Design and Optimization of Chlordiazepoxide Solid Self-Microemulsifying Drug Delivery System
Design and Optimization of Chlordiazepoxide Solid Self-Microemulsifying Drug Delivery System
Design and Optimization of Chlordiazepoxide Solid Self-Microemulsifying Drug Delivery System
ISSN: 0974-6943
*Corresponding author.
Hitesh C. Bari
Department of Pharmaceutics,
Bharati Vidyapeeth College of Pharmacy,
Kolhapur, India.
Tel.: + 91-22/28461080
E-mail:barihitesh99@gmail.com
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Solubility (mg/ml) at 25 C
Ethyl oleate
Captex 355
Captex 800
Maisine 35-1
Capryol 90
Labrasol
Tween 80
Cremophor RH40
PEG 400
1.600.09
1.370.05
0.3920.13
1.490.06
1.350.04
28.7430.16
22.430.06
92.520.11
19.890.18
3, region of 4 and 5 were quite similar). Four formulations of different combinations were
selected from phase diagram denoted by dots for further studies. The selected microemulsion
formulations were exposed to freeze thaw cycling and centrifugation at 2000 rpm, which
conformed the thermodynamic stability of microemulsion. Compositions of selected four
formulations were shown in Table2.
Sr. no.
Formulation
Drug (mg)/10 gm
%Composition (w/w)
Oil
Labrasol
Cremophor RH40
1
2
3
4
ME1
ME2
ME3
ME4
350
350
350
350
12.1
15.0
16.0
19.9
17.8
17.3
17.1
16.3
70.1
67.7
66.9
63.8
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1
2
3
4
ME1
ME2
ME3
ME4
56.97
58.64
65.94
72.43
-23.1
-22.1
-21.1
-19.1
Figure2: Powder X-ray diffractograms of pure drug (A), physical mixture (B), ME2 (C) and ME3 (D
Time (min)
Figure5: In-vitro release profile of solid SMEDDS formulation and
Librium in SGF
% Cumulative drug release
a
b
Figure4: SEM images of solid SMEDDS (a: x2000, bar-10 m; b: x5000,
bar-5 m)
Sr. no.
Figure3: DSC curves of CDP (A), physical mixture (B), ME2 (C), ME3
(D)
Time (min)
Figure6: In-vitro release profile of solid SMEDDS formulation and
Librium in phosphate buffer pH5.8
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Time (min)
Figure7: In-vitro release profile of solid SMEDDS formulation and
Librium in phosphate buffer pH7.0
7.
8.
9.
and 7.0). ME4 formulation failed to show > 90% drug release because of increased globule
size but it passes the dissolution test criteria as per USP. This observation can be
explained by the fact that CDP has ionizable group and thus its solubility and dissolution
is pH dependent. But in same case one can also conclude that in case of solid SMEDDS
formulation, dissolution of chlordiazepoxide is pH independent.
4. CONCLUSION
In the present investigation, the solid SMEDDS of chlordiazepoxide was prepared by
spray drying, using water-soluble maltodextrin as solid carrier for direct filling into hard
gelatin capsule for oral administration. The solid SMEDDS consisted of well-separated
spherical particles and maintained the rapid self-emulsifying ability as that of liquid
SMEDDS. Both DSC measurements and X-ray diffraction analysis suggested that chlordiazepoxide in the solid SMEDDS was in the amorphous molecular dispersion state. In
vitro dissolution test showed that the solid SMEDDS had a faster in vitro release rate than
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