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Preparation of carbamazepine-Soluplus solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting.
Eur J Pharm Biopharm. 2013 May; 84(1):228-37.EJ

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) 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 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 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 ∼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 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.

Authors+Show Affiliations

Department of Pharmaceutical Technology and Cosmetology, University of Belgrade, Belgrade, Serbia. jelena.djuris@pharmacy.bg.ac.rsNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23333900

Citation

Djuris, Jelena, et al. "Preparation of carbamazepine-Soluplus Solid Dispersions By Hot-melt Extrusion, and Prediction of Drug-polymer Miscibility By Thermodynamic Model Fitting." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 84, no. 1, 2013, pp. 228-37.
Djuris J, Nikolakakis I, Ibric S, et al. Preparation of carbamazepine-Soluplus solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting. Eur J Pharm Biopharm. 2013;84(1):228-37.
Djuris, J., Nikolakakis, I., Ibric, S., Djuric, Z., & Kachrimanis, K. (2013). Preparation of carbamazepine-Soluplus solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 84(1), 228-37. https://doi.org/10.1016/j.ejpb.2012.12.018
Djuris J, et al. Preparation of carbamazepine-Soluplus Solid Dispersions By Hot-melt Extrusion, and Prediction of Drug-polymer Miscibility By Thermodynamic Model Fitting. Eur J Pharm Biopharm. 2013;84(1):228-37. PubMed PMID: 23333900.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preparation of carbamazepine-Soluplus solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting. AU - Djuris,Jelena, AU - Nikolakakis,Ioannis, AU - Ibric,Svetlana, AU - Djuric,Zorica, AU - Kachrimanis,Kyriakos, Y1 - 2013/01/18/ PY - 2012/09/20/received PY - 2012/12/23/revised PY - 2012/12/26/accepted PY - 2013/1/22/entrez PY - 2013/1/22/pubmed PY - 2014/1/17/medline SP - 228 EP - 37 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 84 IS - 1 N2 - 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) 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 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 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 ∼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 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. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/23333900/Preparation_of_carbamazepine_Soluplus_solid_dispersions_by_hot_melt_extrusion_and_prediction_of_drug_polymer_miscibility_by_thermodynamic_model_fitting_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(13)00004-0 DB - PRIME DP - Unbound Medicine ER -