Development of a solid oral dosage form containing Artemisia afra extract

Abstract

Artemisia afra is a medicinal plant traditionally used in the form of a tea infusion. The process of preparing an infusion is time-consuming with potential variation in phytochemical compounds as well as poor stability after extraction. Artemisia afra is a popular medicinal plant, however, it is not yet available in a properly designed solid oral dosage form. A product in a solid oral dosage form containing A. afra will be beneficial, especially in view of the poor organoleptic properties of the water-based infusion or tea. By employing a scientific formulation approach such as the SeDeM Expert Diagram System (SeDeM EDS), the formulation time can be shortened to identify an optimised powder formulation for direct compression of tablets. In this study, a solid oral dosage form containing A. afra extract was formulated. Artemisia afra was chemically characterised, and four phytochemical markers were identified to be quantified using a validated high-performance liquid chromatography (HPLC) analytical method. The method was applied to quantify the four selected A. afra phytochemical markers (selected based on peak heights) in preparations or powders containing A. afra with respect to morin hydrate equivalent values. The HPLC analytical method, using morin hydrate as an internal standard, was validated with regards to accuracy, precision, linearity, specificity, limit of detection and limit of quantification. Morin hydrate was added to all the A. afra samples to quantify each of the selected phytochemical marker molecules as milligram morin hydrate equivalents per gram of dry extract weight (mg MHE/g). Aqueous A. afra extracts were prepared at four temperatures (25ºC, 50ºC, 70ºC, and 96ºC). The HPLC method was applied to determine the amount of mg MHE/g for the four selected phytochemical markers. Frozen A. afra extracts were freeze-dried to determine the dry extract powder yields. Results showed that extracts prepared at 96ºC yielded the highest dry powder extract and produced the highest amount of mg MHE/g for the four phytochemical marker molecules. Bulk aqueous A. afra extracts were subsequently prepared at 96ºC. Bulk A. afra frozen extracts were freeze-dried and the dry powder extract was used in combination with excipients to formulate a solid oral dosage form. Furthermore, extracts prepared from A. afra plant material, each derived from a different location, were compared with regards to phytochemical composition and dry extract powder yield. Variances in phytochemical composition between A. afra plants from different regions were observed, and the dry powder yields differed slightly. The SeDeM EDS was employed to develop a directly compressible tablet containing A. afra extract. First, the powder flow properties of the dried A. afra extract powder were characterised using the SeDeM EDS. The values of 12 powder flow parameters were calculated and grouped

into five relevant SeDeM incidences, after which a polygon was drafted to obtain a graphical representation of the flow properties of the A. afra dry powder extract. Six excipients were also characterised using the SeDeM EDS, and corresponding polygons were constructed for each excipient. Based on excipient profiles, and the profile of the A. afra extract, tricalcium citrate was selected as the corrective excipient to compensate for the deficient properties of the A. afra extract. A small percentage of binder, lubricant and disintegrant was added to the tricalcium citrate (excipient to compensate for the deficient flow properties of the A. afra powder extract) and was again characterised with SeDeM EDS. Finally, the ratio of A. afra dry extract to excipient mixture required to formulate a final powder mixture for tabletting was calculated. The formulated tablet mass was calculated based on 200 mg of dry A. afra powder extract inside each tablet. The A. afra dry powder extract was mixed with the corrective excipient mixture and compressed into 12 mm diameter flat faced tablets weighing 667 mg each. Tablets were packed into 13 containers of 60 tablets each, ready for 12 weeks stability testing and evaluation in terms of an assay, weight variation, hardness, friability, disintegration, and dissolution behaviour. All tablet samples complied with the BP specifications for uniformity of weight, friability, and disintegration. Assay results showed that the tabletting process immediately impacted the mg MHE/g phytochemical marker molecules 2 – 4, as they lost more than 35% in mg MHE/g after direct compression. Accelerated stability conditions of 25°C/60% relative humidity resulted in a slight reduction in mg MHE/g for phytochemical marker molecule 1 after 12 weeks, however a noticeable decrease in mg MHE/g was observed for phytochemical marker molecules 2 – 4 after 12 weeks. All four phytochemical marker molecules showed a more significant decrease in mg MHE/g at accelerated stability conditions of 40°C/75% relative humidity. Dissolution results showed that an increase in tablet hardness led to a reduced dissolution rate, and the reduction in MHE/g after the tabletting process shown by the assay results led to a maximum dissolution percentage of approximately 65% for phytochemical markers 2 – 3, and 48% for phytochemical marker 4. Tabletting had less of an impact on phytochemical marker 1.