Solid dispersions of dihydroartemisinin in polyvinylpyrrolidone.

In the present study the physicochemical characteristics of dihydroartemisinin, polyvinylpyrrolidone and their solid dispersions were evaluated at various proportions of drug and polyvinylpyrrolidone. These properties were investigated with X-ray diffraction, fourier transform infrared spectrophotometry, differential scanning calorimetry, equilibrium solubility at twenty five and thirty seven degree centigrade. X-ray diffraction analysis detected that dihydroartemisinin became more amorphous as drug carrier ratio was enhanced in solid dispersions. Fourier transform infrared spectra suggested that there was a hydrogen bonding interaction between dihydroartemisinin and polyvinylpyrrolidone in all solid dispersions. These interactions reflected the changes in crystalline structures of dihydroartemisinin. The thermal behavior of dihydroartemisinin was unusual as it exhibited melting exotherm instead of endotherm. In solid dispersions containing varying contents of polyvinylpyrrolidone, enthalpy change and peak area were enhanced while melting onset temperature decreased with increase in polyvinylpyrrolidone proportion. This was attributed to a solid-state interaction. Equilibrium solubility of dihydroartemisinin increased sixty-fold due to induction of polyvinylpyrrolidone. When this solubility was compared among thirty-seven and twenty five degree centigrade in solid dispersions, it was up to seven times more at higher temperature. Physicochemical characteristics of solid dispersions containing drug carrier ratio of one: nine prepared in acetonitrile, ethanol, methanol and tetrahydrofuran showed differences which indicated that properties of medium i.e. dielectric constant, dipole moment and structure, influenced the amount of amorphousness and related properties of dihydroartemisinin.

Improving the solubility and bioavailability of dihydroartemisinin by solid dispersions and inclusion complexes.

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-ß-cyclodextrin (HPßCD), 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-HPßCD 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-HPßCD complexes and 50-times in DHA-PVPK30. The improved solubility using the four polymers was in the following order: HPßCD > PVPK30 > PVPK25 > PVPK15. Values of area under curve (AUC) and half life (t(1/2)) of DHA-PVPK30 were highest followed by DHA-HPßCD, DHA-PVPK15 and DHA-PVPK25. V(d)/f of DHA-PVPK30 was 7-fold. DHA-HPßCD, 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.

Purification of PEGylated nanoparticles using tangential flow filtration (TFF).

A tangential flow filtration system was evaluated to purify PEGylated nanoparticles. Two widely used surfactants, PVA and sodium cholate were efficiently removed from an empty nanoparticles suspension using the proposed system. During drug loading, surfactant (PVA) was observed to be entrapped within the core of the nanoparticle to a higher extent, hence was purified at a comparatively slower rate. The presence of dextran sulfate enhanced the drug loading but also resulted in reduced purification rate; this was described by the hypothesis of PVA inclusion within the core of the nanoparticles. Practically, it was possible to correlate the slow purification rate of PVA to its reduced filtration flow during the purification of the empty and loaded nanoparticles containing dextran sulfate. Indirectly, this system was capable of revealing the influence of an excipient and drug on the nanoparticle surface.