TY - JOUR
T1 - Crystal habit modification and polymorphic stability assessment of a long-acting β2-adrenergic agonist
AU - Tulcidas, Ameessa
AU - Lourenço, Nuno M.T.
AU - Antunes, Rafael
AU - Santos, Bruno
AU - Pawlowski, Sylwin
AU - Rocha, Fernando
N1 - info:eu-repo/grantAgreement/FCT/5876/147218/PT#
info:eu-repo/grantAgreement/FCT/5876/147284/PT#
POCI-01-0145-FEDER – 007265.
POCI-01-0145-FEDER-006939.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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 β2-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 °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 °C, a new slurry test was performed at a temperature above the melting point of the starting material (80 °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.
AB - 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 β2-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 °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 °C, a new slurry test was performed at a temperature above the melting point of the starting material (80 °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.
UR - http://www.scopus.com/inward/record.url?scp=85066824782&partnerID=8YFLogxK
U2 - 10.1039/c9ce00309f
DO - 10.1039/c9ce00309f
M3 - Article
AN - SCOPUS:85066824782
SN - 1466-8033
VL - 21
SP - 3460
EP - 3470
JO - CrystEngComm
JF - CrystEngComm
IS - 22
ER -