Quality of anthelminthic medicines available in Jimma Ethiopia.

Soil-transmitted helminthiasis and schistosomiasis are major public health problems in Ethiopia. Mass deworming of at-risk population using a single dose administration of 400mg albendazole (ABZ) or 500mg mebendazole (MBZ) for treatment of common intestinal worms and 40mg of praziquantel (PZQ) per kg body weight for treatment of schistosomiasis is one of the strategies recommended by World Health Organization (WHO) in order to control the morbidity of soil-transmitted helminthiasis and schistosomiasis. Since storage condition, climate, way of transportation and distribution route could all affect the quality of medicines, regular assessment by surveys is very critical to ensure the therapeutic outcome, to minimize risk of toxicity to the patient and resistance of parasites. Therefore, this study was conducted to assess the pharmaceutical quality of ABZ, MBZ and PZQ tablet brands commonly available in Jimma town (south west Ethiopia). Retail pharmacies (n=10) operating in Jimma town were selected using simple random sampling method. Samples of anthelminthic medicines available in the selected pharmacies were collected. Sample information was recorded and encompassed trade name, active ingredient name, manufacturer's name and full address, labeled medicine strength, dosage form, number of units per container, dosage statement, batch/lot number, manufacturing and expiry dates, storage information and presence of leaflets/package insert. Moreover, a first visual inspection was performed encompassing uniformity of color, uniformity of size, breaks, cracks, splits, embedded surface spots or visual contaminations. Finally, physico-chemical quality attributes investigated encompassed mass uniformity, quantity of active pharmaceutical ingredient (API), disintegration and dissolution, all following Pharmacopoeial test methods The physical characteristics of dosage form, packaging and labeling information of all samples complied with criteria given in the WHO checklists. The mass uniformity of tablets of each brand of ABZ, MBZ and PZQ complied with the pharmacopoeial specification limits, i.e no more than 2 individual masses >5% of average tablet weight, and none deviate by more than 10%. The quantity of APIs in all investigated tablet brands were within the 90-110% label claim (l.c.) limits, ranging between 95.05 and 110.09% l.c. Disintegration times were in line with the pharmacopoeial specification limit for immediate release (IR) tablets, ranging between 0.5 and 13min. However, the dissolution results (mean±SD, n=6) of one ABZ brand (i.e. Wormin®, Q=59.21±0.99% at 30min) and two PZQ brands (i.e. Bermoxel®, Q=63.43%±0.7 and Distocide®, Q=62.43%±1.67, at 75min) showed poor dissolution, failing the United States Pharmacopoeia (USP) dissolution specification limit.

Quality of medicines commonly used in the treatment of soil transmitted helminths and giardia in ethiopia: a nationwide survey.

BACKGROUND: The presence of poor quality medicines in the market is a global threat on public health, especially in developing countries. Therefore, we assessed the quality of two commonly used anthelminthic drugs [mebendazole (MEB) and albendazole (ALB)] and one antiprotozoal drug [tinidazole (TNZ)] in Ethiopia. METHODS/PRINCIPAL FINDINGS: A multilevel stratified random sampling, with as strata the different levels of supply chain system in Ethiopia, geographic areas and government/privately owned medicines outlets, was used to collect the drug samples using mystery shoppers. The three drugs (106 samples) were collected from 38 drug outlets (government/privately owned) in 7 major cities in Ethiopia between January and March 2012. All samples underwent visual and physical inspection for labeling and packaging before physico-chemical quality testing and evaluated based on individual monographs in Pharmacopoeias for identification, assay/content, dosage uniformity, dissolution, disintegration and friability. In addition, quality risk was analyzed using failure mode effect analysis (FMEA) and a risk priority number (RPN) was assigned to each quality attribute. A clinically rationalized desirability function was applied in quantification of the overall quality of each medicine. Overall, 45.3% (48/106) of the tested samples were substandard, i.e. not meeting the pharmacopoeial quality specifications claimed by their manufacturers. Assay was the quality attribute most often out-of-specification, with 29.2% (31/106) failure of the total samples. The highest failure was observed for MEB (19/42, 45.2%), followed by TNZ (10/39, 25.6%) and ALB (2/25, 8.0%). The risk analysis showed that assay (RPN = 512) is the most critical quality attribute, followed by dissolution (RPN = 336). Based on Derringer's desirability function, samples were classified into excellent (14/106,13%), good (24/106, 23%), acceptable (38/106, 36%%), low (29/106, 27%) and bad (1/106,1%) quality. CONCLUSIONS/SIGNIFICANCE: This study evidenced that there is a relatively high prevalence of poor quality MEB, ALB and TNZ in Ethiopia: up to 45% if pharmacopoeial acceptance criteria are used in the traditional, dichotomous approach, and 28% if the new risk-based desirability approach was applied. The study identified assay as the most critical quality attributes. The country of origin was the most significant factor determining poor quality status of the investigated medicines in Ethiopia.

Effectiveness of various anthelmintics in the treatment of moniliformiasis in experimentally infected Wistar rats.

Humans occasionally become infected with acanthocephalans, particularly Moniliformis moniliformis. Although several anthelmintics have been used, no controlled studies have been conducted to assess the efficacy of common anthelmintics in the treatment of moniliformiasis. The effectiveness of pyrantel pamoate, ivermectin, praziquantel, niclosamide, thiabendazole, and mebendazole was evaluated in the treatment of moniliformiasis in laboratory-infected female Wistar rats. Pyrantel pamoate and ivermectin were wholly unsuccessful in the treatment of moniliformiasis. A single dose of thiabendazole lead to a 40% reduction and two doses lead to a 57% reduction of worm burden after 2 weeks. The most effective drug in the treatment of moniliformiasis in rats was mebendazole, for which two doses resulted in a 69% reduction in worm burden after 2 weeks; however, 50% of the rats receiving the treatment died within 2 weeks after first administration of the drug. Two surviving rats that had been treated with mebendazole exhibited evidence of hepatic dysfunction characterized by extremely elevated levels of alkaline phosphatase in conjuction with depressed serum albumin levels. It is hypothesized that Mo. moniliformis may metabolize the drug and release a metabolite that is highly toxic to the host. On the basis of these data, thiabendazole is recommended as the drug of choice for the treatment of human acanthocephaliasis until more extensive testing can be conducted.

Rapid determination of the antiparasitic drugs flubendazole and febantel in feeds by HPLC with ultraviolet detection.

A rapid and very effective analytical procedure for the simultaneous HPLC determination of two anthelmintics, Flubendazole (FLUB) and Febantel (FEBA), in swine and poultry feeds was developed and tested. The ground feed samples were extracted using dimethylformamide. The extracts were directly analyzed, without any purification, on a reversed-phase ODS column (150 mm x 4.6 mm, 5 microm) with acetonitrile-phosphate buffer (pH 3; 0.017 M) as mobile phase. Ultraviolet detection of FLUB and FEBA was carried out at 300 nm. The method was validated for specificity, linearity, accuracy, repeatability, limit of detection and limit of quantification. The limits of detection (LOD) of FLUB and FEBA in feeds, based on a detector signal-to-noise ratio of 3, were 3 mg kg(-1) and the lowest levels tested in feeds by this procedure (limit of quantification, LOQ) were 10 mg kg(-1). The mean recovery of FLUB and FEBA from spiked samples, in a concentration range of 10-200 mg kg(-1), was 98% with a CV% of 4% and 99% with a CV% of 2%, respectively.

Quality evaluation of generic drugs by dissolution test: changing the USP dissolution medium to distinguish between active and non-active mebendazole polymorphs.

Mebendazole is practically insoluble in water and studies of its polymorphism has led to the identification and characterization of three polymorphic forms (A, B, C) displaying solubility and therapeutic differences that show that polymorph C is therapeutically favored. The objective of this study was to adjust the USP dissolution test for mebendazole so that it was able to distinguish between the dissolution properties of three mebendazole polymorphs. This would provide generic manufacturers with one more test to ensure that the therapeutically active polymorph C is used. The results obtained in this study show that the USP dissolution test conditions were not able to distinguish between the dissolution properties of completely dispersed mebendazole polymorphs with comparable particle sizes. When sodium lauryl sulfate was removed from the dissolution medium, the percentage dissolved versus time profiles changed so that polymorph C dissolved faster (70% within 120 min) compared to polymorph B (37% within 120 min) and polymorph A (20% within 120 min).