Quality assessment of oral antimalarial and antiretroviral medicines used by public health systems in Sahel countries.

Malaria and Human Immunodeficiency Virus infections are among the top 10 causes of death in low income countries. Furthermore, many medicines used in these treatment areas are substandard, which contributes to the high death rate. Using a monitoring system to identify substandard and falsified medicines, the study aims to evaluate the quality of antimalarial and antiretroviral medicines in Sahel countries, assessing site conditions, compliance of medicines with pharmacopoeia tests, formulation equivalence with a reference medicine, and the influence of climate on quality attributes. Ultra Performance Liquid Chromatography methods for eight active pharmaceutical ingredients were validated following the International Conference for Harmonization guideline for its detection and quantification. Quality control consists of visual inspections to detect any misinformation or imperfections and pharmacopeial testing to determine the quality of pharmaceutical products. Medicines which complied with uniformity dosage units and dissolution tests were stored under accelerated conditions for 6 months. Artemether/Lumefantrine and Lopinavir/Ritonavir formulations failed uniformity dosage units and disintegration tests respectively, detecting a total of 28.6% substandard medicines. After 6 months stored under accelerated conditions (40 °C // 75% relative humidity) simulating climatic conditions in Sahel countries, some medicines failed pharmacopeia tests. It demonstrated the influence of these two factors in their quality attributes. This study emphasizes the need of certified quality control laboratories as well as the need for regulatory systems to maintain standards in pharmaceutical manufacturing and distribution in these countries, especially when medicines are transported to rural areas where these climatic conditions are harsher.

A pharmaceutical monitoring system to assess the quality of antituberculosis drug products used in Mauritania.

The quality of drug products may be affected from manufacture to dispensing, particularly at high temperature and humidity as in Mauritania. This country is not included in the World Health Organization reports on poor quality products due to the lack of a qualified laboratory and monitoring system. Ensuring the quality of medicine is even more relevant in the case of diseases such as Tuberculosis, due to its high prevalence, complex treatment and continuous bacterial resistance. The aim was to develop a monitoring system to assess the quality of antituberculosis drugs products, by the substandard detection based on European and United States Pharmacopeial recommendations regarding quality control. In addition to studying the influence of accelerated storage conditions (40 ± 2°C/75 ± 5% relative humidity) on their qualities and comparing the dissolution profiles to contrast the quality. 18 antituberculosis drug products were taken from Europe and Mauritania, and quality was studied through visual inspection and according to the compliance of the mass uniformity, uniformity of dosage units, dissolution, disintegration and friability pharmacopeial tests. Furthermore, a dissolution profile comparison was carried out to examine quality. A stability study was conducted to assess the influence of climatic conditions on the content and the dissolved amount of the active pharmaceutical ingredients, which were determined by an ultra-performance liquid chromatography system. As result, 69.3% of 13 Mauritanian formulations had a substandard quality mainly due to non-compliance with the test for friability or content uniformity of these medicines. All European drug products complied with pharmacopeia specifications. In addition, storage conditions affected the dissolution rate of ethambutol and the uniformity of the 4 antituberculosis combination drug products.

Development and Optimization of a New UPLC-UV/MS Method through DoE and MLR for Detecting Substandard Drug Products to Treat Tuberculosis.

Drug products used for treating tuberculosis are one of the most widely reported medicines to be classified as falsified or substandard in low- and middle-income countries, representing a major hazard to health. The aim of this study was, firstly, to develop an ultra-performance liquid chromatography (UPLC) method which is able to analyze fixed combination tablets with up to four active pharmaceutical ingredients, including isoniazid, pyrazinamide, rifampicin, and ethambutol. Secondly, we aimed to optimize it through the design of experiments and multi-linear regression based on a central composite design and to validate it according to the guidelines of the International Conference on Harmonization. The application of this tools enabled the identification of the influential factors (flow rate, formic acid, and temperature) and their effects on the studied responses (retention factor and percentage for each drug) as part of the quality by design approach. The method proved to be to be linear in the range from 5.0 to 15 µg/mL for isoniazid, pyrazinamide, and rifampicin, being precise (<1%) and accurate (97−101%). In addition, the method validated for ethambutol proved to be linear from 1.4 to 4.2 µg/mL, as well as precise (0.54%) and accurate (97.3%). The method was stability indicated for all the active pharmaceutical ingredients studied and was able to detect two substandard formulations sampled on the African market.

Stability Study of Isoniazid and Rifampicin Oral Solutions Using Hydroxypropyl-Β-Cyclodextrin to Treat Tuberculosis in Paediatrics.

(1) Background: First-line antituberculosis treatment in paediatrics entails the administration of Isoniazid, Pyrazinamide, and Rifampicin. This study examines the possibility of developing a combined dose liquid formulation for oral use that would facilitate dose adjustment and adherence to treatment for younger children. (2) Methods: The active pharmaceutical ingredients stability under in vitro paediatric digestive pH conditions have been checked. The samples were studied as individual or fixed combined paediatric dosages to determine the pH of maximum stability. The use of hydroxypropyl-ß-cyclodextrin to improve Rifampicin solubility and the use of ascorbic acid to increase the stability of the formulation have been studied. (3) Results: Maximum stability of combined doses was determined at pH 7.4, and maximum complexation at pH 8.0. Taking this into account, formulations presented the minimum dose of two active pharmaceutical ingredients dissolved. The addition of ascorbic acid at 0.1% w/v enables the detection of a higher remaining quantity of both drugs after three days of storage at 5 °C. (4) Conclusions: a formulation which combines the minimum paediatric dosages dissolved recommended by WHO for Isoniazid and Rifampicin has been developed. Future assays are needed to prolong the stability of the formulation with the aim of incorporating Pyrazinamide to the solution.