Protein binding of glipizide using equilibrium dialysis technique: effects of hydrogen ion concentration, drug concentration and ionic strength

The objective of this research was to investigate the effects of hydrogen ion concentration, drug concentration and ionic strength on the binding affinity of glipizide to albumin protein. Different buffer solutions of different pH values (pH 6.7, 7.5 and 8.5), different drug concentrations (2.45 mg, 4.82 mg and 9.42 mg), and phosphate buffer solutions pH 7.5 of different ionic strength (0.1, 0.4 and 1.0) were prepared. The effects of pH, drug concentration and ionic strength on the amount of glipizide bounded to 0.25 g bovine albumin was investigated. As the pH of the solution was increased from pH 6.4 to pH 8.5, milligrams drug bounded to gram protein (r value) decreased from 8.2 mg to 3.84 mg/g protein. Also as the ionic strength of the solution was increased from 0.1 to 1.0, the r value decreased from 10.76 mg to 3.96 mg/g protein. However, the r value did not change significantly with increasing of drug from 2.45 mg to 9.42 mg/25 ml. The r value was 7.36 mg/g protein when concentration of the drug was 2.45 mg/25 ml and 7.4 mg/g protein when the concentration of the drug was 9.42 mg/25 ml. This study demonstrated that factors such as high pH and high ionic strength can alter drug-protein binding and consequently increase free drug in plasma and increase bioavailability of slightly water insoluble drug such as antidiabetic drugs.

Preliminary evaluation of glipizide spheres and compacts from spheres prepared by cross-linking technique

The objective of this research was to use the natural polymer Carrageenan to obtain controlled release spheres loaded with glipizide using the cross-linking technique. The effect of polymer level and drug load were investigated. The drug was dispersed in Carrageenan solution and the dispersion was dropped by a device containing 3 disposable syringes into cross-linking solution containing 3 calcium chloride. After 15 minutes residence time, the spheres were collected by decantation and dried in hot air oven at 38 degrees C +/- 2 degrees C for 24 hours. The dried spheres were successfully compacted into tablets using rotary Manesty B-3B machine equipped with 12/32 inches round flat face punches, target tablet weight was 400 mg +/- 5. As the polymer level was increased in the sphere formulation, the drug release rate was increased. However, as the drug level was increased in the sphere formulation, the release rate was decreased. This trend was also true for tablets compacted from spheres. The scanning electron microscope photographs supported the dissolution data. More cracks and rough surface were observed in tablets compacted from spheres containing high polymer level and low drug level.

Drug release from carbomer 934 matrices

The main objective of this investigation was to describe the mechanismof drug release from Carbomer 934 hydrogel matrices and to evaluate the effect of polymer level, diluent type, and matrix restriction using customized device (that permits only one surface of the tablet to be exposed to the dissolution medium) on theophylline release from Carbomer matrices. Formulations containing theophylline (10 percent), Carbomer (10 percent, 30, 50 percent), direct compressible diluent (lactose fast flo, Avicel PH-101, Emcompress) and magnesium stearate (0.75 percent) were compressed at a target tablet weight of 450 mg and target hardness of 7-9 Kp. USP Apparatus 1, was used to test the drug release and Korsmeyer equation was used to describe the mechanism of drug release from Carbomer matrices. Results show that the release profile and release mechanism from Carbomer matrices were influenced by Carbomer level, diluent type, and matrix restriction. In general the release mechanism was anomalous (non-Fickian) except for 10 percent and 30 percent Carbomer level and in Avicel PH-101 matrices, where, the release mechanism appears to follow super case II where, the n exponent has value greater than 0.89. All formulations selected appear to follow zero order release only up to 120 minutes. Restriction of tablet surface resulted in a shift toward Fickian release. This study demonstrated that it is possible to modify the drug release mechanism and rate, by changing polymer level, diluent type, and imposing physical restriction on the surface of the matrix.

Mechanisms of chlorpheniramine maleate release from hydrophilic swellable polymer systems

The main objective of this work is to attempt to understand better the mechanism of release of highly water soluble drugs from a swellable polymer and to quantify the amount of drug released. Tablets containing 10 per cent w/w drug, hydroxypropylmethylcellulose E4M (10 per cent w/w, 20 per cent w/w and 30 per cent w/w), 1 per cent w/w magnesium stearate and quantity sufficient to 100 per cent w/w with Lactose Fast Flo as diluent were prepared using the direct compression method. The amount of drug released due to Fickian diffusion and non-Fickian diffusion (polymer relaxation) was quantified at different time intervals. In order to determine if the drug release was Fickian diffusion or non-Fickian diffusion, the exponent n obtained from the equation: Mt/M yen = Ktn was calculated. It was found to be above 0.5 for restricted and unrestricted systems indicating non-Fickian diffusion. Also, the approximate contribution of Fickian diffusion and polymer relaxation to the non-Fickian anomalous release process was calculated. The data obtained from one tablet surface and all surfaces exposed to the dissolution medium demonstrated that Fickian diffusion predominated for the first hour. After one hour of testing dissolution, the relaxational mechanism predominated. The percent drug release from restricted matrices at 6 hours of dissolution testing was 77.9 per cent by polymer relaxation and 27.9 per cent by Fickian diffusion.

Controlled release of theophylline from inert matrices: effect of channeling material on release rate

Sustained release theophylline tablets containing stearic acid wax and lactose fast flo as chanelling agent were prepared and evaluated. The fusion technique was used for dispersing the drug in the different levels of stearic acid. The release rate of theophylline from the prepared tablets increased with the increase of the level of the channeling material in the formula. The drug release from tablets containing high level of wax (30 and 60 per cent ) and low level of channeling material (59 per cent and 29 per cent ) followed the diffusion controlled model for inert porous matrix. The drug release increased significantly with the increase of lactose fast flow level in the formula. After 2 hours of testing dissolution, the tablets start to erode and the mechanism of drug release deviate from the diffusion controlled model. The mechanism of drug release was dependent on the level of the channeling material in the matrix

Ethylcellulose as a carrier for controlled-release acetaminophen tablets

In this study ethylcellulose was evaluated as a carrier for preparation of prolonged release acetaminophen tablets. Solid dispersions containing three levels of ethylcellulose and acetaminophen (1:3; 1:1; 3:1) were prepared by the solvent method. Also physical mixtures at the same level of ethylcellulose and acetaminophen were prepared. Systems composed of solid dispersion or physical mixture containing the equivalent weight of 50 mg acetaminophen, Emcompress as diluent and 1 per cent magnesium stearate as lubricant were compressed into tablets and tested for dissolution. The dissolution data showed that the drug release decreased as the level of ethylcellulose increased in the solid dispersion formulations. The drug release from tablets prepared with solid dispersion followed the diffusion controlled model for inert porous matrix, while the drug release from tablets prepared with physical mixture followed the first-order kinetic model