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Producing Amorphous Solid Dispersions via Co-Precipitation and Spray Drying: Impact to Physicochemical and Biopharmaceutical Properties.
J Pharm Sci. 2018 01; 107(1):183-191.JP

Abstract

Many small-molecule active pharmaceutical ingredients (APIs) exhibit low aqueous solubility and benefit from generation of amorphous dispersions of the API and polymer to improve their dissolution properties. Spray drying and hot-melt extrusion are 2 common methods to produce these dispersions; however, for some systems, these approaches may not be optimal, and it would be beneficial to have an alternative route. Herein, amorphous solid dispersions of compound A, a low-solubility weak acid, and copovidone were made by conventional spray drying and co-precipitation. The physicochemical properties of the 2 materials were assessed via X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, and scanning electron microscopy. The amorphous dispersions were then formulated and tableted, and the performance was assessed in vivo and in vitro. In human dissolution studies, the co-precipitation tablets had slightly slower dissolution than the spray-dried dispersion, but both reached full release of compound A. In canine in vitro dissolution studies, the tablets showed comparable dissolution profiles. Finally, canine pharmacokinetic studies showed that the materials had comparable values for the area under the curve, bioavailability, and Cmax. Based on the summarized data, we conclude that for some APIs, co-precipitation is a viable alternative to spray drying to make solid amorphous dispersions while maintaining desirable physicochemical and biopharmaceutical characteristics.

Authors+Show Affiliations

Department of Analytical Sciences, Pharmaceutical Sciences and Clinical Supplies, MRL, Rahway, New Jersey 07065. Electronic address: amanda.mann@merck.com.Department of Chemical Engineering Research and Development, Chemistry, MRL, Rahway, New Jersey 07065.Department of Chemical Engineering Research and Development, Chemistry, MRL, Rahway, New Jersey 07065.Formulation Development, Merck Animal Health, Rahway, New Jersey 07065.Analytical Sciences, Merck Animal Health, Rahway, New Jersey 07065.Formulation Sciences, Pharmaceutical Sciences and Clinical Supplies, MRL, Rahway, New Jersey 07065.Department of Preformulation Sciences, Pharmaceutical Sciences and Clinical Supplies, MRL, Rahway, New Jersey 07065.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28711592

Citation

Mann, Amanda K P., et al. "Producing Amorphous Solid Dispersions Via Co-Precipitation and Spray Drying: Impact to Physicochemical and Biopharmaceutical Properties." Journal of Pharmaceutical Sciences, vol. 107, no. 1, 2018, pp. 183-191.
Mann AKP, Schenck L, Koynov A, et al. Producing Amorphous Solid Dispersions via Co-Precipitation and Spray Drying: Impact to Physicochemical and Biopharmaceutical Properties. J Pharm Sci. 2018;107(1):183-191.
Mann, A. K. P., Schenck, L., Koynov, A., Rumondor, A. C. F., Jin, X., Marota, M., & Dalton, C. (2018). Producing Amorphous Solid Dispersions via Co-Precipitation and Spray Drying: Impact to Physicochemical and Biopharmaceutical Properties. Journal of Pharmaceutical Sciences, 107(1), 183-191. https://doi.org/10.1016/j.xphs.2017.07.001
Mann AKP, et al. Producing Amorphous Solid Dispersions Via Co-Precipitation and Spray Drying: Impact to Physicochemical and Biopharmaceutical Properties. J Pharm Sci. 2018;107(1):183-191. PubMed PMID: 28711592.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Producing Amorphous Solid Dispersions via Co-Precipitation and Spray Drying: Impact to Physicochemical and Biopharmaceutical Properties. AU - Mann,Amanda K P, AU - Schenck,Luke, AU - Koynov,Athanas, AU - Rumondor,Alfred C F, AU - Jin,Xiaoling, AU - Marota,Melanie, AU - Dalton,Chad, Y1 - 2017/07/12/ PY - 2017/04/07/received PY - 2017/06/05/revised PY - 2017/07/06/accepted PY - 2017/7/18/pubmed PY - 2018/7/26/medline PY - 2017/7/17/entrez KW - amorphous KW - bioavailability KW - dissolution KW - physical characterization KW - physicochemical properties KW - precipitation KW - solid dispersion KW - spray drying SP - 183 EP - 191 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 107 IS - 1 N2 - Many small-molecule active pharmaceutical ingredients (APIs) exhibit low aqueous solubility and benefit from generation of amorphous dispersions of the API and polymer to improve their dissolution properties. Spray drying and hot-melt extrusion are 2 common methods to produce these dispersions; however, for some systems, these approaches may not be optimal, and it would be beneficial to have an alternative route. Herein, amorphous solid dispersions of compound A, a low-solubility weak acid, and copovidone were made by conventional spray drying and co-precipitation. The physicochemical properties of the 2 materials were assessed via X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, and scanning electron microscopy. The amorphous dispersions were then formulated and tableted, and the performance was assessed in vivo and in vitro. In human dissolution studies, the co-precipitation tablets had slightly slower dissolution than the spray-dried dispersion, but both reached full release of compound A. In canine in vitro dissolution studies, the tablets showed comparable dissolution profiles. Finally, canine pharmacokinetic studies showed that the materials had comparable values for the area under the curve, bioavailability, and Cmax. Based on the summarized data, we conclude that for some APIs, co-precipitation is a viable alternative to spray drying to make solid amorphous dispersions while maintaining desirable physicochemical and biopharmaceutical characteristics. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/28711592/Producing_Amorphous_Solid_Dispersions_via_Co_Precipitation_and_Spray_Drying:_Impact_to_Physicochemical_and_Biopharmaceutical_Properties_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(17)30494-X DB - PRIME DP - Unbound Medicine ER -