Evaluation of USP apparatus 3 for dissolution testing of immediate-release products.
We sought to evaluate whether U.S. Pharmacopeia (USP) apparatus 3 can be used as an alternative to USP apparatus 2 for dissolution testing of immediate-release (IR) dosage forms. Highly soluble drugs, metoprolol and ranitidine, and poorly soluble drugs, acyclovir and furosemide, were chosen as model drugs. The dissolution profiles of both innovator and generic IR products were determined using USP apparatus 2 at 50 rpm and apparatus 3 at 5, 15, and 25 dips per minute (dpm). The dissolution profiles from USP apparatus 3 were compared to those from USP apparatus 2 using the f(2) similarity test. The dissolution profile from USP apparatus 3 generally depends on the agitation rate, with a faster agitation rate producing a faster dissolution rate. It was found that USP apparatus 3 at the extreme low end of the possible agitation range, such as 5 dpm, gave hydrodynamic conditions equivalent to USP apparatus 2 at 50 rpm. With appropriate agitation rate, USP apparatus 3 can produce similar dissolution profiles to USP apparatus 2 or distinguish dissolution characteristics for the IR products of metoprolol, ranitidine, and acyclovir. Incomplete dissolution was observed for the furosemide tablets using USP apparatus 3. Although it is primarily designed for the release testing of extended-release products, USP apparatus 3 may be used for the dissolution testing of IR products of highly soluble drugs, such as metoprolol and ranitidine, and some IR products of poorly soluble drugs, such as acyclovir. USP apparatus 3 offers the advantages of avoiding cone formation and mimicking the changes in physiochemical conditions and mechanical forces experienced by products in the gastrointestinal tract.
Yu
Lawrence X
LX
Food and Drug Administration, Office of Pharmaceutical Science, Rockville, MD 20857, USA. yul@cder.fda.gov
Wang
Jin T
JT
Hussain
Ajaz S
AS
D000212:Acyclovir / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000493:pharmacokinetics; D001682:Biological Availability; D004232:Diuretics / Q000493:pharmacokinetics; D005665:Furosemide / Q000493:pharmacokinetics; D006635:Histamine H2 Antagonists / Q000493:pharmacokinetics; D008790:Metoprolol / Q000493:pharmacokinetics; D011899:Ranitidine / Q000493:pharmacokinetics; D012995:Solubility; D013565:Sympatholytics / Q000493:pharmacokinetics; D013607:Tablets / Q000493:pharmacokinetics; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*; D013997:Time Factors
D000998:Antiviral Agents; D004232:Diuretics; D006635:Histamine H2 Antagonists; D013565:Sympatholytics; D013607:Tablets; D005665:Furosemide; D011899:Ranitidine; D008790:Metoprolol; D000212:Acyclovir