In situ monitoring of carbamazepine–nicotinamide cocrystal intrinsic dissolution behaviour

Insight into Flufenamic Acid Cocrystal Dissolution in the Presence of a Polymer in Solution: from Single Crystal to Powder Dissolution

“…5 In this study, through rational selection of a coformer as well as the dissolution medium in the presence of a polymeric additive, we aimed to provide mechanistic insights into the intrinsic relationship among dissolution, supersaturation and precipitation for pharmaceutical cocrystals. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Figure S6] observed by AFM.…”

“…4 However, maintaining such a supersaturated state is challenging because of the tendency for rapid precipitation of a more stable form of the parent drug during dissolution. 5,6 In order to maximise the potential of cocrystals, it is critical to include inhibitors in a formulation to prevent or delay the precipitation of the parent drug during dissolution. [7][8][9][10][11][12][13] Although polymeric crystallization inhibitors have been extensively studied in many other systems, in particular amorphous solid dispersions, 14,15 such studies are still rare for cocrystal based formulations.…”

Investigation of the Effect of Hydroxypropyl Methylcellulose on the Phase Transformation and Release Profiles of Carbamazepine-Nicotinamide Cocrystal

“…It is known that the hydroxyl groups of HPMC attach to CBZ at the site of water binding and therefore its transformation to the dihydrate form is inhibited. In this study it was initially expected that HPMC would also inhibit the transformation of CBZ-NIC cocrystal to CBZ DH during dissolution because the change of crystalline properties of CBZ-NIC cocrystal during dissolution can reduce the advantages of the improved dissolution rate and solubility, resulting in a poor drug absorption and bioavailability (3,5). Unfortunately, the study has shown that HPMC did not inhibit the phase transformation of CBZ-NIC cocrystal to CBZ DH in both the aqueous solutions and sustained release HPMC matrix tablets.…”

“…It comprises of a sample flow cell, syringe pump, temperature control unit, UV lamp and detector, and control and data analysis system, which was the same as that used in our previous studies (3,5 …”

“…For example, in our previous studywe have shown that the solution mediated phase transformation of the carbamazepine-nicotinamide (CBZ-NIC) cocrystal had greatly reduced the enhancement of its apparent solubility and dissolution rate (3). In order to inhibit the form conversion of the cocrystals in aqueous media, recent studies have shown that the inclusion of a surfactant in the formulation as the potential to overcome the limitations caused by the rapid dissociation of cocrystals and concomitant recrystallization of the poorly soluble forms in aqueous media (4)(5)(6).Obviously careful section of both the cocrystal form and the excipients is an essential part of successful product development.…”