Influence of beta-cyclodextrin on the phase transition in carbamazepine polymorphs

Cvetkovski, Aleksandar and Drakalska, Elena (2023) Influence of beta-cyclodextrin on the phase transition in carbamazepine polymorphs. In: 14th Central European Symposium of Pharmceutical Technology (CESPT), 28-30 Sept 2023, Ohrid, R.Macedonia.

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Abstract

Carbamazepin (CBZ), a widespread used antiepileptic drug, branded as Tegretol, firstly was launched in form of Active Pharmaceutical Ingredient (API) as a commercially available polymorphic form III. Additionally, crystallographic studies on crystal packing motifs of carbamazepine molecules in crystal lattices, reveal that, a part of the firstly confirmed structure of polymorphic form III, this drug exists in three other polymorphic forms I, II and IV, as well as pseudopolymorph, dihyrdate form. [1] Further solid-state testing confirmed that in terms of thermodynamical stability CBZ III and I are related as enantiotropic pair, former exerting higher stability at ambient temperatures, up to phase transition temperature (Tt≈71℃) when it is transformed in the later with melting temperature at 193 ℃. Due to the polarity of the CBZ molecule that is carbamylated derivative of iminostilbene, consequently that determine its lipophilicity, CBZ belongs to BCS class II of low water solubility and high permeability drug. Compromising the differences in crystal packing between CBZ polymorphs III and I that exert differences in density and solubility with the requirements for sufficient plasma concentration available for favorable crossing the blood-brain barrier (BBB) and reaching receptor sites, remain the challenge for crystal engineering CBZ polymorphs with functional excipients which, based on their molecular structures, are appropriate for formation either of inclusion complexes (IC) or co-crystals (CC). In terms of processing the CBZ polymorph, either with solvents or by mechanochemical treatments, both technologies impose phase transition; the first one causes transformation of anhydrous polymorphs to CBZ dihydrate, and second lead to interconversion of stable to metastable forms by thermomechanical activation on crystal particle surface [2]. The outlined research objectives address the testing of the influence of beta cyclodextrin (BCD), native cyclic oligosaccharide, on controlling the phase transition of CBZ form III to form I, respectively toward the formation of inclusion complex by non-covalent interactions between nonpolar part of CBZ molecule and hydrophobic CBD cavity that interact each other in stoichiometric ratio.

Item Type:	Conference or Workshop Item (Poster)
Subjects:	Medical and Health Sciences > Basic medicine Engineering and Technology > Chemical engineering Natural sciences > Chemical sciences Engineering and Technology > Materials engineering Engineering and Technology > Nano-technology
Divisions:	Faculty of Medical Science
Depositing User:	Aleksandar Cvetkovski
Date Deposited:	28 Sep 2023 08:55
Last Modified:	28 Sep 2023 08:55
URI:	https://eprints.ugd.edu.mk/id/eprint/32257

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