The objective of the present work undertaken was to enhance the solubility and dissolution rate of valsartan a poorly water soluble antihypertensive, by preparation of solid dispersion granules which would additionally allow easy compression into tablets. The dispersion granules were prepared using a hot melt granulation technique which involved preparation of a homogenous dispersion of valsartan in gelucire-50/13 melt, followed by its adsorption on to the surface of aeroperl-300pharma, an inert adsorbent. A two-factor, three-level (32) statistical design was implemented to quantitate the influence of gelucire-50/13 and aeroperl-300pharma on the dissolution profile and flow properties of the dispersion granules, where gelucire-50/13 and aeroperl-300pharma were chosen as independent variables, while dissolution and flow properties were chosen as dependent variables. The dispersion granules were characterized for their in-vitro dissolution rate and flow properties. An appropriate statistical model was arrived at and a significantly enhanced dissolution rate and flow properties were exhibited with the optimized formulation. The formulation was further characterized by FTIR, DSC, XRD and SEM analysis. FTIR spectrum revealed some drug excipient interactions. DSC and XRD data indicated the retention of amorphous form of valsartan. SEM confirmed the homogeneity and surface adsorption of the gelucire-50/13 melt on aeroperl-300pharma leading to enhanced surface area and thus dissolution rate. The tablets of optimized dispersion granules were formulated and evaluated. The in-vitro dissolution rate of these tablets was significantly better in comparison with marketed formulation. In conclusion the statistical model enabled us to understand the effects of formulation variables on the dispersion granules of valsartan.

Gastroesophageal reflux disease (GERD) is caused by excessive reflux of gastric content and duodenal bile into the esophagus, and impaired clearance of refluxate from the esophagus. In this perspective, raft-forming antireflux formulations offer better alternatives to the conventional therapies for treatment of uncomplicated GERD. In addition to the alginate-based systems, various natural polysaccharides have generated interest as raft-forming agents because of their bioadhesive/mucoprotective nature. Inclination of current therapy is towards natural products for healing of the disease, which also underlines the market potential of this class, demanding for thorough investigation and development of evaluation methods with better in vitro-in vivo correlation.

The potential of Compritol(®)888 ATO as a release modifier to retard the release of highly water soluble drug, metoprolol succinate (MPL) was exploited. Different ratios of Compritol(®)888 ATO versus MPL were utilized and the effect of various formulation methods was evaluated to sustain the release of MPL. MPL: Compritol(®)888 ATO in 1:2 ratio could successfully retard the release of MPL. Melt granulation method "as hot process" was found to be effective when compared to direct compression and wet granulation. The in vitro release characteristics of tablets were studied in pH 6.8 phosphate buffer at 50 rpm using USP Type II apparatus. Formulation F7 retarded MPL release with ~90% release after 20 h. Stability studies showed no significant difference (f2>50) in MPL release profile after three months of storage period at 25 ± 2°C/60 ± 5% RH and 40 ± 2°C/75 ± 5% RH. The bioavailability of sustained release tablets, F7 was compared with commercially available tablets, MetXL50 in 12 healthy human volunteers in a crossover design. Plasma concentration of MPL was determined using HPLC with fluorescence detector. IVIVC correlation was obtained by deconvoluting the plasma concentration-time curve using a model independent Wagner-Nelson method. Correlations of fraction of drug dissolved in vitro and fraction of drug absorbed in vivo displayed a significant linear relationship for sustained release tablets of MPL.

No abstract

Metoprolol succinate (MPL), a know cardioselective β-1 adrenergic blocker is widely used to treat cardiovascular diseases like angina pectoris, heart failure, myocardial infarction, hypertension, arrhythmias and others [1][2][3] . MPL is highly water soluble with a half life of 4-6 h which may lead to adverse effects on overdose like severe weakness, fainting, trouble in breathing and very slow heartbeat [4][5] . This resulted in development of sustained release (SR) formulations of MPL like Toprol-XL tablets composed of controlled release pellets which provides slow release of the drug. However, preparation of pellets is a complicated, tedious and time consuming process.Lipidic and polymeric materials are widely used to modulate the release of drugs from the pharmaceutical dosage forms to achieve greater safety and efficacy. Matrix tablets prepared using lipidic excipients are widely accepted due to their simplicity and ease of formulation. The release of drugs is modified by using and optimizing different ratios of the lipids and drugs. Compritol ® 888ATO (COM), a lipid excipient with IIG and GRAS status along with excellent tableting properties provides sustained and controlled release of drugs where in release mechanism is based on diffusion and erosion [6][7] . Considering