Considerations on the Kinetic Processes in the Preparation of Ternary Co-Amorphous Systems by Milling
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Ball Milling of Ternary Co-Amorphous Systems (A − B + C)
2.2.2. Preparation of Physical Mixtures
2.2.3. Characterization of Solid-State Properties by X-ray Powder Diffraction (XRPD)
2.2.4. Determination of the Glass Transition Temperature by Differential Scanning Calorimetry (DSC)
2.2.5. Calculation of the Theoretical Tgs Using the Gordon-Taylor Equation
2.2.6. Investigation of Intermolecular Interactions by FT-IR
2.2.7. Multivariate Data Analysis
3. Results and Discussion
3.1. Characterisation of Binary CAR Systems
3.2. Influence of Milling Time on the Ternary Systems
3.3. Identifying Intermolecular Interactions by Principal Component Analysis (PCA) of FT-IR Spectra
3.4. Development of Ternary Phase Diagrams
3.4.1. Solid-State form in A − B + C Ternary Systems
Investigation of the Solid-State form of TRP
Investigation of the Solid-State form of CAR
- The first thermal event is between 40 and 65 °C. This event corresponds to the Tg (with enthalpic relaxation, data shown as total heat flow) of the CAR − HPMC + TRP ternary system, which is 63.9 °C as shown in the reversing heat flow signal in Figure 2d.
- The onset point of the second endothermic peak is 107.4 °C and the peak maximum is at 111.1 °C. This can be explained as a melting event of crystalline CAR. Since pure CAR will be fully amorphized after 60 min of milling, the occurrence of this event shows that recrystallization of CAR in the ternary system happens during the grinding process.
- The third thermal event at 147.3 °C corresponds to the Tg of TRP, which proves the separation of TRP from the ternary system during the grinding process.
- The starting point of the fourth endothermic peak is 231.1 °C and the endpoint is 256.0 °C. This event is attributed to the melting of TRP.
3.4.2. Calculation of Phase Composition
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Samples | Component A − B Ratio (w/w) | Component C Ratio (w/w) |
---|---|---|
CAR − TRP + HPMC | CAR (60.5%) − TRP (30.4%) | HPMC (9.1%) |
CAR − HPMC + TRP | CAR (60.5%) − HPMC (9.1%) | TRP (30.4%) |
TRP − HPMC + CAR | TRP (30.4%) − HPMC (9.1%) | CAR (60.5%) |
Samples | CAR (w/w) | TRP (w/w) | HPMC (w/w) |
---|---|---|---|
TRP + extra 10% w/w HPMC PM | - | 90.9% | 9.1% |
CAR + TRP [1:1] + extra 10% HPMC PM | 60.5% | 30.4% | 9.1% |
Samples | CAR (w/w) | TRP (w/w) | HPMC (w/w) |
---|---|---|---|
CAR-TRP | 66.6% | 33.4% | - |
CAR-HPMC | 90.9% | - | 9.1% |
TRP-HPMC | - | 90.9% | 9.1% |
CAR-TRP-HPMC | 60.5% | 30.4% | 9.1% |
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Wang, Y.; Rades, T.; Grohganz, H. Considerations on the Kinetic Processes in the Preparation of Ternary Co-Amorphous Systems by Milling. Pharmaceutics 2023, 15, 172. https://doi.org/10.3390/pharmaceutics15010172
Wang Y, Rades T, Grohganz H. Considerations on the Kinetic Processes in the Preparation of Ternary Co-Amorphous Systems by Milling. Pharmaceutics. 2023; 15(1):172. https://doi.org/10.3390/pharmaceutics15010172
Chicago/Turabian StyleWang, Yixuan, Thomas Rades, and Holger Grohganz. 2023. "Considerations on the Kinetic Processes in the Preparation of Ternary Co-Amorphous Systems by Milling" Pharmaceutics 15, no. 1: 172. https://doi.org/10.3390/pharmaceutics15010172
APA StyleWang, Y., Rades, T., & Grohganz, H. (2023). Considerations on the Kinetic Processes in the Preparation of Ternary Co-Amorphous Systems by Milling. Pharmaceutics, 15(1), 172. https://doi.org/10.3390/pharmaceutics15010172