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Molecular Factors Governing the Liquid and Glassy States Recrystallization of Celecoxib in Binary Mixtures with Excipients of Different Molecular Weights.
Mol Pharm. 2017 04 03; 14(4):1154-1168.MP

Abstract

Transformation of poorly water-soluble crystalline pharmaceuticals to the amorphous form is one of the most promising strategies to improve their oral bioavailability. Unfortunately, the amorphous drugs are usually thermodynamically unstable and may quickly return to their crystalline form. A very promising way to enhance the physical stability of amorphous drugs is to prepare amorphous compositions of APIs with certain excipients which can be characterized by significantly different molecular weights, such as polymers, acetate saccharides, and other APIs. By using different experimental techniques (broadband dielectric spectroscopy, differential scanning calorimetry, X-ray diffraction) we compare the effect of adding the large molecular weight polymer-polyvinylpyrrolidone (PVP K30)-and the small molecular weight excipient-octaacetylmaltose (acMAL)-on molecular dynamics as well as the tendency to recrystallization of the amorphous celecoxib (CEL) in the amorphous solid dispersions: CEL-PVP and CEL-acMAL. The physical stability investigations of the binary systems were performed in both the supercooled liquid and glassy states. We found that acMAL is a better inhibitor of recrystallization of amorphous CEL than PVP K30 deep in the glassy state (T < Tg). In contrast, PVP K30 is a better crystallization inhibitor of CEL than acMAL in the supercooled liquid state (at T > Tg). We discuss molecular factors governing the recrystallization of amorphous CEL in examined solid dispersions.

Authors+Show Affiliations

Institute of Physics, University of Silesia in Katowice , ul. Uniwersytecka 4, 40-007 Katowice, Poland. Silesian Center for Education and Interdisciplinary Research , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.Institute of Physics, University of Silesia in Katowice , ul. Uniwersytecka 4, 40-007 Katowice, Poland. Silesian Center for Education and Interdisciplinary Research , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.Institute of Physics, University of Silesia in Katowice , ul. Uniwersytecka 4, 40-007 Katowice, Poland. Silesian Center for Education and Interdisciplinary Research , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.Institute of Physics, University of Silesia in Katowice , ul. Uniwersytecka 4, 40-007 Katowice, Poland. Silesian Center for Education and Interdisciplinary Research , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.Institute of Physics, University of Silesia in Katowice , ul. Uniwersytecka 4, 40-007 Katowice, Poland. Silesian Center for Education and Interdisciplinary Research , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.Institute of Physics, University of Silesia in Katowice , ul. Uniwersytecka 4, 40-007 Katowice, Poland. Silesian Center for Education and Interdisciplinary Research , ul. 75 Pułku Piechoty 1a, 41-500 Chorzów, Poland.

Pub Type(s)

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

Language

eng

PubMed ID

28241116

Citation

Grzybowska, K, et al. "Molecular Factors Governing the Liquid and Glassy States Recrystallization of Celecoxib in Binary Mixtures With Excipients of Different Molecular Weights." Molecular Pharmaceutics, vol. 14, no. 4, 2017, pp. 1154-1168.
Grzybowska K, Chmiel K, Knapik-Kowalczuk J, et al. Molecular Factors Governing the Liquid and Glassy States Recrystallization of Celecoxib in Binary Mixtures with Excipients of Different Molecular Weights. Mol Pharm. 2017;14(4):1154-1168.
Grzybowska, K., Chmiel, K., Knapik-Kowalczuk, J., Grzybowski, A., Jurkiewicz, K., & Paluch, M. (2017). Molecular Factors Governing the Liquid and Glassy States Recrystallization of Celecoxib in Binary Mixtures with Excipients of Different Molecular Weights. Molecular Pharmaceutics, 14(4), 1154-1168. https://doi.org/10.1021/acs.molpharmaceut.6b01056
Grzybowska K, et al. Molecular Factors Governing the Liquid and Glassy States Recrystallization of Celecoxib in Binary Mixtures With Excipients of Different Molecular Weights. Mol Pharm. 2017 04 3;14(4):1154-1168. PubMed PMID: 28241116.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular Factors Governing the Liquid and Glassy States Recrystallization of Celecoxib in Binary Mixtures with Excipients of Different Molecular Weights. AU - Grzybowska,K, AU - Chmiel,K, AU - Knapik-Kowalczuk,J, AU - Grzybowski,A, AU - Jurkiewicz,K, AU - Paluch,M, Y1 - 2017/03/08/ PY - 2017/2/28/pubmed PY - 2017/10/27/medline PY - 2017/2/28/entrez KW - amorphous drug KW - celecoxib KW - crystallization KW - devitrification KW - glass transition KW - molecular dynamics KW - physical stability KW - solid dispersion SP - 1154 EP - 1168 JF - Molecular pharmaceutics JO - Mol. Pharm. VL - 14 IS - 4 N2 - Transformation of poorly water-soluble crystalline pharmaceuticals to the amorphous form is one of the most promising strategies to improve their oral bioavailability. Unfortunately, the amorphous drugs are usually thermodynamically unstable and may quickly return to their crystalline form. A very promising way to enhance the physical stability of amorphous drugs is to prepare amorphous compositions of APIs with certain excipients which can be characterized by significantly different molecular weights, such as polymers, acetate saccharides, and other APIs. By using different experimental techniques (broadband dielectric spectroscopy, differential scanning calorimetry, X-ray diffraction) we compare the effect of adding the large molecular weight polymer-polyvinylpyrrolidone (PVP K30)-and the small molecular weight excipient-octaacetylmaltose (acMAL)-on molecular dynamics as well as the tendency to recrystallization of the amorphous celecoxib (CEL) in the amorphous solid dispersions: CEL-PVP and CEL-acMAL. The physical stability investigations of the binary systems were performed in both the supercooled liquid and glassy states. We found that acMAL is a better inhibitor of recrystallization of amorphous CEL than PVP K30 deep in the glassy state (T < Tg). In contrast, PVP K30 is a better crystallization inhibitor of CEL than acMAL in the supercooled liquid state (at T > Tg). We discuss molecular factors governing the recrystallization of amorphous CEL in examined solid dispersions. SN - 1543-8392 UR - https://www.unboundmedicine.com/medline/citation/28241116/Molecular_Factors_Governing_the_Liquid_and_Glassy_States_Recrystallization_of_Celecoxib_in_Binary_Mixtures_with_Excipients_of_Different_Molecular_Weights_ L2 - https://dx.doi.org/10.1021/acs.molpharmaceut.6b01056 DB - PRIME DP - Unbound Medicine ER -