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

Abstract

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 twolevel 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 (r 2 = 0.999) over the concentration range of 6.25-100 μg/ml. The results for precision were within the acceptance limit (%RSD < 2). The percent relative standard deviation (< 2%) and statistically non-significant (p > 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 evaluation of FDC ART/LUM tablets.

Quality assessment of oral antimalarial and antiretroviral medicines used by public health systems in Sahel countries

“…Regarding the dissolution test, the water medium was tested but LMF did not dissolve, even after 3 hours, because it is insoluble in water and AMT was partly dissolved as previous reports indicated [ 44 ]. Then, 0.1 N chloride acid (HCl) containing 1% benzalkonium chloride was used to perform the AMT/LMF tablets dissolution test just employing 6 units and not 12 (in the first stage of dissolution test) as the proposed USP monograph recommends [ 34 ].…”

“…Dissolution tests were performed following USP recommendations, see Table 1 [ 43 ]. In the case of AMT/LMF tablets, as an official monography is not available, different mediums were studied based on literature [ 34 , 44 ]. For all medicines, paddle apparatus was used [ 33 , 34 , 36 , 45 ].…”

Orally Deliverable Dual-Targeted Pellets for the Synergistic Treatment of Ulcerative Colitis

“…The pH dissolution method was used to evaluate drug release from pellets. 26 The GPs quickly disintegrated completely in the artificial gastric juice, resulting in a high release rate (pH 1.2, cumulative release over 98% in 5 min). The release of BBR from EPs was determined by using a ChP (2020 edition) dissolution apparatus II (basket method) at a rotation speed of 100 r/min in 750 mL of dissolution medium at 37 ± 0.5 °C under sink conditions.…”

Discriminative Dissolution Method Development Through an aQbD Approach

“…The general procedure to develop a dissolution method includes (1) understanding the properties of drug substance and drug product, (2) evaluating sink conditions, (3) optimizing the dissolution conditions, and (4) evaluating the dissolution profiles and finalizing the method conditions [14][15][16][17][18][19][20][21]. One-factor-at-a-time (OFAT) approach is commonly used for process and method optimization [22,23]. Although this approach is straightforward and easy to implement, it may take longer to identify the optimal conditions that yield an appropriate dissolution profile with sufficient discrimination power.…”