Pharmaceutical Research, Vol. 17, No. 4, 2000 Short Communications Stubberud (8) reported on the weakening effect of moisture Effect of the Storage Conditions on the sorption on the tensile strength and the physical stability of Tensile Strength of Tablets in compacts of crystalline and partly amorphous lactose, alone and in binary mixtures with PVP. Alderborn and Ahlneck (9) Relation to the Enthalpy Relaxation of assessed the effect of air humidity on the post compaction the Binder changes in tensile strength of tablets formulated with different pharmaceutical excipients. They found that changes in tablet strength were probably due to a rearrangement of solid material within the tablet that was facilitated by sorbed water. Rees F. Kiekens, 1 R. Zelko, 2 and J. P. Remon 1,3 and Tsardaka (10) examined the effects of moisture on the viscoelastic deformation during compaction of modified starch Received September 8, 1999; accepted January 7, 2000 using creep tests and Heckel plots. They reported that the mois- ture, by facilitating elastic and plastic deformation, not only KEY WORDS: water; PVP; glassy; rubbery; enthalpy relaxation; tensile strength; tablets. altered the compression behaviour of the material, but also its recovery during decompression in the die. The objective of this work was to study the enthalpy INTRODUCTION relaxation of PVP powder samples stored at different relative From a pharmaceutical technological standpoint, interac- humidities and to find a correlation between the tensile strength tions mean those processes that take place during the prepara- of the compacts containing PVP and stored at the same relative tion, storage and administration of a drug product and that may humidities as the pure PVP powder samples, and the enthalpy contribute to changes of the original state of active ingredients relaxation during the applied isotherm recovery process of PVP and/or additives and/or the dosage form as well. Amorphous powder samples stored under various conditions. polymer excipients are often highly reactive and unstable to mechanical and thermal stresses above their glass transition MATERIALS AND METHODS temperatures (T g ) and this may result in significant variation in some of their key physico-mechanical properties. Whilst Materials many of those excipients, like various types of PVP polymers, Polyvinylpyrrolidone (PVP, Kollidon K25, BASF, Lud- have T g values above the normal operating temperatures, the wigshafen, Germany) was selected as an amorphous binder and plasticising effect of residual solvents, absorbed water and other MicroperlT AQ (Sovitec Glaverbel, Fleurus, Belgium) glass additives could affect their long term performance and stability microspheres with a mean diameter of 38 mm, as an inert in pharmaceutical dosage forms by a Tg reduction (1–3). The substrate for the preparation of tablets. long term physical stability of amorphous pharmaceutical mate- rials is controlled by the type and rate of their molecular motions Tablet Preparation (4,5). Physical aging in polymeric systems is the term used to describe the time dependence of changes in the behavior of 12 batches of 6 tablets were produced using a wet granula- an amorphous polymer held at temperatures below the glass tion procedure, which consisted of 100 g MicroperlT AQ and transition. Volume relaxation and enthalpy relaxation are two 10 ml of a 15% (w/v) PVP aqueous solution. Next the wet manifestations of physical aging, and they can be used to follow granulated mass was compressed into a specially designed this process (6). By use of differential scanning calorimetry punch and die-system using a force of 10 kg so forming 12 (DSC) the structural relaxation in amorphous polymers can be mm diameter tablets. The tablets were dried in a hot air drier investigated with a high reproducibility. During such a DSC at 608C for 24 h (Memmert, ULE 600, Schwabach, Germany). experiment a polymer sample is subjected to a more or less complicated thermal history, which starts at a temperature T 0 Storage Conditions (above the glass transition temperature) and involves periods Two batches of the dried tablets were transferred into each of heating or cooling at constant rates as well as isothermal of the 6 dessicators (at 25%, 35%, 45%, 55%, 65% and 75% stages, finishing at a temperature T 1 in the glassy state. Then R.H.) and stored at room temperature for two storage periods the specific heat at constant pressure is measured during a of 1 week and 1 month, respectively. PVP powder samples heating scan at constant rate between T 1 and T 0 . The C p versus were also kept under the same storage conditions. T curve thus obtained depends on the thermal history of the sample and contains information about structural relaxation, Water Content Determination which occured both in the process previous to the measurement The determination of the water content of the PVP powder and during the measuring scan itself (7). samples was performed by Karl-Fischer titration (Mettler Toledo DL 35, Lot, Belgium) using dry methanol and HydranalT Composite 5 (Riedel-De-Hae¨n, Seelze, Germany). 1 Laboratory of Pharmaceutical Technology, University of Gent, Harel- bekestraat 72, B-9000, Gent, Belgium. Morphology of PVP Samples 2 Pharmaceutical Institute, Semmelweis University of Medicine, The morphological examination of stored PVP powder Ho˜gyes E. u. 7., H-1092 Budapest, Hungary. samples was performed by scanning electron microscopy (SEM, 3 To whom correspondence should be addressed. (e-mail: jeanpaul.remon@rug.ac.be) Jeol JSM, Japan). 490 0724-8741/00/0400-0490$18.00/0 q 2000 Plenum Publishing Corporation