[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to make use of small size of immediate-release (IR) pellet and amorphous state of solid dispersion to increase solubility of celecoxib (CLX), a drug in BCS class II. Primary, binary and ternary solid dispersions were developed to choose the final components for solid dispersion. A ternary novel solid dispersion was prepared by incorporation of one aqueous soluble polymer (povidone k17; PVP 17PF), Methacrylate copolymer-based gastric soluble polymer (Eudragit® EPO) and one pH modulator (MgO). This combination was effective to increase solubility in pH 1.2 up to 25–30 %. The mechanism of solubility enhancement was proven by DSC, PRXD, and FT-IR. Accordingly, hydrogen bonding or electrostatic interaction of CLX with PVP/Eudragit® EPO was the main cause to form the amorphous state of CLX within polymer cluster which increasing solubility of drug. Besides, MgO played an important role to change microenviroment for solid dispersion. Pellets containing this solid dispersion were prepared by extrusion and spheronization technique. Effect of four kinds of additive (calcium hydrogen phosphate dihydrate, NaHCO3, crospovidone, and sodium dodecyl sulfate) on dissolution of CLX from IR pellet was also determined. Because of highest dissolution rate, formulation using sodium dodecyl sulfate was used for pharmacokinetics study. Solid dispersion-IR pellet formulation presented bioequivalence and lower variability in comparison with reference product.
Journal of Pharmaceutical Investigation. 06/2012; 42(3).
[Show abstract][Hide abstract] ABSTRACT: This study was conducted primarily to improve the solubility of rebamipide, a poorly water-soluble anti-ulcer drug, using novel ternary solid dispersion (SD) systems and secondly to evaluate the effect of solubility enhancement on its pharmacokinetic (PK) and pharmacodynamic (PD) profile. After dissolving the three components in aqueous medium, ternary SD containing the drug, sodium hydroxide (NaOH) and PVP-VA 64 was achieved by spray drying method, which was used as primary SD. Poloxamer 407, a surfactant polymer, was incorporated in this primary SD by four different methods: co-grinding, physical mixing, melting or spray drying. SD was then characterized by dissolution test, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR). The spray dried SD of poloxamer 407 together with primary SD displayed highest dissolution rate of the drug of about 70% after 2 h. DSC, PXRD and FT-IR characterized the amorphous state and molecular dispersion of the drug in the SD. PK and PD studies in Sprague-Dawley rats revealed that the bioavailability of the drug using optimal SD was about twofold higher than that of reference product, and the irritation area of stomach was significantly reduced in the ulcer-induced rat model using optimal SD as compared to the reference product.
Drug Development and Industrial Pharmacy 04/2012; · 2.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rebamipide, a novel anti-ulcer agent, is listed in biopharmaceutics classification class IV because of its low aqueous solubility and permeability. Consequently, the bioavailability of rebamipide is under 10% in humans. The aim of this study was to increase the solubility and determine the effect of solubility enhancement on the bioavailability and efficacy of rebamipide (RBM).
After taking into account the physiochemical properties of RBM (solubility, melting point, dosage etc.), solid dispersion was chosen as the solubility enhancement method. A rebamipide solid dispersion system containing the drug, l-lysine, PVP-VA 64 and poloxamer 407 was obtained from a spray-drying method. Solubility enhancement of RBM from the solid dispersion was determined by a dissolution test in 900 ml at pH 1.2. The bioavailability and efficacy of RBM solid dispersion were evaluated in a rat model.
The aqueous solubility of RBM was improved 62.17 times by solid dispersion. The oral bioavailability of the drug was also increased 1.74-fold from solid dispersion compared with the reference product in a rat model. With regard to the anti-ulcer effect, the percentage inhibition of the solid dispersion was 2.71 times higher than that of the reference product in the ulcer-induced rat model.
A solid dispersion of rebamipide was successfully formulated using the spray-drying method. Bioavailability and efficacy of rebamipide were increased significantly by solubility enhancement of the drug.
The Journal of pharmacy and pharmacology. 12/2011; 63(12):1539-47.