The aim of present study was to develop N-carboxymethyl chitosan (MCC) coated Indinavir (INV)-loaded SLNs. IDV is HIV protease inhibitor with a short half-life, extensive first-pass metabolism and variable pH-dependent oral absorption. To overcome these drawbacks SLN was prepared for intestinal lymphatic drug transport. Screening of lipid was done on the basis of solubility of INV in different lipids. Compritol 888ATO was selected. Screening of surfactant was done by preparing INV-SLNs by high speed homogenization (HSH) followed by ultra sonication method and evaluated for particle size, zeta potential and PDI. Poloxamer 188 was selected. Optimization of formulation was done by 32 full factorial design. Independent variables were selected as conc. of surfactant and drug:lipid ratio while dependent variable as a particle size, zeta potential and %entrapment efficiency. Optimized formulation showed particle size 166.2 nm and zeta potential -15.9 and highest EE 83.69%. The Optimized formulation was converted into positively charged SLNs by using stearylamine as charge modifier in lipid phase. Effect of different conc. of stearlyamine was also done and then optimised formulation was used for coating with MCC polymer (1%) by overnight stirring. MCC coated SLNs was confirmed by change in zeta-potential and particle size. Particle size after coating was found to be 249.1 and zeta potential -9.37. Morphological study of optimized formulation was confirmed by SEM analysis. Comparative in-vitro drug release of INV-SLN and MCC coated INV-SLNs was done in 6.8 pH phosphate buffer for 12 hrs and 0.1N HCl for 2 hrs. Similarly in-vivo study was done by using Wistar rats. Relative oral bioavailability of MCC coated INV-SLNs was significantly increased as compared with INV-SLNs and INV-suspension. Stability-study was done as per ICH guidelines.
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