Evaluating the availability of essential drugs for hypertension, diabetes and asthma in rural Rwanda, 2018.

SETTING: Hypertension, diabetes mellitus and asthma are on the rise in developing countries, including Rwanda; there is thus a need to ensure uninterrupted drug availability. OBJECTIVES: To assess 1) the frequency and duration of drug stock-outs; 2) lead time duration 3) monthly stock levels; and 4) drug quantities requested vs. quantity delivered for captopril, metformin and inhaled salbutamol between January and December 2018 Kirehe District, Rwanda. DESIGN: This was a cross-sectional study using secondary programme data. RESULTS: The median annual stock-outs for captopril, metformin and inhaled salbutamol were respectively 4 (IQR 3-4), 3 (IQR 2-3) and 4 (IQR 4-5) at rural health facilities (RHCs); no stock-outs occurred at the district hospital. For all three drugs, the median lead time was 7.5 days (IQR 5.5-11.5) at the hospital vs. 5 days (IQR 3-6) in RHCs. Stock status for captopril was below the 4-week minimum stock level for 2/12 months at the hospital vs. 7/12 months at the RHCs, while metformin and inhaled salbutamol were below the 4-week minimum stock levels for respectively 1/12 and 4/12 months at both hospital and RHCs. Total drug quantities delivered were less than the combined total quantities requested in respectively 8/12, 5/12 and 8/12 months for captopril, metformin and inhaled salbutamol. CONCLUSION: There is a need to regularly and effectively monitor drug stock levels and ensure timely and sufficient stock replenishment to avert stock-outs.

CONTEXTE: L'hypertension, le diabète sucré et l'asthme augmentent progressivement dans les pays en développement, y compris le Rwanda ; il est donc nécessaire d'assurer une disponibilité ininterrompue des médicaments. OBJECTIFS: Évaluer 1) la fréquence et la durée des ruptures de stock de médicaments ; 2) durée du délai d'approvisionnement ; 3) niveaux de stock mensuels ; et 4) quantités de médicaments demandées par rapport aux quantités livrées pour le captopril, la metformine et le salbutamol inhalé ; entre janvier et décembre 2018 dans le district rural de Kirehe, au Rwanda. METHODE: Il s'agissait d'une étude transversale utilisant des données secondaires de programme. RÉSULTATS: Les ruptures de stock annuelles médianes pour le captopril, la metformine et le salbutamol inhalé étaient respectivement de 4 (intervalle interquartile [IQR] 3­4), 3 (IQR 2­3) et 4 (IQR 4­5) dans les Centre de Santé ruraux et aucune rupture de stock n'est survenue à l'hôpital de district. Pour les trois médicaments, le délai d'approvisionnement médian était de 7,5 jours (IQR 5,5­11,5) à l'hôpital contre 5 jours (IQR 3­6) dans les services sanitaires ruraux. L'état des stocks de captopril était inférieur au niveau de stock minimum de 4 semaines pendant 2/12 mois à l'hôpital contre 7/12 mois aux services sanitaires ruraux, tandis que pour la metformine et le salbutamol inhalé ils étaient inférieurs aux niveaux de stock minimum de 4 semaines pour 1/12 et 4/12 mois à l'hôpital et dans les Centre de Santé ruraux, respectivement. Les quantités totales de médicaments livrées étaient inférieures aux quantités totales combinées et demandées en 8/12, 5/12 et 8/12 mois pour le captopril, la metformine et le salbutamol inhalé, respectivement. CONCLUSION: Il est indispensable de surveiller régulièrement et convenablement les niveaux des stocks de médicaments et d'assurer un réapprovisionnement en temps propice et en quantité appropriée pour éviter les ruptures de stock.

Quinine sulphate pellets for flexible pediatric drug dosing: formulation development and evaluation of taste-masking efficiency using the electronic tongue.

The purpose of this study was to develop a taste-masked quinine sulphate dosage form as a flexible pediatric formulation tool. Pellets were produced as they offer more flexibility to body weight dose adaptation and therefore represent an alternative to tablet breaking in pediatrics. Quinine sulphate pellets were produced via extrusion-spheronisation. Next pellets were coated using Eudragit E PO to obtain a taste-masked formulation. Using 15% dibutyl sebacate (based on polymer weight) as a plasticizer in the formulation caused rapid pellet agglomeration during storage at 40 degrees C and 75% relative humidity. Using stearic acid (15% based on polymer weight) as plasticizer yielded pellets which were less sensitive to sticking. Quinine sulphate release in water within the first 5 min of dissolution testing: 9.2%, 5.9% and 2.1% of the drug dose was released from pellets coated with 10%, 20% and 30% (w/w) Eudragit E PO, respectively. These observations correlated well with the bitterness score of the formulations determined via the Astree electronic tongue and its Bitterness Prediction Module, showing that 20% (w/w) Eudragit E PO was required to obtain a homogeneous film and to delay quinine sulphate release sufficiently to mask the bitterness after drug administration. In acid medium immediate quinine sulphate release was obtained.

Taste-masked quinine pamoate tablets for treatment of children with uncomplicated Plasmodium falciparum malaria.

UNLABELLED: Children with uncomplicated malaria are generally treated with oral medication, except those unable to take oral drugs. Even though quinine has shown to be effective in treatment of African children with uncomplicated malaria its high bitterness limited the paediatric use. This study aimed to develop taste-masked quinine tablets suitable for children and offering dosing flexibility to adjust the quinine dose in function of body weight. METHODS: Insoluble quinine pamoate was used to formulate fast-disintegrating tablets, using a specific tablet design (rectangular tablet which can be divided into 8 subunits) to allow dosing flexibility. The physical properties of tablets were evaluated in vitro, as well as the quinine bioavailability in healthy adults (n=18) and the efficacy for treatment of children with uncomplicated Plasmodium falciparum malaria (n=56) using a 7-day regimen of 8 mg quinine/kg. RESULTS: Quinine pamoate tablets complied with the pharmacopoeial requirements for mass uniformity, friability, content uniformity, breakability, disintegration and dissolution. The quinine pharmacokinetic parameters after single administration of a quinine pamoate tablet were similar to a commercially available quinine sulfate tablet. The fast decline in parasitemia (28.6%/24h), the reduction rate of fever (all children were apyretic after 72 h) and the steady state quinine plasma concentration (5.7-15.8 microg/ml) proved the efficacy of the quinine pamoate tablets against P. falciparum. CONCLUSION: Fast-dispersible and taste-masked quinine pamoate tablets improved dosing accuracy, allowed easy administration and resulted in a high efficacy during the treatment of children with uncomplicated malaria.

Taste-masked quinine sulphate pellets: bio-availability in adults and steady-state plasma concentrations in children with uncomplicated Plasmodium falciparum malaria.

BACKGROUND: Quinine sulphate (QS), like most other antimalarials, is in tablet form designed for adults. In children, treatment is based on breaking the tablets to adapt the dose to the child's bodyweight. However, poor breakability owing to the tablet design or the absence of a score line can lead to inaccurate dosage. Furthermore, QS is very bitter which reduces its acceptability to children. QS taste-masked pellets have been developed which offer more flexibility in adapting dosage to a child's weight. AIMS: To evaluate the oral bio-availability of QS taste-masked pellets in healthy adult volunteers and to determine steady-state plasma concentrations in children aged <5 years with uncomplicated Plasmodium falciparum malaria. METHODS: Healthy adult volunteers at Kigali University Hospital received a single dose of 600 mg QS as taste-masked pellets or as commercially available tablets. A total of 56 children <5 years with uncomplicated P. falciparum malaria were recruited among patients attending Butare University Hospital and nearby health centres and treated with QS taste-masked pellets, 10-12.5 mg/kg every 8 h for 7 days. Quinine steady-state plasma concentrations were assessed on the 4th day of treatment. RESULTS: Following administration of taste-masked pellets to healthy adult volunteers, peak plasma concentration (C(max)) and area-under-the-curve (AUC) (C(max) 4.7 microg x ml(-1), AUC(0-24) 63.5 microg x h x ml(-1)) were significantly higher (p<0.05) than for tablets (C(max) 3.7 microg x ml(-1), AUC(0-24) 52.4 microg x h x ml(-1)), but still within the limits reported for quinine. The steady-state concentrations in children were in the therapeutic range for quinine. All the children recovered and completed the 14-day follow-up. CONCLUSION: QS taste-masked pellets offered the possibility to easily adjust the dose to the bodyweight of the child and can be used as an alternative to dividing tablets.

The quality of essential antimicrobial and antimalarial drugs marketed in Rwanda and Tanzania: influence of tropical storage conditions on in vitro dissolution.

OBJECTIVE: The quality of 33 formulations of essential antimicrobial and antimalarial drugs (amoxicillin capsules, metronidazole tablets, sulfamethoxazole/trimethoprim tablets, quinine tablets and sulphadoxine/pyrimethamine tablets) marketed in Rwanda and Tanzania was assessed and the influence of tropical storage conditions on potency and in vitro dissolution investigated. METHODS: Drug content and in vitro dissolution were determined immediately after purchase and during 6-month storage under simulated tropical conditions (75% relative humidity, 40 degrees C) using the methods described in the USP 24 monographs on the drugs concerned. RESULTS AND DISCUSSION: At the time of purchase, the drug content of all the formulations was within the limits recommended by the USP 24, but after 6-month storage, the drug content of one sulfamethoxazole/trimethoprim and one quinine formulation were found to be substandard. Immediately after purchase, four formulations (three sulfamethoxazole/trimethoprim and one sulphadoxine/pyrimethamine combination) failed the USP 24 dissolution test. Except for three metronidazole and one quinine formulations, dissolution tests performed after 6 months of storage under simulated tropical conditions showed that drug release remained within the USP 24 recommended values. CONCLUSION: In both countries, essential drug formulations met pharmacopoeial potency requirements, but some had a poor in vitro drug release profiles. Some of the formulations tested were not stable upon storage under simulated tropical conditions.