Industrial production of fast disintegrating tablets by direct compression.

During the last decade, fast disintegrating tablets (FDT), also known as fast melting, fast dispersing, orodispersible, rapid dissolve, rapid melt, and/or quick disintegrating tablets, have drawn a great deal of attention because they are particularly suitable for patients with dysphagia (pediatric and geriatric population) and for situations where additional water intake is not possible. Technologies usually adopted for the manufacturing of FDTs are lyophilization, molding (compression or heat), granulation and direct compression (Fu et al.; 2004). The production of FDTs by direct compression offers advantages from the industrial point of view as it is easier, less expensive and based on a well established technology. The aim of the research was to obtain a simple formulation suitable for the production of FDTs by direct compression on both pilot and production scale. Different formulations have been evaluated containing a well established filler like sorbitol (Neosorb, Roquette) or a new directly compressible excipient (F-Melt type C, Fuji) and three different super disintegrants like Sodium Carboxymethyl Cellulose (Ac-Di-Sol, FMC), Sodium Starch Gliycolate (Explotab, JRS), Cross Linked PVP (Kollidon CL-SF, BASF). Placebo FDT batches (36) have been preliminarily manufactured by a rotary tablet press (Pressima, IMA) varying parameters like filler type (Neosorb, F-melt), super disintegrant type and its amount (1%, 2%, 5% w/w) and compression force (16 kN, 22 kN). Technological tests (uniformity of mass, friability, crushing strength and disintegration time) have been performed for all batches; the model drug Diclofenac Potassium, a well known NSAD useful for fast treatment of migraine, has been utilised to produce batches using the optimal formulative and operative parameters found in the preliminary study. Results obtained show that all placebo tablets (diameter 15 mm, weight 350 mg), except for two batches, complied with the EP limits for weight variation and friability. Moreover combining F-melt and Kollidon CL-SF at 5% and using 22 kN as compression force, tablet disintegration time has been reduced to less then 30 seconds maintaining crushing strenght values (around 7,3 kP) suitable for the subsequent handling and packaging phases. Tablets produced with 50 mg of Diclofenac Potassium have maintained suitable technological properties such as no friability, crushing strenght 7,3 kP and disintegration time definitely lower (less than 50 seconds) than EP limits for orodispersible tablets. As a conclusion, formulation and operative parameters suitable for FDT production by direct compression on pilot scale have been identified; further studies concerning scale up on a production scale tablet press and the following packaging steps are in progress