The impact of particle size and moisture content in the formulation development of orally disintegrating tablets

Abstract

Orally disintegrating tablets (ODTs) are a solid dosage form that liquefies inside the mouth upon interaction with saliva. ODTs are suitable for young and other populations who have difficulties swallowing solid dosage forms such as capsules and conventional tablets. ODTs overcome the disadvantages of oral liquid dosage, and are both physically and chemically more stable than liquids, and can be designed for modified release. They can enhance patient adherence. They should weight less than 500 mg and have a good balance between short disintegration time and hardness. These characteristics have been studied extensively, e.g. enhancing disintegrating time by adding disintegrants, and the enhancing hardness using microwave irradiation. This paper examined the impact of particle size and moisture content on ODTs’ characterization (powder flow, hardness, disintegrating, friability, wetting time, absorption ratio and drug release). The formulations included 20% microcrystalline cellulose (MCC: 50 µm, 100 µm or 180 µm) as a binder. It was found that particle size can impact tablet properties: low friability and high hardness were associated with large particle size. However, large particle size increases the wetting time and disintegration time. Large particle size increased powder flow somewhat, but flowability remained poor. To enhance the powder flowability, a second batch was prepared by wet granulation with differing moisture content. The flowability and friability were found to be enhanced by wet granulation. Moisture content also affects tablet properties: hardness increased with high moisture content, but no clear relationship was found between moisture content and disintegration time. In the last batch, four formulations were prepared—two by direct compression, and two by wet granulation, each method being applied to a range of particle sizes. Direct-compression formulations exhibited poor flow. Among the wet-granulation formulations, flow and disintegration time were better with small particles, which is explained by the big granule size that small particles could generate, resulting in a large number of inter-granule contact surfaces that increases liquid ingress. However, big particles increase the compatibility of the tablets, which increases their hardness and decreases their friability. In addition, it gave faster and more reliable drug release. Effects of moisture content depended on other factors. Hardness was related to the active pharmaceutical ingredient when a certain moisture content was required to achieve high hardness; after that, increasing the moisture content decreased hardness. Powder flow was related to the critical moisture level of the powder, which was undetermined in this study. Disintegration time was not related to moisture content.