Injection moulded controlled release amorphous solid dispersions: Synchronized drug and polymer release for robust performance

YesA study has been carried out to investigate controlled release performance of caplet shaped injection moulded (IM) amorphous solid dispersion (ASD) tablets based on the model drug AZD0837 and polyethylene oxide (PEO). The physical/chemical storage stability and release robustness of the IM tablets were characterized and compared to that of conventional extended release (ER) hydrophilic matrix tablets of the same raw materials and compositions manufactured via direct compression (DC). To gain an improved understanding of the release mechanisms, the dissolution of both the polymer and the drug were studied. Under conditions where the amount of dissolution media was limited, the controlled release ASD IM tablets demonstrated complete and synchronized release of both PEO and AZD0837 whereas the release of AZD0837 was found to be slower and incomplete from conventional direct compressed ER hydrophilic matrix tablets. Results clearly indicated that AZD0837 remained amorphous throughout the dissolution process and was maintained in a supersaturated state and hence kept stable with the aid of the polymeric carrier when released in a synchronized manner. In addition, it was found that the IM tablets were robust to variation in hydrodynamics of the environment and PEO molecular weight.The research was funded by AstraZeneca, Sweden

Simultaneous probing of swelling, erosion and dissolution by NMR-microimaging – Effect of solubility of additives on HPMC matrix tablets

Extensive studies of extended release tablets based on hydrophilic polymers have illuminated several aspects linked to their functionality. However, in some respects key factors affecting the mechanisms of release are yet unexplored. In the present study, a novel NMR-microimaging method has been used to study the influence of the solubility of additives in extended release hydroxypropyl methylcellulose (HPMC) matrix tablets. During the course of the tablet dissolution the movement of the swelling and erosion fronts were studied simultaneously to the release of both polymer and additives. Moreover, the focused beam reflectance measurement (FBRM) technology was for the first time assessed for both release and dissolution rate studies of poorly soluble particles. The studied formulations comprised solely HPMC, 40% HPMC and 60% mannitol (Cs = 240 mg/ml) and 40% HPMC and 60% dicalcium phosphate (DCP) (Cs = 0.05 mg/ml). The dissolution rate of the tablets was highest for the HPMC/mannitol formulation, followed by HPMC/DCP and plain HPMC tablet. A contrasting order was found regarding the degree and kinetics of swelling. The results were interpreted in light of how the mass transport in the gel layer is influenced by the solubility of additives. A mechanistic model, considering osmotic pressure gradient and the effective diffusion of the dissolution medium in the gel is proposed