Influence of Formulation Factors and Compression Force on Release Profile of Sustained Release Metoprolol Tablets using Compritol(®) 888ATO as Lipid Excipient.

Tablets containing metoprolol succinate and Compritol(®) 888ATO in the ratio of 1:2 yielded the desired sustained release profile in phosphate buffer pH 6.8 when evaluated using USP type II paddle apparatus and was selected as the optimized formulation. Robustness of optimized formulation was assessed by studying the effect of factors like varying source of metoprolol succinate and Compritol(®) 888ATO, compression force and hydroalcoholic dissolution medium on the release profile. No significant difference (P>0.05) in release profile was observed when metoprolol succinate from three different sources and Compritol(®) 888ATO from two different batches were used. Release profile of sustained release tablets of metoprolol succinate in media containing various concentrations of ethanol was comparable with media devoid of ethanol as evaluated by f2 test. This indicated that release profile of sustained release tablets of metoprolol succinate was reliable with no significant change due to variation in source of active pharmaceutical ingredient, particularly due to particle size distribution. Sustained release tablets of metoprolol succinate yielded release pattern within specifications irrespective of presence or absence of ethanol in the medium indicating that release properties of Compritol(®) 888ATO matrix are not affected by ethanol. Tablets compressed at compression force of <100 kg/cm(2) exhibited low hardness with total porosity of 15.39% and significantly increased (P<0.05) metoprolol succinate release as compared to tablets compressed at 2000 kg/cm(2) with 6.90% of total porosity revealing influence of compression force. Compritol(®) 888ATO holds great potential in providing reliable and controlled release profile of highly water soluble metoprolol succinate.

Compritol®888 ATO a lipid excipient for sustained release of highly water soluble active: formulation, scale-up and IVIVC study.

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.

Design, optimization, preparation and evaluation of dispersion granules of valsartan and formulation into tablets.

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.

Raft-forming agents: antireflux formulations.

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.