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

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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 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 < 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 evalua-tion of FDC ART/LUM tablets.
Keywords
Parasitology, Infectious Diseases

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MLA
Yohannes, Sileshi Belew, et al. “Development of a Dissolution Method for Lumefantrine and Artemether in Immediate Release Fixed Dose Artemether/Lumefantrine Tablets.” Malaria Journal, vol. 19, BMC, 2020.
APA
Yohannes, S. B., Suleman, S., Duguma, M., Teshome, H., Wynendaele, E., Duchateau, L., & De Spiegeleer, B. (2020). Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets. Malaria Journal, 19.
Chicago author-date
Yohannes, Sileshi Belew, Sultan Suleman, Markos Duguma, Henok Teshome, Evelien Wynendaele, Luc Duchateau, and Bart De Spiegeleer. 2020. “Development of a Dissolution Method for Lumefantrine and Artemether in Immediate Release Fixed Dose Artemether/Lumefantrine Tablets.” Malaria Journal 19.
Chicago author-date (all authors)
Yohannes, Sileshi Belew, Sultan Suleman, Markos Duguma, Henok Teshome, Evelien Wynendaele, Luc Duchateau, and Bart De Spiegeleer. 2020. “Development of a Dissolution Method for Lumefantrine and Artemether in Immediate Release Fixed Dose Artemether/Lumefantrine Tablets.” Malaria Journal 19.
Vancouver
1.
Yohannes SB, Suleman S, Duguma M, Teshome H, Wynendaele E, Duchateau L, et al. Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets. Malaria Journal. 2020;19.
IEEE
[1]
S. B. Yohannes et al., “Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets,” Malaria Journal, vol. 19, 2020.
@article{8659434,
  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 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 <   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 evalua-tion of FDC ART/LUM tablets.},
  articleno    = {139},
  author       = {Yohannes, Sileshi Belew and Suleman, Sultan and Duguma, Markos and Teshome, Henok and Wynendaele, Evelien and Duchateau, Luc and De Spiegeleer, Bart},
  issn         = {1475-2875},
  journal      = {Malaria Journal},
  keywords     = {Parasitology,Infectious Diseases},
  language     = {eng},
  publisher    = {BMC},
  title        = {Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets},
  url          = {http://dx.doi.org/10.1186/s12936-020-03209-5},
  volume       = {19},
  year         = {2020},
}

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