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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.


XRD patterns of (A) ARTM-Sol-PEG 400 (1 : 2), (B) ARTM-Sol-Lutrol F127 (1 : 2), and (C) ARTM-Sol-Lutrol F68 (1 : 2).
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fig7: XRD patterns of (A) ARTM-Sol-PEG 400 (1 : 2), (B) ARTM-Sol-Lutrol F127 (1 : 2), and (C) ARTM-Sol-Lutrol F68 (1 : 2).

Mentions: The X-ray diffractograms of ARTM show sharp multiple peaks, indicating the crystalline nature of the drug. Several distinct peaks similar to crystalline ARTM were observed in the physical mixture of polymers with the drug, again indicating the crystalline nature of the drug in the mixture. Pure ARTM shows characteristic peaks intensities which indicate its % crystallinity. As shown in Figure 9 major specific intensities of ARTM are observed at 59045, 7826, and 9872. In the case of melt extrudates from F1 to F9, the characteristic of these peaks of ARTM disappeared and percentage crystallinity also decreases variably. While in the melt extrudates from F10–F15 the intensity of ARTM characteristic peaks has decreased to acceptable amount. From the XRD studies of both fresh and aged SD formulations confirms the amorphous nature of ARTM with the polymers after HME (Figures 7, 8, and 9).


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)

XRD patterns of (A) ARTM-Sol-PEG 400 (1 : 2), (B) ARTM-Sol-Lutrol F127 (1 : 2), and (C) ARTM-Sol-Lutrol F68 (1 : 2).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig7: XRD patterns of (A) ARTM-Sol-PEG 400 (1 : 2), (B) ARTM-Sol-Lutrol F127 (1 : 2), and (C) ARTM-Sol-Lutrol F68 (1 : 2).
Mentions: The X-ray diffractograms of ARTM show sharp multiple peaks, indicating the crystalline nature of the drug. Several distinct peaks similar to crystalline ARTM were observed in the physical mixture of polymers with the drug, again indicating the crystalline nature of the drug in the mixture. Pure ARTM shows characteristic peaks intensities which indicate its % crystallinity. As shown in Figure 9 major specific intensities of ARTM are observed at 59045, 7826, and 9872. In the case of melt extrudates from F1 to F9, the characteristic of these peaks of ARTM disappeared and percentage crystallinity also decreases variably. While in the melt extrudates from F10–F15 the intensity of ARTM characteristic peaks has decreased to acceptable amount. From the XRD studies of both fresh and aged SD formulations confirms the amorphous nature of ARTM with the polymers after HME (Figures 7, 8, and 9).

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.