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Ternary system of dihydroartemisinin with hydroxypropyl-β-cyclodextrin and lecithin: simultaneous enhancement of drug solubility and stability in aqueous solutions.
J Pharm Biomed Anal. 2013 Sep; 83:141-8.JP

Abstract

The purpose of this study was to simultaneously improve the solubility and stability of dihydroartemisinin (DHA) in aqueous solutions by a ternary cyclodextrin system comprised of DHA, hydroxypropyl-β-cyclodextrin (HP-β-CD) and a third auxiliary substance. Solubility and phase solubility studies were carried out to evaluate the solubilizing efficiency of HP-β-CD in association with various auxiliary substances. Then, the solid binary (DHA-HP-β-CD or DHA-lecithin) and ternary systems were prepared and characterized by Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC) and power X-ray diffraction (PXRD). The effect of the ternary system on the solubility, dissolution and stability of DHA in aqueous solutions was also investigated. As a result, the soybean lecithin was found to be the most promising third component in terms of solubility enhancement. For the solid characterization, the disappearance of the drug crystallinity indicated the formation of new solid phases, implicating the formation of the ternary system. The dissolution rate of the solid ternary system was much faster than that of the drug alone and binary systems. Importantly, compared with binary systems, the ternary system showed a significant improvement in the stability of DHA in Hank's balanced salt solutions (pH 7.4). The solubility and stability of DHA in aqueous solutions were simultaneously enhanced by the ternary system, which might be attributed to the possible formation of a ternary complex. For the ternary interactions, results of molecular docking studies further indicated that the lecithin covered the top of the wide rim of HP-β-CD and surrounded around the peroxide bridging of DHA, providing the possibility for the ternary complex formation. In summary, the ternary system prepared in our study, with simultaneous enhancement of DHA solubility and stability in aqueous solutions, might have an important pharmaceutical potential in the development of a better oral formulation of DHA.

Authors+Show Affiliations

Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23732534

Citation

Wang, Dan, et al. "Ternary System of Dihydroartemisinin With Hydroxypropyl-β-cyclodextrin and Lecithin: Simultaneous Enhancement of Drug Solubility and Stability in Aqueous Solutions." Journal of Pharmaceutical and Biomedical Analysis, vol. 83, 2013, pp. 141-8.
Wang D, Li H, Gu J, et al. Ternary system of dihydroartemisinin with hydroxypropyl-β-cyclodextrin and lecithin: simultaneous enhancement of drug solubility and stability in aqueous solutions. J Pharm Biomed Anal. 2013;83:141-8.
Wang, D., Li, H., Gu, J., Guo, T., Yang, S., Guo, Z., Zhang, X., Zhu, W., & Zhang, J. (2013). Ternary system of dihydroartemisinin with hydroxypropyl-β-cyclodextrin and lecithin: simultaneous enhancement of drug solubility and stability in aqueous solutions. Journal of Pharmaceutical and Biomedical Analysis, 83, 141-8. https://doi.org/10.1016/j.jpba.2013.05.001
Wang D, et al. Ternary System of Dihydroartemisinin With Hydroxypropyl-β-cyclodextrin and Lecithin: Simultaneous Enhancement of Drug Solubility and Stability in Aqueous Solutions. J Pharm Biomed Anal. 2013;83:141-8. PubMed PMID: 23732534.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ternary system of dihydroartemisinin with hydroxypropyl-β-cyclodextrin and lecithin: simultaneous enhancement of drug solubility and stability in aqueous solutions. AU - Wang,Dan, AU - Li,Haiyan, AU - Gu,Jingkai, AU - Guo,Tao, AU - Yang,Shuo, AU - Guo,Zhen, AU - Zhang,Xueju, AU - Zhu,Weifeng, AU - Zhang,Jiwen, Y1 - 2013/05/13/ PY - 2013/02/18/received PY - 2013/04/27/revised PY - 2013/05/01/accepted PY - 2013/6/5/entrez PY - 2013/6/5/pubmed PY - 2014/3/25/medline SP - 141 EP - 8 JF - Journal of pharmaceutical and biomedical analysis JO - J Pharm Biomed Anal VL - 83 N2 - The purpose of this study was to simultaneously improve the solubility and stability of dihydroartemisinin (DHA) in aqueous solutions by a ternary cyclodextrin system comprised of DHA, hydroxypropyl-β-cyclodextrin (HP-β-CD) and a third auxiliary substance. Solubility and phase solubility studies were carried out to evaluate the solubilizing efficiency of HP-β-CD in association with various auxiliary substances. Then, the solid binary (DHA-HP-β-CD or DHA-lecithin) and ternary systems were prepared and characterized by Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC) and power X-ray diffraction (PXRD). The effect of the ternary system on the solubility, dissolution and stability of DHA in aqueous solutions was also investigated. As a result, the soybean lecithin was found to be the most promising third component in terms of solubility enhancement. For the solid characterization, the disappearance of the drug crystallinity indicated the formation of new solid phases, implicating the formation of the ternary system. The dissolution rate of the solid ternary system was much faster than that of the drug alone and binary systems. Importantly, compared with binary systems, the ternary system showed a significant improvement in the stability of DHA in Hank's balanced salt solutions (pH 7.4). The solubility and stability of DHA in aqueous solutions were simultaneously enhanced by the ternary system, which might be attributed to the possible formation of a ternary complex. For the ternary interactions, results of molecular docking studies further indicated that the lecithin covered the top of the wide rim of HP-β-CD and surrounded around the peroxide bridging of DHA, providing the possibility for the ternary complex formation. In summary, the ternary system prepared in our study, with simultaneous enhancement of DHA solubility and stability in aqueous solutions, might have an important pharmaceutical potential in the development of a better oral formulation of DHA. SN - 1873-264X UR - https://www.unboundmedicine.com/medline/citation/23732534/Ternary_system_of_dihydroartemisinin_with_hydroxypropyl_β_cyclodextrin_and_lecithin:_simultaneous_enhancement_of_drug_solubility_and_stability_in_aqueous_solutions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0731-7085(13)00194-5 DB - PRIME DP - Unbound Medicine ER -