Drug Release From Reservoir Pellets Compacted With Some Excipients Of Different Physical Properties

European Journal of Pharmaceutical Sciences 20 (2003) 469–479

Drug release from reservoir pellets compacted with some excipients of different physical properties
Åsa Tunón, Elisabet Börjesson, Göran Frenning, Göran Alderborn∗
Department of Pharmacy, Uppsala Univerity, P.O. Box 580, SE-751 23 Uppsala, Sweden Received 16 April 2003; received in revised form 19 September 2003; accepted 19September 2003

Abstract The aim of the present study was to investigate the influence of the size and the porosity of excipient microcrystalline cellulose (MCC) particles on the densification and the deformation during compaction and the consequent effect on the drug release from reservoir pellets. Drug pellets consisting of salicylic acid and microcrystalline cellulose were prepared byextrusion-spheronisation and spray-coated with ethyl cellulose (ethanol solution). Excipient pellets of different size and porosity were prepared by extrusion-spheronisation or direct spheronisation. Five binary mixtures of reservoir pellets and excipient particles were prepared in the proportion 1:7 and lubricated. After compaction the reservoir pellets were retrieved and analysed to determine theintragranular porosity, surface area, shape and drug release. The reservoir pellets were shown to undergo extensive deformation and densification during compaction, resulting in a preserved or even prolonged drug release time. The mode of deformation of the reservoir pellets seems to be critical for the compression-induced change in drug release. Formation of large indents has a negative effect on the releasetime, while the use of small particles or small deformable agglomerates has a protective effect. We also hypothesize that the coating structure changes during compaction and the final structure of the coating is the net effect of two parallel processes, one reducing and one prolonging the drug transport time across the coating. © 2003 Elsevier B.V. All rights reserved.
Keywords: Reservoir pellet;Excipient particle; Particle size; Intragranular porosity; Compression behaviour; Drug release

1. Introduction A design principle of increasing importance for controlled release preparations is the compaction of barrier-coated pellets into disintegrating multiple unit tablets. One challenge in the production of such tablets is maintaining the modified drug release after compaction, as theapplication of compaction pressure can lead to structural changes in the film coating and, consequently, altered drug release. The compression-induced changes in the structure of the film coating can depend on formulation factors, such as the type and amount of coating, the properties and structure of the pellet core and the incorporation of excipient particles with protective properties. The protectiveeffect of excipients depends on material properties such as compression characteristics and particle size. A number of researchers (Mount and Schwartz, 1996; Lundqvist et al., 1997, 1998; Pinto et al., 1997; Iloañusi and
Corresponding author. Tel.: +46-18-471-44-73; fax: +46-18-471-42-23. E-mail address: goran.alderborn@farmaci.uu.se (G. Alderborn). 0928-0987/$ – see front matter © 2003 ElsevierB.V. All rights reserved. doi:10.1016/j.ejps.2003.09.009
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Schwartz, 1998; Salako et al., 1998; Nicklasson and Alderborn, 1999; Vergote et al., 2002) have incorporated different soft materials in pellets to modify their deformability and to enhance their protective effect. Habib et al. (2002) used freeze-drying to prepare protective pellets that exhibited both plastic deformation and brittlefracture characteristics. As far as the size of excipient particles is concerned, some studies have recommended the use of small particles, while others have recommended large ones. Wagner et al. (2000) compacted reservoir pellets (Eudragit FS 30 D coated) using microcrystalline cellulose (MCC) as the excipient, either as a powder or in the form of granules. They found the drug release to be less...