Chaitanya Sagar, Kanipotu (2013) Formulation Development and Evaluation of Ophthalmic Solution of Timolol Maleate 0.5%. Masters thesis, C L Baid Metha College of Pharmacy, Chennai.
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Abstract
Ophthalmic preparations are specialized dosage forms designed to be instilled onto the external surface of eye (topical), administered inside (intraocular), adjacent to the eye (periocular) or used in conjunction with any special device. Ophthalmic preparations are similar to parenteral dosage form in their requirements for sterility as well as consideration for osmotic pressure (tonicity), preservation, and tissue compatibility, avoidance of pyrogens and particulate matter and suitable packaging. Ophthalmic solutions are most often multidose product containing suitable preservative(s) to meet compendial Preservative Efficacy Test (USP, Ph Eu, JP) requirements. There are several ophthalmic preparations, but ophthalmic solution was selected for study because solutions are most widely dosage form among the ophthalmics. Ophthalmic solution has several advantages like easy manufacturing, low cost, better dose uniformity, more ocular bioavailability, Improved ratio of local activity versus systemic effects, not induce a foreign-body sensation, long-lasting blurring, or a very bad aftertaste, sterilizable at industrial scale by a recognized process, compatible with an efficient antimicrobial preservative, or packaging. Drug selected for the study, Timolol is a first-generation Beta blockers have effective action by the reduction of intra ocular pressure in Chronic open angle glaucoma, as well as in the treatment of Hypertension. Compared with other β- blockers, this drug has broader clinical applications in the treatment of Glaucoma. Important factors to be considered in formulating an ophthalmic solution includes Clarity, Sterility, Osmolarity, pH, buffering, preservative, Solubility, Stability in appropriate vehicle. Viscosity, Suitable packaging and storage of finished product. Benzalkonium chloride, a popular preservative for pharmaceutical products, is a complex mixture since the alkyl portion of the molecule is derived from natural sources. The chain lengths are principally C12 to C16, however the antimicrobial activity increases with the proportion of longer chain lengths. Unfortunately the tendency to adsorb plastics also increases with chain length i.e. the most effective constituents of the mixture may be preferentially adsorbed. Method preferred for sterilization of the ophthalmic solution was filtration sterilization. Containers commonly used for ophthalmic products include glass containers, and polyethylene containers. Glass containers and polyethylene containers are said to be superior in maintaining stability of ophthalmic preparations. Amber glass containers are often used where the product is suspected of being a light sensitive. The amber color is imparted by addition of iron and manganese oxides. Plastic dropper bottle have been favored because they weight loss, are more resistant to shock and other mechanical influences, cost less and offer more design possibilities. Polyethylenes, that is, low density polyethylene with or without additives. BFS containers are manufactured by Blow-Fill-Seal (BFS) technology. Three Piece Container name itself indicates system contains three components viz... body, nozzle, and cap. Out of which, body and nozzle are made up of various grades of polymers of low density polyethylene whereas caps are made up of high density polyethylene. The aim of the present study was to formulate a formulation for Timolol maleate (0.5%) ophthalmic solution using different concentration of Benzalkonium chloride as preservative. While reducing the concentration of Benzalkonium chloride it must be keep in mind that added quantity of preservative must meet compendial requirement of Preservative Efficacy Testing. The present research work was also planned to provide the data about the selection of suitable primary packaging material for Timolol maleate (0.5%) ophthalmic solution to achieve the better stability during the shelf life of the product. As there are several factors responsible for the incompatibility of packaging material with the product, most suitable packaging material must be selected. The proposed formula was optimized by varying the concentration of Benzalkonium chloride. The quantities of Timolol maleate and other excipients were kept constant. As the aim of the present study was to optimize the concentration of BKC in formulation for Timolol maleate (0.5%) ophthalmic solution. Batches were planned by taking different concentrations viz.0.0 % v/v, 0.01%,0.012%, 0.016%, and 0.02% ,0.024 % v/v of Benzalkonium chloride. For all six batches Preservative Efficacy Testing was carried out according to British Pharmacopoeia. After performing Preservative efficacy testing, optimized batch was filled into three types of container and were subjected to accelerated conditions. Accelerated condition for semi-permeable containers (40ºC ± 2ºC/ NMT 25%) and for glass containers (40ºC ± 2ºC/ 75% ± 5% RH) were chosen for storage for stability/compatibility study. Finished product was analyzed for the parameters Appearance, Assay of Timolol maleate and Benzalkonium chloride, pH, Osmolality, drop size, and water loss. CONCLUSION: 1. From the results of Preservative efficacy test, it was found that Benzalkonium chloride (0.02% v/v) and (0.024% v/v) showed 2 log reductions at 6 hours and 5 log reductions at 24 hours and no recovery at 28th day for bacteria. For fungi it showed log reduction as stated in criteria, 2 log reductions at 7th day and no recovery at 28th day. Both these concentrations passed the criteria according to British Pharmacopoeia. As the aim of study was to minimize the concentration, it will be preferable to use 0.02% v/v concentration of BKC in Timolol maleate 0.5% ophthalmic solution. 2. In case of container compatibility study, results for Assay of Timolol maleate and Benzalkonium chloride, pH, Osmolality, drop size and water loss are within range of specifications for Three piece containers, BFS containers and Glass containers. But Three piece containers showed better results for compatibility with Timolol ophthalmic solution as compared to the BFS and Glass containers. Therefore Three piece containers (Low density polyethylene, PE 1840 H) are the best containers for Timolol maleate (0.5%) ophthalmic solution.
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | Formulation, Development, Evaluation, Ophthalmic Solution, Timolol Maleate. |
| Subjects: | PHARMACY > Pharmaceutics |
| Depositing User: | Ravindran C |
| Date Deposited: | 14 Jul 2017 06:16 |
| Last Modified: | 01 Jan 2022 18:02 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/1686 |
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