Influence of process parameters and equipment on dry foam formulation properties using indomethacin as model drug

Abstract

Dry foam technology was developed to overcome insufficient oral bioavailability of poorly soluble and wettable active pharmaceutical ingredients (APIs). It is intended to enable a faster and more efficient dissolution by avoiding API agglomeration and floating of non-wetted API particles. The aim of this study was to investigate the influence of process parameters, such as paste water content and type of equipment used on dry foam morphology, granule characteristics and dissolution behavior of the corresponding tablets using indomethacin as model compound. Multiple analytical methods, namely scanning electron microscopy, X-ray micro-computed tomography and mercury porosimetry, specific surface area analysis and sieve analysis were employed. Dissolution of dry foam formulation tablets was compared to a reference formulation in biorelevant media. Process parameters proved to have a distinct influence on dry foam morphology and granule characteristics, correlations between paste viscosity and pore size distribution could be observed. Dissolution behavior of indomethacin was improved by dry foam technology compared to the reference formulation. Variation of process parameters within the studied ranges did not alter the characteristics of the dry foam formulation dissolution behavior. Therefore, dry foam technology seems a promising future technology with the option of continuous manufacturing.

Keywords: API; BCS; DCS; DF; Dissolution rate; Dry foam; IDM; Indomethacin; Maltodextrin; Process parameters; RF; SDS; SSA; VBT; VDC; Vacuum drying; X-ray micro-computed tomography; X-ray μ-CT; active pharmaceutical ingredient; apparent viscosity at a shear rate of 1001/s; biopharmaceutics classification system; developability classification system; dry foam; indomethacin; reference formulation; sodium dodecyl sulfate; specific surface area; vacuum belt dryer; vacuum drying cabinet; η(100).