Drug Shelf Life and Release Limits Estimation Based on Manufacturing Process Capability
Abstract
:1. Introduction
2. Materials and Methods
2.1. Insulin HPLC Determination
2.1.1. Analysis of Samples
2.1.2. Long-Term Stability Study
2.2. Process Capacity Indices
2.3. Stability Data Analysis
3. Results and Discussion
3.1. HPLC Validation and Uncertainty Determination
3.2. Process Capability
3.3. Stability
3.4. Release Limits
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Sigma Level | Cpk | Lower | Upper |
---|---|---|---|
3 | 1.00 | 2.700 × 10−3 | 1.350 × 10−3 |
4 | 1.33 | 6.607 × 10−5 | 3.304 × 10−5 |
5 | 1.66 | 6.358 × 10−7 | 3.179 × 10−7 |
6 | 2.00 | 1.973 × 10−9 | 9.866 × 10−10 |
Group 1 | n | min | max | mean | sd | Cpk |
---|---|---|---|---|---|---|
#1 | 22 | 1.447 | 1.474 | 1.463 | 8.602 × 10−3 | 2.49 |
#2 | 22 | 1.444 | 1.471 | 1.460 | 7.256 × 10−3 | 3.07 |
#4 | 28 | 1.443 | 1.488 | 1.465 | 9.757 × 10−3 | 2.12 |
Group 2 | ||||||
#3 | 34 | 1.435 | 1.477 | 1.462 | 8.311 × 10−3 | 2.61 |
#5 | 30 | 1.450 | 1.482 | 1.467 | 9.193 × 10−3 | 2.17 |
#6 | 8 | 1.451 | 1.477 | 1.465 | 9.639 × 10−3 | 2.14 |
Parameter | Lower | Estimate | Upper |
---|---|---|---|
Intercept | 1.4597 | 1.4625 | 1.4652 |
Batch sd | 1.80 × 10−4 | 1.59 × 10−3 | 1.41 × 10−2 |
Residual sd | 7.37 × 10−3 | 8.70 × 10−3 | 1.03 × 10−2 |
Batch | b0 | b1 | RSD | TICH |
---|---|---|---|---|
1 | 1.461 | −8.204 × 10−3 | 1.360 × 10−2 | 7.95 |
2 | 1.460 | −7.939 × 10−3 | 1.210 × 10−2 | 8.30 |
4 | 1.470 | −9.980 × 10−3 | 1.275 × 10−2 | 7.61 |
Poolability | 1.464 | −8.708 × 10−3 | 1.186 × 10−2 | 8.73 |
Source of Variation | Sum of Square | DF | Mean Square | F | Pr (>F) |
---|---|---|---|---|---|
Intercept | 5.235 | 1 | 5.235 | 31808 | 0.000 |
Times | 7.459 × 10−3 | 1 | 7.459 × 10−3 | 45.319 | 0.000 |
Batch | 1.507 × 10−4 | 2 | 7.536 × 10−5 | 0.458 | 0.643 |
Times × Batch | 2.730 × 10−4 | 2 | 1.365 × 10−4 | 0.829 | 0.460 |
Residuals | 1.975 × 10−3 | 12 | 1.646 × 10−4 |
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Oliva, A.; Llabrés, M. Drug Shelf Life and Release Limits Estimation Based on Manufacturing Process Capability. Pharmaceutics 2023, 15, 1070. https://doi.org/10.3390/pharmaceutics15041070
Oliva A, Llabrés M. Drug Shelf Life and Release Limits Estimation Based on Manufacturing Process Capability. Pharmaceutics. 2023; 15(4):1070. https://doi.org/10.3390/pharmaceutics15041070
Chicago/Turabian StyleOliva, Alexis, and Matías Llabrés. 2023. "Drug Shelf Life and Release Limits Estimation Based on Manufacturing Process Capability" Pharmaceutics 15, no. 4: 1070. https://doi.org/10.3390/pharmaceutics15041070
APA StyleOliva, A., & Llabrés, M. (2023). Drug Shelf Life and Release Limits Estimation Based on Manufacturing Process Capability. Pharmaceutics, 15(4), 1070. https://doi.org/10.3390/pharmaceutics15041070