Formulation and development of tablets based on Ludipress and scale-up from laboratory to production scale.

Abstract

In spite of the wealth of experience available in the pharmaceutical industry, tablet formulations are still largely developed on an empirical basis, and the scale-up from laboratory to production is a time-consuming and costly process. Using Ludipress greatly simplifies formulation development and the manufacturing process because only the active ingredient Ludipress and a lubricant need to be mixed briefly before being compressed into tablets. The studies described here were designed to investigate the scale-up of Ludipress-based formulations from laboratory to production scale, and to predict changes in tablet properties due to changes in format, compaction pressure, and the use of different tablet presses. It was found that the tensile strength of tablets made of Ludipress increased linearly with compaction pressures up to 300 MPa. It was also independent of the geometry of the tablets (diameter, thickness, shape). It is therefore possible to give an equation with which the compaction pressure required to achieve a given hardness can be calculated for a given tablet form. The equation has to be modified slightly to convert from a single-punch press to a rotary tableting machine. Tablets produced in the rotary machine at the same pressure have a slightly higher tensile strength. The rate of increase in pressure, and therefore the throughput, has no effect on the tensile strength of Ludipress tablets. It is thought that a certain minimum dwell time is responsible for this difference. The production of tablets based on Ludipress can be scaled up from one rotary press to another without problem if the powder mixtures are prepared with the same mixing energy. The tensile strength curve determined for tablets made with Ludipress alone can also be applied to tablets with a small quantity (< 10%) of an active ingredient.