Anomalous dissolution behavior of celecoxib in PVP/Isomalt solid dispersions prepared using spray drier

Abstract

Celecoxib is a COX II inhibitor NSAID which is used for joint pains, rheumatoid arthritis and osteoarthritis, however due to its poor water solubility it shows very low oral bioavailability. Using solid dispersion formulations is one of the most promising strategies to increase solubility of poorly water Soluble drugs. The purpose of this study is dissolution enhancement of celecoxib by preparation of solid dispersions via spray drying technique using PVP and Isomalt as hydrophilic carriers. Different ratios of celecoxib, Isomalt and PVP K30 (7:3:0, 5:5:0,3:7:0, 1:9:0 and 3:5:2,3:2:5) were prepared from 2 hydroalcoholic solutions (70:30 ethanol:water) using spray drier. Particle size analyzing, saturation solubility, SEM, DSC, FT-IR, XRPD and dissolution studies in 0.25 SDS and 0.04 M Na3HPO4 mediums were performed. Stability of samples was also studied after a week and a month storage at 75 humidity condition. The results showed that the saturation solubility of celecoxib in solid dispersion samples is 20-30 folds higher than raw celecoxib. Similar results have been shown for dissolution studies. Solid state analyses showed glass solution state of celecoxib in PVP/Isomalt matrixes. FTIR studies exhibited the formation of hydrogen bonding between celecoxib and PVP in these samples. Spray dried celecoxib (amorphous celecoxib) without usage of carrier showed lower dissolution rate compare to its crystalline state (in 0.25 SDS dissolution medium) whilst these results is vise versa in Na3PO4 dissolution medium. Interestingly almost all samples exhibited higher dissolution rate (in 0.25 SDS) after storage in 75 humidity. XRPD analysis demonstrated the crystallization of amorphous celecoxib after 1 month storage. In general using PVP K30 and Isomalt as hydrophilic carriers could increase solubility and dissolution rate of celecoxib in solid dispersion formulations. (C) 2016 Elsevier B.V. All rights reserved.