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Building a better particle: Leveraging physicochemical understanding of amorphous solid dispersions and a hierarchical particle approach for improved delivery at high drug loadings.
Int J Pharm. 2019 Mar 25; 559:147-155.IJ

Abstract

Amorphous solid dispersions are a promising option for managing compounds with poor aqueous solubility. However, for compounds with high melting points, thermal stability limitations, or poor solubility in volatile solvents, conventional routes of hot melt extrusion or spray drying may not be viable. Co-precipitated amorphous dispersions (cPAD) can provide a solution. For the material studied in this paper, the cPAD material that was seemingly identical to spray dried material in terms of being single phase amorphous (as measured by DSC and XRD) but showed slower dissolution behavior. It was identified that physical properties of the cPAD material could be improved to enhance wettability and improve dissolution performance. This was achieved by incorporating the cPAD material into a matrix of water soluble excipients generated via evaporative isolation routes. Importantly, this approach appears to offer another route to further increase the drug load in final dosage units and is significant as increased drug loading generally results in slower or incomplete release. Results showed successful proof of concept via in vitro biorelevant dissolution and confirmatory canine pharmacokinetic studies yielding comparable exposure for capsules comprised of conventional spray dried material as well as capsules with elevated drug load comprised of cPAD hierarchical particles.

Authors+Show Affiliations

Particle Engineering Labs, Chemical Engineering R&D, Merck & Co., Inc, Rahway, NJ 07065, USA. Electronic address: Luke.Schenck@Merck.com.Department of Analytical Sciences, Pharmaceutical Sciences, Merck & Co., Inc, Rahway, NJ 07065, USA. Electronic address: Amanda.Mann@Merck.com.Preformulation, Pharmaceutical Sciences Merck & Co., Inc, West Point, PA 19486, USA.Biopharmaceutics and Specialty Dosage Forms, Pharmaceutical Sciences, Merck & Co., Inc, West Point, PA 19486, USA.MMC, Process Research and Design, Merck & Co., Inc, Rahway, NJ 07065, USA.OFST, Pharmaceutical Sciences, Merck & Co., Inc, West Point, PA 19486, USA.Department of Analytical Sciences, Pharmaceutical Sciences, Merck & Co., Inc, Rahway, NJ 07065, USA.Department of Analytical Sciences, Pharmaceutical Sciences, Merck & Co., Inc, Rahway, NJ 07065, USA.Technology Labs, Chemical Engineering R&D, Merck & Co., Inc, Rahway, NJ 07065, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30654058

Citation

Schenck, Luke, et al. "Building a Better Particle: Leveraging Physicochemical Understanding of Amorphous Solid Dispersions and a Hierarchical Particle Approach for Improved Delivery at High Drug Loadings." International Journal of Pharmaceutics, vol. 559, 2019, pp. 147-155.
Schenck L, Mann AKP, Liu Z, et al. Building a better particle: Leveraging physicochemical understanding of amorphous solid dispersions and a hierarchical particle approach for improved delivery at high drug loadings. Int J Pharm. 2019;559:147-155.
Schenck, L., Mann, A. K. P., Liu, Z., Milewski, M., Zhang, S., Ren, J., Dewitt, K., Hermans, A., & Cote, A. (2019). Building a better particle: Leveraging physicochemical understanding of amorphous solid dispersions and a hierarchical particle approach for improved delivery at high drug loadings. International Journal of Pharmaceutics, 559, 147-155. https://doi.org/10.1016/j.ijpharm.2019.01.009
Schenck L, et al. Building a Better Particle: Leveraging Physicochemical Understanding of Amorphous Solid Dispersions and a Hierarchical Particle Approach for Improved Delivery at High Drug Loadings. Int J Pharm. 2019 Mar 25;559:147-155. PubMed PMID: 30654058.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Building a better particle: Leveraging physicochemical understanding of amorphous solid dispersions and a hierarchical particle approach for improved delivery at high drug loadings. AU - Schenck,Luke, AU - Mann,Amanda K P, AU - Liu,Zhen, AU - Milewski,Mikolaj, AU - Zhang,Siwei, AU - Ren,Jie, AU - Dewitt,Kristel, AU - Hermans,Andre, AU - Cote,Aaron, Y1 - 2019/01/14/ PY - 2018/11/13/received PY - 2019/01/03/revised PY - 2019/01/07/accepted PY - 2019/1/18/pubmed PY - 2019/6/14/medline PY - 2019/1/18/entrez KW - Amorphous solid dispersion KW - Bioavailability KW - Dissolution KW - Precipitation KW - Spray drying KW - Thin film evaporation SP - 147 EP - 155 JF - International journal of pharmaceutics JO - Int J Pharm VL - 559 N2 - Amorphous solid dispersions are a promising option for managing compounds with poor aqueous solubility. However, for compounds with high melting points, thermal stability limitations, or poor solubility in volatile solvents, conventional routes of hot melt extrusion or spray drying may not be viable. Co-precipitated amorphous dispersions (cPAD) can provide a solution. For the material studied in this paper, the cPAD material that was seemingly identical to spray dried material in terms of being single phase amorphous (as measured by DSC and XRD) but showed slower dissolution behavior. It was identified that physical properties of the cPAD material could be improved to enhance wettability and improve dissolution performance. This was achieved by incorporating the cPAD material into a matrix of water soluble excipients generated via evaporative isolation routes. Importantly, this approach appears to offer another route to further increase the drug load in final dosage units and is significant as increased drug loading generally results in slower or incomplete release. Results showed successful proof of concept via in vitro biorelevant dissolution and confirmatory canine pharmacokinetic studies yielding comparable exposure for capsules comprised of conventional spray dried material as well as capsules with elevated drug load comprised of cPAD hierarchical particles. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/30654058/Building_a_better_particle:_Leveraging_physicochemical_understanding_of_amorphous_solid_dispersions_and_a_hierarchical_particle_approach_for_improved_delivery_at_high_drug_loadings_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(19)30035-3 DB - PRIME DP - Unbound Medicine ER -