Ž . Powder Technology 114 2001 118–124 www.elsevier.comrlocaterpowtec Development of spherical crystal agglomerates of an aspartic acid salt for direct tablet making P. Szabo-Revesz a, ) , H. Goczo a , K. Pintye-Hodi a , P. Kasa jr a , I. Eros a , ´ ´´ ¨ ˜ ´ ´ ˜ M. Hasznos-Nezdei b , B. Farkas c a Albert Szent-Gyorgyi Medical UniÕersity, Department of Pharmaceutical Technology, PO Box 121, H-6701 Szeged, Hungary ¨ b Research Institute of Chemical and Process Engineering, Pannon UniÕersity of Agricultural Sciences, PO Box 125, H-8200 Veszprem, Hungary ´ c EGIS Pharmaceuticals Ltd., Kereszturi u. 30-38, H-1106 Budapest, Hungary ´ Received 1 December 1998; received in revised form 1 September 1999; accepted 29 March 2000 Abstract Agglomerates of an aspartic acid salt were developed by means of a non-typical spherical crystallization technique. The aspartic acid Ž . salt was crystallized by a salting-out method combined with cooling. Traditional mechanical stirring crystallization samples A and B and Ž . the recirculation process sample C were used. The control material was commercial aspartic acid salt with very poor flowability and compressibility. The particle sizes of the samples were measured by sieve analysis. The morphology of the crystals and crystal agglomerates was controlled by SEM. The specific surfaces of the products were determined by the BET method and the micropore volumes were calculated via the BJH theory. The Carr index, rearrangement constant, plasticity and compressibility values were Ž . calculated. The samples were controlled by thermoanalytical investigations TG, DTG and DSC . Both of the crystallization techniques used resulted in spherical agglomerates of the aspartic acid salt with very good flowability and compressibility parameters. Primarily Ž . sample B, with a closed Acauliflower-likeB structure, can be suggested for tablet making involving a large mass e.g., chewable tablets by direct tablet pressing. Faster initial cooling rate and slower stirring rate were very favourable in the building-up of crystal agglomerates of sample B with a closed structure and a large particles. Sample B can be suggested further for capsule filling because of its high poured density, very good flowability and fast rearrangement. q 2001 Elsevier Science S.A. All rights reserved. Keywords: Aspartic acid salt; Crystallization; Spherical agglomerates; Flowability; Compressibility 1. Introduction Direct compression is a modern method in tablet manu- Ž . facturing. Many processing steps granulation, drying, etc. are eliminated in direct compression, and additionally wet Ž technology cannot be used with sensitive agents e.g., in . wx effervescent tablet making 1 . However, the use of this technique, which seems quite simple, depends on - the particle size and the particle size distribution of the materials, and in connection with this, - the flowability of the crystals, consistent with the production rates of modern compression technologies, ) Corresponding author. Tel.: q 36-62-455-576; fax: q 36-62-455-571. Ž . E-mail address: revesz@pharma.szote.u-szeged.hu P. Szabo-Revesz . ´ ´´ - the bulk density of the powder, in order to feed the correct amount of drug into a die cavity, and - the compressibility of the powder. Some drug crystals exhibit appropriate such properties, but many materials have very poor flowability and com- wx pressibility 2 . For tablet making from the latter materials, possible solutions may be the following: wx Ž - the use of wet granulation, agglomeration 3 if this is possible with regard to the drug stability; - the use of direct tablet making with AgoodB excipients, Ž which promote direct compression though this might . not be favourable in terms of powder flow ; - the use of direct pressing with spherical agglomerates of drug crystals with good flowability and compressibil- ity properties. 0032-5910r01r$ - see front matter q 2001 Elsevier Science S.A. All rights reserved. Ž . PII: S0032-5910 00 00272-2