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Comparative study of the potential of poly(2-ethyl-2-oxazoline) as carrier in the formulation of amorphous solid dispersions of poorly soluble drugs.
Eur J Pharm Biopharm. 2019 Nov; 144:79-90.EJ

Abstract

Despite the fact that solid dispersions are gaining momentum, the number of polymers that have been used as a carrier during the past 50 years is rather limited. Recently, the poly(2-alkyl-2-oxazoline) (PAOx) polymer class profiled itself as a versatile platform for a wide variety of applications in drug delivery, including their use as amorphous solid dispersion (ASD) carrier. The aim of this study was to investigate the potential of poly(2-ethyl-2-oxazoline) (PEtOx) by applying a benchmark approach with well-known, commercially available carriers (i.e. polyvinylpyrrolidone (PVP) K30, poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) 64 and hydroxypropylmethylcellulose (HPMC)). For this purpose, itraconazole (ITC) and fenofibrate (FFB) were selected as poorly water-soluble model drugs. The four polymers were compared by establishing their supersaturation maintaining potential and by investigating their capability as carrier for ASDs with high drug loadings. Spray drying, as well as hot melt extrusion and cryo-milling were implemented as ASD manufacturing technologies for comparative evaluation. For each manufacturing technique, the formulations with the highest possible drug loadings were tested with respect to in vitro drug release kinetics. This study indicates that PEtOx is able to maintain supersaturation of the drugs to a similar extent as the commercially available polymers and that ASDs with comparable drug loadings can be manufactured. The results of the in vitro dissolution tests reveal that high drug release can be obtained for PEtOx formulations. Overall, proof-of-concept is provided for the potential of PEtOx for drug formulation purposes.

Authors+Show Affiliations

KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, 3000 Leuven, Belgium.KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, 3000 Leuven, Belgium.Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC), Department Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Gent, Belgium.Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC), Department Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Gent, Belgium.Supramolecular Chemistry Group, Centre of Macromolecular Chemistry (CMaC), Department Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Gent, Belgium.KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, 3000 Leuven, Belgium. Electronic address: guy.vandenmooter@kuleuven.be.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

31499162

Citation

Boel, Eline, et al. "Comparative Study of the Potential of Poly(2-ethyl-2-oxazoline) as Carrier in the Formulation of Amorphous Solid Dispersions of Poorly Soluble Drugs." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 144, 2019, pp. 79-90.
Boel E, Smeets A, Vergaelen M, et al. Comparative study of the potential of poly(2-ethyl-2-oxazoline) as carrier in the formulation of amorphous solid dispersions of poorly soluble drugs. Eur J Pharm Biopharm. 2019;144:79-90.
Boel, E., Smeets, A., Vergaelen, M., De la Rosa, V. R., Hoogenboom, R., & Van den Mooter, G. (2019). Comparative study of the potential of poly(2-ethyl-2-oxazoline) as carrier in the formulation of amorphous solid dispersions of poorly soluble drugs. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 144, 79-90. https://doi.org/10.1016/j.ejpb.2019.09.005
Boel E, et al. Comparative Study of the Potential of Poly(2-ethyl-2-oxazoline) as Carrier in the Formulation of Amorphous Solid Dispersions of Poorly Soluble Drugs. Eur J Pharm Biopharm. 2019;144:79-90. PubMed PMID: 31499162.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative study of the potential of poly(2-ethyl-2-oxazoline) as carrier in the formulation of amorphous solid dispersions of poorly soluble drugs. AU - Boel,Eline, AU - Smeets,Annelies, AU - Vergaelen,Maarten, AU - De la Rosa,Victor R, AU - Hoogenboom,Richard, AU - Van den Mooter,Guy, Y1 - 2019/09/06/ PY - 2019/06/20/received PY - 2019/08/08/revised PY - 2019/09/06/accepted PY - 2019/9/10/pubmed PY - 2019/11/27/medline PY - 2019/9/10/entrez KW - Amorphous solid dispersion KW - Cryo-milling KW - Hot melt extrusion KW - Poly(2-ethyl-2-oxazoline) KW - Spray drying SP - 79 EP - 90 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 144 N2 - Despite the fact that solid dispersions are gaining momentum, the number of polymers that have been used as a carrier during the past 50 years is rather limited. Recently, the poly(2-alkyl-2-oxazoline) (PAOx) polymer class profiled itself as a versatile platform for a wide variety of applications in drug delivery, including their use as amorphous solid dispersion (ASD) carrier. The aim of this study was to investigate the potential of poly(2-ethyl-2-oxazoline) (PEtOx) by applying a benchmark approach with well-known, commercially available carriers (i.e. polyvinylpyrrolidone (PVP) K30, poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) 64 and hydroxypropylmethylcellulose (HPMC)). For this purpose, itraconazole (ITC) and fenofibrate (FFB) were selected as poorly water-soluble model drugs. The four polymers were compared by establishing their supersaturation maintaining potential and by investigating their capability as carrier for ASDs with high drug loadings. Spray drying, as well as hot melt extrusion and cryo-milling were implemented as ASD manufacturing technologies for comparative evaluation. For each manufacturing technique, the formulations with the highest possible drug loadings were tested with respect to in vitro drug release kinetics. This study indicates that PEtOx is able to maintain supersaturation of the drugs to a similar extent as the commercially available polymers and that ASDs with comparable drug loadings can be manufactured. The results of the in vitro dissolution tests reveal that high drug release can be obtained for PEtOx formulations. Overall, proof-of-concept is provided for the potential of PEtOx for drug formulation purposes. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/31499162/Comparative_study_of_the_potential_of_poly_2_ethyl_2_oxazoline__as_carrier_in_the_formulation_of_amorphous_solid_dispersions_of_poorly_soluble_drugs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(19)30764-7 DB - PRIME DP - Unbound Medicine ER -