Preparation, Characterization and Evaluation of Quetiapine Fumarate Solid Lipid Nanoparticles to Improve the Oral Bioavailability

Quetiapine fumarate is an antipsychotic drug with poor oral bioavailability (9%) due to first-pass metabolism. Present work is an attempt to improve oral bioavailability of quetiapine fumarate by incorporating in solid lipid nanoparticles (SLN). Six quetiapine fumarate SLN formulations were developed using three different lipids by hot homogenisation followed by ultrasonication. The drug excipient compatibility was studied by differential scanning calorimetry (DSC). Stable quetiapine fumarate SLNs having a mean particle size of 200–250？nm with entrapment efficiency varying in between 80% and 92% were developed. The physical stability of optimized formulation F3 was checked at room temperature for 2？months. Comparative bioavailability studies were conducted in male Wistar rats after oral administration of quetiapine fumarate suspension and SLN formulation. The relative bioavailability of quetiapine fumarate from optimized SLN preparation was increased by 3.71 times when compared with the reference quetiapine fumarate suspension. The obtained results are indicative of SLNs as potential lipid carriers for improving the bioavailability of quetiapine fumarate by minimizing first-pass metabolism. 1. Introduction Quetiapine fumarate is an antipsychotic drug with plasma half life of 6？h and poor oral bioavailability (9%) due to extensive first-pass metabolism [1]. Possible methods to avoid first-pass metabolism include transdermal, buccal, rectal, and parenteral routes of administration. Oral route is the most commonly used and preferred route for the delivery of drugs, although several factors like pH of GIT, residence time, and solubility can affect drug absorption or availability by this route. Lymphatic delivery is an alternative choice to avoid first-pass metabolism in oral drug delivery. Enhanced lymphatic transport of drugs reduces the hepatic first-pass metabolism and improves oral bioavailability, because intestinal lymph vessels drain directly into thoracic duct, further in to the venous blood, thus bypassing the portal circulation [2, 3]. The main function of the lymphatic system is to facilitate absorption of long-chain fatty acids via chylomicron formation. Two different lipid-based approaches are known to enhance the lymphatic transport, which include construction of a highly lipophilic prodrug and incorporation of drug in a lipid carrier [4]. Solid lipid nanoparticles (SLNs) are an alternative nanoparticulate carrier system to polymeric nanoparticles, liposomes, and o/w emulsions [5–8]. Aqueous SLN dispersions are composed of lipid which is solid