DEVELOPMENT OF IN-SITU GEL FOR NA TAMYCIN OPHTALMIC DRUG DELIVERY

• Main Author: Suharyani, Ine
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/66665
• Institution: Institut Teknologi Bandung

Natamycin is an antifungi isolated from Streptomyces natalensis Sp. which possesses activity against a variety of yeast and filamentous fungi, including Candida, Aspergillus, Cephalosporium, Fusarium and Penicillium. In ophthalmic drug delivery system, a drug is expected to have prolonged retention time in precornea to increase it bioavailability and decrease the systemic effect of this drug. Sodium alginate used as gelling agent due to it biodegradable and mucoadhesive properties. The aims of this study is to develope of in situ gelling system formulation consist of natamycin for ophtalmic drug delivery system. In this research, in situ gelling system made in two kind of dossage forms: nanosuspension and inclusion complex with hydroxyprophyl beta cyclodextrine (HP fiCD). Natamycin nanosuspension is made by using Tween 80, PEG 400, benzalconium chloride and sodium alginate. Optimization is done for concentration of sodium alginate as gelling agent and PEG 400 as co-surfactant; time for milling, stiring with ultra-turrax, and sonification. It was also done for the speed of stirring. Inclusion complexes with HP,13CD is prepared by solubilization method. Then the solvent were removed using freeze drying method Furthermore, gel of the inclusion complex powder is made using sodium alginate, benzalconium chloride and isotonic phosphate buffer. Optimization is done for concentration of sodium alginate which give an optimum gelation effect. Evaluation of nanosuspension were included of particle size analysis, the value of polidispersity index, and physical stability. While evaluation for inclusion complex dossage form was physical stability. Both preparation were also test for eye iritation and mucoadhesive force . The morphology of particles of both formulation were observed using Scanning Electron Microscop (SEM). The optimum formula of nanosuspension found in this study was contained of 8.7% PEG 400, 0.25% of sodium alginate and 10% of Tween 80. The particle size of this suspension was still in the range of nano suspension size until the 13th day, then the particles size increased until in the range of micro size which were 1300-2600 nm until 84 days. Although the particles size become larger but it is still in the range of particle size that allowed to used in ophtalmic suspension which was not more then 5 pm. The result obtained,from physical stability test showed that pH, viscosity and concentration of natamycin in both of formulation are stable during the study. The result of irritation test of these dossage forms showed that the dosage suggesting that then was no iritation effect in animal test. The amount of natamycin diffuse from each dosage form were 17.08+0.22% for nanosuspension and 83.07+0.55% for inclusion complex after 24th hours. Mucoadhesive force for nanosuspension was 10.68+0.59 1V/cm- and for inclusion complex dossage form 9.02+0.54 N/cm2.