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Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting
Hot-melt extrusion (HME) is a dust- and solvent-free continuous process enabling the preparation of a variety of solid dosage forms containing solid dispersions of poorly soluble drugs into thermoplastic-polymers. Miscibility of drug and polymer is a prerequisite for stable solid dispersion formation. The present study investigates the feasibility of forming solid dispersions of carbamazepine (CBZ) into polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus (R)) by hot-melt extrusion. Physicochemical properties of the raw materials, extrudates, co-melted products, and corresponding physical mixtures were characterized by thermo-gravimetric analysis (TGA), differential. scanning calorimetry (DSC), attenuated total reflectance infrared (ATR-FTIR) spectroscopy and hot stage microscopy (HSM), while miscibility of CBZ and Soluplus (R) was estimated on the basis of the Flory-Huggins theory, Hansen solubility parameters, and solid-liquid equilibrium equation. I...t was found that hot-melt extrusion of carbamazepine and Soluplus (R) is feasible on a single-screw hot-melt extruder without the addition of plasticizers. DSC analysis and FTIR spectroscopy revealed that a molecular dispersion is formed when the content of CBZ does not exceed similar to 5% w/w while higher CBZ content results in a microcrystalline dispersion of CBZ form III crystals, with the molecularly dispersed percentage increasing with extrusion temperature, at the risk of inducing transformation to the undesirable form I of CBZ. Thermodynamic modeling elucidated potential limitations and temperature dependence of solubility/dispersibility of carbamazepine in Soluplus (R) hot-melt extrudates. The results obtained by thermodynamic models are in agreement with the findings of the HME processing, encouraging therefore their further application in the HME process development.
TY - JOUR
AU - Đuriš, Jelena
AU - Nikolakakis, Ioannis
AU - Ibrić, Svetlana
AU - Đurić, Zorica
AU - Kachrimanis, Kyriakos
PY - 2013
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1997
AB - Hot-melt extrusion (HME) is a dust- and solvent-free continuous process enabling the preparation of a variety of solid dosage forms containing solid dispersions of poorly soluble drugs into thermoplastic-polymers. Miscibility of drug and polymer is a prerequisite for stable solid dispersion formation. The present study investigates the feasibility of forming solid dispersions of carbamazepine (CBZ) into polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus (R)) by hot-melt extrusion. Physicochemical properties of the raw materials, extrudates, co-melted products, and corresponding physical mixtures were characterized by thermo-gravimetric analysis (TGA), differential. scanning calorimetry (DSC), attenuated total reflectance infrared (ATR-FTIR) spectroscopy and hot stage microscopy (HSM), while miscibility of CBZ and Soluplus (R) was estimated on the basis of the Flory-Huggins theory, Hansen solubility parameters, and solid-liquid equilibrium equation. It was found that hot-melt extrusion of carbamazepine and Soluplus (R) is feasible on a single-screw hot-melt extruder without the addition of plasticizers. DSC analysis and FTIR spectroscopy revealed that a molecular dispersion is formed when the content of CBZ does not exceed similar to 5% w/w while higher CBZ content results in a microcrystalline dispersion of CBZ form III crystals, with the molecularly dispersed percentage increasing with extrusion temperature, at the risk of inducing transformation to the undesirable form I of CBZ. Thermodynamic modeling elucidated potential limitations and temperature dependence of solubility/dispersibility of carbamazepine in Soluplus (R) hot-melt extrudates. The results obtained by thermodynamic models are in agreement with the findings of the HME processing, encouraging therefore their further application in the HME process development.
PB - Elsevier Science BV, Amsterdam
T2 - European Journal of Pharmaceutics and Biopharmaceutics
T1 - Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting
VL - 84
IS - 1
SP - 228
EP - 237
DO - 10.1016/j.ejpb.2012.12.018
ER -
@article{
author = "Đuriš, Jelena and Nikolakakis, Ioannis and Ibrić, Svetlana and Đurić, Zorica and Kachrimanis, Kyriakos",
year = "2013",
abstract = "Hot-melt extrusion (HME) is a dust- and solvent-free continuous process enabling the preparation of a variety of solid dosage forms containing solid dispersions of poorly soluble drugs into thermoplastic-polymers. Miscibility of drug and polymer is a prerequisite for stable solid dispersion formation. The present study investigates the feasibility of forming solid dispersions of carbamazepine (CBZ) into polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus (R)) by hot-melt extrusion. Physicochemical properties of the raw materials, extrudates, co-melted products, and corresponding physical mixtures were characterized by thermo-gravimetric analysis (TGA), differential. scanning calorimetry (DSC), attenuated total reflectance infrared (ATR-FTIR) spectroscopy and hot stage microscopy (HSM), while miscibility of CBZ and Soluplus (R) was estimated on the basis of the Flory-Huggins theory, Hansen solubility parameters, and solid-liquid equilibrium equation. It was found that hot-melt extrusion of carbamazepine and Soluplus (R) is feasible on a single-screw hot-melt extruder without the addition of plasticizers. DSC analysis and FTIR spectroscopy revealed that a molecular dispersion is formed when the content of CBZ does not exceed similar to 5% w/w while higher CBZ content results in a microcrystalline dispersion of CBZ form III crystals, with the molecularly dispersed percentage increasing with extrusion temperature, at the risk of inducing transformation to the undesirable form I of CBZ. Thermodynamic modeling elucidated potential limitations and temperature dependence of solubility/dispersibility of carbamazepine in Soluplus (R) hot-melt extrudates. The results obtained by thermodynamic models are in agreement with the findings of the HME processing, encouraging therefore their further application in the HME process development.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
title = "Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting",
volume = "84",
number = "1",
pages = "228-237",
doi = "10.1016/j.ejpb.2012.12.018"
}
Đuriš, J., Nikolakakis, I., Ibrić, S., Đurić, Z.,& Kachrimanis, K.. (2013). Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting. in European Journal of Pharmaceutics and Biopharmaceutics
Elsevier Science BV, Amsterdam., 84(1), 228-237.
https://doi.org/10.1016/j.ejpb.2012.12.018
Đuriš J, Nikolakakis I, Ibrić S, Đurić Z, Kachrimanis K. Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting. in European Journal of Pharmaceutics and Biopharmaceutics. 2013;84(1):228-237.
doi:10.1016/j.ejpb.2012.12.018 .
Đuriš, Jelena, Nikolakakis, Ioannis, Ibrić, Svetlana, Đurić, Zorica, Kachrimanis, Kyriakos, "Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting" in European Journal of Pharmaceutics and Biopharmaceutics, 84, no. 1 (2013):228-237,
https://doi.org/10.1016/j.ejpb.2012.12.018 . .
