APPLICATION OF DESIGN SPACE OPTIMIZATION STRATEGY TO THE DEVELOPMENT OF LC METHODS FOR SIMULTANEOUS ANALYSIS OF 18 ANTIRETROVIRAL MEDICINES AND 4 MAJOR EXCIPIENTS USED IN VARIOUS PHARMACEUTICAL FORMULATIONS

peer reviewedtAs one of the world’s most significant public health challenges in low- and middle-income countries,HIV/AIDS deserves to be treated with appropriate medicines, however which are not spared from coun-terfeiting. For that, we developed screening and specific HPLC methods that can analyze 18 antiretroviralmedicines (ARV) and 4 major excipients. Design of experiments and design space methodology wereinitially applied for 15 ARV and the 4 excipients with prediction thanks to Monte Carlo simulations andfocusing on rapidity and affordability thus using short column and low cost organic solvent (methanol)in gradient mode with 10 mM buffer solutions of ammonium hydrogen carbonate. Two other specificmethods dedicated to ARV in liquid and in solid dosage formulations were also predicted and opti-mized. We checked the ability of one method for the analysis of a fixed-dose combination composedby emtricitabine/tenofovir/efavirenz in tablet formulations. Satisfying validation results were obtainedby applying the total error approach taking into account the accuracy profile as decision tool. Then, thevalidated method was applied to test two samples coded A and B, and claimed to contain the tested ARV.Assay results were satisfying only for sample B

Comparative Phytochemical Composition and Hypoglycemic Activity of Some Plants Used by Traditional Healers to Treat Diabetes in Kisangani

peer reviewedBackground: Phytochemical and Biological studies are always needed to define chemical composition, bioactivity and toxicity of plants from folk medicines before integrating them into conventional medicines. Here we compared phytochemical composition and antihyperglycemic activity of some plants used in Kisangani to treat diabetes. Methods: The plants tested are Aloe vera (AV), Bidens pilosa (BP), Cassia alata (CA), Cassia occidentalis (CO), Catharanthus roseus pink flower (CRp), Catharanthus roseus white flower or alba (CRw), Mangifera indica (MI), Morinda lucida (ML), Morinda morindoides (MM), Panda oleosa (PO), Terminalia catappa (TC), and Vernonia amygdalina (VA). Their content in polyphenols, saponins, alkaloids and mineral ash were compared. Hyperglycemia was induced in rabbits by oral glucose tolerance test with glibenclamide 0.2 mg/kg as reference. Blood glucose level was assayed by Folin-Wu photometric method. The mean percentage in glucose level reduction (MPR) was calculated from control untreated animals. The relative potency of each extract (RP) was calculated from glibenclamide MPR taken as 100%. Results: Flavonoids, tannins and saponins, were the main components; alkaloids were found only in CRp, CRw, ML and MM. The water content varied from 67% to 88%; Total ashes content was lower in roots (9%) than other parts (11-16%). Glibenclamide gave MPR=56.8% and RP=100%. MPR and RP for plant extracts were, ML(29.8%; 52.4%), CA(31.9%; 56.2%), MI(46.6%; 81.9%), MM(46.6%; 81.9%), TC(47.2%; 83.1%), VA(49.4%; 86.9%), CO(54.4%; 95.8%), CRw(57.4%; 101.0%), BP(60.8%; 107.0%), CRp(63.2%; 111.1%), AV(64.5%; 113.4%), PO(83.2%;146.3%). Conclusion: All plants but Panda oleosa have been studied by others; the main phytochemical groups reported have been confirmed in the local species. All plants exhibited some antihyperglycemic activity, differing however by their relative potency

Antihyperglycemic Activity of Vernonia amygdalina Leaf Extracts, Hibiscus esculentus Fruit Extract and Garcinia kola Seed Extract from Kisangani Plants

Objective: Many plants used in traditional medicine still need to be studied scientifically in order to verify their medical usefulness and standardize their pharmaceutical properties. The present study aimed at evaluating the antihyperglycemic activity of aqueous and alcoholic extracts from local species of Vernonia amygdalina Delile (Va), Hibiscus esculentus (He) and Garcinia kola Heckel (Gk). Methods: The tests were done on Va-aqueous, Va-ethanolic, Va-butanolic and Va-saponin leaf extracts; He-aqueous fruit extract and Gk-aqueous seed extract. The extracts were prepared using conventional methods. The activity was evaluated in male rabbits given orally 100 mg of extracts per Kg BW and overloaded with glucose (4 g/Kg) 30 minutes later. Glibenclamide 0.2 mg/Kg was given as reference positive control. A negative control group of untreated animals was also included. Blood samples were collected on the animal ear at different times. The assay was performed using a handheld Glucometer®. Results: The percentages of reduction in glycemia calculated on the basis of the negative control values were 60.5% for glibenclamide, 70.5% for Va-ethanol, 57.6% for Va-aqueous, 42.2% for Va-butanol, 54.5% for He-aqueous and 58.7% for Gk-aqueous. Va-saponins fraction was inactive; it increased the baseline glycemia instead of reducing. Conclusion: All extracts have a relative reduction activity comparable to glibenclamide with the exception of Va-saponins. Improved tradimedicines can be prepared with ethanolic or polyphenolic dry extracts

Simple LC Isocratic Methods Development, Validation, and Application in the Analysis of Poor Quality Antimalarial Medicines

peer reviewedLiquid chromatographic methods in isocratic mode for the analysis of poor quality medicines are privileged due to their simplicity and facility in methods development. They are generally fast; do not need to be re-equilibrated between sample injections; have larger flexibility with acceptable changes on different column dimensions; and are applicable to LC systems equipped with simple or high developed pumps. In this study, we focused on developing simple isocratic methods using classical mobile phase composed by methanol and ammonium formate buffer for the analysis of most common antimalarial medicines marketed in malaria endemic countries and susceptible of being counterfeit/falsified, substandard and degraded. The selected medicines were quinine and related cinchona alkaloids in tablets and injectable forms; artemether/ lumefantrine tablets; and artemisinin compounds (arteether, artemether, and artesunate) in injectable forms. The current methods were developed thanks to simple methodological approach consisting in sequential isocratic runs through adjustment or adaptation of existing methods to obtain optimal analytical conditions without complex design of experiments that might be long and costly. Then, the new methods presented shorter analysis time; allowed increase of sample analysis throughput; and obviously consumed little mobile phase solvents on classical analytical columns: 50 - 250 mm of length (L), 4.6 mm of internal diameter (I.D.), and 3.5 - 5.0 μm of particle size (dp)

QUALITY ASSESSMENT OF MEDICINES MARKETED IN RWANDA, July-Oct. 2011

Développement, Validation et Transfert de méthodes analytiques génériques pour lutter contre la contrefaçon des médicament

Generic screening chromatographic methods to fight against poor quality medicines

peer reviewedPoor quality medicines are a danger and a threat to public health. In this context, several generic analytical methods have been developed to screen molecules of interest grouped by pharmacological class using an innovative strategy based on design of experiments followed in some cases by independent component analysis and calculation of design space. Once validated via the classical total error measurement approach, these methods were applied to quantify antimalarial, non-steroidal anti-inflammatory and antibiotic medicines. Alarming results regarding the dosage of these drugs widely used by people confirm the need to fight against this scourge.Projet Falsification/Contrefaço

Analytical Tools and Strategic Approach to Detect Poor Quality Medicines, Identify Unknown Components, and Timely Alerts for Appropriate Measures: Case Study of Antimalarial Medicines

peer reviewedNowadays, the circulation of poor quality medicines is becoming an alarming worldwide phenomenon with serious public health and socio-economic concerns. The situation is particularly critical in developing countries where drug quality assurance and regulatory systems for drug manufacturing, importation, distribution and sales are weak. A sustained vigilance on poor quality medicines that regroup counterfeit/falsified, substandard and degraded medicines is therefore required to ensure patient safety and genuine medicines integrity. A case situation is illustrated including a strategic approach and analytical tools that were found useful to detect poor quality medicines, identify unknown components, and timely alerts for appropriate measures against the spread of those harmful products. Several suspected medicines randomly sampled in several strategic Rwandan areas were firstly check-controlled by means of visual inspection and then applying several analytical techniques from simple to more complex ones. The following medicines were studied: quinine sulfate tablets, artemisinin-based combination tablets, and artesunate powders for injection. Taking into account the pharmaceutical forms and the chemical characteristics, the following tests were applied: uniformity of mass, friability, disintegration, fluorescence, identification and assay. They were followed by more complex analytical techniques that allowed more comprehension of abnormal findings among which the presence of a wrong active pharmaceutical ingredient in quinine sulfate tablets which is mainly discussed in this paper to illustrate a strategic approach and various analytical tools that can be used in detecting and identifying unknown component in poor quality medicines