CHARACTERIZATION OF ARIPIPRAZOLE SOLVATE WITH ETHANOL AND POLYMORPHIC FORMS PRODUCED DURING ITS HEATING

Marta Łaszcz ,  Adam Pietraszko ,  Magdalena M. Glice ,  Łukasz S. Kaczmarek ,  Katarzyna Badowska-Rosłonek ,  Katarzyna Korczak ,  Wioleta Maruszak ,  Hanna M. Beczkowicz 

Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland
Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland

Abstract

Aripiprazole (7-[4-[4- (2,3-dichlorophenyl) piperazin-1-yl] butoxy]-3,4- dihydro- 1H quinolin-2-one) is an anti - psychotic drug.

In this work a solvate with ethanol of Aripiprazole (2(C23H27Cl2N3O2)·C2H5OH) was fully characterized by means of the single crystal and the powder X-ray diffraction [1]. The studies revealed that the solvate crystallizes in space group P-1, Z=2 with unit cell parameters: a=7.796(2), b=10.694(4), c=15.608(7) Å and a=84.61(3), b=80.35(3), g=73.43(3)o. The ethanol molecule is incorporated in dimmers of Aripiprazole between chloro-derivative aromatic rings.

Thermal analysis and IR techniques additionally confirmed a presence of the ethanol molecule in Aripiprazole. XRPD, IR techniques revealed that the polymorph I can be obtained by a heating the solvate at the temperature of 100 oC but DSC analysis showed a presence of another form dash - the polymorph II [2]. Probably a quantity of polymorph II was too small for XRPD and IR detection. Further heating, up to 145 oC (temperature between two endo- peaks on a DSC curve), brought about a growth of polymorph II seeds what was observed by XRPD, IR and DSC techniques.

[1] "Sposób wytwarzania aripiprazolu w farmaceutycznie użytecznych formach polimorficznych", Ł.Kaczmarek, M.Łaszcz, A.Pietraszko, W.Szelejewski (na rzecz Polpharma SA) Data zgłoszenia 16.12.2005, Nr zgłoszenia P-378363.

[2] "Study on Crystal Transformation of Aripiprazol", Satoshi Aoki, Takuji Bando, Noriyuki Kobayshi, The fourth Japan-Korea symposium on separation Technology.

 

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Presentation: Poster at V Multidyscyplinarna Konferencja Nauki o Leku, by Marta Łaszcz
See On-line Journal of V Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2006-03-14 13:36
Revised:   2009-06-07 00:44