title: Preparation and characterization of fast dissolving flurbiprofen and esomeprazole solid dispersion using spray drying technique.
abstract: We aimed to develop an immediate-release flurbiprofen (FLU) and esomeprazole (ESO) combination formulation with enhanced gastric aqueous solubility and dissolution rate. Aqueous solubility can be enhanced by formulating solid dispersions (SDs) with a polyvinylpyrrolidone (PVP)-K30 hydrophilic carrier, using spray-drying technique. Aqueous and gastric pH dissolution can be achieved by macro-environmental pH modulation using sodium bicarbonate (NaHCO3) and magnesium hydroxide (Mg(OH)2) as the alkaline buffer. FLU/ESO-loaded SDs (FLU/ESO-SDs) significantly improved aqueous solubility of both drugs, compared to each drug powder. Dissolution studies in gastric pH and water were compared with the microenvironmental pH modulated formulations. The optimized FLU/ESO-SD powder formulation consisted of FLU/ESO/PVP-K30/sodium carbonate (Na2CO3) in a weight ratio 1:0.22:1.5:0.3, filled in the inner capsule. The outer capsule consisted of NaHCO3 and Mg(OH)2, which created the macro-environmental pH modulation. Increased aqueous and gastric pH dissolution of FLU and ESO from the SD was attributed to the alkaline buffer effects and most importantly, to drug transformation from crystalline to amorphous SD powder, clearly revealed by scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction studies. Thus, the combined FLU and ESO SD powder can be effectively delivered as an immediate-release formulation using the macro-environmental pH modulation concept.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Roshan
authors.initials: R
authors.lastname: Pradhan
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Tuan Hiep
authors.initials: TH
authors.lastname: Tran
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Sung Yub
authors.initials: SY
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Kyu Bong
authors.initials: KB
authors.lastname: Woo
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea.
authors.forename: Yong Joo
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea. Electronic address: csyong@yu.ac.kr.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea. Electronic address: jongohkim@yu.ac.kr.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D003890:Desiccation / Q000379:methods; D004339:Drug Compounding; D064098:Esomeprazole / Q000737:chemistry*; D005480:Flurbiprofen / Q000737:chemistry*; D005750:Gastric Juice / Q000737:chemistry; D011208:Powders; D054328:Proton Pump Inhibitors / Q000737:chemistry*; D012995:Solubility; D013535:Suspensions
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011208:Powders; D054328:Proton Pump Inhibitors; D013535:Suspensions; D005480:Flurbiprofen; D064098:Esomeprazole
keywords: Dissolution; Esomeprazole; Flurbiprofen; Solid dispersion; Solubility; Spray-drying