title: Effects of coformers on phase transformation and release profiles of carbamazepine cocrystals in hydroxypropyl methylcellulose based matrix tablets.
abstract: The aim of this study was to investigate the effects of coformers on phase transformation and release profiles of carbamazepine (CBZ) cocrystals in hydroxypropyl methylcellulose (HPMC) based matrix tablets. It has been found that selection of different coformers of saccharin (SAC) and cinnamic acid (CIN) can affect the stability of CBZ cocrystals in solution, resulting in significant differences in the apparent solubility of CBZ. The dissolution advantage of CBZ-SAC cocrystals can only be shown for a short period during dissolution because of the fast conversion to its dihydrate form (DH). HPMC can partially inhibit the crystallisation of CBZ DH during dissolution of CBZ-SAC cocrystal. However, the increased viscosity of HPMC dissolution medium reduced the dissolution rate of CBZ-SAC cocrystals. Therefore the CBZ-SAC cocrystal formulation did not show any significant advantage in CBZ release rate. In contrast the improved CBZ dissolution rate of CBZ-CIN cocrystal can be realised in both solution and formulation due to its high stability. In conclusion, exploring and understanding the mechanisms of the phase transformation of pharmaceutical cocrystals in aqueous medium for selection of lead cocrystals is the key for success of product development.
authors.affiliation: School of pharmacy, De Montfort University, Leicester, LE1 9BH, UK.
authors.forename: Shi
authors.initials: S
authors.lastname: Qiu
authors.affiliation: School of pharmacy, De Montfort University, Leicester, LE1 9BH, UK. Electronic address: mli@dmu.ac.uk.
authors.forename: Mingzhong
authors.initials: M
authors.lastname: Li
mesh_terms: D002152:Calorimetry, Differential Scanning; D002220:Carbamazepine / Q000737:chemistry*; D002934:Cinnamates / Q000737:chemistry*; D003460:Crystallization; D065546:Drug Liberation; D065347:Hypromellose Derivatives / Q000737:chemistry*; D033362:Powder Diffraction; D012439:Saccharin / Q000737:chemistry*; D012995:Solubility; D012996:Solutions; D013607:Tablets; D014961:X-Ray Diffraction
chemical_list: D002934:Cinnamates; D012996:Solutions; D013607:Tablets; C029010:cinnamic acid; D002220:Carbamazepine; D065347:Hypromellose Derivatives; D012439:Saccharin
keywords: Carbamazepine–cinnamic acid (CBZ–CIN) cocrystal; Carbamazepine–saccharin (CBZ–SAC) cocrystal; Hydroxyproply methylcellulose (HPMC); Solution mediated phase transformation