ointments Contact lens solutions Ophthalmic inserts

3. Ideal Characteristics Sterile Free from foreign particulate matter Isotonic with lachrymal secretion PH equal to 7.4 Optimum viscosity (25-50cps) Proper preservative

4. Micro-organisms causing eye infections Bacteria Staphylococcus aureus Proteus vulgaris Bacillus subtilis Pseudomonas aeuroginosa Virus Sterility Adenoviruses Autoclaving, bacteria proof filters, bactericide addition

5. An inflamed eye is sensitive to particulate matter Presence of foreign particles 1) discomfort 2) abrade epithelium 3) pathogenic invasion Clarification of ophthalmic solutions is necessary Filtration medium microporous plastic membrane sintered glass smooth filter paper Foreign Particles Ultrafine state of medicaments in suspensions

6. Isotonicity & pH: Instillation of solution having unfavourable osmotic pressure pH causes of discomfort Sensitivity of eye to variations in osmotic pressure is less than variations in pH Tears have pH 7.4 and good buffering power Neutralize unbuffered solutions (pH 3.5 – 10.5) provided volume is small Discomfort is caused due to Concentrated solutions of acidic drugs Highly buffered solutions Physical or chemical nature of medicaments and preservatives Ex: Local anaesthetic amethocaine cause discomfort due to surface activity and ability to denature proteins

7. Viscosity Thickening agent Prolong contact with eye & Therapeutic response Ex. Hypromellose , PVA (1-4%), PEG, MC. Ideal thickening agent Easy to filter Easy to sterilize Compatible Optimum refractive index Not used in eye drops and eye lotion

8. Preservatives Protects from dangerous organisms introduced during removal of successive treatments Aqueous drops supplied in multiple containers must contain preservative Ideal preservative Rapidly effective Harmless to eye Compatible Stable Ex: Phenyl mercuric nitrate or acetate Benzalkonium chloride Chlorhexidine acetate Less preferable Parabens Chlorocresol and thiomersal

9. EYE DROPS

10. Eye Drops Eye drops are sterile aqueous or oily solutions or suspensions of drug for instilling into conjunctiva sac with dropper. Used for anaesthetic anti-inflammatory antiseptic diagnostic miotic mydriatic

11. Formulation: Thickening agent Preservatives Chemical stabilizers pH adjusters Reducing agent Sequestering agent Chemical stabilization: Stabilizers are added to reduce degradation sterilization storage Degraded product less active toxic effects

12. Stabilization methods 1. pH adjustment (buffers) Reduce discomfort due to irritation by maintaining constant pH Maintain chemical stability temp. change leaking of alkali groups Improve clinical response keep drug in unionised form facilitating absorption of drug Ex: Boric acid vehicle Special boric acid vehicle Isotonic phosphate vehicle Sodium acid phosphate Sodium citrate

13. Wetting agents: Increase solubility and drug penetration Ex: polysorbate – 20, 80. isotonicity adjusters: Same osmotic pressure as tear fluids Ex: Nacl (0.9%), boric acid (1.9%)

14. 2. Reducing agent Provide protection from oxidation Air is replaced by inert gas Gets oxidized in preference to medicament Ex. Sodiummetabisulphite , Sodiumthiosulphate 3. Sequestering agent limits the decomposition, remove heavy metals. Alone or with reducing agent Ex. EDTA Preparation of eye drops: Preparation of fungicidal and bactericidal vehicle Solution of medicaments and adjuncts Clarification Sterilization

15. 1. Preparation of bactericidal and fungicidal vehicle: Preservative solution should be freshly made Storage of stock solution present problems Mercurial compounds incompatible with aluminium strongly absorbed by rubber loss potency in polythene containers Deposition of metallic mercury Benzalkonium chloride Absorbed by polyvinyl chloride Develop a deposit when in contact with rubber line Chlorhexidine acetate Slightly degrades on autoclaving Inactivated by cork All the above compounds require protection from light

16. Precautions to use Stock solutions in emergency Caps and rubber closures must be pre-treated Wads of closures should be of silicon rubber for benzalkonium chloride solution Chlorhexidine solution should not be over-exposed during autoclaving Phenyl mercuric nitrate solutions should be rejected if there is a fine precipitate Storage solutions to be sterilized before storage and covered with a readily breakable seal

17. 2. Dissolution of drugs and adjuncts Depending upon the solubility of the medicament ex. Chloramphenicol is more soluble in boric acid-borax buffer of pH 7 Heating assists solution of preservative ex. Phenylmercuric nitrate or acetate Some has to be dissolved in cold and in an atmosphere of nitrogen gas

18. 3. Clarification Passing through microporous plastic membrane Mean pore size of 0.8um/ whatmann filter paper (56 grade) Particle free solution depends not only on filter but also on particle free equipment and containers

19. 4. Sterilization Heating in an autoclave Maintaining at 98-100 C for 30 min. Filtration Pore size 0.22-+0.02um Diameter of membranes - 13 & 25 mm

20. Swinnex holders for small volumes-(separable type)

21. Millex filter unit-sealed type

22. Volume supplied Small volume Each container not more than 10ml Separate containers if more than 10ml Large volume Contamination is more Difficult in storing and usage Containers Single-Application Packs - Minims unit Multi-application containers Traditional eye drop bottle Teat bottle Screw capped Plastic bottle Amber coloured Neutral glass Rubber teat

23. Instructions to use Eye drops Wash hands Pull lower eye lid down gently with one hand If the dropper is separate, squeeze rubber bulb while dropper is in bottle to bring the liquid into dropper or replace on bottle Holding dropper above eye, drop medicine inside lower lid while looking up Release lower lid Try to keep eye open and not blink for at least 30 seconds

24. Labelling : For external use only Store in cool place Discard the preparation one month after its first opening Do not use the preparation if irritation persists Ex: Physostigmine eye drops Physostigmine sulphate – 0.5 g Sodium meta bisulphate – 0.2 g Benzalkonium chloride solution – 0.02 ml Purified water- qs to 100 ml

25. EYE OINTMENT

26. Eye ointment Semisolid preparations based on oleaginous/ water washable bases packed in collapsible tubes for easy transfer in to eye cavity by pressure. Formulation: Medicament – water/ oil soluble Ointment base Sterilized by heating method Free from irritation Diffuse drug uniformly throughout Melt at body temperature

27. Ointment bases: Yellow soft paraffin- 80 g Liquid paraffin- 10 g Wool fat- 10 g Yellow soft paraffin- obtained form petroleum Liquid paraffin- reduce viscocity of preparation, for easy removal from tube. Wool fat- emulsification of product

28. Preparation of Eye ointment Wool fat + yellow soft paraffin Melt Add liquid paraffin Coarse filter paper Container Add medicament Sterilization (Dry- 160 C for 2 hr) Pack in sterile container

29. Water soluble Water insoluble Insoluble in water and base Dissolved in minimum volume Methods of incorporating the medicament medicament sterilization Incorporating in melted base Finely powdered Mixing with molten base Extremely fine 10-90um

30. Containers: Single application containers (soft capsule) Multiple - Sterilized tin, aluminum or plastic collapsible tubes with nozzles (extemporaneous) Tube sealed in package from which removal is not possible and screw cap covered with readily breakable seal Prevent contamination during use

31. Labelling : For external use only Store in cool place Avoid contamination during use Ex: Atropine eye ointment (B.P) Atropine sulphate – 1 g Sterile base – 100 g

32. EYE LOTIONS

33. Eye lotions Def: These are sterile aqueous solutions intended for washing the eyes to remove irritant or foreign body Characteristics of eye lotions Sterile No foreign particles Isotonic with lachrymal secretion Neutral pH to avoid irritation and discomfort

34. Usage: Supplied in conc. forms Before use dilute with warm water Can be store for 2 days. Application: Clean eye bath / Sterile fabric dressing If large volume flow through eye. Formulation: Drug – NaCl , NaHCO 3 , boric acid, borax. Vehicle – water Iso -osmotic agent

35. Preparation of eye lotions: Dissolution of drug in vehicle Clarification Sterilization Ex: Sodium chloride eye lotion (B.P.C) Sodium chloride – 9 g Purified water – qs to 1000 ml 800 ml purified water + 9 g NaCl Solution + 200 ml purified water 1000 ml lotion Sintered glass filter (Grade-4) Transfer in to container & seal Sterilization by autoclaving

36. Containers: Properly sealed containing screw cap with either rubber, plastic or other impervious cap liner Must not contain cork coloured and fluted Resistant to autoclaving. Labelling: Not to be taken orally Avoid contamination during use Discard any unused part after 24hrs or a week after first opening FOR EXTERNAL USE ONLY

37. Eye Suspension Rarely used Conditions: Drug insoluble in vehicle Drug unstable in liquid form For sustained action. Ideal characteristics: Sterile Desired viscosity Isotonic Fine particle size to prevent irritation Particle should be uniformly dispersed on shaking Packed in suitable container.

38. CONTACT LENS SOLUTIONS

39. Contact lens: Are small visual devices made with curved pieces of plastic Shaped in a way to confirm directly to the wearing eye

40. TYPES Hard Contact lens Rigid gas permeable Soft contact lens Hard hydrophobic polymethylmethacrylate Rigid and flexible(silicone) More permeable to oxygen than soft lens Better vision,durable Easier to clean Most common lens Hydrophilic Immediate comfort More permeable to oxygen Difficult to get used to Uncomfortable to wear Does not allow oxygen to pass

41. Contact lens care Should always be kept clean, disinfected and hydrated using contact lens solutions Contact lens solutions for Rigid gas permeable / Hard lenses: Wetting and Rewetting drop (WRW) Cleaning /Disinfecting/Storage solutions (CDS) Extra strength cleaner (ESC) Contact lens solutions for Soft lenses : Cleaning solution Storage solution (CDS)

42. 1. Wetting and rewetting drop (WRW ): Contains polymeric wetting and cushioning agents Used for wetting lens before insertion For longer wear and more comfort Composition of Wetting solution Wetting agent : Polysorbate - 80 (0.5%) Antimicrobial agent : Benzalkonium chloride (0.004%), chlorohexidine actate (0.005%) Isotonicity adjusting substances : NaCL , KCL Buffering agen ts : Boric acid/borax buffer pH 8.4 – 8.6 Thickening agents : Polyvinyl alcohol or other cellulose derivative

43. 2. Cleaning/Disinfecting/Storage Solution (CDS ): Sterile solution that cleans and disinfects Provides sterile, hydrating storage Preventing lens wrapage & adherence of contaminants to the lens. Composition of storage solutions Nonionic surfactant - cleaning Mixture of preservatives – prevent microbial growth Note: change solution frequently as preservative action reduces.

44. 3. 'Extra Strength' Cleaner (ESC): Sterile, non-preserved solution Cleans surface deposits of oils, lipids, salts and cosmetic residue. Hydrophilic, soft & flexible type Cleaning solution - heating in 0.9 % NaCL solution. Storage solution (CDS ) Note: Soft lenses absorb drug / preservative from ophthalmic preparations & should be removed before administration. Soft Contact lens

45. Evaluations of ophthalmic products: Sterility test Clarity test Leakage test Pyrogen test Volume of packing: Liquid (10-25 ml) Semi solid (less than 5 g) Containers: Glass – TYPE-I glass bottles + stoppers for ophthalmic injections & sterile powders Plastic - HDPE, LDPE containers & collapsible tubes. Evaluation of containers: Uniformity of volume Leakage test Collapsibility test

46. THANK YOU…..