Preparation and Properties of Phenytoin Silica Complex Nanoparticles
- PDF / 331,736 Bytes
- 6 Pages / 414.72 x 648 pts Page_size
- 42 Downloads / 184 Views
Mat. Res. Soc. Symp. Proc. Vol. 501 ©1998 Materials Research Society
from the beginning [method (a)] and after sol formation [method (b)]. The TEOS solution composites by the molar ratio TEOS(1): EtOH(7): H20(11): HCI(0.07). Ethanol (EtOH) was preliminarily dehydrated by using molecular sieve 3A. The complex is termed as P1. Acryl amide (AAm; Kishida Chemicals) was added to some experiments of method (a) in order to control the affinity between the drug and silica gel. The amount of AAm added relative to PT was 1, 5 or 10 by weight and termed as PlAl, PlA5 and P1A10, respectively. The time of the delay of PT addition for the method (b) in Fig. I was chosen to be 6h and 10h. Samples are then termed as 6P1 and 10PI, respectively. The gel complex, obtained by drying at 50'C for 17h in a glass tray was crushed to use the size fraction between 75!im and 149•Im.
TEOS
TEOSJ H20 LHCIJ .. LCtOHJ Fig. 1 Flow
scheme of two different methods (mixing sequences) (a) and (b).
(a)
(ECH EtOHH LSol
(_Gel
H2
PT] AA
.. JHCI
f-EtCH]
P
~o (b) (b)
Gel
Characterization Morphology and granulometrical properties were observed by scanning and transmission microscopes. Crystallographical changes were monitored by X-ray diffractometry. Chemical interaction between the drug and silica gel was examined by infrared spectroscopy and thermal analyses. Rate of dissolution either in EtOH or water was determined in the following manner. A drug complex with net content of PT 20mg was put into a glass flask. 100cm 3 of the solvent, either EtOH or deionized water, was added to the flask and stirred at a constant rate. The rate was measured either at 37°C or 10'C. 1.5 cm 3 of the solution was taken by using a micro-syringe equipped with a membrane filter (cellulose acetate, 0.2[tm). 1.0 cm 3 of the solution was discarded to avoid the effect of drug adsorption on the filter paper. The rest of the solution was subjected to analysis of PT by a high performance liquid chromatography (HPLC; Hewlett Packard, HP-1500). phydroxy benzoic acid n-propyl ester was used as an internal standard. RESULTS Dissolution into EtOH The apparent solubility of the phenytoin into ethanol decreases by 322
complex formation to less than 30%, as shown in Fig. 2. This indicates that a part of the drug has been tightly bound to the silica gel. The amount of the drug released further decreases by adding acryl amide (AAm), but is still high enough to examine the dissolution behavior into an aqueous solution. .AAA
200
*
PT
150
I
E
I
1001 50
P1
50
25
P1A5
0
M
40
0
60 PA) I0M 1Pn Time(min)
20
40
60
80 100 120
Time(ain)
Fig. 3 Change in the concentration of PT in 0 water measured at 37 C of the intact PT and composites, P1, PlAl, P1A5 and P1AIO.
Fig. 2 Change in the concentration of PT in ethanol of the intact PT and representative composites, P1 and PIA5.
-0.5
,2'-1.5
C.,
C
-2 -9
5K -25 0
0.5
1
1.5
10 15 20 Time (min)
2
Time (min)
30
Fig. 4 Dissolution kinetics represented by the first-order rate equation of the sample (a): prepared
Data Loading...
