Questions and Answers February 2018
William Brown and Margareth Marques
The following questions have been submitted by readers of Dissolution Technologies. Margareth Marques, Ph. D. and Will Brown, United States Phamacopeia, authored responses to each of the questions.
*Note: These are opinions and interpretations of the authors, and are not necessarily the official viewpoints of the USP
Email for correspondence: email@example.com
Q There is no recommended procedure in USP for the performance verification of USP apparatus 6 (rotating cylinder). The recommendation in the USP general chapter <724> Drug Release is to evaluate it using the same procedure as for USP apparatus 2 (paddle). Since the cylinders are not used in this evaluation, is it necessary to keep cylinders and vessels paired?
A Keeping the cylinders and vessels paired during the dissolution/drug release testing will facilitate the investigation of any deviations found during the testing.
Q Several USP monographs that have multiple dissolution tests always have the statement, “If the product complies with this test, the labeling indicates that it meets USP Dissolution Test X.” What does USP mean by labeling?
A This labeling requirement is only for products sold in the US. For products sold in other regions, the local regulatory agency needs to be contacted. In USP, the term labeling designates all labels and other written, printed, or graphic matter on an article's immediate container or on, or in, any package or wrapper in which it is enclosed, except any outer shipping container. Most companies display the information regarding the appropriate dissolution test in the leaflet.
Q Are there any limits for the evaluation of specificity/ selectivity in dissolution procedures?
A See USP General Chapter <1092> The Dissolution Procedure: Development and Validation, under section 5. Validation, 5.1 Specificity/Placebo Interference, where it is stated that any interference should not exceed 2%.
Q The quantitative procedure in a particular dissolution test is by spectrophotometric determination in the UV range. We observed negative absorbance values. Can we use them in the calculations?
A Negative absorbance values indicate that the composition of the sample and of the standard are different. Verify whether the spectrophotometer was zeroed with a blank with the appropriate composition and that the sample and standard solutions are made using the same solvents. The blank needs to have a similar composition as the sample solution, excluding the analyte.
Q What are the options to deaerate dissolution media?
A There is a procedure in the USP General Chapter <711> Dissolution, where the medium is heated under gentle agitation to 41 °C, then immediately filtered under a vacuum using a 0.45-µm filter or less while vigorous stirring, and continued stirring under a vacuum for about 5 min. The paper describes and discusses the pros and cons of various procedures that can be used to dearate dissolution media:
Degenhardt, O.S.; Waters, B.; Rebelo-Cameirao, A.; Meyer, A.; Brunner, H.; Nicholas P. Toltl, N. P., Comparison of the effectiveness of various deaeration techniques. Dissolution Technol. 2004, 11, 6-11. DOI: 10.14227/DT110104P6
Q We are developing a dissolution test for an orodispersible film. Preliminary tests were performed using the USP apparatus 1 (basket). Because the dimensions of the film exceed those of the basket, we would like to know possible alternatives to run this test. Can the film be bent to fit into the dimension of the basket? Can the film be cut and its weight considered in the calculation of the amount released? Can USP apparatus 2 be used with accessories to hold the film in place?
A While folding the film may complicate access by the medium to the entire surface of the film, an option may be to form a loose ring that conforms to the basket cylinder. Remember that dissolution tests should be run with the dosage form as close as possible to how it will be used by the patient. The dosage form can only be cut if the labeling states that the patient can cut it.
When developing dissolution procedures, you should always start using equipment described in pharmacopeias. You should consider evaluating the use of USP apparatus 5 and 6 and the paddle-over-extraction-cell described in the European Pharmacopoeia before looking for other alternatives. If they are not appropriate, the next step is to consider modifications of the compendial equipment.
Modifications will require appropriate justification. The use of non-compendial equipment is a last resource, but only if there are data to show that compendial apparatuses were not appropriate for the product. In any case, the discriminatory power of the method using noncompendial equipment will need to be demonstrated.