Crystal habit modification and polymorphic stability assessment of a long-acting β2-adrenergic agonist

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Ameessa Tulcidas (Author) FEUP; Nuno M. T. Lourenço (Author) Other; Rafael Antunes (Author) Other; Bruno Santos (Author) Other; Sylwin Pawlowski (Author) Other; Fernando Rocha (Author) FEUP

Journal

Title: CrystEngComm

Vol. 21 No. 22

Pages: 3460-3470

ISSN: 1466-8033

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 2 Citations

Associated Projects

LEPABE - Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia

Other information

Authenticus ID: P-00Q-P3W

DOI: 10.1039/c9ce00309f

Abstract (EN): Properties such as particle orientation, flowability, packing, compaction, syringeability, suspension stability and dissolution are the most influenced by changes in the crystal habit and polymorphic form of a drug substance. The crystal habit of a drug substance (long-acting beta 2-adrenergic agonist (LABA)), as well as its purity and polymorphic stability, was studied after performing slurry tests with 1,2-dimethoxyethane : heptane solution at 50 degrees C. In these slurry tests, the product was kept suspended and undissolved, with agitation, for polymorphic conversion evaluation. Since no significant modifications were observed in the crystal shape and dimensions at 50 degrees C, a new slurry test was performed at a temperature above the melting point of the starting material (80 degrees C). In the latter test, it was possible to obtain crystals with increased dimensions by 480% compared with the starting material. Additionally, the desired polymorphic form (form I) was obtained as well as an acceptable purity of approximately 99%. These are promising results, not only for downstream purposes, but also concerning the bioavailability of the drug substance. This work shows that working at a temperature higher than the melting point of the compound seems to modify the crystal habit of the product.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11