Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Experimental Design
2.3. Preparing Powder Blends
2.4. Evaluation of Blends
2.4.1. Flowability
2.4.2. Bulk Density
2.4.3. Powder Compaction
2.5. Tableting Process
2.6. Evaluation of the Prepared Tablets
2.6.1. Weight Variation
2.6.2. Tensile Strength and Friability
2.6.3. Disintegration of Tablets
2.6.4. In Vitro Dissolution
3. Results and Discussion
3.1. Results of the Model Fitting
3.2. Influence of Variables on Powder Flow
Run | Angle of Repose (°) | Bulk Density (g/mL) | Tensile Strength (MPa) |
---|---|---|---|
1 | 39.21 ± 0.223 | 0.259 ± 0.033 | 6.49 ± 0.228 |
2 | 38.42 ± 0.337 | 0.262 ± 0.051 | 6.28 ± 0.336 |
3 | 35.13 ± 0.188 | 0.274 ± 0.113 | 6.37 ± 0.265 |
4 | 32.71 ± 0.164 | 0.297 ± 0.025 | 4.63 ± 0.335 |
5 | 29.84 ± 0.198 | 0.301 ± 0.083 | 4.72 ± 0.287 |
6 | 28.31 ± 0.253 | 0.321 ± 0.036 | 4.57 ± 0.235 |
7 | 33.16 ± 0.266 | 0.298 ± 0.081 | 3.86 ± 0.361 |
8 | 33.21 ± 0.321 | 0.296 ± 0.061 | 3.46 ± 0.384 |
9 | 33.41 ± 0.244 | 0.301 ± 0.021 | 3.91 ± 0.236 |
3.3. Influence of Variables on Bulk Density of Powder Blend
3.4. Influence of Variables on Blend Compaction
3.5. Optimization of Independent Variables
3.6. Tableting of Optimized CNG–Silica Blend
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Coded Levels | Weight Percent of Nano-Sized Colloidal Silica (%w/w) | Mixing Time (min) |
---|---|---|
−1 | 0.5 | 5 |
0 | 1 | 10 |
+1 | 1.5 | 15 |
Run | Weight Percent of Silica Nanoparticles (%w/w) | Mixing Time (min) |
---|---|---|
1 | 0.5 | 5 |
2 | 0.5 | 10 |
3 | 0.5 | 15 |
4 | 1 | 5 |
5 | 1 | 10 |
6 | 1 | 15 |
7 | 1.5 | 5 |
8 | 1.5 | 10 |
9 | 1.5 | 15 |
Ingredients | %w/w | Quantity (g) |
---|---|---|
Canagliflozin | 84.12 | 252.36 |
Nano-sized colloidal silica | 0.88 | 2.64 |
Polyvinylpyrrolidone (PVP K25) | 10 | 30 |
Croscarmellose sodium (CCS) | 5 | 15 |
Responses | Suggested Model | p-Value | R2 | Adjusted R2 | Predicted R2 | Adequate Precision |
---|---|---|---|---|---|---|
Y1: Angle of repose (°) | Quadratic | 0.0002 | 0.9688 | 0.9429 | 0.7421 | 19.308 |
Y2: Bulk density (g/mL) | Quadratic | 0.002 | 0.9306 | 0.8727 | 0.7343 | 12.047 |
Y3: Tensile strength (MPa) | Quadratic | <0.0001 | 0.9887 | 0.9793 | 0.9211 | 27.446 |
Variables | Coefficient Estimate | Sum of Squares | Standard Error | F-Value | p-Value | 95% CI Low | 95% CI High |
---|---|---|---|---|---|---|---|
Y1: Angle of repose (Quadratic model) | |||||||
Intercept | 30.19 | - | 0.3761 | - | - | 29.27 | 31.11 |
X1 | −2.16 | 28.08 | 0.3364 | 41.36 | 0.0007 | −2.99 | −1.34 |
X2 | −1.37 | 11.29 | 0.3364 | 16.63 | 0.0065 | −2.19 | −0.548 |
X1X2 | 1.08 | 4.69 | 0.4120 | 6.90 | 0.0392 | 0.074 | 2.09 |
X12 | 5.26 | 73.82 | 0.5046 | 108.72 | <0.0001 | 4.03 | 6.50 |
X22 | −0.0437 | 0.0051 | 0.5046 | 0.0075 | 0.9337 | −1.28 | 1.19 |
Y2: Bulk density (Quadratic model) | |||||||
Intercept | 0.3075 | - | 0.0033 | - | - | 0.2995 | 0.3155 |
X1 | 0.0167 | 0.0017 | 0.0029 | 32.33 | 0.0013 | 0.0095 | 0.0238 |
X2 | 0.007 | 0.0003 | 0.0029 | 5.70 | 0.0542 | −0.0002 | 0.0142 |
X1X2 | −0.003 | 0.000 | 0.0036 | 0.6983 | 0.4354 | −0.0118 | 0.0058 |
X12 | −0.0275 | 0.002 | 0.0044 | 39.12 | 0.0008 | −0.0383 | −0.0167 |
X22 | 0.0025 | 0.000 | 0.0044 | 0.3233 | 0.5903 | −0.0383 | −0.0133 |
Y3: Tensile strength (Quadratic model) | |||||||
Intercept | 4.61 | - | 0.066 | - | - | 4.45 | 4.78 |
X1 | −1.32 | 10.43 | 0.059 | 498.47 | <0.0001 | −1.46 | −1.17 |
X2 | −0.0217 | 0.0028 | 0.059 | 0.1346 | 0.7263 | −0.1662 | 0.1228 |
X1X2 | 0.0425 | 0.0072 | 0.0723 | 0.3454 | 0.5782 | −0.1345 | 0.2195 |
X12 | 0.3763 | 0.3775 | 0.0886 | 18.05 | 0.0054 | 0.1595 | 0.5930 |
X22 | 0.1063 | 0.0301 | 0.0886 | 1.44 | 0.2755 | −0.1105 | 0.3230 |
Variables | Target | Range | Weight | Importance Co-Efficient |
---|---|---|---|---|
Input | ||||
Silica weight percent | In range | 0.5–1.5% | 1 | NA * |
Mixing time | In range | 5–15 min | 1 | NA |
Output | ||||
Angle of repose | Minimize | 28.31–39.21° | 1 | +++ |
Bulk density | Maximize | 0.259–0.321 g/mL | 1 | +++ |
Tensile strength | 5 | 3.46–4.99 MPa | 1 | +++ |
Variables | Value | ||
---|---|---|---|
Weight percent of nano-sized silica | 0.889%w/w | ||
Mixing time | 15 min | ||
Overall desirability = 0.924 | |||
Responses | Predicted Values | Experimental Values | Relative Error (%) |
Angle of repose (°) | 29.27 | 29.91 ± 0.225 | −2.18 |
Bulk density (g/mL) | 0.312 | 0.308 ± 0.124 | 4.04 |
Tensile strength (MPa) | 4.99 | 5.06 ± 0.662 | −1.40 |
Properties | Optimized CNG–Silica Blend | Control Blend ** |
---|---|---|
RSD of weight variation (%) | 0.92 | 2.54 |
Ejection force (MPa) | 104 ± 3 * | 169 ± 5 |
Friability (%) | 0.02 ± 0.16 | 0.06 ± 0.14 |
Tensile strength (MPa) | 5.06 ± 0.662 | 6.72 ± 0.81 |
Disintegration time (min) | 6 ± 0.44 * | 14 ± 0.79 |
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Alrobaian, M.; Alalaiwe, A.; Almalki, Z.S.; Fayed, M.H. Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica. Pharmaceutics 2023, 15, 2552. https://doi.org/10.3390/pharmaceutics15112552
Alrobaian M, Alalaiwe A, Almalki ZS, Fayed MH. Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica. Pharmaceutics. 2023; 15(11):2552. https://doi.org/10.3390/pharmaceutics15112552
Chicago/Turabian StyleAlrobaian, Majed, Ahmed Alalaiwe, Ziyad S. Almalki, and Mohamed H. Fayed. 2023. "Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica" Pharmaceutics 15, no. 11: 2552. https://doi.org/10.3390/pharmaceutics15112552
APA StyleAlrobaian, M., Alalaiwe, A., Almalki, Z. S., & Fayed, M. H. (2023). Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica. Pharmaceutics, 15(11), 2552. https://doi.org/10.3390/pharmaceutics15112552