We developed an apparatus in order to measure adhesive force between fine particles, and fine particles against substrates with flat surface by the direct separation method. This apparatus was able to measure adhesive force with high resolution (approximately 2 nN) and monitor the behavior of each particle by a microscope and image analyzer when particles were separated from each other, and calculate the adhesive force of the particle. Here, the adhesive forces of some kinds of pharmaceutical particles were measured, and the effects of moisture, shape and triboelectrification of the particles on the force were investigated. Among organic particles (corn starch, potato starch and lactose), potato starch showed the highest adhesive force, and lactose showed the lowest adhesive force against substrates with flat surface. In the case of moisture adsorptive particles, the force of adhesion increased rapidly with the moisture content under high relative humidity. In the case of moisture non-adsorptive particles, the force was affected by particle shape and triboelectrification.

The direct compressing method for tableting has some advantages over the wet-process granulation compressing method such as lower manufacture cost and less frequent process validation due to fewer operation processes and fluctuation factors. However, in the direct compressing method, the flowability and the compressibility of the mixture of powdery ingredients and the drug content uniformity are important problems, and studies have been performed to solve these problems. The Standard Formulation Research Association which belongs to the Particulate Preparation and Design Group of the Society of Powder Technology of Japan has also studied the direct compression method. A previous study by this association compared 3 types of lactose (anhydrous lactose, lactose monohydrate 100 M and lactose monohydrate 200 M) which differ in physiochemical properties, and showed that tablets prepared according to a formulation containing lactose monohydrate (200 M) had moderate hardness and were rapidly disintegrated. However, in the standard formulation containing lactose monohydrate (200 M), the flowability of the mixture powder was low (angle of repose of the mixture, ≧50º), and the flow of the mixture powder in the tableting machine was not uniform, and therefore, continuous tableting was expected to be difficult.

In this study, we improved the flowability of the mixture powder during tableting by surface modifying, which allowed continuous tableting with the standard formulation by direct compression without reducing tablet quality. In addition, the flowability of the mixture powder was further improved by adjusting the particle size of lactose, which resulted in a decrease in the variation of the tablet weight. Thus, we found the potentiality of tableting with the standard formulation by direct compression on a manufacturing scale.