Enhanced Boosting of Oral Absorption of Lopinavir Through Electrospray Coencapsulation with Ritonavir.

In vivo activities of absorption enhancers coencapsulated with poorly absorptive drugs in the same enteric-coated particles were evaluated. Lopinavir [a substrate of cytochrome P450 3A (CYP3A)] and ritonavir (an inhibitor of CYP3A-mediatd metabolism) were used as a model drug and a model absorption enhancer, respectively. Lopinavir and ritonavir were encapsulated into enteric-coated particles as amorphous forms using coaxial electrospray deposition. The electrospray treatment resulted in dramatic improvement of dissolution profiles of both compounds, probably because of complete amorphization and superior dispersion efficiency of the particles. Poor absorption of lopinavir in rats was observed after oral administration of enteric-coated particles containing lopinavir alone. When the particles were coadministered with enteric-coated particles containing ritonavir alone, lopinavir absorption was boosted. The boosting effect was further enhanced when ritonavir was coencapsulated with lopinavir into the same enteric-coated particles. A significant increase in area under the plasma concentration-time curve reflected an extension of mean residence time rather than an elevation of Cmax . Lopinavir absorption was improved presumably because lopinavir was always accompanied by a practical amount of ritonavir required for the boosting during the gastrointestinal transit of the particles. Not only did the electrospray coencapsulation technique improve drug absorption, but also increased trough concentration that might result in the reduction of the number of doses.

Preparation of fenofibrate solid dispersion using electrospray deposition and improvement in oral absorption by instantaneous post-heating of the formulation.

A coaxial electrospray technique was applied to a poorly soluble drug, fenofibrate (FEN), to increase its bioavailability. A particulate core-shell solid dispersion was designed using poly(methacrylic acid-co-methyl methacrylate) (Eudragit L-100) as a shell material and poly(vinyl pyrrolidone) K12-17 as a dispersant for FEN in the core phase. Although 58% of FEN remained in the crystalline state in the electrosprayed formulation, the dissolution behavior was significantly improved due to decrease in particle size, decrease in crystallinity, and increase in dispersion efficiency. The formulation was subjected to post-heating at 100 °C for 30 s to transform the remaining crystals into the amorphous state to further improve the dissolution behavior. Oral bioavailability was also on the order of: heated formulation>intact formulation>crystalline FEN. Instantaneous heating significantly improved the performance of the formulation despite its simple procedure, and thus can be a powerful step to be incorporated in the formulation manufacturing process.