Design of a Re-Dispersible High Drug Load Amorphous Formulation.

Autor:	Oberoi HS; NCE-Formulation Sciences, AbbVie Inc., North Chicago, IL, USA. Electronic address: hardeep.oberoi@abbvie.com., Arce F; Current Affiliation: Bristol Myers Squibb, NJ, USA., Purohit HS; NCE-Formulation Sciences, AbbVie Inc., North Chicago, IL, USA., Yu M; NCE-Formulation Sciences, AbbVie Inc., North Chicago, IL, USA., Fowler CA; NCE-Formulation Sciences, AbbVie Inc., North Chicago, IL, USA., Zhou D; Current Affiliation: BeiGene, USA., Law D; NCE-Formulation Sciences, AbbVie Inc., North Chicago, IL, USA. Electronic address: Devalina.law@abbvie.com.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2023 Jan; Vol. 112 (1), pp. 250-263. Date of Electronic Publication: 2022 Oct 13.
DOI:	10.1016/j.xphs.2022.10.002
Abstrakt:	Amorphous solid dispersions (ASD) are a commonly used enabling formulation technology to drive oral absorption of poorly soluble drugs. To ensure adequate solid-state stability and dissolution characteristics, the ASD formulation design typically has ≤ 25% drug loading. Exposed to aqueous media, ASD formulations can produce drug-rich colloidal dispersion with particle size < 500 nm. This in situ formation of colloidal particles requires incorporation of excess excipients in the formulation. The concept of using engineered drug-rich particles having comparable size as those generated by ASDs in aqueous media is explored with the goal of increasing drug loading in the solid dosage form. Utilizing ABT-530 as model compound, a controlled solvent-antisolvent precipitation method resulted in a dilute suspension that contained drug-rich (90% (w/w)) amorphous nanoparticles (ANP). The precipitation process was optimized to yield a suspension containing < 300 nm ANP. A systematic evaluation of formulation properties and process variables resulted in the generation of dry powders composed of 1-8 µm agglomerates of nanoparticles which in contact with water regenerated the colloidal suspension having particle size comparable to primary particles. Thus, this work demonstrates an approach to designing a re-dispersible ANP based powder containing ≥90% w/w ABT-530 that could be used in preparation of a high drug load solid dosage form. Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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