Discovered two polymorphs and two solvates of lamotrigine-tolfenamic acid salt: Thermal behavior and crystal morphological differences.
Int J Pharm
; 628: 122310, 2022 Nov 25.
Article
de En
| MEDLINE
| ID: mdl-36270552
ABSTRACT
Multi-component pharmaceutical systems such as cocrystal and salt have gained popularity in academia and industry due to their ability to regulate the poor physicochemical properties of active pharmaceutical ingredients (APIs). However, different crystal states, namely polymorphs are becoming a key factor influencing future clinical drug safety. It remains an under explored field, particularly how to hit the polymorphs of multi-components system quickly and effectively. For the first time, a novel drug-drug salt of lamotrigine (LAM)-tolfenamic acid (TOL) with two polymorphs and two solvates were discovered in this study. Forms I and II exist in rhombohedral and block crystal morphologies, whereas methanol and ethanol solvates are crystallized as rods and flakes, respectively. Further physicochemical properties were characterized and compared between parent compounds and the four crystal forms. The apparent solubilities of the new four crystal forms were higher than TOL but lower than LAM. The intrinsic dissolution rates of all crystal forms at 37.0 °C followed a similar trend, and all crystal forms were non-hygroscopic (<1.0%). Two stable polymorphs provide a new choice for the further formulation development.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Cristallisation
Langue:
En
Journal:
Int J Pharm
Année:
2022
Type de document:
Article
Pays d'affiliation:
Chine