Development and evaluation of lipid based drug delivery of bosentan

Abstract

To avoid problems of conventional therapy of drug delivery and reduced dose, SR matrix tablet of Bosentan prepared using lipid base material as matrices. Primary screening of polymer was done by selecting different lipid base materials like COM, Eudragit RSPO, PRE, Glycerly mono stearate (GMS) and Cetosteryl alcohol (CA). All the batches developed by direct compression method. Theoretical drug release pattern was carried out for dose calculation up to 24 hrs. All the batches were evaluated for hardness, variation in weight, thickness and friability (Physicochemical parameters). FTIR study and In vitro drug release performed along with experimental design. From the drug release profile, COM (F1) showed batter retardant effect and PRE (F2) showed effective burst release. Remaining formulations (F3-F5) were not able to release the drug as per theoretical drug release profile. After selecting lipid matrices it was optimized by 32 full factorial design by applying analysis of variance (ANOVA). Concentration of Compritol and Precirol were selected as an independent factor while time require for 20% drug release (Y1) and time require for 80% drug release (Y2) were selected as response. Optimized batch showed drug release 99.45% at 24 hrs with desire burst release. Pharmacokinetic study displayed exact fit model is Higuchi model having R2 value 0.9886. Combination of two lipid base material PRE and COM exhibit most desire sustained release as compare to individual. newlineBosentan loaded nanostructured lipid carriers (NLCs) developed by hot homogenization technique using high-speed homogenization along with ultra-sonication. Optimization done by response surface methodology to identify the influence of solid to liquid lipid ratio (X1) and surfactant strength (X2) on the particle size (Y1) and drug loading (Y2). From the pre-formulation study, Transcutol HP, Poloxamer 188 and PRE elected as a liquid lipid, surfactant and solid lipid respectively. Optimize formula having solid to liquid lipid ratio (85:15) %w/w and surfactant str