Formulation development of artemether 20 mg/ lumefantrine 120 mg fixed dose combination tablet

Abstract

ABSTRACT Background: The World Health Organization (WHO) recommends artemisinin based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by P. falciparum parasite. By combining two active ingredients with different mechanisms of action, ACTs are the most effective antimalarial medicines available today. In Tanzania, access and affordability of antimalarials are limited, because there is only one Pharmaceutical Industry that manufactures Artemether Lumefantrine (ALU) tablets. Consequently, more than 90% of antimalarials are imported from other countries in abroad. Aim of the study: The objective of this study is to develop a formulation of Artemether 20 mg/ Lumefantrine 120 mg Fixed Dose Combination Tablet. Methods and Materials: This was an experimental study conducted at Muhimbili University of Health and Allied Sciences, specifically in the Pharmaceutical Analysis Laboratory and Research and Development (R and D) Laboratory. The Active Pharmaceutical Ingredients (APIs) used in pre-formulation and formulation development are Artemether and Lumefantrine, while the excipients are Hydroxypropyl Cellulose, Sodium Lauryl sulphate, Croscarmellose, stearate, Magnesium, Polysorbate 80 and Colloidal Silicon anhydrous. Mortar and pestle were used to mix each excipient with Active Pharmaceutical Ingredient (API) in the ratio of 1:1; and the resultant mixtures were stored in Relative Humidity of 75±5% and Temperature of 40 ͦ C ±2 ◦C), room temperature 30◦C± 2◦C and in oven of 50◦C. Physical and chemical compatibility were assessed by using sense organs, HPTLC and NIR on day 0, after 14 and 90 days respectively. D-Optimal design expert version 7 software was used to get eight trial formulations. The formulations were evaluated and results were used to obtain seven predicted formulations. From these seven formulations, only one formulation was selected for optimization. Results: Pre-formulation showed that APIs and excipients were compatible within the studied period of 90 days. Formulation development was successfully performed by using a wet granulation method where by the optimized formulation which had Artemether 20 mg, Lumefantrine 120 mg, 2 milliliters of Polysorbate 80, Aerosil 4.75 mg, Hydroxypropyl cellulose 3.5 mg, Croscarmellose 4.5 mg and Microcrystalline cellulose 80 mg, gave good results of dissolution, tisintegration time, friability and assay that are comparable to the innovator drug. Conclusion: A formulation of Artemether 20 mg and Lumefantrine 120 mg fixed dose combination tablet was successfully developed by wet granulation method. This indicates that, scale up by our local Pharmaceutical industries may be done by adopting this formula but they should adhere to official compendia. Adoption of this formula will lead to mass production of this medicine as a result it will improve its availability and affordability.