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Investigation into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: A Rational Step toward the Design and Development of a Multicomponent Amorphous System.
Mol Pharm. 2018 09 04; 15(9):3796-3812.MP

Abstract

The formulation of oral amorphous solid dispersions (ASD) includes the use of excipients to improve physical stability and enhance bioavailability. Combinations of excipients (polymers and surfactants) are often employed in pharmaceutical products to improve the delivery of poorly water-soluble drugs. However, additive interactions in multicomponent ASD systems have not been extensively studied and may promote crystallization in an unpredictable manner, which in turn may affect the physical stability and dissolution profile of the product. The main aim of this study was to understand the effect of different surfactant and polymer combinations on the solid-state properties and dissolution behavior of ternary spray-dried solid dispersions of dipyridamole and cinnarizine. The surfactants chosen for this study were sodium dodecyl sulfate and poloxamer 188, and the model polymers used were polyvinylpyrrolidone K30 and hydroxypropyl methylcellulose K100. The spray-dried ternary dispersions maintained higher supersaturation compared to either the crystalline drug equilibrium solubility or their respective physical mixtures. However, rapid and variable dissolution behavior was observed for different formulations. The maximum supersaturation level was observed with drug-polymer-polymer ternary dispersions. On the other hand, incorporating the surfactant into binary (drug-polymer) and ternary (drug-polymer-polymer) ASDs adversely affected the physical stability and dissolution by promoting crystallization. On the basis of these observations, a thorough investigation into the impact of combinations of additives on amorphous drug crystallization during dissolution and stability studies is recommended in order to develop optimized formulations of supersaturating dosage forms.

Authors+Show Affiliations

Synthesis and Solid State Pharmaceutical Centre (SSPC), Pharmaceutical and Molecular Biotechnology Research Centre (PMBRC) , Waterford Institute of Technology , Cork Road , Waterford , Ireland.Synthesis and Solid State Pharmaceutical Centre (SSPC), Pharmaceutical and Molecular Biotechnology Research Centre (PMBRC) , Waterford Institute of Technology , Cork Road , Waterford , Ireland.Synthesis and Solid State Pharmaceutical Centre (SSPC), Pharmaceutical and Molecular Biotechnology Research Centre (PMBRC) , Waterford Institute of Technology , Cork Road , Waterford , Ireland.

Pub Type(s)

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

Language

eng

PubMed ID

30020788

Citation

Baghel, Shrawan, et al. "Investigation Into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: a Rational Step Toward the Design and Development of a Multicomponent Amorphous System." Molecular Pharmaceutics, vol. 15, no. 9, 2018, pp. 3796-3812.
Baghel S, Cathcart H, O'Reilly NJ. Investigation into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: A Rational Step toward the Design and Development of a Multicomponent Amorphous System. Mol Pharm. 2018;15(9):3796-3812.
Baghel, S., Cathcart, H., & O'Reilly, N. J. (2018). Investigation into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: A Rational Step toward the Design and Development of a Multicomponent Amorphous System. Molecular Pharmaceutics, 15(9), 3796-3812. https://doi.org/10.1021/acs.molpharmaceut.8b00306
Baghel S, Cathcart H, O'Reilly NJ. Investigation Into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: a Rational Step Toward the Design and Development of a Multicomponent Amorphous System. Mol Pharm. 2018 09 4;15(9):3796-3812. PubMed PMID: 30020788.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: A Rational Step toward the Design and Development of a Multicomponent Amorphous System. AU - Baghel,Shrawan, AU - Cathcart,Helen, AU - O'Reilly,Niall J, Y1 - 2018/07/30/ PY - 2018/7/19/pubmed PY - 2019/8/3/medline PY - 2018/7/19/entrez KW - amorphous solid dispersion KW - crystallization KW - dissolution KW - drug−polymer interaction KW - nuclear magnetic resonance KW - spray drying KW - supersaturation KW - surfactant KW - synergism SP - 3796 EP - 3812 JF - Molecular pharmaceutics JO - Mol. Pharm. VL - 15 IS - 9 N2 - The formulation of oral amorphous solid dispersions (ASD) includes the use of excipients to improve physical stability and enhance bioavailability. Combinations of excipients (polymers and surfactants) are often employed in pharmaceutical products to improve the delivery of poorly water-soluble drugs. However, additive interactions in multicomponent ASD systems have not been extensively studied and may promote crystallization in an unpredictable manner, which in turn may affect the physical stability and dissolution profile of the product. The main aim of this study was to understand the effect of different surfactant and polymer combinations on the solid-state properties and dissolution behavior of ternary spray-dried solid dispersions of dipyridamole and cinnarizine. The surfactants chosen for this study were sodium dodecyl sulfate and poloxamer 188, and the model polymers used were polyvinylpyrrolidone K30 and hydroxypropyl methylcellulose K100. The spray-dried ternary dispersions maintained higher supersaturation compared to either the crystalline drug equilibrium solubility or their respective physical mixtures. However, rapid and variable dissolution behavior was observed for different formulations. The maximum supersaturation level was observed with drug-polymer-polymer ternary dispersions. On the other hand, incorporating the surfactant into binary (drug-polymer) and ternary (drug-polymer-polymer) ASDs adversely affected the physical stability and dissolution by promoting crystallization. On the basis of these observations, a thorough investigation into the impact of combinations of additives on amorphous drug crystallization during dissolution and stability studies is recommended in order to develop optimized formulations of supersaturating dosage forms. SN - 1543-8392 UR - https://www.unboundmedicine.com/medline/citation/30020788/Investigation_into_the_Solid_State_Properties_and_Dissolution_Profile_of_Spray_Dried_Ternary_Amorphous_Solid_Dispersions:_A_Rational_Step_toward_the_Design_and_Development_of_a_Multicomponent_Amorphous_System_ L2 - https://dx.doi.org/10.1021/acs.molpharmaceut.8b00306 DB - PRIME DP - Unbound Medicine ER -