Studies of variability in dissolution testing with USP apparatus 2.

In this study, gauge repeatability and reproducibility (gauge R&R) was used to analyze variability for USP apparatus 2 dissolution measurement systems. Experiments were designed to assess the variability due to apparatus, operator, and sample tablet. Since dissolution testing is a destructive test, a nested model was used for data analysis. Additionally, perturbation tests with both disintegrating and nondisintegrating tablets were performed to study the variability due to sample position within the dissolution vessel. For the gauge R&R study, two well-trained chemists used two mechanically calibrated USP apparatus 2 units. Six tests were performed by each operator on each apparatus. Evaluation of dissolution test results at 30 min using an internal DPA calibrator tablet NCDA#2 (10 mg prednisone) indicates that the main contribution to the total variance, approximately 70%, is due to the sample tablets, approximately 25% is from the apparatus and approximately 5% is due to the operators. There is no significant difference between operators and apparatuses as shown by the gauge R&R studies. In addition, dissolution results can be strongly affected by the position of the tablet within the vessel. Similarity (f1) and dissimilarity (f2) factors were calculated to statistically evaluate differences between perturbed and normal dissolution tests.

Quality assessment of internet pharmaceutical products using traditional and non-traditional analytical techniques.

This work investigated the use of non-traditional analytical methods to evaluate the quality of a variety of pharmaceutical products purchased via internet sites from foreign sources and compared the results with those obtained from conventional quality assurance methods. Traditional analytical techniques employing HPLC for potency, content uniformity, chromatographic purity and drug release profiles were used to evaluate the quality of five selected drug products (fluoxetine hydrochloride, levothyroxine sodium, metformin hydrochloride, phenytoin sodium, and warfarin sodium). Non-traditional techniques, such as near infrared spectroscopy (NIR), NIR imaging and thermogravimetric analysis (TGA), were employed to verify the results and investigate their potential as alternative testing methods. Two of 20 samples failed USP monographs for quality attributes. The additional analytical methods found 11 of 20 samples had different formulations when compared to the U.S. product. Seven of the 20 samples arrived in questionable containers, and 19 of 20 had incomplete labeling. Only 1 of the 20 samples had final packaging similar to the U.S. products. The non-traditional techniques complemented the traditional techniques used and highlighted additional quality issues for the products tested. For example, these methods detected suspect manufacturing issues (such as blending), which were not evident from traditional testing alone.

In vitro dissolution of oral modified-release tablets and capsules in ethanolic media.

In 2005, Palladone, an extended-release capsule, was withdrawn from the market after clinical testing showed subjects who took the product with alcohol had increased levels of drug in their blood. To better understand this phenomenon, we studied the in vitro drug release of 27 oral modified-release products in alcohol-containing media. In 40% alcoholic medium, 9 of 10 capsules and 2 of 17 tablets show accelerated drug release. When a high percentage of the total dose is released in a short period of time, the extended-release product is then performing like an immediate release formulation. Products were also tested in 5% and 20% alcoholic media and in simulated gastric fluid (without enzyme) containing 20% alcohol. No tested capsules or tablets exhibited a significant increase in drug release in media containing only 5% alcohol. The current study indicates that in vitro dissolution may provide evidence regarding the ruggedness of formulations to ingested alcohol.