Abstract

IMPROVEMENT ON THE ORAL BIOAVAILABILITY OF ARTEMETHER BY A DESIGNED SUPERSATURABLE SELF EMULSIFYING DRUG DELIVERY SYSTEM AS A POTENTIAL FOR PREVENTION OF IN VIVO DRUG CRYSTALLIZATION

Ugwu Calister Elochukwu*, Obitte Nicholas Chinedu and Onunkwo Godswill Chukwunweike

Abstract

The oral bioavailability of artemether is low, which is ascribed to its poor aqueous solubility. To address the potential of the in vivo supersaturation problem, artemether-loaded supersaturable self emulsifying drug delivery system was formulated using hydroxypropyl methylcellulose. The solubility studies of the vehicles were carried out. The S-SEDDS loaded with 40 mg of the drug was formulated with a 5 % hydroxypropyl methylcellulose. The following evaluation tests: Pre/post formulation visual isotropicity, emulsification time, refrigeration cycle, centrifugation, viscosity, pH, loading efficiency, and crystallization/precipitation studies were carried out. The loading capacities were high in the range of 90 ± 0.023 to 98.71 ± 0.036 %. In vitro release studies of the formulations were carried out in simulated gastric fluid without pepsin (pH, 1.2) and stimulated intestinal fluid without pancreatin (pH, 6.8) respectively. Drug release data were subjected to kinetics studies. Results showed that ARM had high solubility in Triacetin®, Labrasol® and Transcutol® P. The descending order of drug release profiles of batches include T3 > T4> T2 > T1 and T4 > T3 > T2 > T1 in SGF and SIF respectively. The photomicrograph showed that at 5 h there was a trace of crystals in the self emulsifying drug delivery system formulation containing no hydroxypropyl methylcellulose unlike in the supersaturable self emulsifying drug delivery system formulation. Therefore, the potential in vivo crystal formation of artemether was inhibited by formulation of Supersaturable emulsifying drug delivery system using hydroxypropyl methylcellulose as a crystal inhibitor.

Keywords: Hydroxypropyl methylcellulose; Microemulsion; Supersaturable-Self emulsifying drug delivery system; Crystallization.