methylcellulose and alfuzosin

Multiparticulate floating drug delivery systems have proven potential as controlled-release gastroretentive drug delivery systems that avoid the "all or none" gastric emptying nature of single-unit floating dosage forms. An objective of the presence investigation was to develop calcium silicate (CaSi)/calcium alginate (Ca-Alg)/hydroxypropyl methylcellulose (HPMC) mucoadhesive-floating beads that provide time- and site-specific drug release of alfuzosin hydrochloride (Alf). Beads were prepared by simultaneous internal and external gelation method utilizing 3(2) factorial design as an experimental design; with two main factors evaluated for their influence on the prepared beads; the concentration of CaSi as floating aid (X (1)) and the percentage of HPMC as viscosity enhancer and mucoadhesive polymer (X (2)), each of them was tested in three levels. Developed formulations were evaluated for yield, entrapment efficiency, particle size, surface topography, and buoyancy. Differential scanning calorimetry, Fourier transform infrared spectroscopy, in vitro drug release, as well as in vitro mucoadhesion using rat stomach mucosal membrane were also conducted. Percentage yield and entrapment efficiency ranged from 57.03% to 78.51% and from 49.78% to 83.26%, respectively. Statistical analysis using ANOVA proved that increasing the concentration of either CaSi or HPMC significantly increased the beads yield. Both CaSi and HPMC concentrations were found to significantly affect Alf release from the beads. Additionally, higher CaSi concentration significantly increased the beads diameter while HPMC concentration showed significant positive effect on the beads mucoadhesive properties. CaSi/Ca-Alg/HPMC beads represent simple floating-mucoadhesive gastroretentive system that could be useful in chronopharmacotherapy of benign prostatic hyperplasia.

Topics: Animals; Calcium Compounds; Chemistry, Pharmaceutical; Drug Delivery Systems; Gastrointestinal Tract; Hypromellose Derivatives; Male; Methylcellulose; Quinazolines; Rats; Silicates; Tissue Adhesives

We have assessed the kinetics of drug release in relation to the full or partial hydration and swelling of matrices under standard and modified United States Pharmacopeia (USP) apparatus II using a novel index, defined as the symmetrical shape factor. The symmetrical shape factor describes the regularity of the hydration rate of the matrix perimeter relative to its central regions.. Monolithic and three-layer matrices based on hypromellose, polyethylene oxide, Kollidon SR, theophylline, diltiazem hydrochloride and alfuzosin hydrochloride were subjected to dissolution testing.. Our results indicated that Kollidon SR matrices and the three-layer composite systems with and without effervescing components were not significantly affected by the dissolution conditions. However, in the case of the floating monolithic systems based on hypromellose and polyethylene oxide, both release profiles and swelling dynamics in accordance with the similarity factor (f(2)) and symmetrical shape factor values were significantly influenced.. The symmetrical shape factor values were positively impacted. Consequently the drug release kinetics were more predictable and reproducible. The modified USP method resulted in a more synchronized axial and radial swelling with symmetrical shape factor values approaching unity. Data further indicated that the modified USP method provided for complete matrix hydration and swelling as the dosage form remained fully submerged, allowing for more reliable release mimicking the in-vivo conditions.

Topics: Delayed-Action Preparations; Diltiazem; Drug Carriers; Excipients; Hypromellose Derivatives; Kinetics; Methylcellulose; Polyethylene Glycols; Povidone; Quinazolines; Solubility; Tablets; Technology, Pharmaceutical; Theophylline

A composite gastro-retentive matrix for zero-order delivery of highly soluble drug alfuzosin hydrochloride (10mg) has been designed and characterized. Two systems containing polyethylene oxide (PEO), hydroxypropylmethylcellulose (HPMC), sodium bicarbonate, citric acid and polyvinyl pyrrolidone were dry blended and compressed into triple layer and bi-layer composite matrices. Dissolution studies using the USP 27 paddle method at 100 and 50rpm in pH 2.0 and 6.8 were performed using UV spectroscopy at 244nm, with automatic sampling over a 24h period using a marketed product as a reference to calculate the "f(2)" factor. Textural characteristics of each layer, the composite matrix as a whole, and floatation potential were determined under conditions similar to dissolution. Percent matrix swelling and erosion along with digital images were also obtained. Both systems proved to be effective in providing prolonged floatation, zero-order release, and complete disentanglement and erosion based on the analysis of data with "f(2)" of 68 and 71 for PEO and HPMC based systems, respectively. The kinetics of drug release, swelling and erosion, and dynamics of textural changes during dissolution for the designed composite systems offer a novel approach for developing gastro-retentive drug delivery system that has potential to enhance bioavailability and site-specific delivery to the proximal small intestine.

Topics: Adrenergic alpha-Antagonists; Cellulose; Delayed-Action Preparations; Drug Delivery Systems; Excipients; Hydrogen-Ion Concentration; Hypromellose Derivatives; Mechanics; Methylcellulose; Polyethylene Glycols; Polymers; Quinazolines; Tablets; Water

The present study is an attempt to formulate a controlled-release matrix tablet formulation for alfuzosin hydrochloride by using low viscous hydroxy propyl methyl cellulose (HPMC K-100 and HPMC 15cps) and its comparison with marketed product. Different batches of tablets containing 10 mg of alfuzosin were prepared by direct compression technique and evaluated for their physical properties, drug content, and in vitro drug release. All the formulations had a good physical integrity, and the drug content between the batches did not vary by more than 1%. Drug release from the matrix tablets was carried out for 12 hr and showed that the release rate was not highly significant with different ratios of HPMC K-100 and HPMC15cps. Similar dissolution profiles were observed between formulation F3 and the marketed product throughout the study period. The calculated regression coefficients showed a higher r2 value with zero-order kinetics and Higuchi model in all the cases. Although both the models could be applicable, zero-order kinetics seems to be better. Hence, it can be concluded that the use of low viscous hydrophilic polymer of different grades (HPMC K-100 and HPMC 15cps) can control the alfuzosin release for a period of 12 hr and was comparable to the marketed product.

Topics: Adrenergic alpha-Antagonists; Analysis of Variance; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Compounding; Hypromellose Derivatives; Methylcellulose; Quinazolines; Tablets; Viscosity