Surface area normalized dissolution to study differences in itraconazole-copovidone solid dispersions prepared by spray-drying and hot melt extrusion

Abstract

Amorphous solid dispersions of itraconazole (ITZ) and copovidone (PVPVA 64) at 1:1 to 1:9 drug-polymer ratios were prepared using spray-drying (SD) and hot melt (HM) extrusion for comparative evaluation. Surface area normalized dissolution studies were carried out using a modified intrinsic dissolution rate (IDR) assembly and rate of release of drug as well as polymer were quantified using ultraviolet spectroscopy. The melt quenched amorphous form of ITZ provided an 18-fold dissolution advantage over the crystalline form. In general, dispersions prepared by either SD or HM showed similar dissolution profiles in terms of drug release. Both drug-controlled and polymer-controlled ITZ dissolution rates were observed, depending on the drug loading, where a switch from a drug-controlled to a polymer-controlled regime was observed when the drug loading was approximately 20% or lower. The impact of the spray drying solvent composition was studied and found to have a large effect on the drug release rate for dispersions containing a drug loading of 20%. Electron microscopy showed differences in surface morphology (scanning) and internal structure (transmission) in these dispersions as a function of solvent system. X-ray photoelectron spectroscopy (XPS) revealed differences in the surface composition of drug and polymer whereby poorly dissolving systems showed drug enrichment. This study provides insight into the complex interplay between formulation, processing and performance of amorphous solid dispersion systems.

Keywords: Amorphous solid dispersions; Hot melt extrusion; Intrinsic dissolution; Spray-drying.