Ophthalmic Preparations PDF

Ophthalmic Preparations These preparations may be categorized as follows: - Eye drops including solutions, emulsions and suspensions of active medicaments for instillation into the conjunctival sac. -Eye lotions for irrigating and cleansing the eye surface, or for impregnating eye dressings - Eye...

Ophthalmic Preparations These preparations may be categorized as follows: - Eye drops including solutions, emulsions and suspensions of active medicaments for instillation into the conjunctival sac. -Eye lotions for irrigating and cleansing the eye surface, or for impregnating eye dressings - Eye ointments, creams and gels containing active ingredient(s) for application to the lid margins These preparations may be categorized as follows: Contact lens solutions to facilitate the wearing and care of contact lenses Parenteral products for intracorneal, ‫التحميل‬ intravitreous or ‫…يجري‬ retrobulbar injection Ophthalmic inserts placed in the conjunctival sac and designed to release active ingredient over a prolonged period Powders for the preparation of eye drops and eye lotions.  It is necessary that all ophthalmic preparations are sterile and essentially free from foreign particles. Medicaments contained in ophthalmic products include: Anaesthetics used topically in surgical procedures Anti-infectives such as antibacterials, antifungals and antivirals Anti-inflammatories such as corticosteroids and antihistamines Antiglaucoma agents to reduce intraocular pressure, such as beta- blockers ‫…يجري التحميل‬ Astringents such as zinc sulphate Diagnostic agents such as fluorescein which highlight damage to the epithelial tissue Miotics such as pilocarpine which constrict the pupil and contract the ciliary muscle, increasing drainage from the anterior chamber Mydriatics and cycloplegics such as atropine, which dilate the pupil and paralyse the ciliary muscle and thus facilitate the examination of the interior of the eye.  Formulation of eye drops The components of an eye drop formulation are: - Active ingredient(s) to produce desired therapeutic effect - Vehicle, aqueous but occasionally may be oil - Antimicrobial preservative to eliminate any microbial contamination during use and thus maintain sterility; it should not interact adversely with the active ingredient(s) - Adjuvants to adjust tonicity, viscosity or pH  Antimicrobial preservatives - Should be included in all eye drops except: 1- Eye drops specifically formulated for use during intraocular surgery. 2- Diagnostic dyes should preferably be supplied as single-dose preparations 3- Eye drops supplied as single-dose preparations (tear replacements)  Antimicrobial preservatives Benzalkonium chloride - It is in over 70% of commercially produced eye drops. - usually at 0.1% w/v. - It is a mixture of alkylbenzyldimethyl ammonium compounds. Benzalkonium chloride  Benzalkonium chloride- Activity - It is stable to sterilization by autoclaving. The compound has a rapid bactericidal action against a wide range of Gram-positive and Gram-negative organisms. - It destroys the external structures of the cell (cell envelope). ‫…يجري التحميل‬ - Activity is reduced in the presence of multivalent cations (Mg2+, Ca2+). - It also has its activity reduced if heated with methylcellulose or formulated with anionic surfactants.  Benzalkonium chloride- Activity - its activity against Gram-negative organisms is greatly enhanced by chelating agents such as disodium edetate.  Benzalkonium chloride- Activity -The surface activity of benzalkonium chloride may be used to enhance the transcorneal passage of non-lipid-soluble drugs such as carbachol. - it is important not to use benzalkonium chloride to preserve local anaesthetic eye drops which abolish the blink reflex  Antimicrobial preservatives Chlorhexidine acetate or gluconate - is a cationic biguanide bactericide with antibacterial properties in aqueous solution similar to benzalkonium chloride. Chlorhexidine acetate or gluconate- Activity - It is used at 0.01% w/v. -Its antibacterial activity is enhanced by aromatic alcohols and by disodium edetate. -Activity decreases by anionic surfactants.  Antimicrobial preservatives Chlorobutanol - used at 0.5% w/v, MOA unknown - The main disadvantages are: 1- its volatility, 2- absorption by plastic containers and 3- lack of stability at autoclave temperatures  Antimicrobial preservatives Organic mercurials - Phenylmercuric acetate and nitrate and thiomersal - Used at concentrations of 0.001–0.004% w/v, -  Organic mercurials - Absorption by rubber is marked. - should not be used in eye drops which require prolonged usage because this can lead to intraocular deposition of mercury (mercurialentis)  Tonicity - In practice, the eye will tolerate small volumes of eye drops having tonicities in the range equivalent to 0.7–1.5% w/v sodium chloride. - It is always best to be equivalent to 0.9% NaCl - Some preparations are themselves hypertonic  Viscosity enhancers - Increasing the viscosity of an eye drop increases the residence time of the drop in the eye and results in increased penetration and therapeutic action of the drug. - Greatly important for artificial tears Viscosity enhancers- Hypromellose Hydroxypropyl derivative of methylcellulose The most popular cellulose derivative employed for enhancing viscosity  Viscosity enhancers Polyvinyl alcohol Polyvinylpyrrolidone, polyethylene glycol Dextrin Sodium hyalurinate Used with active ingredients or alone  pH adjustment - The pH offers best stability during preparation and storage. - The pH offers the best therapeutic activity. - The comfort of the patient. - The lachrymal fluid has a pH of 7.2–7.4 and also possesses considerable buffering capacity.  Antioxidants Primarily are reducing agents. Active ingredients requiring protection include: adrenaline (epinephrine), proxymetacaine, sulfacetamide, tetracaine, phenylephrine and physostigmine  Antioxidants - Mostly used antioxidants: - Sodium metabisulphite and sodium sulphite Sulfite reacts with and consumes dissolved oxygen in aqueous solutions:  2SO32- + O2 --------- >2SO4 2- Sterilization of ophthalmic products - This can take the form of: 1- Autoclaving at 115 C for 30 min or 121 C for 15 min 2- Filtration through a membrane filter having a 0.22 µm pore size into sterile containers using strict aseptic technique. Filling should take place under Grade A laminar airflow conditions 3- Dry-heat sterilization at 160 Cfor 2 h is employed for non-aqueous preparations such as liquid paraffin eye drops.  Instillation of eye drops Tilt head back and with one hand gently pull down lower eyelid to form a pouch between the eye and the eyelid. ‫التحميل‬ Drop a single drop into‫…يجري‬ the preformed pouch. Do not touch the dropper on the eye or eyelid Release lower lid. Try not to blink more than usual as this removes the medicine from the eye.