Fast dissolving fillers in dry foam formulation

Abstract

Dry foam technology was developed as alternative granulation technique to overcome insufficient oral bioavailability of poorly soluble and wettable active pharmaceutical ingredients (APIs). In recent studies the type of filler showed to have a distinct influence on dry foam morphology as well as dissolution characteristics. Isomalt for instance improved the initial dissolution rate of fenofibrate dry foam formulation tablets. In this study the hypothesis that fast dissolving low molecular weight fillers improve dissolution rate and alter dry foam morphology should be confirmed with two APIs with different aqueous solubility (indomethacin, orlistat), in three different filler combinations, namely maltodextrin 21D, isomalt and 1:1 mixture of mannitol and maltodextrin 21D. In addition the dissolution behaviour of dry foam tablets was compared to fluid bed granulation formulations with the same drug loading and to an orlistat marketed formulation (Alli® 60mg capsules) in FaSSIF using USP 2 paddle apparatus and HPLC analysis after filtration.Dry foams prepared with low molecular weight fillers revealed more compact and less porous structures compared to dry foams containing maltodextrin 21D. Interestingly, their rough surface still resulted in increased surface area compared to the other formulations. The initial dissolution behaviour of indomethacin and orlistat dry foam tablets was improved by using isomalt and the mannitol–maltodextrin mixture as filler. All indomethacin formulations reached complete dissolution of the applied dose, whereas the total amount of dissolved orlistat was increased compared to the fluid bed granule tablets and the marketed formulation Alli® by using low molecular weight fillers in dry foam formulations. The improved dissolution behaviour of Orlistat dry foam tablets using low molecular weight fillers was additionally confirmed in USP monography dissolution medium.