Application of Mathematical Models to Determine the Feasibility of Amorphous Drug Layering in Pan Coaters
Abstract
:1. Introduction
2. Methods
2.1. Description of Amorphous Drug Coating Process in Pan Coaters
- Selection of a suitable polymer that is compatible with the API, which can maintain the amorphous state of the API during application of the coating to the tablets, and ensure that once the final dosage form is consumed by the patient, the amorphous nature of the API is maintained right up to the delivery to the primary site of absorption.
- Selection of a suitable solvent system that is capable of dissolving both the polymer and the API. Ideally, the solvent should be a single component system. If a solvent mixture is selected, ideally, a constant boiling (i.e., an azeotrope) mixture should be used or one where the least volatile solvent in the mixture can maintain both the API and polymer in the solution.
- Design of an optimized coating process that allows the coating to be uniformly deposited on the substrate, and allows for the control of the drying process, so that once a dry coating is formed on the substrate, the API still retains its amorphous characteristics.
- Creating a coating solution by dissolving the polymer and the API in the requisite solvent system;
- Loading the tablet cores into the coating pan;
- Warming the tablets until they reach the required temperature;
- Coating the tablets by using the optimal coating process conditions described below;
- Drying the coated tablets at the conclusion of the coating process to remove traces of residual solvent(s);
- Cooling the tablets;
- Emptying the coating pan.
2.2. Acceptance Value and Its Relationship to Accuracy and Precision in Pan Coating Processes
3. Results and Discussion
3.1. Factors Affecting Accuracy (X)
- 0.15% for 98.5–101.5% specification limit on X
- 0.51% for 95–105% specification limit on X.
3.2. Factors Affecting Precision (CV)
3.3. Practical Implications
3.3.1. Performance and Cost Comparison to Pellet Systems
3.3.2. Other Considerations
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
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Unit Operations | Micronization of API | Solvent Spray Drying | Hot-Melt Extrusion | MUPS | Drug Layering onto Pellets | Drug Layering onto Tablets |
---|---|---|---|---|---|---|
Micronization | ✓ | ✗ | ✗ | ✗ | ✗ | ✗ |
Blending | ✓ | ✓ | ✓ | ✓ | ✗ | ✗ |
Spray Drying | ✗ | ✓ | ✗ | ✗ | ✗ | ✗ |
Extrusion | ✗ | ✗ | ✓ | ✗ | ✗ | ✗ |
Delumping/Milling | ↔ | ↔ | ✓ | ✗ | ✗ | ✗ |
Tableting | ✓ | ✓ | ✓ | ✓ | ✗ | ✗ |
Coating (Drug Layering or Other) | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ |
Encapsulation | ✗ | ✗ | ✗ | ✗ | ✓ | ✗ |
Total Unit Ops | 4 (5) | 4 (5) | 5 | 3 | 2 | 1 |
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Choi, M.; Porter, S.C.; Meisen, A. Application of Mathematical Models to Determine the Feasibility of Amorphous Drug Layering in Pan Coaters. Pharmaceutics 2022, 14, 149. https://doi.org/10.3390/pharmaceutics14010149
Choi M, Porter SC, Meisen A. Application of Mathematical Models to Determine the Feasibility of Amorphous Drug Layering in Pan Coaters. Pharmaceutics. 2022; 14(1):149. https://doi.org/10.3390/pharmaceutics14010149
Chicago/Turabian StyleChoi, Michael, Stuart C. Porter, and Axel Meisen. 2022. "Application of Mathematical Models to Determine the Feasibility of Amorphous Drug Layering in Pan Coaters" Pharmaceutics 14, no. 1: 149. https://doi.org/10.3390/pharmaceutics14010149
APA StyleChoi, M., Porter, S. C., & Meisen, A. (2022). Application of Mathematical Models to Determine the Feasibility of Amorphous Drug Layering in Pan Coaters. Pharmaceutics, 14(1), 149. https://doi.org/10.3390/pharmaceutics14010149