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Projection of Target Drug Particle Size in Oral Formulations Using the Refined Developability Classification System (rDCS)

ORCID
0000-0001-7918-0865
Affiliation
Fraunhofer Institute of Translational Medicine and Pharmacology, 60596 Frankfurt am Main, Germany
Beran, Kristian;
ORCID
0000-0002-4725-3107
Affiliation
Janssen Research & Development, Pharmaceutical & Material Sciences, 2340 Beerse, Belgium
Hermans, Eline;
ORCID
0000-0003-4894-7765
Affiliation
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230 Odense, Denmark
Holm, René;
Affiliation
Janssen Research & Development, Discovery Pharmaceutics, La Jolla, CA 92121, USA
Sepassi, Kia;
Affiliation
Fraunhofer Institute of Translational Medicine and Pharmacology, 60596 Frankfurt am Main, Germany
Dressman, Jennifer

Dissolution limitations to oral absorption can occur if the time required for dissolution is longer than the transit time across the small intestine and/or if dissolution is slower than the drug’s permeation through the gut wall. These limitations most often occur for poorly soluble drugs. A standard method for overcoming dissolution issues is to reduce the particle size of the (solid) drug. Building on the refined Developability Classification System (rDCS), this work establishes a novel set of equations with which the appropriate degree of particle size reduction needed to mitigate dissolution limitations to absorption can be calculated. According to the type of data available, the appropriate equation(s) for each situation can be applied. Three case examples are used to illustrate implementation of the equations: voriconazole, lemborexant and istradefylline. Although for voriconazole (rDCS Class I) target radius (r target ) estimates indicate that particle size reduction is unnecessary, for lemborexant (rDCS Class I) a radius of ≤20 µm would be required to improve absorption. For istradefylline (rDCS Class IIb) the r target was approximately 12 µm. Results are commensurate with literature information for these three drugs, signaling that the equations are suitable for application to a wide variety of drug substances.

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