Abstract. The objectives were to characterize propranolol hydrochloride-loaded matrix tablets using guar gum, xanthan gum, and hydroxypropylmethylcellulose (HPMC) as rate-retarding polymers. Tablets were prepared by wet granulation using these polymers alone and in combination, and physical properties of the granules and tablets were studied. Drug release was evaluated in simulated gastric and intestinal media. Rugged tablets with appropriate physical properties were obtained. Empirical and semi-empirical models were fit to release data to elucidate release mechanisms. Guar gum alone was unable to control drug release until a 1:3 drug/gum ratio, where the release pattern matched a Higuchi profile. Matrix tablets incorporating HPMC provided near zero-order release over 12 h and erosion was a contributing mechanism. Combinations of HPMC with guar or xanthan gum resulted in a Higuchi release profile, revealing the dominance of the high viscosity gel formed by HPMC. As the single rate-retarding polymer, xanthan gum retarded release over 24 h and the Higuchi model best fit the data. When mixed with guar gum, at 10% or 20% xanthan levels, xanthan gum was unable to control release. However, tablets containing 30% guar gum and 30% xanthan gum behaved as if xanthan gum was the sole rate-retarding gum and drug was released by Fickian diffusion. Release profiles from certain tablets match 12-h literature profiles and the 24-h profile of Inderal ® LA. The results confirm that guar gum, xanthan gum, and HPMC can be used for the successful preparation of sustained release oral propranolol hydrochoride tablets.
Drug release from polymeric matrix systems is the rate-limiting step for drug bioavailability and is determined by drug solubility; most drugs show pH-dependent solubility. Polymeric matrices remain in the gastrointestinal tract for a longer period of time and are exposed to environments of varying pH, which can adversely affect drug release. In the present study, the pH-independent drug release of domperidone was achieved by modifying the microenvironmental pH of a swollen polymeric matrix using acidic excipients (citric acid and tartaric acid). Matrices were prepared by a water-based, wet-granulation technique and evaluated for various official and unofficial parameters. In vitro drug release was studied using USP dissolution apparatus and pH 6.80 phosphate buffer as dissolution medium. Release kinetics was evaluated according to various mathematical models.Results show that domperidone release can be effectively modified by inclusion of acidic excipients in the formulations. Acidic excipients modulated microenvironmental pH and avoided the effect of dissolution medium pH on drug release. The resultant formulations are easy to prepare and scale up for commercial manufacturing. Better pH-independent release, following zero-order kinetics, was achieved with tartaric acid.
Intrinsic dissolution testing has been applied for characterization of pure API with respect to its dissolution behavior. The effect of formulation factors and processing parameters on dissolution rate is evaluated by dissolution testing of the final product, which is a time and resource-consuming process. Our objective was to use intrinsic dissolution testing for determining the effect of processing parameters on drug release. In the present study, an intrinsic dissolution testing method was developed for atenolol and validated according to the standard guidelines using USP-recommended dissolution media. Various experimental variables (compaction pressure and rotation speed of the disk) were optimized by studying at three levels. Atenolol was subjected to granulation in a super mixer granulator by applying standard wet granulation protocols. Granulation time and binder concentration were taken as process variables while dissolution rate was a response variable. Dissolution media had no interference with sample analysis, and all validation parameters for the developed method were in an acceptable range (%RSD > 1). The intrinsic dissolution rate of atenolol (1.84 ± 0.13 mg/cm 2 min) was high due to its better solubility in dissolution media. The dissolution rate of atenolol was decreased by granulating with PVP under different conditions. We concluded that intrinsic dissolution testing method can be applied for determining the effect of processing parameters on dissolution rate of the API at the pre-compression level. This method will reduce experimentation for optimization of dissolution rate and will spare time and resources.
Hydralazine hydrochloride is an antihypertensive used alone or in combination with isosorbide nitrate for the treatment of congestive heart failure. Since control of blood pressure should be continuous, sustained release delivery of this drug is considered therapeutically beneficial. Core beads for oral administration of this drug were prepared by extrusion-spheronization. Using experimental design to define the coat that was applied, the core beads were coated using a fluid bed coater to different coat thickness with combinations of two commercially available products dissolved in a hydroalcoholic solvent. The coat is a film with a combination of ethylcellulose and hydroxypropylcellulose that can provide desirable release profiles. Visually spherical and rugged bead products were obtained. Two products were identified that exhibited essentially a zero order release profile following a 2-h lag time with release of greater than 70% of the drug over the next 10 h in simulated intestinal fluid.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.