Influence of higher rates of agitation on release patterns of immediate-release drug products.
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.
Shah
V P
VP
Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD 20857.
Gurbarg
M
M
Noory
A
A
Dighe
S
S
Skelly
J P
JP
D002738:Chloroquine / Q000008:administration & dosage / Q000737:chemistry; D006118:Griseofulvin / Q000008:administration & dosage / Q000737:chemistry; D006886:Hydroxychloroquine / Q000008:administration & dosage / Q000737:chemistry; D007520:Isocarboxazid / Q000008:administration & dosage / Q000737:chemistry; D011319:Primaquine / Q000008:administration & dosage / Q000737:chemistry; D011786:Quality Control; D012995:Solubility; D013411:Sulfadiazine / Q000008:administration & dosage / Q000737:chemistry; D013607:Tablets / Q000737:chemistry*
D013607:Tablets; D013411:Sulfadiazine; D006118:Griseofulvin; D007520:Isocarboxazid; D006886:Hydroxychloroquine; D002738:Chloroquine; D011319:Primaquine