title: 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 0.04M Na3HPO4mediums 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 Na3PO4dissolution 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 1month storage. In general using PVP K30 and Isomalt as hydrophilic carriers could increase solubility and dissolution rate of celecoxib in solid dispersion formulations.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: royaghanavaty@yahoo.com.
authors.forename: Roya
authors.initials: R
authors.lastname: Ghanavati
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: az.taheri@pharm.mui.ac.ir.
authors.forename: Azade
authors.initials: A
authors.lastname: Taheri
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address: a.r.homayouni@gmail.com.
authors.forename: Alireza
authors.initials: A
authors.lastname: Homayouni
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D000068579:Celecoxib / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D004187:Disaccharides / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011205:Povidone / Q000031:analogs & derivatives* / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013402:Sugar Alcohols / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004187:Disaccharides; D004337:Drug Carriers; D013402:Sugar Alcohols; C077842:polyvinylpolypyrrolidone; C016640:Palatinit; D011205:Povidone; D000068579:Celecoxib
keywords: Celecoxib; Isomalt; PVP; Solid dispersion; Spray drying