Effect of penetration enhancers on the permeability of ketoconazole gels through rabbit skin

The influence of several penetration enhancers on the percutaneous penetration of ketoconazole [KC] from hydroxypropylmethyl cellulose [HPMC], sodium carboxymethyl cellulose [NaCMC] and carbopol 934 gel formulations was investigated. Skin permeation studies were performed using Franz-type diffusion cells and full-thickness abdominal rabbit skin. Various types of compounds such as oleic acid [OA], menthol [M] and isopropyl myristate [IPM] in various concentrations were employed as penetration enhancers. The steady-state flux, permeability coefficients, and enhancement ratios ER of [offlux] KC for each formulation were calculated. The results showed that the skin permeability of KC from gels tested was significantly increased [P< 0.05] by 10% w/w OA, 5% w/w M and 5% w/w IPM. ER [flux] of KC gels containing 10% OA were 19.5, 16.4 and 11.9 for NaCMC, HPMC and carbopol gel respectively. ER [flux] of 5% w/w M were 13.5, 13.3 and 10.9 for HPMC, NaCMC and carbopol gel respectively. About 11 fold increase in the ER [flux] at 5% w/w IPM for all gels. Kinetic analysis of the data indicated that the permeation of [KC] from different gel formulations obeyed Higuchi-diffusion model. In conclusion, OA, M and IPM could be considered as penetration enhancers for KC topical formulations

Phonophoresis of theophylline through cellophane membrane and rabbit skin

The influence of ultrasound waves upon the permeation of theophylline through cellophane membrane and rabbit skin was studied in vitro. Sonication was carried out with continuous mode at intensities [0.5, 1, 1.5, and 2 W/cm 2 at constant frequency 800 KHz for one sr. Different gel formulations with [hydroxypropylmethyl cellulose, sodium carboxymethylcellulose and carbopol 934P] in different concentrations [1-4% w/w] were utilized. Phonophoresis of theophylline through rabbit skin were significantly less than that obtained with the cellophane membrane. Ultrasound application has showed a significant increase in the amount of theophylline permeation with increasing intensity. For all the tested gelling agents, the amount of drug released was decreased by increasing polymer concentrations. The Flux values were 5.99, 3.69 and 2.4 [micro g/min cm 2] for 2% HPMC, 4% Na CMC and 2% carbopol 934P gels respectively. It was found that drug release from HPMC gels obeys Zero-Order model while its release from Na CMC and carbopol 934P were fitted with First-Order and Higuchi-diffusion model respectively

Preparation of metronidazole microcapsules for sustained delivery

Metronidazole is widely used in the treatment of both intestinal and extra-intestinal amebiasis. However, conventional administration usually shows unpleasant taste, nausea, epigastric distress and stomatitis. To avoid these unwanted side effects, a multiple-emulsification technique was used in the preparation of metronidazole microsphere using a mixture of ethyl cellulose [EC] and methyl cellulose [MC] as a matrix. Methyl cellulose was added to enhance drugs release from ethyl cellulose matrix, because the drug has a relatively long t 1/2 [about 16 to 12 hours]. Particles size analysis results showed that the extent of size distribution was reduced with enhancing the stirring rate and the microcapsule size was reduced as the emulsifier concentration was increased up to 2% w/w. This was the optimum concentration of the emulsifiers required for the multiple emulsification. The results, also, showed no correlation between the HLB of the used emulsifiers and the microcapsule size. The in vitro drug release was studied and prolonged release were obtained where 80-90% of metronidazole was released within 6-8 hours depending on drug: polymer ratio. Further, an increase in the amount of water-soluble MC increased the drug released rate

Studies on microencapsulated granules: Effect of drug-binder solubilities and added diluents on core properties and microencapsulation characteristics

This work was designed to elucidate how drugs with various solubilities could behave when made into uniform core by granulation, microencapsulated and subjected to dissolution. Ascorbic acid and paracetamol [chosen as model drugs] were granulated with hydro- alcoholic solutions containing different amounts of water to allow for different degrees of drug solubilities. The porosities of the formed granules were measured and found to vary with drug solubilities in the granulating solutions. The granules were microencapsulated with ethylcellulose, then tested for their polymer contents which found to increase progressively with increasing core porosities. Corresponding decreases in drug release dc/dt and permeability constants P were also observed and their values depended on the presence of other insoluble or soluble diluents in the core materials. Although the release kinetics were apparently first order for the whole samples, yet the duration of the linear segments in the dissolution curves were more pronounced for the less porous cores regardless of the drug being used. An extended investigation on microencapsulated granules of fixed porosities prepared by dry granulation [slugging] has proved the above findings