A comparative study of the in vitro dissolution profiles of commercially available clarithromycin oral dosage forms in Nairobi county, Kenya
Clarithromycin (6-O-methylerythromycin A) is a semi-synthetic macrolide derived from erythromycin A. It has improved acid stability, higher oral bioavailability and less gastrointestinal side effects than the naturally occurring macrolides. It is indicated in the treatment of upper respiratory tract infections due to Streptococcus pyogenes, Haemophilus influenzae, Streptococcus pneumoniae, Haemophilus parainfluenzae, Mycoplasma pneumoniae and Chlamydia pneumoniae. It is effective against skin infections due to Staphylococcus aureus and Streptococcus pyogenes. It is also used in the treatment of disseminated mycobacterial infections due to Mycobacterium avium and Mycobacterium intracellulare. It forms the cornerstone of treatment of MAC infections in HIV-AIDS and is an important component of triple therapy regimens for eradication of H. pylori in peptic ulcer disease and chronic gastritis. Despite its improved acid stability compared to erythromycin, clarithromycin undergoes degradation to microbiologically inactive products when subjected to acidic conditions and low gastric pH. It also has poor aqueous solubility that is pH-dependent and a dissolution rate-limited absorption. In the present study, a comparative dissolution profiling of oral clarithromycin products in Nairobi County, Kenya was carried out with a view to determining its stability in dissolution media of varying pH values. For this reason, dissolution profile tests were carried out at pH 1.2, 4.5 and 6.8 in order to mimic gastric and intestinal conditions. The tests were run for 60 and 90 minutes for clarithromycin tablets and suspensions respectively. The study was aimed at determining the pharmaceutical equivalence of generic clarithromycin oral preparations to the innovator products. All products tested complied with pharmacopoeial assay specifications. They also complied with single-point dissolution specifications. However, significant differences were observed in their dissolution profiles. At pH 1.2, 50% (six out of twelve) of tablet products failed to meet the specifications for similarity factor in relation to the innovator product. At pH 4.5, 33% (four out of twelve) of tablet products were non-compliant while 50% non-compliance was noted at pH 6.8 with six out of the twelve tablet products failing to meet the specifications. None of the suspensions tested met the requirement for similarity factor in relation to the innovator suspension. Overall, only 25% (four out of sixteen) of all products tested complied with the specifications for similarity factor in relation to the innovator products. The equivalence patterns observed in this study indicate that assay and single-point dissolution tests are not sufficient to demonstrate pharmaceutical equivalence between innovator products and their generic equivalents. As a minimum requirement, it would be necessary to carry out comparative dissolution profiling of generic products in order for them to be certified as interchangeable with the innovator products.