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Improvement of aripiprazole solubility by complexation with (2-hydroxy)propyl-β-cyclodextrin using spray drying technique.
- Source :
-
AAPS PharmSciTech [AAPS PharmSciTech] 2012 Jun; Vol. 13 (2), pp. 623-31. Date of Electronic Publication: 2012 Apr 26. - Publication Year :
- 2012
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Abstract
- Due to the fact that the number of new poorly soluble active pharmaceutical ingredients is increasing, it is important to investigate the possibilities of improvement of their solubility in order to obtain a final pharmaceutical formulation with enhanced bioavailability. One of the strategies to increase drug solubility is the inclusion of the APIs in cyclodextrins. The aim of this study was to investigate the possibility of aripiprazole solubility improvement by inclusion in (2-hydroxy)propyl-β-cyclodextrin (HPBCD) and simultaneous manipulation of pH of the medium and addition of polyvinylpyrrolidone. Aripiprazole-HPBCD complexes were prepared by spray drying aqueous drug-HPBCD solutions, and their properties were compared with those prepared by solvent-drop co-grinding and physical mixing. The obtained powders were characterized by thermoanalytical methods (TGA and DSC), FTIR spectroscopy, their dissolution properties were assessed, while the binding of aripiprazole into the cavity of HPBCD was studied by molecular docking simulations. The solubilization capacity was found to be dependent on pH as well as the buffer solution's ionic composition. The presence of PVP in the formulation could affect the solubilization capacity significantly, but further experimentation is required before its effect is fully understood. On the basis of solubility studies, the drug/HPBCD stoichiometry was found to be 1:3. The spray-dried products were free of crystalline aripiprazole, they possessed higher solubility and dissolution rate, and were stable enough over a prolonged period of storage. Spray drying of cyclodextrin solutions proved to be an appropriate and efficient technique for the preparation of highly soluble inclusion compounds of aripiprazole and HPBCD.
- Subjects :
- 2-Hydroxypropyl-beta-cyclodextrin
Aripiprazole
Calorimetry, Differential Scanning
Chemistry, Pharmaceutical
Computer Simulation
Drug Stability
Hydrogen-Ion Concentration
Kinetics
Models, Chemical
Molecular Structure
Povidone chemistry
Powders
Solubility
Solvents chemistry
Spectroscopy, Fourier Transform Infrared
Thermogravimetry
Water chemistry
Antipsychotic Agents chemistry
Drug Carriers
Piperazines chemistry
Quinolones chemistry
Technology, Pharmaceutical methods
beta-Cyclodextrins chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1530-9932
- Volume :
- 13
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- AAPS PharmSciTech
- Publication Type :
- Academic Journal
- Accession number :
- 22535520
- Full Text :
- https://doi.org/10.1208/s12249-012-9786-3