Simultaneous quantification of drug and coformer during cocrystal dissolution using in situ UV spectroscopy and multicomponent analysis
Original scientific article
DOI:
https://doi.org/10.5599/admet.3274Keywords:
Carbamazepine, congruent, supersaturation, precipitation inhibitor, in situ UV probeAbstract
Background and purpose: The primary objective of this study was to assess the feasibility of applying in situ UV spectroscopy in combination with multicomponent analysis (MCA) to simultaneously quantify the dissolution of a drug and its coformer from a cocrystal. A secondary objective was to determine whether this approach can support a mechanistic understanding of cocrystal dissolution. Experimental approach: The rotating-vessel μDISS system equipped with an in situ UV probe was used for dissolution tests. Carbamazepine (CBZ) cocrystals with saccharin, nicotinamide, and 2,4-dihydroxybenzoic acid were used as model compounds. The concentrations of CBZ and each coformer were simultaneously quantified using MCA of the in situ UV spectra. Key results: The concentrations of CBZ and the coformer were successfully quantified by MCA throughout the dissolution process. In the absence of a polymeric precipitation inhibitor (PPI), the dissolution of CBZ from the cocrystal reached only 20%, and no supersaturation was observed, whereas the coformers were rapidly released. In contrast, in the presence of PPIs, the dissolution of CBZ from the cocrystal increased to supersaturated levels, while the dissolution of the coformer decreased. Supersaturation of CBZ was achieved when CBZ and the coformer dissolved congruently. A PPI may interfere with the molecular dissociation of CBZ and the coformer from the cocrystal surface, resulting in a slower release of both CBZ and the coformer. This effect may have reduced the local CBZ concentration at the particle surface and, consequently, slowed the precipitation of CBZ dihydrate on the particle surface. Conclusion: MCA enables the simultaneous quantification of a drug and its coformer from in situ UV spectra during cocrystal dissolution testing. This analytical approach provides valuable insights into the dissolution mechanisms of cocrystals.
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