In vitro and in vivo evaluation of porous lactose/mannitol carriers for solubility enhancement of poorly water-soluble drugs

Abstract

The application of porous materials as drug carriers represents a new solubility enhancement strategy for poorly soluble drugs. In this study, porous lactose or mannitol carriers were prepared by a combined spray drying and template removal method with Indomethacin loaded as a model drug. In vitro dissolution test and in vivo absorption study were employed to evaluate the capacity of the porous carriers on solubility enhancement of Indomethacin. Porous lactose carriers displayed higher surface area and larger pore volume than that of mannitol, which was consistent with the corresponding amount of drug loading. Compared with the physical mixtures, indomethacin loaded into the porous carriers displayed significantly higher dissolution rate, with more than 80% of the loaded drug released in 10 min. Results of animal experiments in beagle dogs showed that the prepared Indomethacin-loaded porous lactose can enhance the in vivo absorption of Indomethacin. The analysis in gender difference suggested that Indomethacin was absorbed faster in female beagle dogs than that in male. The fabrication of porous framework from food-grade materials and the proved effectiveness on solubility enhancement further expand the capability of spray drying engineering of pharmaceutical particles.