Some aspects of the quality of certain pharmaceutical products from Nigeria and Thailand

The concept of quality as applied to pharmaceutical products is discussed and various official definitions of this are reviewed. Pharmacopoeial control of quality is also discussed as are the limitations of some of the analytical methods employed. The importance of appropriate systems of quality assurance during manufacture of pharmaceutical products in the maintenance of product quality is highlighted. Drug decomposition, manufacturing processes and ingredients and counterfeiting are identified as being possible causes of substandard product quality. Examples of cases involving these are reviewed. It is recognised that the majority of literature reports regarding substandard quality pharmaceutical products contained no objective data and relied on anecdotal evidence to substantiate any claims made by the authors. It is also found that, in general, in the reports where objective data are given the methods employed to obtain such data were not appropriately validated. The present work uses appropriately developed and validated analytical methodology for assessment of product quality and bases any conclusions made on the data generated. Samples of pharmaceutical products available to the general public in areas of Nigeria and Thailand were collected in a methodical manner using an appropriate sample collection protocol with an associated sample collection form. Samples were then subjected to a series of quality assessment measures. These were visual inspection, assay for active ingredient(s) and assessment of in vitro dissolution for solid dosage forms. The results of all measurements were recorded on a quality assessment report form and based on these the quality of the product was judged. Samples of alleged known counterfeit products from Nigeria were also assessed in the same manner. The drug substances selected for this study were chloroquine, ampicillin, cloxacillin, amoxycillin, tetracycline and co-trimoxazole. This selection was based on the importance of the drugs to the health care of a large proportion of the population in the two countries studied and samples were obtained from both pharmacy and non-pharmacy drug outlets. Development and validation of the analytical methodology employed in this study is described, either from first principles for amoxycillin and the combination of ampicillin and cioxacillin, or modifications of previously reported methods for all other drugs. Particular attention is paid to the validation procedures as this is recognised as being of prime importance. The methods developed utilise high-performance liquid chromatography and are capable of assaying the active ingredient(s) while simultaneously detecting major drug decomposition products and manufacturing precursors for each drug included in the study. This is intended to facilitate the assessment of product quality and to provide additional information regarding the cause of any substandard quality detected. The results generated by the analyses are objectively assessed and indicate that 36.5% of the samples tested were substandard with respect to pharmacopoeial limits on content of active ingredient(s). In addition, a number of samples were found to contain no active ingredient. The in vitro dissolution results are also assessed and a number of samples do not comply with pharmacopoeial limits, despite having correct amounts of activeingredient. The possible implications and causes of non-compliance with in vitro dissolution standards are discussed. Decomposition is shown to be the cause of poor quality in a number of the samples but overall poor manufacturing appeared to be prevalent. The analyses generated little evidence to indicate fraudulent manufacturing or counterfeiting. Treatment failure and selection of drug-resistant organisms are considered as possible outcomes of the use of substandard drugs.