Unravelling the polymorphic characteristics of carbamazepine through additive-assisted sonocrystallisation

ABSTRACT

This paper investigates the influence of additives on the antisolvent crystallisation process of carbamazepine (CBZ) using methanol as the solvent and water as the antisolvent, with ultrasonic irradiation at a specific solvent-to-antisolvent (S/A) ratio of 1:2 and a 30-watt power ultrasonic horn. Various additives, such as Hydroxypropyl Methyl Cellulose (HPMC), Bovine Serum Albumin (BSA), Tween 80, and Sodium Dodecyl Sulphate (SDS), were employed to examine their effects on the morphology, stability (including suspension and thermal stability), crystallinity, and polymorphism of CBZ crystals. Raw CBZ exhibited irregular shapes during crystallisation, while SDS addition resulted in both plate-like and needle-like crystals. Conversely, BSA, HPMC, and Tween 80 induced the formation of needle, plate, and block-like crystal structures, respectively. Suspension stability ranked as SDS > BSA > HPMC > Tween 80. Regarding polymorphism, HPMC favoured Form 1, BSA and SDS favoured Form IV, and Tween 80 favoured Form I. Additionally, Tween 80 depicted similar preference for Form I polymorph as HPMC. Notably, Form II and Form III polymorphs were present to varying degrees in all samples, except for Tween 80. This study provides crucial insights into the controlled crystallisation of CBZ and the impact of additives on crystal properties, offering valuable information for tailoring CBZ crystal production for specific pharmaceutical applications.

GRAPHICAL ABSTRACT

KEYWORDS:

• Carbamazepine
• additive
• antisolvent crystallisation
• ultrasound
• polymorph

Disclosure statement

No potential conflict of interest was reported by the author(s).