Critical points in the formulation of pharmaceutical swellable controlled release dosage forms——Influence of particle size

Swellable matrix represents one of the most employed controlled release systems. These dosage forms provide slow release of drugs to reduce the fluctuation of drug concentration in plasma in order to improve the efficiency of treatment and/or to reduce adverse effects. The application of the concepts of statistical physics has allowed discovering the existence of critical points in the formulation of swellable matrices. These points, representing the volume fractions of the tablet components where the properties of the matrix diverge or change suddenly, provide important knowledge of how to rationalize the design of swellable matrices. The critical points are generally related to the percolation threshold of one of the components of the formulation, which corresponds to a geometrical phase transition of this component, passing from isolation to spanning the whole system. The last section of the paper is devoted to more recent findings concerning the influence of particle size of the components on the percolation threshold of the matrix forming polymer, and therefore on the release behaviour of the matrix. Knowledge of the excipient percolation threshold allows a more rational design of swellable matrices, according to the guidelines of the regulatory authorities concerning science-based formulation and quality by design.

NbB_(2)Modified Al-Cu Alloys Fabricated by Freeze-Ablation Casting under High Cooling Rate Solidification

At present,improving the properties of aluminum alloys is generally achieved by increasing the cooling rate of the melt and adding micro-nano particles.Controlling the cooling rate of the melt to improve the refining effect of grain refiner is still a difficult problem in the aluminum alloy casting industry.An innovative and environmentally friendly casting process,known as freeze ablation,was introduced during the preparation of an Al–NbB_(2) intermediate alloy.This process significantly enhanced the cooling rate of the melt.The results indicated that the Al–NbB_(2) intermediate alloy produced under high cooling rates had a noticeable refining effect on Al–Cu alloys,with smaller NbB2 particles demonstrating superior refining performance.The average grain size of the refined Al–Cu alloy decreased from 154 to 69μm,the tensile strength increased by 12%,the fluidity increased by 18.4%,and the hot tearing index decreased from 144 to 12.The matching degree between NbB_(2) andα-Al was calculated using high-resolution transmission electron microscopy and the edge-to-edge model.It was found that the atomic interplanar spacing and the interatomic spacing mismatch between NbB_(2)’s<1120>plane and Al were both less than 10%,which further proved that NbB2 could serve as an effective nucleation site forα-Al grains to achieve grain refinement.