Mathematical Modelling and Spectroscopic Imaging of Multi-component Tablet dissolution

The dissolution characteristics of pharmaceutical tablets are key to determining the bioavailability of the active pharmaceutical ingredient (API) and it is therefore vital to understand the physical processes that affect drug release. As well as the API, tablets also consist of a supporting polymer matrix (known as the excipient) and other compounds such as fillers, binders, lubricants etc. The overall release of the API depends not only on the individual dissolution characteristics of the various components and their proportion in the formulation, but also on their interactions. Tablet microstructure and granule arrangement [1–4] within the tablet are also important. By understanding the tablet microstructure and dissolution properties of the various components, it will be possible to model how a tablet will release the API given a specific formulation, leading to better tablet designs. Currently available models describing drug release from tablets tend to be empirical correlations that do not describe the underlying physical processes but rather provide an overall description of the drug release profile. Such models are of limited use for predicting tablet performance and for tablet design. Complexities arise when dealing with phenomena-based modelling of interacting multi-component systems. In these cases, the physical properties of each component such as solubility and diffusivity is affected by the presence and concentration of the other species. Often the excipient is a swelling polymer (e.g. Hydroxypropylmethylcellulose or Microcrystalline cellulose) that can form a gel layer around the tablet during dissolution. This gel layer slows water ingress and drug diffusion also forms a macroscopic transport process as the swelling moves drug particles away from the tablet core. A computer model will need to take these processes into account if a tablet is to be modelled accurately.