Effect of powder characteristics on oral tablet disintegration

Abstract

This report describes an investigation of the factors affecting disintegration time in the mouth (DTM) of rapidly disintegrating tablets. The relation between DTM and stationary time of upper punch displacement (STP) was examined using a tableting process analyzer (TabAll). Results indicated that the bulk density of mixed excipient powder used for tablet preparation affects both DTM and STP. As the value of bulk density increased, STP became longer and DTM shorter. The results of a combination of granules and powder with or without a drug showed liner relation between apparent volume (reciprocal of bulk density) and DTM (r² = 0.7332). For a DTM less than 60 s, a formulation with a bulk density greater 0.5 g/mL should be chosen with a compression force of 5 kN. The hardness of tablets could be greater than 3 kg if at least one high-compressibility excipient was used in the formulation.

Introduction

In a society in which people are living longer, drug dosage forms that can improve elderly patient compliance are needed. Many elderly patients find it difficult to swallow tablets or capsules (Hanawa, 1997). For this reason, rapidly disintegrating tablets (RDT) have been developed. RDT are a convenient oral dosage form for patients who have difficulty swallowing conventional tablets or capsules, because the tablet rapidly disintegrates with a small amount of water or saliva in the oral cavity. Recently, companies have developed various types of RDTs by freeze-drying (Seager, 1998), a molding tableting system (Kato et al., 2001), and using saccharides (Mizumoto et al., 2005). However, these methods require specific apparatus or techniques for the manufacturing of RDTs. Therefore, the development of a method that does not require any special apparatus is needed.

Previous studies reported that RDT can be prepared by direct compression using microcrystalline cellulose in combination with low-substituted hydroxypropylcellulose or spherical sugar granules (Watanabe et al., 1995, Ishikawa et al., 2001). In addition, a novel method for predicting disintegration time in the mouth (DTM) of RDT by compaction analysis using a tableting process analyzer (TabAll) has been reported (Shibata et al., 2004). Stationary time of upper punch displacement (STP) can be used to predict disintegration time. The change in upper punch displacement during compaction is shown in Fig. 1. Time stopping displacement on upper punch displacement profiles during compaction of tablet was defined as STP, which correlated with DTM. This result suggested that some common factor influences STP and DTM.

The aim of this study was to find a method for screening new RDT formulations and determining the factors affecting tablet disintegration in the mouth. First the factors affecting STP was investigated using a variety of powders. Then, the relation between factors affecting STP and DTM of RDT was evaluated to find a useful screening method.