Development and Evaluation of Raloxifene-Hydrochloride-Loaded Supersaturatable SMEDDS Containing an Acidifier
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Solubility Screening Tests
2.3. Preparation of RLH-Loaded S-SMEDDSs Containing Hydrophilic Polymers
2.4. Selection of an Acidifier/pH Modifier, and In Vitro Dissolution and Stability Testing
3. Results and Discussion
3.1. Solubility Screening Test
3.2. RLH-Loaded S-SMEDDSs Containing Hydrophilic Polymers
3.3. Improvement of Dissolution Behavior: Acidifier and Stability Testing
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Vehicle | Solubility (mg/mL) |
---|---|
Oil | |
Triethyl citrate (TEC) | 0.58 ± 0.02 |
Capryol™ 90 | 0.52 ± 0.02 |
Glyceryl triacetate | 0.38 ± 0.04 |
Labrafil M® 1944 CS | 0.16 ± 0.01 |
Labrafil M® 2125 CS | 0.15 ± 0.00 |
Lauroglycol™ 90 | 0.21 ± 0.01 |
Lauroglycol™ FCC | 0.09 ± 0.00 |
Capryol™ PGMC | 0.51 ± 0.02 |
Pluorol® Oleique CC 497 | 0.04 ± 0.00 |
Surfactant | |
Cremophor® EL | 0.82 ± 0.11 |
Cremophor® RH 40 | 1.35 ± 0.48 |
Labrasol® | 11.59 ± 0.76 |
Transcutol® P | 8.41 ± 0.62 |
Span® 20 | 0.08 ± 0.05 |
Span® 80 | 0.01 ± 0.01 |
Tween® 20 | 28.38 ± 3.07 |
Tween® 80 | 18.78 ± 5.44 |
Brij® 97 | 1.44 ± 0.41 |
Glyceride | |
Glycerine | 6.50 ± 1.37 |
Polyethylene glycol (PEG) | 9.39 ± 2.21 |
PEG 200 | 31.14 ± 1.54 |
PEG 400 | 17.86 ± 5.11 |
Propylene glycol (PG) | 11.74 ± 0.55 |
Ingredients (w/w, %) | Solubility (mg/g) | ||
---|---|---|---|
Tween® 20 | Labrasol® | PEG 200 | |
100 | 31.14 ± 1.54 | ||
100 | 11.59 ± 0.76 | ||
100 | 28.38 ± 3.07 | ||
20 | 80 | 39.07 ± 0.71 | |
25 | 75 | 30.47 ± 2.19 | |
33.3 | 66.7 | 30.88 ± 3.39 | |
50 | 50 | 27.42 ± 1.19 | |
66.7 | 33.3 | 19.68 ± 2.28 | |
75 | 25 | 28.28 ± 1.26 | |
80 | 20 | 20.68 ± 1.72 | |
20 | 80 | 28.70 ± 0.73 | |
25 | 75 | 24.76 ± 0.76 | |
33.3 | 66.7 | 19.68 ± 2.63 | |
50 | 50 | 11.90 ± 2.07 | |
66.7 | 33.3 | 9.16 ± 0.66 | |
75 | 25 | 10.10 ± 0.75 | |
80 | 20 | 16.12 ± 2.78 | |
25 | 25 | 50 | 26.16 ± 1.94 |
25 | 50 | 25 | 20.33 ± 2.97 |
No. | Triethyl Citrate | Capryol 90™ | Tween® 20 | Labrasol® | PEG 200 | Solubility (mg/g) |
---|---|---|---|---|---|---|
1 | 5 | 95 | 23.10 ± 3.07 | |||
2 | 10 | 90 | 22.52 ± 0.71 | |||
3 | 5 | 19 | 76 | 32.75 ± 1.76 | ||
4 | 5 | 20 | 75 | 37.96 ± 1.98 | ||
5 | 5 | 40 | 55 | 30.88 ± 0.37 | ||
6 | 5 | 75 | 20 | 22.95 ± 0.04 | ||
7 | 5 | 30 | 10 | 55 | 31.70 ± 1.87 | |
8 | 5 | 27.14 | 13.57 | 54.29 | 15.20 ± 1.44 | |
9 | 5 | 23.75 | 23.75 | 47.5 | 23.50 ± 3.19 | |
10 | 5 | 20 | 75 | 24.48 ± 2.30 | ||
11 | 10 | 10 | 80 | 23.36 ± 0.49 | ||
12 | 10 | 18 | 72 | 29.84 ± 0.84 | ||
13 | 5 | 20 | 75 | 36.83 ± 1.33 | ||
14 | 5 | 19 | 76 | 32.75 ± 1.76 | ||
15 | 10 | 18 | 72 | 24.80 ± 1.82 |
Formulation | Particle Size (nm) | Polydispersity Index | Zeta Potential (mV) |
---|---|---|---|
A (S-SMEDDS) | 1316.67 ± 72.57 | 0.18 ± 0.04 | 33.80 ± 0.75 |
B (S-SMEDDS) | 190.73 ± 2.15 | 0.25 ± 0.04 | 54.97 ± 2.14 |
A-1 (pH-modified S-SMEDDS) | 266.57 ± 3.56 | 0.73 ± 0.01 | 33.80 ± 1.97 |
B-1 (pH-modified S-SMEDDS) | 195.50 ± 2.90 | 0.22 ± 0.01 | 57.23 ± 1.38 |
Formulation | Solubility (mg/mL) | ||
---|---|---|---|
Water | pH 1.2 | pH 6.8 | |
A (S-SMEDDS) | 8.89 ± 0.12 | 0.79 ± 0.19 | 0.22 ± 0.03 |
B (S-SMEDDS) | 13.13 ± 0.35 | 2.86 ± 0.42 | 1.10 ± 0.03 |
A-1 (pH-modified S-SMEDDS) | 11.57 ± 0.45 | 3.28 ± 0.24 | 1.95 ± 0.89 |
B-1 (pH-modified S-SMEDDS) | 11.65 ± 0.55 | 6.05 ± 0.41 | 3.46 ± 0.15 |
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Lee, J.-H.; Kim, H.H.; Cho, Y.H.; Koo, T.-S.; Lee, G.W. Development and Evaluation of Raloxifene-Hydrochloride-Loaded Supersaturatable SMEDDS Containing an Acidifier. Pharmaceutics 2018, 10, 78. https://doi.org/10.3390/pharmaceutics10030078
Lee J-H, Kim HH, Cho YH, Koo T-S, Lee GW. Development and Evaluation of Raloxifene-Hydrochloride-Loaded Supersaturatable SMEDDS Containing an Acidifier. Pharmaceutics. 2018; 10(3):78. https://doi.org/10.3390/pharmaceutics10030078
Chicago/Turabian StyleLee, Jong-Hwa, Hak Hyung Kim, Young Ho Cho, Tae-Sung Koo, and Gye Won Lee. 2018. "Development and Evaluation of Raloxifene-Hydrochloride-Loaded Supersaturatable SMEDDS Containing an Acidifier" Pharmaceutics 10, no. 3: 78. https://doi.org/10.3390/pharmaceutics10030078
APA StyleLee, J.-H., Kim, H. H., Cho, Y. H., Koo, T.-S., & Lee, G. W. (2018). Development and Evaluation of Raloxifene-Hydrochloride-Loaded Supersaturatable SMEDDS Containing an Acidifier. Pharmaceutics, 10(3), 78. https://doi.org/10.3390/pharmaceutics10030078