Effect of penetration enhancers on the transdermal delivery of isradipine through excised rabbit skin

Transdermal delivery is proposed for the calcium channel blocker isradipine, to overcome its poor oral bioavailability caused mainly by extensive first pass metabolism. This drug is approved for the treatment of angina pectoris and hypertension. In this study, the effect of penetration enhancers on the permeation of isradipine through rabbit skin was studied utilizing improved Franz diffusion cells. Three penetration enhancers including oleic acid, azone and 1, 8-cineole at three concentrations [2.5, 5.0 and 10% w/v] were investigated at drug concentration of 20 mg/ml in presence of propylene glycol as a vehicle. Results of the penetration enhancer permeability studies revealed that for all enhancers studied, increasing the enhancer concentration lead to a linear increase in the amount diffused. In addition, at 10% penetration enhancer concentration, the cumulative amount diffused over 24 hour period [Mean +/- SEM] was calculated to be 22965 +/- 4490, 12617 +/- 902, 10917 +/- 950 ng for oleic acid, azone and cineole, respectively compared to the control calculated to be 794 +/- 75 ng. This clearly shows that among the different enhancers studied, oleic acid at a concentration of 10% resulted in the highest amount of isradipine diffusing through the rabbit skin. Permeation parameters namely: steady state flux, enhancement factor and permeability coefficient were also calculated in presence and absence of enhancers [control]. Results showed enhancement factors [Mean +/- SEM] of 28.9 +/- 8.08, 14.3 +/- 1.09 and 12.7 +/- 1.47 for oleic acid, azone and cineole, respectively with oleic acid showing highest diffusion enhancement. The permeability coefficient [P] data revealed similar trend. These results clearly indicate that the penetration enhancers tested succeeded in significantly increasing diffusion of isradipine through skin which affirms the feasibility of using a transdermal delivery system for isradipine for treatment of angina pectoris and hypertension

Brand and generic medications: are they interchangeable?

Generic substitution has become a common practice since the late 1970s in the United States. At that time, many of these generics caused bioavailability problems, which fueled suspicions about their efficacy and safety, and the Food and Drug Administration [PDA] standards for bioequivalence. In Saudi Arabia, the increasing number of local products raised several concerns with regard to switching from brands to generics. Our objective was to review and examine the basis of the controversy surrounding brand and generic interchangeability and to explore a practical approach in pursuing a switch. Articles indexed initially under terms such as generic medications, generic substitution, bioequivalence and bioinequivalence were identified. These terms were used to search the indexing service, MEDLINE [1966-2006]. References from the extracted articles, and additional data sources, including the Code of Federal Regulations and Regulatory Guidance from the FDA Center for Drug Evaluation and Research were also reviewed. For most drugs, bioequivalence testing generally should enable clinicians to routinely substitute generic for innovator products. However, for narrow therapeutic, critical dose drugs, or for highly variable drugs, safe switching between products cannot be assured. These drugs need special precautions and blood level monitoring upon switching. FDA firmly believes that approved generic and brand drugs can be dispensed with the full expectation that the consumer will receive the same clinical benefit. Performing the switch process is an advisable practice to reduce health care costs in countries with strong post-marketing surveillance program, but caution is to be exercised when narrow therapeutic index drugs or highly variable drugs are prescribed

Effects of sphere size, polymer to drug ratio and plasticizer concentration on the release of theophylline from ethylcellulose microspheres

Theophylline sustained release microspheres were prepared by applying the non-solvent addition method. The in-vitro release of the drug from the prepared microspheres of different size ranges [