1. EYE PREPARATIONS

2. Plan 1. Characterize of the eye preparations. 2. Classification of the eye preparations. 3. Particularly of the technology eye preparations. 4. Eye drops. 5. Packaging for the eye drops. 6. Semisolid eye preparations. 7. Solid eye preparations.

3. Classification of the eye preparations 1. Liquid eye preparations. 2. Semisolid eye preparations. 3. Solid eye preparations. 4. Ophthalmic injections. 5. Ophthalmic drugs under pressure.

4. Classification of the eye preparations -eye drops -eye lotions -semi-solid eye preparations -ophthalmic inserts

5. Ophthalmic injections: а) Subconjunctive are introduced in the conjunctive bag and MS diffuses through sclera in the eye. б) Retrobulbare are introduced after eyeball.

6. Requirements to the ophthalmic injections: apyrogenity, apyrogenity, sterility, sterility, stability, stability, absence of mechanical and microbial inclusions, absence of mechanical and microbial inclusions, should be isotonic, should be isotonic, accuracy of the dosing, accuracy of the dosing, convenience of the using, convenience of the using, should have prolonged action. should have prolonged action.

7. Classification of the MS in the eye drugs depend on their degree of stability during sterilization: 1. They withstand temperature impact about 100-120 ºС during 30 min (are prepared without stabilizers). 2. They don’t withstand temperature impact. 3. They withstand temperature impact about 100 ºС during 15 - 30 min (are prepared wit stabilizers).

8. Eye drops – sterile aqua's or oil solutions or thickness suspensions of the MS, which are introduced in the eye by drops way on the eye cornea or conjunctive bag of the low eyelid. Requirements for the eye drugs: 1. Transparency. 2. Costumes’ properties. 3. Convenience of using. 4. Should be packed in the packages which prevent they opening by children.

9. Solutions for eye drops: Aqua for injections Sterile fat oils (peach, almond) Buffers solutions Vaseline oil

10. Technological stages of the eye drops production:  Preparing of the solutions and MS.  Dissolving of the MS and auxiliary substances.  Filtering.  Filling and sealing.  Sterilization.  Quality control.  Packaging, labeling.

12. Sterilization Autoclaving at 115°C for 30 min. or 121°C for 15 min. Heating at 98 - 100°C for 30 minu. together with either benzalkonium chloride 0.01% w/v or chlorhexidine acetate 0.01% w/v or phenylmercuric acetate or nitrate 0.002% w/v or thiomersal 0.01% w/v. Filtration through a membrane filter having a 0.22μm pore size into sterile containers using strict aseptic technique. Filling should take place under Grade A laminar airflow conditions. The filter assembly is sterilized by autoclaving before use. Dry heat sterilization at 160°C for 2 hours is employed for non-aqueous preparations such as liquid paraffin eye drops. Silicone rubber teats must be used.

13. Auxiliary substances for stabilization of the eye drops:  Buffers solutions.  Preservatives (mertiolat, chlorbutanolhydrat, bensalconium chloride, phenyl mercuric nitrates).  Antioxidants: acid boric, acid boric with levomicethinum, sodium citrate, sodium carbonate.  Biopolymers: PVS, PAA, aqua's solutions of Methyl cellulose in concentration 0,5 – 2 %, CMC, Na CMC, PVP, PEG-400.

14. Type of the package for eye preparations depend on material:  glass package  polymeric

15. Characterization of the glass package: Disadvantage: 1. Friability of the materials. 2. Lixiviation. 3. Big volume of the drops. 4. Contamination at using of the pipette.

16. Characterization of the polymeric package: Advantage: 1. Inertia of the material. 2. Stability. 3. Strength, hardness, rigidity. 4. Easy processing of the polymeric package. 5. Big capacity. 6. They guarantee sterility of the solutions at using.

17. General appearance of the tubing- dropper

18. Technology "blowing-filling- sealing” for drops production Sanitary preparing of production. The formation of protective caps. Production of sterile corps. Preparation of solution. Sterile filtration. Filling and sealing. Marking corps of the dropper. Assembly corps and caps. Packaging and labeling.

19. Ophthalmic suspension – thickness suspensions of the powder in the aqua's or oil dispersible medium. Methods of obtaining: 1. Dispersive. 2. Condensation.

20. 1. Dispersive – suspension is formed via gradual decreasing size of the insoluble substance (milling). 2. Condensation - suspension is formed via gradual increasing size of the insoluble substance, which was in the ion, molecules and colloidal state. Methods of obtaining suspension:

21. inserts – is sterile drugs are intended for inserting in the conjunctive sac. They consist of matrix, which includes MS in the membrane controlling rate of the medicines substances release. Ophthalmic inserts – is sterile drugs are intended for inserting in the conjunctive sac. They consist of matrix, which includes MS in the membrane controlling rate of the medicines substances release. Ophthalmic inserts are solid or semi-solid preparations of suitable size and shape, designed to be inserted in the conjunctival sac, to produce an ocular effect.

22. Advantages of inserts: Advantages of ophthalmic inserts: 1. Accuracy of dosing. 2. Convenience of using. 3. Prolonged action. 4. Absence of the allergic reaction. 5. Shorter time of the coarse treatment in 2-3 time.

23. Classification of the eye inserts: Soluble Insoluble Soluble in the biological liquid – is matrices with homogenous dispersible MS, which is included (or not) in the hydrophobic layer. Layer isn’t penetrated for active substances.

24. Soluble ophthalmic inserts: 1. Natural polymers (collagen) are base of the inserts. 2. Artificial (man-made) polymers (methylcellulose) are base of the inserts. Disadvantages: - High rate of penetration of tear fluid. - Blurred vision.

25. Classification of insoluble ophthalmic inserts: a) Diffuse system, consisting of a central reservoir with drugs in it. b) Osmotic system, consisting of the central part surrounded by the peripheral part. The central part has as simple reservoir and two different departments. In the reservoir there is MS and auxiliary substances to create osmotic pressure. c) Hydrophilic contact lenses is a coherent system that consists of a polymer that allows you to keep aqueous solutions of the MS or solid components.

26. Classification of the contact lenses: 1. Rigid 2. Semi-rigid 3. Elastomeric 4. Soft hydrophilic 5. Biopolimeric

27. Characterization of the contact lenses: Advantage of the lenses – they are able to correct refractive defects of vision and improves visual acuity. Disadvantage  Permanent contact with hands.  Required frequent washing, which causes the risk of contamination and loss of drugs  High price.

28. Powders for eye-drops and powders for eye lotions are supplied in a dry, sterile form to be dissolved or suspended in an appropriate liquid vehicle at the time of administration.Requirements: 1. Should be easy solved, without dissolved residue. 2. Absents of the irritating eye components. 3. Should be sterile. 4. After dilution to meet the requirements for eye drops.

29. They may contain excipients to facilitate dissolution or dispersion, to prevent caking, to adjust the tonicity, to adjust or stabilise the pH or to stabilise the preparation. After dissolution or suspension in the prescribed liquid, they comply with the requirements for eye-drops or eye lotions, as appropriate.

30. Eye lotions are sterile aqueous solutions intended for use in washing or bathing the eye or for impregnating eye dressings. Eye lotions may contain excipients, for example to adjust the tonicity or the viscosity of the preparation or to adjust or stabilise the pH. These substances do not adversely affect the intended action or, at the concentrations used, cause undue local irritation.

31. Eye lotions supplied in multidose containers contain a suitable antimicrobial preservative in appropriate concentration except when the preparation itself has adequate antimicrobial properties. The antimicrobial preservative chosen is compatible with the other ingredients of the preparation and remains effective throughout the period of time during which the eye lotions are in use.

32. If eye lotions are prescribed without an antimicrobial preservative, they are supplied in single-dose containers. Eye lotions intended for use in surgical procedures or in first-aid treatment do not contain an antimicrobial preservative and are supplied in single-dose containers.

33. Eye lotions examined under suitable conditions of visibility, are practically clear and practically free from particles. The containers for multidose preparations do not contain more than 200 ml of eye lotion, unless otherwise justified and authorised.

34. Requirements of an eye lotion :  Sterile and usually containing no preservative  Isotonic with lachrymal fluid  Neutral pH  Large volume but not greater than 200 mL  Non-irritant to ocular tissue

35. Labelling 1. Title identifying the product and concentration of contents 2. ‘Sterile until opened’ 3. ‘Not to be taken’ 4. ‘Use once and discard remaining solution’ 5. Expiry date

36. Preserved eye lotion would need the additional labelling: ‘Avoid contamination of contents during use’ ‘Discard remaining solutions not more than 4 weeks after first opening’ The lotions should be supplied in coloured fluted bottles and sealed to exclude microorganisms.

37. Semi-solid eye preparations are sterile ointments, creams or gels intended for application to the conjunctiva. They contain one or more active substances dissolved or dispersed in a suitable basis. They have a homogeneous appearance. Semi-solid eye preparations comply with the requirements of the monograph on Semi- solid preparations for cutaneous application. The basis is non-irritant to the conjunctiva.

38. Semi-solid eye preparations are packed in small, sterilised collapsible tubes fitted or provided with a cannula and having a content of not more than 5 g of the preparation. The tubes must be well-closed to prevent microbial contamination. Semi-solid eye preparations may also be packed in suitably designed single-dose containers. The containers, or the nozzles of tubes, are of such a shape as to facilitate administration without contamination. Tubes are tamper-proof.

39. Ointments have the disadvantage of temporarily interfering with vision, but have the advantage over liquids of providing greater total drug bioavailability. However, ointments take a longer time to reach peak absorption.

40. Requirements to the semi-solid eye drugs 1. Sterility 2. The absence of irritating 3. Stability 4. A good distribution of MS 5. Softness consistency 6. Good contact with eye 7. Rapid formation of thinnest film on the eyeball 8. Lack of adhesion for ever 9. There should be soft, and at 15-50 º C have a stable viscosity.

41. Technology of the eye ointments 1. Preparing of the ointments base 2. Production of the ointments base 3. Filtering of the ointments base 4. Introducing MS in the ointments base 5. Homogeny of the ointment 6. Packaging, labeling.

42. Eye ointments are normally prepared using aseptic techniques to incorporate the finely powdered active ingredient or a sterilized concentrated solution of the medicament into the sterile eye ointment basis. Immediately after preparation the eye ointment is filled into the sterile containers which are then sealed so as to exclude microorganisms. The screw cap should be covered with a readily breakable seal.

43. All apparatus used in the preparation of eye ointments must be scrupulously clean and sterile. Certain commercial eye ointments may be sterilized in their final containers using ionising radiation.

44. Preparation of eye ointment basis The paraffins and the wool fat are heated together and filtered, while molten, through a coarse filter paper in a heated funnel into a container which can withstand dry heat sterilization temperatures. The container is closed to exclude microorganisms and together with contents is maintained at 160°C for 2 hours.

45. Containers for eye ointments Eye ointments should be supplied in small sterilized collapsible tubes made of metal or in a suitable plastic. The tube should not contain more than 5g of preparation and must be fitted or provided with a nozzle of a suitable shape to facilitate application to the eye and surrounds without allowing contamination of the contents. The tubes must be suitably sealed to prevent microbial contamination. Eye ointment may also be packed in suitably designed single-dose containers.

46. Labelling The names and percentages of the active ingredients. The date after which the eye ointment is not intended to be used. The conditions under which the eye ointment should be stored – normally at a temperature not exceeding 25°C.. The name and concentration of any antimicrobial preservative or other substance added to the preparation A statement to the effect that the contents are sterile providing the container has not been opened.

47. Eyes pencils are used for cauterization of the mucous membranes. They are prepared by melting the base and MS and then pouring in a special form, where they congeal and harden, losing moisture.

48. Eye sprays is dosed aerosols containing sterile solutions for pulverization, witch are applied by non-contact manner. Advantages 1. Rapid absorption of MS. 2. Aerosol particles are well absorbed by the mucous of the eye. 3. Easy using. 4. High efficiency due to the high dispersion of the MS.

49. Attributed of the quality: DescriptionDescription IdentificationIdentification TransparencyTransparency pHpH ImpuritiesImpurities Volume content of the containerVolume content of the container SterilitySterility ContaminationContamination AssayAssay Particle sizeParticle size Uniformity of content in units of MS ASUniformity of content in units of MS AS