In Vitro and In Vivo Studies on Chitosan Beads of Losartan Duolite AP143 Complex, Optimized by Using Statistical Experimental Design

The aim of the present research work was to develop release modulated beads of losartan potassium complexed with anion exchange resin, Duolite AP143 (cholestyramine). Chitosan was selected as a hydrophilic polymer for the formation of beads which could sustain the release of the drug up to 12 h, along with drug resin complex (DRC). Chitosan beads were prepared using an in-liquid curing method by ionotropic cross-linking or interpolymer linkage with sodium tripolyphosphate (TPP). The formulation of the beads was optimized for entrapment efficiency and drug release using 32 full factorial design. The independent variables selected were DRC/chitosan and percent of TPP. The optimization model was validated for its performance characteristics. Studies revealed that as the concentration of chitosan and TPP was increased, entrapment efficiency and the drug release were found to increase and decrease, respectively. The swelling capacity of chitosan–TPP beads decreased with increasing concentration of TPP. The effect of chitosan concentration and percentage of TPP solution used for cross-linking on entrapment efficiency and drug release rate was extensively investigated. Optimized beads were subjected to in vivo studies in Wistar albino rats to determine the mean arterial blood pressure and compared with marketed formulation. The pharmacodynamic study demonstrates steady blood pressure control for optimized formulation as compared to fluctuated blood pressure for the marketed formulation

Formulation and development of floating capsules of celecoxib: In vitro and in vivo evaluation

The objective of the present study was to develop a hydrodynamically balanced system for celecoxib as single-unit floating capsules. Various grades of low-density polymers were used for formulation of these capsules. The capsules were prepared by physical blending of celecoxib and the polymer in varying ratios. The formulation was optimized on the basis of in vitro buoyancy and in vitro release in citrate phosphate buffer pH 3.0 (with 1% sodium lauryl sulfate). Capsules prepared with polyethylene oxide 60K and Eudragit RL100 gave the best in vitro percentage release and were used as the optimized formulation. By fitting the data into zero-order, first-order, and Higuchi models, we concluded that the release followed zero-order kinetics, as the correlation coefficient (R value) was higher for zero-order release. For gamma scintigraphy studies, celecoxib was radiolabeled with technetium-99m by the stannous reduction method. To achieve the maximum labeling efficiency the process was optimized by studying the reaction at various pH conditions and stannous concentration levels. The radiolabeled complex was added to the optimized capsule, and dissolution studies were performed to ensure that there was no leaching of radioactivity from the capsules. Gamma imaging was performed in rabbits to assess the buoyancy of the optimized formulation. The optimized formulation remained buoyant during 5 hours of gamma scintigraphic studies in rabbits

Effect of hydrophilic swellable polymers on dissolution enhancement of carbamazepine solid dispersions studied using response surface methodology

The objective of this work was to study dissolution enhancement efficiency and solid dispersion formation ability of hydrophilic swellable polymers such as sodium carboxymethyl cellulose (Na-CMC), sodium starch glycolate (SSG), pregelatinized starch (PGS), and hydroxypropylmethyl cellulose (HPMC) with carbamazepine using 32 full factorial design for each of the polymers. Solid dispersions of carbamazepine were prepared using solvent evaporation method with around 70% solvent recovery. The independent variables were the amount of polymer and organic solvent. The dependent variables assessed were percentage drug dissolved at various time points and dispersion efficiency (ie, in terms of particle size of solid dispersion). Solid dispersions were evaluated for percentage drug dissolved, wettability, differential scanning calorimetry, scanning electron microscopy, and angle of repose. Multiple linear regression of results obtained led to equations, which generated contour plots to relate the dependent variables. Similarity factor and mean dissolution time were used to compare dissolution patterns obtained in distilled water and simulated gastric fluid United States Pharmacopeia (USP) XXVI of pH 1.2. Maximum drug dissolution was obtained with polymer order Na-CMC>SSG>PGS>HPMC. Particle size of drug was reduced ≈ 10–15, 3–5, 5–7, and 10–25 times in Na-CMC, SSG, PGS, and HPMC solid dispersions, respectively; whereas wettability of solid dispersions was found in the order of Na-CMC>HPMC>PGS>SSG. Angle of repose was found to be in the range of 29° to 35° for all solid dispersions, which shows good flowability characteristics. HPMC showed increase in drug dissolution up to an optimized level; however, furthers increase in its concentration decreased drug dissolution