The spray drying of acetazolamide as method to modify crystal properties and to improve compression behaviour

Acetazolamide shows a very poor compression ability and tablets must usuall y be produced through a wet granulation process. However, the possibility t o obtain pure acetazolamide for direct compression could be interesting for industrial application. With the scope to obtain a material for direct com pression, three different crystallisation methods were chosen, with respect to acetazolamide solvent solubility. (a) Acetazolamide was dissolved in an ammonia solution and then spray dried. It was possible to characterise the spherical particles as a mixture of two polymorphic forms, I and II by Pow der X-ray diffraction study. (b) Pure form I was obtained by slowly cooling to room temperature a boiling water solution. (c) Pure form II, the market ed form, was obtained by neutralisation of an ammonia solution. Their compr ession behaviour was investigated firstly by a rotary press. Whilst pure po lymorphic forms I and II could not be compressed, the spray dried particles showed very good compression properties. In fact, tablets were obtained on ly by spray dried particles, which show very good properties under compress ion and the absence of capping tendency. On the other hand, it was impossib le to obtain tablets from polymorphic forms I and TI, whatever compression pressures were used. In order to explain their densification mechanism, a s ingle-punch tablet machine, equipped for the measurement of the upper punch displacement in the die, was used. From calculated Heckel's parameters, it was demonstrated that the spray dried material shows a greater particle re arrangement in the initial stage of compression due to its spherical habit and minor wrinkledness of particle surface. The crystalline structure due t o the presence of polymorphic forms I and II concur to lowering the intrins ic elasticity of the material. fact avoids the risk of the rupturing the in terpaticulate bonds, which are formed during the compression, concurring to the consolidation of the tablet. (C) 2001 Elsevier Science B.V. All rights reserved.