Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets

Background:Dissolution of artemether (ART ) and lumefantrine (LUM) active pharmaceutical ingredients (APIs) in fixed dose combination (FDC) ART/LUM tablets is one of the critical quality attributes. Thus, the verification of the release profile of ART and LUM from FDC ART/LUM tablets using a robust and discriminatory dissolution method is crucial. Therefore, the aim of this study was to develop and validate an appropriate dissolution method for quality control of FDC ART/LUM tablets.Methods:The dissolution medium was selected based on saturation solubility data and sink conditions. The effect of agitation speed, pH and surfactant concentration on the release of ART and LUM was evaluated by employing a two-level factorial experiment. The resulting final method was validated for linearity, precision, robustness and API stability. In addition, the discriminatory power of the method was evaluated using expired and unexpired FDC ART/LUM products.Results:A suitable dissolution profile of FDC ART/LUM tablets was obtained in 900 ml HCl (0.025 N, pH 1.6) with 1%Myrj 52 using paddle method at 100 rpm and 37 °C. ART and LUM were analysed using a HPLC method with UV detection at wavelengths of 210 and 335 nm, respectively. The results from the stability study showed that ART and LUM were sufficiently stable in HCl (0.025 N, pH 1.6) with 1%Myrj 52 at 37 °C. The method was linear (r2= 0.999) over the concentration range of 6.25–100 μg/ml. The results for precision were within the acceptance limit (%RSD 0.05) difference in release of ART and LUM observed between deliberately changed dissolution method settings (pH = 1.6 ±0.2 or agitation speed = 100 ±2) and optimized dissolution conditions revealed the robustness of the dissolution method. The method was capable to discriminate among different FDC ART/LUM products with different quality.Conclusions:The developed dissolution method is robust and discriminatory. It can be used in the quality evalua-tion of FDC ART/LUM tablets

Quality of fixed dose artemether/lumefantrine products in Jimma Zone, Ethiopia

Background: Malaria caused by Plasmodium vivax and Plasmodium falciparum is among the major public health problems in most endemic areas of the world. Artemisinin-based combination therapy (ACT) has been recommended as a first-line treatment for uncomplicated Plasmodium falciparum malaria almost in all endemic regions. Since ineffectively regulated medicines in resource limited settings could favour infiltration of poor quality anti-malarial medicines into pharmaceutical supply chain and jeopardize a positive treatment outcome, regular monitoring of the quality of anti-malarial medicines is critical. Thus, the aim of this study was to assess the quality of fixed dose combination (FDC) artemether (ART)/lumefantrine (LUM) tablets available in Jimma zone, Ethiopia. Methods: This study was conducted in Jimma zone, Ethiopia. A total of 74 samples of FDC ART/LUM (20mg ART/120mg LUM) tablets were collected from 27 public facilities. All samples were subjected to visual inspection and the relevant information was recorded. The samples were transported to Jimma University Laboratory of Drug Quality (JuLaDQ) and stored at ambient temperature (20 degrees C to 25 degrees C) until analysis. The Pharmacopoeial conform/non-conform methods and the risk-based Derringer's desirability function approach were employed to assess the pharmaceutical quality of the investigated products. Results: The visual inspection results revealed that there were no signs of falsified in the investigated products. Identification test results of samples indicated that all samples contained the stated active pharmaceutical ingredients (APIs). The results of uniformity of mass indicated that all samples complied with International Pharmacopoeial specification limits. The assay results, expressed as percent label claim (%lc) of ART (89.8 to 108.8%, meanSD=99.1 +/- 3.9%) and LUM (90.0 to 111.9%, mean +/- SD=98.2 +/- 3.8%) revealed that, all samples complied with International Pharmacopoeia acceptance specification limits (i.e. 90-110%lc), except one generic product (IPCA Laboratories Ltd., India) which contains excessive LUM (111.9 +/- 1.7%lc). The risk priority number (RPN) results revealed that assay (RPN=392) is relatively the most critical quality attribute followed by identity (RPN=280) and mass uniformity (40). Quality evaluation based on psycho-physical Harrington's scale revealed that more than 96% of samples were within the acceptable ranges (D >= 0.7-1.0). Conclusions: Both Pharmacopoeial and risk-based desirability function approaches to quality evaluation applied to the investigated products revealed that above 96% FDC ART/LUM tablets circulating in public settings of Jimma zone are of good quality

The genetics of adaptation in domestic farm animals: a review

This review summarizes available information on genetics of adaptation in major livestock species focusing on small ruminants. Adaptation to humans and consequences of domestication on predator aversion, mechanisms of adaptation to available feed and water resources, severe climates and genetic evidence of disease tolerance or resistance have been presented. The latter focuses on gastrointestinal parasites and bacterial diseases. The resource allocation by the animal to production and fitness traits under both optimal and sub-optimal conditions has a genetic background. Such information would help in identifying the most appropriate and adapted genotypes capable of coping with the environmental challenges posed by the production systems or, wherever possible, in adapting the environments to the requirements of the animals

Identification of smallholder farmers and pastoralists’ preferences for sheep breeding traits: choice model approach

Identification of breeding objective traits pertinent to specific production environments with the involvement of target beneficiaries is crucial to the success of a breed improvement program. A choice experiment was conducted in four locations representing different production systems and agro-ecologies that are habitat to four indigenous sheep breeds (Afar, Bonga, Horro and Menz) of Ethiopia with the objective of identifying farmers’/pastoralists’ preferences for sheep breeding traits. Following a synthesis of secondary information and diagnostic surveys, two communities per location consisting of 60 households each having at least four breeding ewes were identified. Producers’ priority attributes used in the choice sets were identified through in-depth production system studies conducted from December 2007 to March 2008. On the basis of prior information, four to seven attributes were used to design choice sets with different profiles in order to capture results that mimic real life of the different communities. The attributes and levels chosen for the sheep profile were as follows: body size (large/small), coat color (brown/white/black), tail type (good/bad) for both rams and ewes; horn (polled/horned) and libido (active/poor) for rams; and lambing interval (three lambings in 2 years/two lambings in 2 years time), mothering ability (good mother/bad mother), twinning rate (twin bearer/single bearer) and milk yield (two cups per milking/one cup per milking) for ewes. A fractional factorial design was implemented to construct the alternatives included in the choice sets. The design resulted in a randomized selection of 48 sheep profiles (24 sets) for both sexes, which were grouped into four blocks with six choice sets each. An individual respondent was presented with one of the four blocks to make his/her choices. Results indicate that producers’ trait preferences were heterogeneous except for body size in rams and mothering ability in ewes where nearly homogeneous preferences were investigated. In the pastoral production system, attention was given to coat color of both breeding rams and ewes, favoring brown and white colors over black. Ram libido influenced producers’ decisions in Bonga, Horro and Menz areas. The influence of milk yield and twinning on respondents’ decision making was high in Afar and Horro, respectively. Breeders in all areas attempt to combine production and reproduction traits as well as they can in order to maximize benefits from their sheep. The elicited measurable objective traits were used to design alternative community-based sheep breeding plans for the four indigenous sheep breeds in their production environments that have been implemented since

Participatory approaches to investigate breeding objectives of livestock keepers

There are distinct breeds suitable for diverse purposes in the different production environments or ecological zones. Farmers in different production systems have different trait preferences and the strategies followed by them are also as diverse as the agro-environments within which they operate. In order to design a viable breeding plan, farmers’ preferences for the different traits need to be investigated. In this paper available tools and methods for defining livestock breeding objective traits are described, discussed and comparisons among them are made. The reviewed tools were: participatory rural appraisal (PRA), choice experiments, ranking of animals from own flock/herd and ranking of others animals. Each methodology may be appropriate to specific situation; however, it is recommended that a combination of approaches be used to precisely capture the breeding objective traits of livestock producers. Elucidation of objective traits using the tools with active involvement of producers can result in appropriate livestock genetic improvement that is well grounded in practical reality and truly reflects owners’ preferences

Community-based alternative breeding plans for indigenous sheep breeds in four agro-ecological zones of Ethiopia

Based on the results of participatory approaches to define traits in the breeding objectives, four scenarios of ram selection and ram use were compared via deterministic modelling of breeding plans for community-based sheep breeding programmes in four diverse agro-ecological regions of Ethiopia. The regions (and production systems) were Afar (pastoral/agro-pastoral), Bonga and Horro (both mixed crop-livestock) and Menz (sheep-barley). The schemes or scenarios differed in terms of selection intensity and duration of ram use. The predicted genetic gains per year in yearling weight (kilograms) were comparable across the schemes but differed among the breeds and ranged from 0.399 to 0.440 in Afar, 0.813 to 0.894 in Bonga, 0.850 to 0.940 in Horro, and 0.616 to 0.699 in Menz. The genetic gains per year in number of lambs born per ewe bred ranged from 0.009 to 0.010 in both Bonga and Horro. The predicted genetic gain in the proportion of lambs weaned per ewe joined was nearly comparable in all breeds ranging from 0.008 to 0.011. The genetic gain per year in milk yield of Afar breed was in the order of 0.018 to 0.020 kg, while the genetic gain per generation for greasy fleece weight (kg) ranged from 0.016 to 0.024 in Menz. Generally, strong selection and shorter duration of ram use for breeding were the preferred options. The expected genetic gains are satisfactory but largely rely on accurate and continuous pedigree and performance recording

Designing and implementation of community-based breeding programs for adapted local sheep breeds in Ethiopia

A presentation prepared for the 5th All Africa Conference on Animal Agriculture and the 18th Annual Meeting of the Ethiopian Society of Animal Production (ESAP), Addis Ababa, October 25-28, 2010