Formulation and optimization of polymeric agglomerates of Bosentan monohydrate by crystallo-co-agglomeration technique

Abstract

Background The polymeric spherical agglomerate of Bosentan monohydrate was prepared by crystallo-co-agglomeration technique, for enhancing the micrometric properties and solubility of the drug. The agglomerates were developed using two distinct solvents, DCM as a good solvent and bridging liquid and water as a weak solvent, respectively. Hydrophilic polymer like HPMC K100M is used as a hardening agent which gives mechanical strength to the agglomerates, and PEG6000 is used as a wetting agent. Other excipients like talc which was used as a size enhancer, and PVA was used as an emulsifier agent. The formulation was optimized by Box–Behnken design. The concentration of talc and PEG6000, as well as rotation speed, was considered as independent variables. The particle size, angle of repose, and % drug content were used as dependent variables to investigate the effect of independent variables on dependent variables. The spherical crystal agglomerates were subjected to various physicochemical evaluations. Results The results revealed that as the concentration of talc and PEG6000 increases, the sphericity and particle size of the agglomerates increase, and at a low agitation, speed agglomerates become more spherical and coarser, which is confirmed by FESEM. The characterization like FTIR confirms no interaction with excipients, while XRPD confirms the polymorphic changes, and gas chromatography (GC) confirms the concentration of residual organic solvents in PDE limits. The optimized formulation of SAs showed a good angle of repose which is 30.33 ± 0.35, and the % cumulative drug release at 20 min was 94.14 ± 0.628%. Finally, the FDTs of the optimized batch were prepared. Conclusions The comparison of the in vitro release study of pure drugs with agglomerates and fast dispersible tablets of agglomerates confirms the solubility improvement. Finally, it can be concluded that the polymorphic crystal agglomerates enhance the solubility and micrometric properties of Bosentan monohydrate.

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“…The measured weight was divided by the total amount of all non-volatile compounds used for the formulation i.e. drugs and excipients 7 .…”

Novel Spherical Trimethoprim–Niflumic Acid Drug–Drug Salt Demonstrates Simultaneous Enhancement of Powder Property and Antibacterial Activity

“…17,18 It has been used to improve the physicochemical properties of APIs based on previous studies. 19 −21 However, the application of CCA technology to achieve simultaneous alteration of bioactivity and powder properties is very few, representing an underexplored research field.…”

“…Owing to the formation of homogeneous crystalline phases and good molecular compatibility of two APIs, cocrystallization is beneficial to overcome challenges (such as content uniformity) faced by the traditional physical mixing of fixed-dose combination drug products. − Based on these two strategies, an emerging technology called crystal- co -agglomeration (CCA) has been developed, combining their advantages . CCA involves cocrystallization by adding a solution of two substances in a good solvent to an antisolvent and the agglomeration of crystals formed using an immiscible bridging liquid. , It has been used to improve the physicochemical properties of APIs based on previous studies. − However, the application of CCA technology to achieve simultaneous alteration of bioactivity and powder properties is very few, representing an underexplored research field.…”