Interdependence of particle properties and bulk powder behavior of indomethacin in quench-cooled molten two-phase solid dispersions

Abstract

Solid dispersions (SDs) hold a proven potential in formulating poorly water-soluble drugs. The present paper investigates the interfacial phenomena associated with the bulk powder flow, water sorption, wetting and dissolution of the SDs prepared by a modified melt and quench-cooling (QC) method. Poorly water-soluble indomethacin (IND) was QC molten with solubilizing graft copolymer (Soluplus®) or polyol sugar alcohol (xylitol, XYL). The interfacial interactions of SDs with air/water were found to be reliant on the type (amorphous/crystalline) and amount of the carrier material used. The final SDs were composed of fused agglomerates (SOL) or large jagged particles (XYL) with good wetting and powder flow properties. The initial dissolution of IND was accelerated by both carrier materials studied. The QC molten SDs with amorphous Soluplus® significantly improved the dissolution rate of IND at pH 6.8 (79.9 ± 0.2% at 30 min) compared to that of pure crystalline drug. The substantial improvement in the dissolution rate of IND was in connection with the amorphous state of the drug being stabilized by Soluplus® in the QC molten SDs. However, it is evident that a strong H-bond formation between the components in some regions of the QC molten SDs can limit the dissolution of IND. The QC molten two-phase SDs with a polyol carrier (XYL) showed rapid and continuous drug release without reaching a plateau.

Synergistic application of continuous granulation and selective laser sintering 3D printing for the development of pharmaceutical dosage forms with enhanced dissolution rates and physical properties

“…Previous research has shown that indomethacin has extremely poor flow properties by the means of Angle of Repose (AOR) and Hausner's ratio [32]. On inspecting indomethacin drug crystals using digital microscopy ( fig.…”

“…IND is a non-steroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-I and COX-II) enzymes non-selectively [31]. IND is deemed practically insoluble in water (0.937e −6 g/mL), moreover, it also exhibits poor flow properties because of its highly irregular crystal habits and inter particulate cohesion [32,33]. Thereby IND was the ideal candidate to test the granulation technique’s applicability for powder bed-based 3D printing (PBF) of drug substances with poor solubility and flow properties.…”

Studies on Ocimum basilicum mucilage based solid dispersions of indomethacin for enhancement of dissolution rate

“…SD's of IND helps in enhancing the overall solubility in various medias, dissolution studies reveals that as compared to pure drug; solid dispersions showed marked increase in dissolution rate. The improvement in dissolution rate may be due to the formation of molecular dispersion of indomethacin in Ocimum basilicum mucilage, leads to partial miscibility, improving the hydrophilic characteristics of the drug substances through interaction with the mucilage [5,9,11].…”

“…It is a poorly water soluble antirheumatic agent. In literature attempts has been mase to improve the dissolution rate of indomethacin by various techniques like supersaturable delivery systems such as amorphous self-micellizing solid dispersions (SmSDs) [5] amorphous indomethacin coating with chitosan [6] mesoporous silica nanorods [7], spray drying with silica, polyvinylpyrrolidone (PVP) or 2-hydroxypropyl-β-cyclodextrin (HPβCD) [8] Indomethacin:tromethamine a highly crystalline salt by hot melt extrusion technology [9] melt-electrospun fibers (MSFs) [10], Solid dispersions by modified melt and quench-cooling (QC) method with graft copolymer (Soluplus®) or polyol sugar alcohol (xylitol) [11], microwave assisted in situ amorphization of indomethacin with PVP [12], coamorphous salts of indomethacin-lysine [13] .…”