QbD based approach for optimization of Tenofovir disoproxil fumarate loaded liquid crystal precursor with improved permeability

Abstract

BCS class III drugs suffer from a drawback of low permeability even though they have high aqueous solubility. The objective of current work was to screen the suitability of glyceryl monooleate (GMO)/Pluronic F127 cubic phase liquid crystals precursors for permeation enhancement and in turn the bioavailability of tenofovir disoproxil fumarate (TDF), a BCS class III drug. Spray-drying method was used for preparation of TDF loaded liquid crystal precursors (LCP) consisting of GMO/Pluronic F127 and lactose monohydrate with an ability to in situ transform into stable cubic phases upon hydration. The quality by design (QbD) approach (Factorial design) was used for batch optimization. Spherical TDF loaded LCP as revealed by scanning electron microscopy photographs when hydrated and analyzed by small angle X-ray scattering confirmed formation of cubic phase. Differential scanning calorimetry and X-ray diffraction studies confirmed the molecular dispersion of TDF in polymer matrix and also suggested the conversion of TDF from crystalline to amorphous form. In vitro TDF release from prepared LCP showed controlled drug release over a period of 10h. Further ex vivo studies revealed permeation enhancing activity of prepared LCP, which was highest when tested in presence of digestive enzyme extract. Thus, formulation of stable liquid crystal powder precursor can serve as an alternative for designing oral delivery system for drugs with low permeability.