Shah V P, Gurbarg M, Noory A, Dighe S, Skelly J P
Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD 20857.
J Pharm Sci. 1992 Jun;81(6):500-3. doi: 10.1002/jps.2600810604.
The dissolution procedure serves as a quality control test to assure batch-to-batch uniformity and bioequivalence of a product once the bioavailability of the product has been established. It can also be used to detect manufacturing and/or process variations that could reduce product bioavailability. Dissolution testing must be conducted at an appropriate agitation rate. Tests conducted at high agitation rates may lose the ability to differentiate between good and bad products. Although the effect of high agitation rates has been known for some time, several immediate-release drug products still have United States Pharmacopeia (USP) monograph dissolution procedures that require very high agitation rates. A systematic survey was conducted on marketed tablets of chloroquine phosphate, griseofulvin, hydroxychloroquine sulfate, isocarboxazide, primaquine phosphate, and sulfadiazine. Each of these products has a USP monograph requiring a dissolution test at a paddle speed of 100 rpm. To study the influence of agitation rate on the dissolution rate of these products, dissolution studies were conducted at paddle speeds of 50, 75, and 100 rpm with the USP apparatus 2 (paddle method). The dissolution rate increased with an increase in the agitation rate from 50 to 75 rpm. However, no significant increase in the dissolution rate was noted with an increase in the agitation rate from 75 to 100 rpm. The data support the position that the higher agitation rate of 100 rpm is not necessary for a quality control procedure or a compendial standard for the products tested.
一旦确定了产品的生物利用度，溶出度测定程序可作为一种质量控制测试，以确保产品批次间的一致性和生物等效性。它还可用于检测可能降低产品生物利用度的生产和/或工艺变化。溶出度测试必须以适当的搅拌速率进行。在高搅拌速率下进行的测试可能会失去区分优质产品和劣质产品的能力。尽管高搅拌速率的影响已经为人所知一段时间了，但仍有几种速释药品的美国药典（USP）专论溶出度测定程序要求非常高的搅拌速率。对市售的磷酸氯喹、灰黄霉素、硫酸羟氯喹、异卡波肼、磷酸伯氨喹和磺胺嘧啶片剂进行了系统调查。这些产品中的每一种都有USP专论，要求在桨板转速为100转/分钟的条件下进行溶出度测试。为了研究搅拌速率对这些产品溶出速率的影响，使用USP装置2（桨板法）在桨板转速为50、75和100转/分钟的条件下进行了溶出度研究。溶出速率随着搅拌速率从50转/分钟增加到75转/分钟而增加。然而，随着搅拌速率从75转/分钟增加到100转/分钟，未观察到溶出速率有显著增加。数据支持这样的观点，即对于所测试的产品，100转/分钟的较高搅拌速率对于质量控制程序或药典标准来说并非必要。
