Comparative assessment of the quality control measurements of ofloxacin innovator and generic drugs present in the lebanese market
Ofloxacin is a well known synthetic second generation fluoroquinolone with a broad antimicrobial spectrum against Gram positive and Gram negative bacteria. Ofloxacin is marketed by several different manufacturers in Lebanon. The availability of multisource generic drug products, with the scope of improving health care delivery to patients via competitive drug pricing, has its attendant problem of ascertaining their quality and interchangeability. The innovator drug product of Ofloxacin is marketed by Sanofi-Aventis under the trade name Tarivid®. Since the patent rights of Tarivid® expired, many generics have been produced by different manufacturers with highly competitive prices. The study was conducted to assess the quality of the Ofloxacin generics available in Lebanon, because the presence of multisource drugs in the Lebanese market poses a serious challenge to physicians and health care professionals. In the present work, different quality control procedures have been studied which includes weight uniformity, hardness, friability, dimensions, disintegration, dissolution, content uniformity, and assay. In addition, the inhibition zone diameter was measured for the different brands. With regard to the hardness test, it was done only for OFXG002 as it was the only brand with uncoated Ofloxacin tablets, the result of its hardness was 4.33kg/cm2 which lies within 4-8 kg/cm2; that of the friability test were less than 1% with the maximum value being 0.19%; that of the disintegration test were less than 15 minutes even for the coated tablets due to the presence of crosscarmelose sodium a superdisintegrant in their composition. All of these previous results comply with USP specifications. The uniformity of weight determination for the four brands gave values that comply with USP specification for tablets weighing greater than 250mg, with a deviation less than 5% from the mean value. With respect to the dissolution rate test in SGF, All brands complied with USP specifications and showed greater than 80% dissolution at 30 minutes. However, there was a wide variation in the dissolution rate profile of the four brands at different time points (10, 20 and 30 minutes).OFXG001 and OFXG002 showed very rapid dissolution rate with almost 41 complete dissolution at 5 minutes and a significantly greater dissolution rate than the innovator.OFX003 had very similar, statistically non significant dissolution rate profile when compared to the innovator. Tarivid® and OFXG003 had slower dissolution profiles than OFXG001and OFXG002 owing to the presence of hydrophobic excipients that delay water penetration into the tablets and hence their dissolution. For the content uniformity test results, the percentage recovery of all brands was within 90-110% of the labeled claim and hence conforming to USP specifications. However, for the assay test, all brands except OFXG001 complied with the pharmacopoeial limit. The assay percentage recovery of OFXG001 was 111.3% ± 0.71 lying outside the accepted limit of 90-110% of the labeled claim. Therefore all brands proved to meet the quality standards of USP except for OFXG001 that fell short of the pharmacopoeial standard in this study. Although all generic brands except OFXG001 comply with USP specifications and despite the fact that Ofloxacin doesn’t belong to narrow therapeutic index drugs, interchangeability between Tarivid® and the two generics during course of therapy is not an advisable approach due to significant differences in the results obtained. These significant differences may result in different pharmacokinetic profiles and different drug plasma level amongst the brands resulting in either subtherapeutic doses to the patient causing bacterial resistance or overdose. Therefore, OFXG002 and OFXG03 generics could be an alternative to Tarivid® only as an initial selection of ofloxacin containing drug.
Prof. Ekram Hassan, Prof. Mohamad Fawzi, Prof. Hania Nakkash