The effect of roller compaction and tableting stresses on pharmaceutical tablet performance

In this research the effect of two fundamental stresses, i.e. the tableting load and roller compaction pressure, on tablet disintegration were investigated. Excipient materials were roller compacted using a range of pressures, and tablets were produced by compressing the consequent granules at varying tableting loads. For this study mannitol, a brittle and soluble material, and microcrystalline cellulose, a deformable and insoluble material, were investigated at varying binary ratios. The tablets were characterised by analysis of the compactibility and a flow cell imaging method was utilised to investigate tablet disintegration in real-time. It was found that the effect of roller compaction (RC) pressure on tablet tensile strength and porosity was dependent on the tableting load used. At low tableting load, the tablet porosity varied depending on the RC pressure used, whereas the tensile strength was largely unaffected. The use of a high tableting load leads to the opposite effect being observed. The tensile strength was highly dependent on the RC pressure used. In terms of the tablet disintegration the RC pressure did not influence the disintegration behaviour when low tableting loads were used as the process was rapid. When higher tableting loads were used, tablets containing granules roller compacted using lower pressure expanded in size larger than when a low RC pressure was used. A low RC pressure also lead to a faster particle release rate was observed

Ce hydrogen deuterium exchange-ms in peptide analysis

CE and hydrogen-deuterium (H/D) exchange MS are useful tools in the analysis and characterisation of peptides. This study reports the facile coupling of these tools in the H/D exchange CE-MS analysis of model and pharmaceutically important peptides, using a sheath flow interface. The peptides varied in mass from 556 (leucine enkephalin) to 1620 Da (bombesin), and in charge state from 0.33 (leucine enkephalin) to 3.0 (substance P). The application of a BGE composed of ammonium formate buffer (25 mM, pD 3.5 in D2O (>98% D atom)), a sheath liquid composed of formic acid (0.25% v/v in D2O) and ACN (30:70 v/v), and dissolving the samples in a mixture of ACN/D2O (50:50 v/v) facilitates complete H/D exchange. Because of complete H/D exchange the ESI mass spectra produced are easy to interpret and comparable to those obtained from LC-MS analysis. The CE-H/D-MS approach has the advantage of requiring lower volumes of deuterated solvents. The b- and y-series fragments produced by using in-source decomposition correspond to those predicted. With the peptides studied, the complete exchange H/D exchange observed with both the molecular and fragment ions helps to confirm both amino acid composition and sequence