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Improving the solubility and bioavailability of dihydroartemisinin by solid dispersions and inclusion complexes.
Arch Pharm Res. 2011 May; 34(5):757-65.AP

Abstract

Dihydroartemisinin (DHA) is a poorly water-soluble drug that displays low bioavailability after oral administration. Attempts have been made to improve the solubility of DHA. Yet, no information is available concerning improved bioavailability. This study aimed to improve the water solubility of DHA by two systems: solid dispersions with polyvinylpyrrolidone (PVPK30, PVPK25, PVPK15) and inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD), as well as improving the bioavailability of both systems. The phase transition of DHA with hydrophilic polymers was evaluated by X-ray diffraction (XRD) and differential scanning calorimetery (DSC). DHA became amorphous in DHA-HPβCD complexes and showed more amorphous behavior in XRD analyses with rise in molecular weight of PVP. Melting onset temperature of DHA decreased, while DSC thermograms revealed the peak area and enhanced enthalpy change (DH) in solid dispersions as well as inclusion complexes. DHA solubility was enhanced 84-fold in DHA-HPβCD complexes and 50-times in DHA-PVPK30. The improved solubility using the four polymers was in the following order: HPβCD > PVPK30 > PVPK25 > PVPK15. Values of area under curve (AUC) and half life (t(1/2)) of DHA-PVPK30 were highest followed by DHA-HPβCD, DHA-PVPK15 and DHA-PVPK25. V(d)/f of DHA-PVPK30 was 7-fold. DHA-HPβCD, DHA-PVPK15 and DHA-PVPK25 showed significantly different pharmacokinetic parameters compared with DHA solutions. The 95% confidence interval was meaningful in AUC and t(1/2). Pharmacokinetic parameters revealed that all four-test preparations were significantly more bioavailable than DHA alone.

Authors+Show Affiliations

Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan. Ansari.Muhammad@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21656361

Citation

Ansari, Muhammad Tayyab, et al. "Improving the Solubility and Bioavailability of Dihydroartemisinin By Solid Dispersions and Inclusion Complexes." Archives of Pharmacal Research, vol. 34, no. 5, 2011, pp. 757-65.
Ansari MT, Batty KT, Iqbal I, et al. Improving the solubility and bioavailability of dihydroartemisinin by solid dispersions and inclusion complexes. Arch Pharm Res. 2011;34(5):757-65.
Ansari, M. T., Batty, K. T., Iqbal, I., & Sunderland, V. B. (2011). Improving the solubility and bioavailability of dihydroartemisinin by solid dispersions and inclusion complexes. Archives of Pharmacal Research, 34(5), 757-65. https://doi.org/10.1007/s12272-011-0509-1
Ansari MT, et al. Improving the Solubility and Bioavailability of Dihydroartemisinin By Solid Dispersions and Inclusion Complexes. Arch Pharm Res. 2011;34(5):757-65. PubMed PMID: 21656361.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improving the solubility and bioavailability of dihydroartemisinin by solid dispersions and inclusion complexes. AU - Ansari,Muhammad Tayyab, AU - Batty,Kevin T, AU - Iqbal,Ijaz, AU - Sunderland,Vivian Bruce, Y1 - 2011/06/09/ PY - 2010/03/04/received PY - 2010/10/18/accepted PY - 2010/10/12/revised PY - 2011/6/10/entrez PY - 2011/6/10/pubmed PY - 2011/10/14/medline SP - 757 EP - 65 JF - Archives of pharmacal research JO - Arch Pharm Res VL - 34 IS - 5 N2 - Dihydroartemisinin (DHA) is a poorly water-soluble drug that displays low bioavailability after oral administration. Attempts have been made to improve the solubility of DHA. Yet, no information is available concerning improved bioavailability. This study aimed to improve the water solubility of DHA by two systems: solid dispersions with polyvinylpyrrolidone (PVPK30, PVPK25, PVPK15) and inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD), as well as improving the bioavailability of both systems. The phase transition of DHA with hydrophilic polymers was evaluated by X-ray diffraction (XRD) and differential scanning calorimetery (DSC). DHA became amorphous in DHA-HPβCD complexes and showed more amorphous behavior in XRD analyses with rise in molecular weight of PVP. Melting onset temperature of DHA decreased, while DSC thermograms revealed the peak area and enhanced enthalpy change (DH) in solid dispersions as well as inclusion complexes. DHA solubility was enhanced 84-fold in DHA-HPβCD complexes and 50-times in DHA-PVPK30. The improved solubility using the four polymers was in the following order: HPβCD > PVPK30 > PVPK25 > PVPK15. Values of area under curve (AUC) and half life (t(1/2)) of DHA-PVPK30 were highest followed by DHA-HPβCD, DHA-PVPK15 and DHA-PVPK25. V(d)/f of DHA-PVPK30 was 7-fold. DHA-HPβCD, DHA-PVPK15 and DHA-PVPK25 showed significantly different pharmacokinetic parameters compared with DHA solutions. The 95% confidence interval was meaningful in AUC and t(1/2). Pharmacokinetic parameters revealed that all four-test preparations were significantly more bioavailable than DHA alone. SN - 0253-6269 UR - https://www.unboundmedicine.com/medline/citation/21656361/Improving_the_solubility_and_bioavailability_of_dihydroartemisinin_by_solid_dispersions_and_inclusion_complexes_ L2 - https://dx.doi.org/10.1007/s12272-011-0509-1 DB - PRIME DP - Unbound Medicine ER -