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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.


Infrared spectroscopic diagrams of pure drug and HME SD formulations.
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Related In: Results  -  Collection


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fig10: Infrared spectroscopic diagrams of pure drug and HME SD formulations.

Mentions: Infrared spectroscopy has been widely used to investigate drug-polymer interactions in solid dispersion systems. In order to evaluate any possible chemical interactions between the drug and carriers, FTIR spectra of ARTM, physical mixtures, and HME formulations were examined (Figure 10). IR spectrum of ARTM presented characteristic peaks alkene at 3228–3420 cm−1 and OH stretch in the range of 2799–2950 cm−1. It also exhibited CO stretch at 1750 cm−1, CH stretching at 2750–2850 cm−1, and C–C stretch in the range of 1580–1650 cm−1. The formulations F1 and F3 showed characteristic peaks at 3414 cm−1, 2954 cm−1, 1604 cm−1, 1137 cm−1, and 991 cm−1. The formulations from F4 and F6 showed characteristic peaks at 3426 cm−1, 2936 cm−1, 1610 cm−1, 1199 cm−1, and 991.99 cm−1. The formulations from F7 and F9 showed characteristic peaks at 3424 cm−1, 2958 cm−1, 1608 cm−1, 1147 cm−1, and 991.87 cm−1. The formulations from F10, F12, and F15 showed characteristic peaks at range 3447 cm−1, 2961 cm−1, 1612 cm−1, 1144 cm−1, and 991.29 cm−1. The spectra of ARTM + Soluplus physical mixture and HME formulations are identical. The ARTM skeleton stretching vibrations are not affected by the addition of polymer, suggesting no interaction between the polymer and drug in the physical and HME mixtures. Lutrol has free hydrogen atoms that can potentially form hydrogen bonds with ARTM in the HME formulations. The carbonyl group is more favourable for hydrogen bonding and intermolecular interactions than the nitrogen atom because of steric hindrance. For HME formulations, the OH stretching bands broadened and the intensity of the bands decreased, indicating some degree of interaction between the proton donating groups of ARTM and the proton accepting groups in the Soluplus.


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)

Infrared spectroscopic diagrams of pure drug and HME SD formulations.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig10: Infrared spectroscopic diagrams of pure drug and HME SD formulations.
Mentions: Infrared spectroscopy has been widely used to investigate drug-polymer interactions in solid dispersion systems. In order to evaluate any possible chemical interactions between the drug and carriers, FTIR spectra of ARTM, physical mixtures, and HME formulations were examined (Figure 10). IR spectrum of ARTM presented characteristic peaks alkene at 3228–3420 cm−1 and OH stretch in the range of 2799–2950 cm−1. It also exhibited CO stretch at 1750 cm−1, CH stretching at 2750–2850 cm−1, and C–C stretch in the range of 1580–1650 cm−1. The formulations F1 and F3 showed characteristic peaks at 3414 cm−1, 2954 cm−1, 1604 cm−1, 1137 cm−1, and 991 cm−1. The formulations from F4 and F6 showed characteristic peaks at 3426 cm−1, 2936 cm−1, 1610 cm−1, 1199 cm−1, and 991.99 cm−1. The formulations from F7 and F9 showed characteristic peaks at 3424 cm−1, 2958 cm−1, 1608 cm−1, 1147 cm−1, and 991.87 cm−1. The formulations from F10, F12, and F15 showed characteristic peaks at range 3447 cm−1, 2961 cm−1, 1612 cm−1, 1144 cm−1, and 991.29 cm−1. The spectra of ARTM + Soluplus physical mixture and HME formulations are identical. The ARTM skeleton stretching vibrations are not affected by the addition of polymer, suggesting no interaction between the polymer and drug in the physical and HME mixtures. Lutrol has free hydrogen atoms that can potentially form hydrogen bonds with ARTM in the HME formulations. The carbonyl group is more favourable for hydrogen bonding and intermolecular interactions than the nitrogen atom because of steric hindrance. For HME formulations, the OH stretching bands broadened and the intensity of the bands decreased, indicating some degree of interaction between the proton donating groups of ARTM and the proton accepting groups in the Soluplus.

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.