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Berven, F.S., et al., 2007. Proteom. Clin. Appl. 1, 699.

e u r o p e a n j o u r n a l o f p h a r m a c e u t

erformed for ketoprofen and l-dopa drugs revealing differentelationships and optimal model types. Geometry of polymeras suggested to be another drug release governing factor

long with matrix viscosity.

oi:10.1016/j.ejps.2008.02.065

7

mproved insight into the dissolution behavior of amorphousrugs by in situ solid-state analysis

arja Savolainen a, K. Kogermann a,b, A. Heinz c, J.altonen a,d, L. Peltonen a, C.J. Strachan d, J. Yliruusi a

Division of Pharmaceutical Technology, Faculty of Pharmacy, Uni-ersity of Helsinki, FinlandDepartment of Pharmacy, University of Tartu, EstoniaSchool of Pharmacy, University of Otago, New ZealandDrug Discovery and Development Technology Center (DDTC), Fac-lty of Pharmacy, University of Helsinki, Finland

The aim of this study was to use in situ Raman spec-roscopy to improve understanding of the phenomena thatccur during dissolution of an amorphous model drug carba-azepine (CBZ). Amorphous CBZ samples were prepared by

ooling the melt. Dissolution tests were done in phosphateuffer (pH 7.2) in a channel flow intrinsic dissolution testpparatus with a sight window for the Raman probe. CBZ dihy-rate tablets were used for reference. Multivariate methodsere applied to the Raman spectra to monitor the solid-state

ransformations occurring during dissolution. X-ray powderiffractometry was used as a reference method. The preparedmorphous CBZ sample did not exhibit a higher dissolutionate than the crystalline dihydrate, since the amorphous CBZransformed to the dihydrate during the dissolution experi-

ent. Based on the partial least squares discriminant analysisPLS-DA) and partial least squares (PLS) regression analysisf the Raman spectra, the transformation proceeded via therystalline anhydrate form.

oi:10.1016/j.ejps.2008.02.066

8

he effect of mixing time of the magnesium stearate on crush-ng strengths of tablets

atu Virtanen a, H. Salokangas b, J. Yliruusi a

Division of Pharmaceutical Technology, University of Helsinki, Fin-andPharmaceutical Product Development, R&D, Orion Corporation,spoo, Finland

This study investigated the change of lubrication effectf magnesium stearate (mgst) when the mixing time andcale were altered. The crushing strengths of tablets, whichere compressed from the mixed powders, were used as

econdary response for lubrication effect. Binary mixturesf microcrystalline cellulose and mgst were mixed in three

cales: laboratory (1 l), pilot (10 l) and production scale (80 l).wo parallel batches were mixed in every scale. The aim waso constitute a relationship between the mixing time of theowders and the crushing strength of the tablets. The crush-

s c i e n c e s 3 4 S ( 2 0 0 8 ) S25–S29 S27

ing strength of the tablets decreased when the mixing timeincreased with all of the batches. With pilot and productionscale this decrease was greater than with laboratory scale. Thisindicates that the results contrived in laboratory scale did notgive the right mixing time for the greater scale sizes withoutaltering the crushing strength of tablets.

doi:10.1016/j.ejps.2008.02.067

RECENT TECHNOLOGIES IN METABOLOMICS, LIPIDOMICSAND PROTEOMICS

O9

Biomarker discovery from mass spectral profiles: A combinedproteomics and multivariate analysis

Tarja Rajalahti a,b, R. Arneberg c,d, F.S. Berven e, A.C.Kroksveen e,f, M. Berle e, K.-M. Myhr a,b,g, C.A. Vedeler a,b,R.J. Ulvik e,h, O.M. Kvalheim i

a Department of Clinical Medicine, University of Bergen, Norwayb Department of Neurology, Haukeland University Hospital, Bergen,Norwayc Center for Integrated Petroleum Research, University of Bergen,Norwayd Pattern Recognition Systems AS, Bergen, Norwaye Institute of Medicine, University of Bergen, Norwayf Institute of Molecular Biology, University of Bergen, Norwayg The National Competence Centre for Multiple Sclerosis, HaukelandUniversity Hospital, Bergen, Norwayh Laboratory of Clinical Biochemistry, Haukeland University Hospi-tal, Bergen, Norwayi Department of Chemistry, University of Bergen, Norway

Cerebrospinal fluid (CSF) is a perfect source to search fornew biomarkers to improve early diagnosis of neurologicaldiseases. In the present study, MALDI-TOF mass spectrom-etry is used to examine the low molecular weight CSFproteome (Berven et al., 2007). Whole mass spectral profilesfrom patients with multiple sclerosis and orthopedic patients(controls) are then pretreated (Arneberg et al., 2007) and ana-lyzed using multivariate techniques. Target projection hasearlier been introduced as a method to transform abstractlatent variables from multivariate regression into easily inter-pretable factors (Kvalheim et al., 1989). In this work, we havedeveloped the approach further to provide information aboutvariables (biomarkers) and objects (end-members) that arealmost exclusively explained by the latent variable producedby target projection on PLS (partial least squares) components.Biomarker candidates are easily and reliably identified usingthis approach. It is also shown to reduce the risk of findingfalse candidates.

e f e r e n c e

Arneberg, R., et al., 2007. Anal. Chem. 79, 7014.

Kvalheim, O.M., et al., 1989. Chemom. Intell. Lab. Syst. 7, 39.

doi:10.1016/j.ejps.2008.02.068