Pharmaceutical Binders and Their Function in Directly Compressed Tablets

In this thesis, the strength-enhancing mechanisms of dry binders in direct compression were studied. The systems investigated were binary mixtures containing various compounds and binders. Among the binders used were a series of different molecular weights of polyethylene glycol. The proposed simplified tablet model describing the fracture path in a tablet during strength testing offers an explanation for the increase in tablet strength caused by the binder. The model and results in this thesis indicate that fractures will usually propagate around the tablet particles and through the interparticulate voids during tablet strength testing. One important characteristic of the binder is its ability to be effectively and evenly distributed through the interparticulate voids in a compound tablet. Characteristics such as high plasticity, low elasticity and a small particle size were associated with a more even distribution and a consequent pronounced effect on pore structure and marked improvement in tablet strength. The strength of tablets containing less plastic binders was governed more by the compactibility of the binder. The tablet porosity, bonding mechanisms and volume reduction mechanisms of the compound also influenced the effect of the binder. For example, the plasticity and particle size of the binder had the most significant effects on tablet strength when the tablet porosity of the compound was relatively low. A combination of the plasticity and the compactibility of the binder determined the strength of tablets when the tablet of a compound was more porous. The positive effect of a binder on pore structure and tablet strength resulted in an increase in the disintegration time. Although addition of a superdisintegrant generally improved the disintegration time, the effect was decreased when the formulation included more deformable binders. The choice of a suitable binder for a tablet formulation requires extensive knowledge of the relative importance of binder properties for enhancing the strength of the tablet and also of the interactions between the various materials constituting a tablet. Thus, the increased knowledge of the functionality of a binder obtained in this thesis enables a more rational approach to tablet formulation. Sofia Mattsson, Department of Pharmacy, Division of Pharmaceutics, Uppsala Biomedical Centre, Box 580, SE-75123 Uppsala, Sweden © Sofia Mattsson 2000 ISSN 0282-7484 ISBN 91-554-4857-7