Pharmaceutica Analytica Acta

Preparation, in vitro evaluation, statistical optimization and in vitro absorption mechanism of carvedilolloaded solid lipid nanoparticles for oral delivery

5^th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems

March 16-18, 2015 Crowne Plaza, Dubai, UAE

Mansi K Shah and Senshang Lin

Posters & Accepted Abstracts: Pharm Anal Acta

Abstract:

The availability of reliable high throughput screening methods for rapid evaluation and prediction of the absorption mechanism is needed with lipid based drug delivery systems especially for solid lipid nanoparticles. Carvedilol-loaded solid lipid nanoparticles (SLN) were prepared using solubility parameter (δ) to select the lipid, and hot homogenization to fabricate SLN. The effect of concentration of Compritol 888 ATO (COMP) and Poloxamer188 (P-188) on particle size of blank SLN was studied using design of experiments (DOE). Further narrow concentration range of COMP and P-188 was selected and carvedilol-loaded SLN were prepared to obtain an optimized formulation which was lyophilized (L-SLN), transformed into enteric compression coated tablet and evaluated for drug release, x-ray diffraction and cellular uptake mechanism. To elucidate the absorption mechanism in detail, cells were subjected to different pretreatments and transport studies. COMP was chosen as lipid due to its least value of Δδ with carvedilol. The optimized formulation (7.5% COMP, 5.0% P-188 and 1.11% carvedilol) had 161 nm particle size and 94.8% entrapment efficiency. The enteric-coated carvedilol-loaded SLN tablet protected carvedilol from acidic environment and similar prolonged release profiles were obtained from L-SLN, core tablet and enteric coated tablet. Absence of crystalline carvedilol XRD peak indicated presence of amorphous carvedilol in SLN. Based upon the results of uptake, pretreatments and transport studies, the main absorption mechanism of carvedilol-loaded SLN could be endocytosis and, more specifically, clathrin mediated endocytosis. Higher carvedilol uptake from SLN compared to drug solution in Caco-2 cell line exhibited a potential prolonged drug release in the body following the lymphatic uptake of carvedilol-loaded SLN which will avoid first pass metabolism and hence higher oral bioavailability.