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Artemether-Soluplus Hot-Melt Extrudate Solid Dispersion Systems for Solubility and Dissolution Rate Enhancement with Amorphous State Characteristics.

Fule RA, Meer TS, Sav AR, Amin PD - J Pharm (Cairo) (2013)

Bottom Line: The results showed that the dissolution rate increased with increasing the ratio of polymer and surfactant to that of drug.The aqueous solubility and dissolution rate of prepared solid dispersion were significantly enhanced.Thus hot-melt extrusion (HME) is a promising technology for improving solubility and dissolution profile of ARTM.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India.

ABSTRACT
This work studied artemether (ARTM) solid dispersion (SD) formulation using mixture of polymer excipient Soluplus, PEG 400, Lutrol F127, and Lutrol F68 melts at temperatures lower than the melting point of ARTM using a laboratory-size, single-screw rotating batch extruder. The effects of three surfactants PEG 400, Lutrol F127, and Lutrol F68 and parameters like mixing temperature, screw rotating speed, and residence time were systematically studied. SEM, XRD, and FT-IR were employed to investigate the evolution of ARTM's dissolution into the molten excipient. Differential scanning calorimetry (DSC) was used to quantitatively study the melting enthalpy evolution of the drug. The results showed that the dissolution rate increased with increasing the ratio of polymer and surfactant to that of drug. It was concluded that the dissolution of the drug in the polymer melt is a convective diffusion process and that laminar distributive mixing can significantly enhance the dissolution rate. The aqueous solubility and dissolution rate of prepared solid dispersion were significantly enhanced. In vitro antimalarial studies revealed marked improvement in IC50 values. Thus hot-melt extrusion (HME) is a promising technology for improving solubility and dissolution profile of ARTM.

No MeSH data available.


DSC thermogram of pure ARTM.
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fig6: DSC thermogram of pure ARTM.

Mentions: The DSC thermograms show that the crystalline ARTM was characterized by a single, sharp melting endotherm at 90°C (ΔH  61.842 Jg−1). The melting endotherm of the ARTM in the physical mixture occurred at 81°C, whereas the melt extrudates had no distinct melting endotherm for the drug. The formation of amorphous solid dispersion is attributed to the molecular interaction between drug and polymer. This indicated that the drug exists in the amorphous state in the melt extrudates. The disappearance of the melting endotherm in the DSC scan of HME suggested that the drug has been converted to the amorphous form during the extrusion process (Figures 4, 5, and 6).


Artemether-Soluplus Hot-Melt Extrudate Solid Dispersion Systems for Solubility and Dissolution Rate Enhancement with Amorphous State Characteristics.

Fule RA, Meer TS, Sav AR, Amin PD - J Pharm (Cairo) (2013)

DSC thermogram of pure ARTM.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4590813&req=5

fig6: DSC thermogram of pure ARTM.
Mentions: The DSC thermograms show that the crystalline ARTM was characterized by a single, sharp melting endotherm at 90°C (ΔH  61.842 Jg−1). The melting endotherm of the ARTM in the physical mixture occurred at 81°C, whereas the melt extrudates had no distinct melting endotherm for the drug. The formation of amorphous solid dispersion is attributed to the molecular interaction between drug and polymer. This indicated that the drug exists in the amorphous state in the melt extrudates. The disappearance of the melting endotherm in the DSC scan of HME suggested that the drug has been converted to the amorphous form during the extrusion process (Figures 4, 5, and 6).

Bottom Line: The results showed that the dissolution rate increased with increasing the ratio of polymer and surfactant to that of drug.The aqueous solubility and dissolution rate of prepared solid dispersion were significantly enhanced.Thus hot-melt extrusion (HME) is a promising technology for improving solubility and dissolution profile of ARTM.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400019, India.

ABSTRACT
This work studied artemether (ARTM) solid dispersion (SD) formulation using mixture of polymer excipient Soluplus, PEG 400, Lutrol F127, and Lutrol F68 melts at temperatures lower than the melting point of ARTM using a laboratory-size, single-screw rotating batch extruder. The effects of three surfactants PEG 400, Lutrol F127, and Lutrol F68 and parameters like mixing temperature, screw rotating speed, and residence time were systematically studied. SEM, XRD, and FT-IR were employed to investigate the evolution of ARTM's dissolution into the molten excipient. Differential scanning calorimetry (DSC) was used to quantitatively study the melting enthalpy evolution of the drug. The results showed that the dissolution rate increased with increasing the ratio of polymer and surfactant to that of drug. It was concluded that the dissolution of the drug in the polymer melt is a convective diffusion process and that laminar distributive mixing can significantly enhance the dissolution rate. The aqueous solubility and dissolution rate of prepared solid dispersion were significantly enhanced. In vitro antimalarial studies revealed marked improvement in IC50 values. Thus hot-melt extrusion (HME) is a promising technology for improving solubility and dissolution profile of ARTM.

No MeSH data available.