Formulation and Characterization of Poorly Water Soluble Drugs by Using Solid Dispersion Technique

Abstract

Lumefantrine is a synthetic antimalarial agent and amino alcohol fluorene derivative has been in use for chloroquine-resistant malarial disease usually in combination. Although the precise mechanism remains unknown, it prevents the creation of and#946;-hematin by making a complex with hemin and prevents nucleic acid and protein synthesis. Systemically available lumefantrine is 99.7% protein bound and principally inactivated in the liver by cytochrome P450 3A4 to desbutyl lumefantrine. Lumefantrine has unpredictable and slow absorption which declines further during the critical phase of the infection. Being a lipophilic agent, poor aqueous solubility and drug efflux through active efflux transporter P-glycoprotein resulting in low intestinal uptake seems to be the major limitation for the unpredictable bioavailability. Lumefantrine, A drug from BCS class II has low aqueous solubility and exhibits a dissolution rate limited absorption wherein enhancing the solubility and dissolution rate of such drug remains the main approach when the attempt to improve the bioavailability are made of the several alternatives, solid dispersion made from dispersing hydrophilic polymeric material that converts crystalline structure into amorphous one, has been a prevalent method. The work elaborated in the thesis describes the formulation, characterization and assessment of solid dispersions containing lumefantrine. with different hydrophilic polymers (Soluplus®, Povidone, Klucel , Copovidone, Lutrol®F68) with added P-glycoprotein efflux inhibitor piperine. The work also characterized the result of enhanced aqueous solubility on the bioavailability in rats. Further, we attempted to reproduce the process at pilot scale at industrial set up using a twin screw extruder. newlineIn this current investigation, the melt technique was utilized to abstain from the use of water to suppress the likelihood of recrystallization. Solubility and dissolution of lumefantrine were enhanced from solid dispersion prepared with soluplus and found to be highest in the