Novel hybrid silica xerogels for stabilization and controlled release of drug.
OBJECTIVE
The goal was to show that incorporation of a model drug into a porous solid matrix with small enough pores should lead to composites in which the drug would be in the amorphous rather than in the crystalline state. Due to spatial constraints, the amorphous state was expected to be temporally highly stable.


METHODS
As a porous solid matrix silica was selected, while nifedipine served as a model drug. The silica-drug composites were prepared using a sol-gel procedure at conditions which yielded pores in the range 2-3 nm. To tune the properties of composites, two silica precursors were combined: tetraethoxysilane (TEOS) and bis-1,2-(triethoxysilyl)ethane (BTSE).


RESULTS
In all composites the amorphous state of nifedipine was proven using several analytical methods. The amorphicity was preserved for at least several months. Drug incorporation into purely TEOS-based silica decreased significantly the release rate. Loosening the structure by addition of BTSE, while preserving the amorphicity, increased the drug dissolution rate. The dissolution behaviour was explained using a combination of the Noyes-Whitney and power law model.


CONCLUSIONS
The observed release patterns could be interesting for therapies requiring a high initial drug concentration in blood plasma, followed by a slower release rate of the remaining drug.
Maver
Uros
U
Faculty of Pharmacy, University of Ljubljana, Askerceva 7m, 1000 Ljubljana, Slovenia.
Godec
Aljaz
A
Bele
Marjan
M
Planinsek
Odon
O
Gaberscek
Miran
M
Srcic
Stane
S
Jamnik
Janko
J
D002121:Calcium Channel Blockers / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004055:Differential Thermal Analysis; D004355:Drug Stability; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D009543:Nifedipine / Q000737:chemistry*; D010316:Particle Size; D012821:Silanes / Q000737:chemistry*; D020034:Silicone Gels / Q000138:chemical synthesis / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D014961:X-Ray Diffraction
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D012821:Silanes; D020034:Silicone Gels; C040733:tetraethoxysilane; D009543:Nifedipine