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Impact of low molecular weight excipient octaacetylmaltose on the liquid crystalline ordering and molecular dynamics in the supercooled liquid and glassy state of itraconazole.
Eur J Pharm Biopharm. 2014 Nov; 88(3):1094-104.EJ

Abstract

Different experimental and theoretical techniques were applied to investigate basic physical properties of very stable and homogeneous solid dispersions formed by itraconazole and octaacetylmaltose. Differential scanning calorimetry as well as semi-empirical calculations have indicated that liquid crystalline ordering in itraconazole was completely suppressed in the binary mixtures. Molecular dynamics studies with the use of broadband dielectric spectroscopy have shown that the width of the structural relaxation process becomes smaller and fragility drops in solid dispersions with respect to the pure itraconazole. Moreover, the dynamics of secondary relaxation processes was affected by acetylated maltose. As demonstrated, β- and γ-secondary modes shift to higher and lower frequencies, respectively. On the other hand, aging experiments revealed that isostructural relaxation times in the glassy state become systematically longer with the addition of modified carbohydrate. This is a very important finding in the context of the current discussion on the factors affecting physical stability of easily crystallizing APIs. It seems that beside intermolecular interactions and local reorientation, the global mobility might control the crystallization of amorphous solid dispersions. Finally, we have demonstrated that itraconazole in binary mixtures dissolves faster and to greater extent with respect to the crystalline and amorphous form of this API.

Authors

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Pub Type(s)

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

Language

eng

PubMed ID

25460155

Citation

Kaminska, E, et al. "Impact of Low Molecular Weight Excipient Octaacetylmaltose On the Liquid Crystalline Ordering and Molecular Dynamics in the Supercooled Liquid and Glassy State of Itraconazole." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 88, no. 3, 2014, pp. 1094-104.
Kaminska E, Tarnacka M, Kolodziejczyk K, et al. Impact of low molecular weight excipient octaacetylmaltose on the liquid crystalline ordering and molecular dynamics in the supercooled liquid and glassy state of itraconazole. Eur J Pharm Biopharm. 2014;88(3):1094-104.
Kaminska, E., Tarnacka, M., Kolodziejczyk, K., Dulski, M., Zakowiecki, D., Hawelek, L., Adrjanowicz, K., Zych, M., Garbacz, G., & Kaminski, K. (2014). Impact of low molecular weight excipient octaacetylmaltose on the liquid crystalline ordering and molecular dynamics in the supercooled liquid and glassy state of itraconazole. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 88(3), 1094-104.
Kaminska E, et al. Impact of Low Molecular Weight Excipient Octaacetylmaltose On the Liquid Crystalline Ordering and Molecular Dynamics in the Supercooled Liquid and Glassy State of Itraconazole. Eur J Pharm Biopharm. 2014;88(3):1094-104. PubMed PMID: 25460155.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of low molecular weight excipient octaacetylmaltose on the liquid crystalline ordering and molecular dynamics in the supercooled liquid and glassy state of itraconazole. AU - Kaminska,E, AU - Tarnacka,M, AU - Kolodziejczyk,K, AU - Dulski,M, AU - Zakowiecki,D, AU - Hawelek,L, AU - Adrjanowicz,K, AU - Zych,M, AU - Garbacz,G, AU - Kaminski,K, PY - 2014/08/01/received PY - 2014/10/09/revised PY - 2014/10/12/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/8/5/medline SP - 1094 EP - 104 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 88 IS - 3 N2 - Different experimental and theoretical techniques were applied to investigate basic physical properties of very stable and homogeneous solid dispersions formed by itraconazole and octaacetylmaltose. Differential scanning calorimetry as well as semi-empirical calculations have indicated that liquid crystalline ordering in itraconazole was completely suppressed in the binary mixtures. Molecular dynamics studies with the use of broadband dielectric spectroscopy have shown that the width of the structural relaxation process becomes smaller and fragility drops in solid dispersions with respect to the pure itraconazole. Moreover, the dynamics of secondary relaxation processes was affected by acetylated maltose. As demonstrated, β- and γ-secondary modes shift to higher and lower frequencies, respectively. On the other hand, aging experiments revealed that isostructural relaxation times in the glassy state become systematically longer with the addition of modified carbohydrate. This is a very important finding in the context of the current discussion on the factors affecting physical stability of easily crystallizing APIs. It seems that beside intermolecular interactions and local reorientation, the global mobility might control the crystallization of amorphous solid dispersions. Finally, we have demonstrated that itraconazole in binary mixtures dissolves faster and to greater extent with respect to the crystalline and amorphous form of this API. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/25460155/Impact_of_low_molecular_weight_excipient_octaacetylmaltose_on_the_liquid_crystalline_ordering_and_molecular_dynamics_in_the_supercooled_liquid_and_glassy_state_of_itraconazole_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(14)00287-2 DB - PRIME DP - Unbound Medicine ER -