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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.


Contour surface plot of Florey-Huggins modelling in prepared SD formulations.
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Related In: Results  -  Collection


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fig18: Contour surface plot of Florey-Huggins modelling in prepared SD formulations.

Mentions: Flory-Huggins lattice theory was developed to better understand the thermodynamics of polymer-drug mixtures by taking into account the entropy of mixing of a drug molecule with the polymer, as well as any enthalpy of mixing contributions. Numerous workers have applied various forms of the FH equation to better understand pharmaceutical systems, including solid dispersion systems. It has been reported that if coexistence  χ ≥ 0.5/M, so there is a presence of slightest degree of unfavorable non-bonding interactions between the drug, polymer, and surfactant mixture which may increase the stability even in amorphous state. As shown in Table 7 the value of FH interaction factor is (χ) not more than or equal to  0.5/M. This is because the entropy of mixing is greatly reduced due to formation of molecular dispersion using HME which means that it is favorable for mixing drug and polymer. Adhesive interaction between drug and polymer is favoured by the reduction in the Tg of SD systems which implicates the miscibility of drug and polymer. It indicates that the developed solid dispersions are thermodynamically stable. The contour surface plot of various parameters used in Flory-Huggins modelling was obtained as shown in Figure 18. The left-hand side parameter of equation, that is, 1/Tmmix and 1/Tmpure  were treated as independent variables and all the other parameters on right-hand side of equation are treated as dependent variables.


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)

Contour surface plot of Florey-Huggins modelling in prepared SD formulations.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig18: Contour surface plot of Florey-Huggins modelling in prepared SD formulations.
Mentions: Flory-Huggins lattice theory was developed to better understand the thermodynamics of polymer-drug mixtures by taking into account the entropy of mixing of a drug molecule with the polymer, as well as any enthalpy of mixing contributions. Numerous workers have applied various forms of the FH equation to better understand pharmaceutical systems, including solid dispersion systems. It has been reported that if coexistence  χ ≥ 0.5/M, so there is a presence of slightest degree of unfavorable non-bonding interactions between the drug, polymer, and surfactant mixture which may increase the stability even in amorphous state. As shown in Table 7 the value of FH interaction factor is (χ) not more than or equal to  0.5/M. This is because the entropy of mixing is greatly reduced due to formation of molecular dispersion using HME which means that it is favorable for mixing drug and polymer. Adhesive interaction between drug and polymer is favoured by the reduction in the Tg of SD systems which implicates the miscibility of drug and polymer. It indicates that the developed solid dispersions are thermodynamically stable. The contour surface plot of various parameters used in Flory-Huggins modelling was obtained as shown in Figure 18. The left-hand side parameter of equation, that is, 1/Tmmix and 1/Tmpure  were treated as independent variables and all the other parameters on right-hand side of equation are treated as dependent variables.

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.