eye drop and ointment.ppt
- 2. Ophthalmic Products • Ophthalmic Products are the sterile products meant for instillation in to the eye in the space between eye leads and eye balls. • These products must be sterile and are prepared under the same conditions and same methods as other Parenteral preparation.
- 3. • Definition : Ophthalmic preparations (eye preparations) are sterile, liquid, semi-solid, or solid preparations that may contain one or more active pharmaceutical ingredient intended for application to the conjunctiva, the conjunctival sac or the eyelids. • They are specialized dosage forms designed to be instilled onto the external surface of the eye (topical), administered inside (intraocular) or adjacent ( periocular ) to the eye or used in conjunction with an ophthalmic device.
- 4. • The most commonly employed ophthalmic dosage forms are solutions, suspensions, and ointments. • The newest dosage forms for ophthalmic drug delivery are: gels, gel-forming solutions, ocular inserts , intravitreal injections and implants.
- 5. ADVANTAGE • They are easily administered by the nurse. • They are easily administered by the patient himself. • They have the quick absorption and effect. • Less visual and systemic side effects. • Increased shelf life. • Better patient compliance.
- 6. DISADVANTAGES • The very short time the solution stays at the eye surface. • Its poor bioavailability. • The instability of the dissolved drug. • The necessity of using preservative.
- 8. 1. Drugs- These contains drugs of various categories including antiseptic, anti- inflammatory agent, mydriatic or miotic properties 2. Preservative- Eye drop should be sterile and should contain preservatives to avoid microbial contamination when container is open. The preservative for ophthalmic use includes benzalkonium chloride, chlorbutanol , phenylmercuric acetate, phenylmercuric nitrate etc.,
- 9. 3. Sterilization- Eye drops are sterilized by autoclaving at 121°C for 15 minutes or by bacteria filter to avoid thermal degradation for example- preservative chlorbutanol hydrolyzes at high temperature 4. Isotonicity - All the solutes including drug contribute to the osmotic pressure of the eye drip, therefore isotonicity of the formula should be calculated and it is adjusted with sodium chloride, for example sodium chloride 0.9% and boric acid 1.9& are iso –osmotic.
- 10. 5.Buffer- the buffer should be added to maintain balance between comfort, solubility, stability and activity of drug. For example the hydrolysed chlorbutanol forms hydrochloride acid making the drop acidic. Whereas certain drug like pilocarpine hydrochloride are acidic. 6.Viscosity- the size of the drop and its residence in eye depends on viscosity of eye drops. Methyl cellulose, hydroxypropyl methycellulose and polyvenyl alcohol are common viscosity inhancer.
- 11. 7. Container- the commonly used container for ophthalmic solutions or suspension is multi- dose container(5ml, 10ml). Glass container is supplied with sterile plastic dropper. Plastic bottles are with built up nozzle. 8. Label- Not for injection. For external use only. Shake well before use. (if it is suspension)
- 12. Ophthalmic Products include: -Eye Drop - Eye Lotion - Eye Ointment - Eye Suspension - Contact Lens Solution
- 13. Essential Characteristics of Different Ophthalmic Preparation 1. Foreign Particles – All the ophthalmic product should be clear and free from the foreign particles, fibers, and filaments 2. Viscosity – In order to prolong the contact time of the drug in the eye, various thickening agents are added in them like polyvinyl alcohol (1-4 %), polyethylene glycol, methyl cellulose. The Thickening agents must have following properties - It should be easy to filter - It should be easy to sterilize - It should be compatible with other ingredient - It should passes the clarity level
- 14. 3. Tonicity – Ophthalmic preparations are must be isotonic with lachrymal secretions to avoid discomfort and irritation. 1.9 % boric acid and sodium acid phosphate buffer are commonly used as isotonic vehicle. 4. pH of the preparation – pH is plays very imp. Role in the therapeutic activity, solubility, stability, and comfort to the patients. The tears have pH near about 7.5. 5. Sterility – The ophthalmic preparation are must be sterile when it prepared. Pseudomonas aeruginosa is very common gram negative bacteria which generally found in the ophthalmic products and it may be cause serious infection to the cornea.
- 15. 6. Surface Activity – The vehicles are used in the ophthalmic preparation must have good wetting ability to penetrate cornea and other tissue. • The Benzoalkonium Chloride, Polysorbate 20, Polysorbate 80, etc are some of surfactant which are commonly used.
- 16. EYE DROPS • Eye Drops are sterile aqueous or oily solutions or suspension of drug that are instilled in to eye with the help of dropper. • The Eye Drops are usually contain drugs having antiseptic, anesthetic, anti inflammatory, etc.
- 17. Disadvantages of eye solutions: • The very short time the solution stays at the eye surface. • The retention of a solution in the eye is influenced by viscosity. • Its poor bioavailability (a major portion i.e. 75% is lost via naso lacrimal drainage). • Examples of topical eye solutions : Atropine sulphate eye drops. Pilocarpine eye drops . Silver nitrate eye drops. Zinc sulphate eye drops.
- 18. Essential characteristics of Eye Drops • They should be sterile. • They should be iso-osmotic with lachrymal secretion. • They should be free from the foreign particles, fibers and filaments. • They should have almost neutral pH. • They should be preserved with suitable bacterioside . • They should remain stable during its storage.
- 19. Adjuvant or Formulating Agents • Thickening Agent - Methyl Cellulose, polyvinyl alcohol, polyethylene glycol these are agents are commonly used for increase the viscosity of eye drop • Buffers – Buffers are added for the maintaining pH of the eye drop. Boric Acid, Sodium Acid Phosphate, Sodium Citrate are used as buffering agent. • Anti Oxidant – These are the agents are added for the prevention of oxidation. Sodium metabisulphate (0.05 – 0.5 %) and sodium thiosulphate (0.1 – 0.2%)
- 20. • Wetting Agent – These agents are used for proper penetration of eye drops in to the cornea of the eye. Polysorbate 20 and Polysorbate 80 are used as wetting agent. • Isotonicity adjustment substances – Eye drops are made isotonic with the lachrymal secretion with the help of various buffers and other solutions.
- 21. Example of Eye Drop Rx Atropine Sulphate 1 g Phenyl Mercuric Nitrate 50.0 ml Solution 0.002 % Purified Water add up to 100 ml • Direction : To be used as directed by Physicians.
- 22. Manufacturing Techniques • Manufactured by dissolution of the active ingredients and a portion of the excipients into all portion of water . • The sterilization of this solution done by heat or by sterilizing Filtration through sterile depth or membrane filter media Into a sterile receptacle. • This sterile solution is then mixed with the additional required Sterile components such as viscosity –imparting agents, Preservatives and so and the solution is brought to final Volume with additional sterile water.
- 23. Packaging • Eye drops have been packaged almost entirely in plastic dropper bottles. • The main advantage of the Dropper are : convenience of use by the patient decreased contamination potential lower weight lower cost • The plastic bottle and dispensing tip is made of low- density polyethylene (LDPE) resin , which provides the necessary flexibility and inertness. • The cap is made of harder resin than the bottle.
- 24. • A special plastic ophthalmic package made of polypropylene is introduced. • The bottle is filled then sterilized by steam under pressure at 121 °C. • Powder for reconstitution also use glass containers , owing to their heat-transfer characteristics, which are necessary during the freeze-drying processes.
- 25. • The glass bottle is made sterile by dry-heat or steam autoclave sterilization. • Amber glass is used for light-resistance.
- 26. Eye Ointment • Eye Ointment are sterile preparations meant for application to the eye. • These are prepared under aseptic conditions and packed in sterile collapsible tubes. • Example Rx Yellow Soft Paraffin 80 gm Liquid Paraffin 10 gm Wool Fat 10 gm
- 27. • Ointments Ophthalmic ointments must be sterile. • The ointment base selected for an ophthalmic ointment must be nonirritating to the eye and must permit the diffusion of the active ingredient throughout the secretions bathing the eye. • Ophthalmic ointments have a longer ocular contact time when compared to many ophthalmic solutions. • One disadvantage to ophthalmic ointments is the blurred vision that occurs as the ointment base melts and is spread across the lens.
- 28. Manufacturing Techniques • Ophthalmic ointment: The ointment base is sterilized by heat and appropriately filtered while molten to remove foreign particulate matter. • It is then placed into a sterile steam jacket kettle to maintain the ointment in a molten state under aseptic conditions, and the previously sterilized active ingredient (s) and excipients are added aseptically. • The entire ointment may be passed through a previously sterilized colloid mill for adequate dispersion of the insoluble components . • After the product is compounded in an aseptic manner ,it is filled into a previously sterilized container .
- 29. Examples • Chloramphenicol ointment. • Tetracycline ointment. • Hydrocortisone ointment.
- 30. Packaging Ophthalmic ointment are packaged in : 1.Small collapsible tin tube usually holding 3.5g of product. the pure tin tube is compatible with a wide range of drugs in petrolatum- based ointments. 2.Aluminum tubes have been used because of their lower cost
- 31. 3.Plastic tubes made from flexible LDPE resins have also been considered as an alternative material. Filled tubes may be tested for leakers. 4.The screw cap is made of polyethylene or polypropylene. 5.The tube can be a source of metal particles and must be cleaned carefully before sterilization (by autoclaving or ethylene oxide).
- 32. Evaluation of Ophthalmic preparations Metal Particles: • This test is required only for ophthalmic ointments. • The presence of metal particles will irritate the corneal or conjunctival surfaces of the eye. • It is performed using 10 ointment tubes. • The content from each tube is completely removed onto a clean 60 - mm - diameter Petri dish which possesses a flat bottom
- 33. • The lid is closed and the product is heated at 85 ° C for 2 h. • Once the product is melted and distributed uniformly, it is cooled to room temperature. • The lid is removed after solidification. • The bottom surface is then viewed through an optical microscope at 30× magnification.
- 34. • The viewing surface is illuminated using an external light source positioned at 45 ° on the top. • The entire bottom surface of the ointment is examined, And the number of particles 50 μm or above are counted using a calibrated eyepiece micrometer. • The USP recommends that the number of such particles in 10 tubes should not exceed 50, with not more than 8 particles in any individual tube.
- 35. • Limits are not met, the test is repeated with an additional 20 tubes. • In this case, the total number of particles in 30 tubes should not exceed 150, and not more than 3 tubes are allowed to contain more than 8 particles .
- 36. Leakage test • This test is mandatory for ophthalmic ointments, which evaluates the intactness of the ointment tube and its seal. • Ten sealed containers are selected, and their exterior surfaces are cleaned. • They are horizontally placed over absorbent blotting paper . • Maintained at 60 ± 3 ° C for 8 h.
- 37. • The test passes if leakage is not observed from any tube. • If leakage is observed, the test is repeated with an additional 20 tubes. • The test passes if not more than 1 tube shows leakage out of 30 tubes .
- 38. Sterility Tests • Ophthalmic semisolids should be free from anaerobic and aerobic bacteria and fungi. • Sterility tests are therefore performed by the: 1. Membrane filtration technique . 2. Direct - inoculation techniques.
- 39. • In the Membrane filtration method : • A solution of test product (1%) is prepared in isopropyl myristate and allowed to penetrate through cellulose nitrate filter with pore size less than 0.45 μ m. • If necessary, gradual suction or pressure is applied to aid filtration.
- 40. • The membrane is then washed three times with 100 - mL quantities of sterile diluting and rinsing fluid and transferred aseptically into fluid thioglycolate (FTG) and soybean – casein digest medium (SBCD) . • The membrane is finally incubated for 14 days. • Growth on FTG medium indicates the presence of anaerobic bacteria.
- 41. • Soybean casein digest medium indicates fungi and aerobic bacteria. • Absence of any growth in both these media establishes the sterility of the product.
- 42. • In the Direct - inoculation technique : 1 part of the product is diluted with 10 parts of sterile diluting and rinsing fluid with the help of an emulsifying agent. Incubated in Fluid thioglycolate ( FTG) and soybean – casein digest medium (SBCD) media for 14 days .
- 43. • In both techniques, the number of test articles is based on the batch size of the product. • If the batch size is less than 200 the containers, either 5% of the containers or 2 containers (whichever is greater) are used. • If the batch size is more than 200, 10 containers are used for sterility testing .
- 44. Thank you