All-trans-retinoic acid loaded ocular microspheres: preparation and in-vitro characterization

Y. Çirpanli1, N. Ünlü1, S. Çalis1, A.A. Hincal1 1 Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, ABSTRACT
Preparation of PLGA (50:50)
with solvent evaporation technique. In-vitro Microspheres
technique. For this purpose, 10 mg retinoic average particle size was measured to be microspheres were determined to be 1,65% microspheres were continued for 11 days. polyvinylalcohol and sodium oleat (4:1). INTRODUCTION
Ultraturrax (T25 basic, IKA, Labortechnik, ocular surfaces connected with reduction or instability of the precorneal tear film. The conjunctival goblet cell regression is one of the important consequence of eye dryness. centrifugation at 15.000 rpm for 15 min; differentiation including goblet cell loss, temperature. All procedure was carried out keratinization occured as a result of KCS and this is called squamous metaplasia (1). Conventional non-surgical treatments are Drug Loading
not directed specificaly to reversing the properly and added into 10 ml of ethanol : acid (tretinoin) has been reported to be phosphate buffer solution (pH 7,4) (7:3). effective in reversing the epithelial changes They were kept in an ultrasonic bath for 3 in dry eye disorders (2). Different dosage min. After the removal of supernatant by forms of retinoic acid including ophthalmic centrifugation, the remaining microparticles were dissolved in 5 ml of dichloromethane have been attempted (3,4). The objective of and this solution was extracted with 10 ml of ethanol : phosphate buffer (pH 7,4) (7:3) microparticles of retinoic acid. The rationale for 1 hr in order to transfer retinoic acid of retinoic acid microparticulate system is from dichloromethane. When the extraction formulation of poorly soluble and chemically evaporated and the resulting solution was labil drug (retinoic acid), and improvement filtered through a membrane filter with a 2003 Controlled Release Society 30th Annual Meeting PROCEEDINGS microspheres released retinoic acid during 1100–USA) equipped with a C18 column (5 µm, 250x4,6 mm, Phenomenex-USA) was used. The mobile phase was a mixture of methanol : acetonitrile : water : acetic acid (80:10:10:0,5). The flow rate was set to 1 mL/min, the detection was performed at 356 nm. Total drug content was calculated as the sum of retinoic acid amounts both on the surface and inside of the microspheres. Particle Size Distribution
Figure 1. SEM photographs of retinoic acid
microspheres containing retinoic acid was measured using laser diffraction particle sizer (Malvern Mastersizer 2000, UK). For Time (day)
Surface Morphology
Figure2. Dissolution profiles of retinoic acid
In this preliminary part of the study, in vitro release of retinoic acid from PLGA stubs with conductive silver paint and then sputted with a 150 Aº thick layer of gold in a Furthermore, stability assessment and in vivo evaluation of the formulation will be In Vitro Release
(50:50) microspheres were investigated in ethanol : phosphate buffer solution (pH 7,4) (7:3). Given amount of microspheres were 2. Tseng, S.C., Maumenee, A.E., Stark, W.J. suspended in the release medium at 37 ± Topical retinoid treatment for various dry- 3. Choi, Y., Kim, S.Y., Kim, S.H., Lee, K.S., Kim, C., Byun, Y. Long-term delivery of all- RESULTS AND DISCUSSION
trans-retinoic acid using biodegradable PLLA/PEG-PLLA blended microspheres. acid were prepared by a yield of 42,79 %. 4. Selek, H., Ünlü, N., Orhan, M., Irkeç, M. The average particle size was measured to emulsion in dry eye. Eur. J. Ophthalmol. 2003 Controlled Release Society 30th Annual Meeting PROCEEDINGS


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