High failure rate of the dissolution tests for 500-mg amoxicillin capsules sold in Cambodia: is it because of the product or the test method?

Abstract

Summaryobjectives During the survey of substandard medicines in Cambodia in 2007, it was found that more than 90% of 500-mg amoxicillin (AMPC) capsules failed the United States Pharmacopeia (USP) 30 TEST 1 dissolution test. In the USP, several monographs provide multiple methods for performing the dissolution test. By using the 500-mg AMPC capsule as an example, we aimed to identify the problems and implications of the USP methods adopted for the dissolution test as a global standard. results All 500-mg AMPC capsules used for the comparison passed the quantitative test. Samples that passed the USP 28 and USP 30 TEST 2 dissolution tests were identical, and the pass rate was 97.1% (34 ⁄ 35), whereas the pass rate with the USP 30 TEST 1 was 8.6% (3 ⁄ 35). The difference in the dissolution results between the three methods was significant (P < 0.0001).conclusion This study revealed that many users would select the most stringent method when multiple methods exist in the USP. This may lead to a high failure rate of the tests. Because USP is a global standard, we recommend that it take into consideration the developing countries and create a more detailed user-friendly manual for selection for appropriate methods.

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Amoxicillin Trihydrate

“…There were 5 in vitro comparative dissolution studies conducted in an aqueous medium according to pharmacopeial methods. The first study, on 35 quality-tested amoxicillin 500 mg capsule products sold in Cambodia, used USP 30 TEST 1, USP 30 TEST 2, and USP 28 methods and showed a high-dissolution failure rate with respect to USP 30 TEST 1 91 (with a pass rate of only 8.6%). By contrast, the pass rate with the USP 30 TEST 2 was 97.1%, and with the USP 28 test, it was 97.1%.…”

“…By contrast, the pass rate with the USP 30 TEST 2 was 97.1%, and with the USP 28 test, it was 97.1%. 91 The second study, conducted with 9 generic brands of amoxicillin 500 mg capsules as well as the innovator product, was carried out according to USP 32, and the interchangeability was gauged by calculating difference and similarity factors. This study found only 2 brands which could show a difference factor (f 1 ) less than 15 and only 1 brand out of 9 which had a similarity factor (f 2 ) more than 50, indicating that most brands did not behave similarly to the innovator product.…”

A Comprehensive Analysis of Select Medicines Collected from Private Drug Outlets of Dhaka City, Bangladesh in a Simple Random Survey

“…The poor dissolution rates of the samples were a persistent problem, an observation which had previously been reported in our studies [56,57,60,61]. As an essential indicator of bioavailability and drug quality, the dissolution test has not been given as much attention as it deserves [58,62,63]. Despite the fact that all of the ESM samples contained the stated amount of API, a poor dissolution rate was observed in the buffer stage of the dissolution test in 10.9% of the ESM samples (Table 3; Figs.…”

Patient safety and public health concerns: poor dissolution rate of pioglitazone tablets obtained from China, Myanmar and internet sites

“…The ineffectiveness of these formulations could easily result in treatment failure. Drug dissolution testing is still being considered to be a minimal requisite in many pharmaceutical quality studies, given that the dissolution testing is one of the key parameter to observe the physicochemical changes in a solid formulation [47]. This study has several limitations.…”