Devang B. Patel, Vivek D. Patel, Robert Sedlock & Rahul V. Haware present a new way to investigate material deformation properties and predict tabletability
Most of the active pharmaceutical ingredients (APIs) are poorly compressible under applied compression pressure. It is very important to understand the deformation properties of the material involved in the formulation to achieve strong tablets.
The Heckel method is widely used to analyse the macroscopic compression properties of the pharmaceutical materials. This method has many limitations, and it is very sensitive to experimental conditions.[1] It is also very prone to negative porosity issues at high compression pressure.[2]
The compression (CM) and decompression modulus (DM) can be derived from force-displacement data generated using a compression simulator. The compression-decompression moduli was used to propose a two dimensional ‘compression-decompression modulus classification system’ (CDMCS).
Determination Of CDM
Vivapur 101, Starch 1500, Emcompress and Tablettose 100 were selected to perform the analysis. These materials were compressed at three different compression pressures (100, 150, 200 MPa) and three different linear compression speeds (0.35, 0.55, 0.75 m/s) using a compression simulator (Presster).
The CM and DM can be determined from the stress versus strain plot. A stress versus strain plot from 5-60 MPa compression pressure exhibited ‘bi-linear’ regions between 5-20 MPa and 20-60 MPa compression pressure (Fig. 1A). This phenomenon indicates the material fragmentation at low pressure followed by deformation. Therefore, a plot of stress vs strain was analysed for two pressure regions; low (5-20 MPa) and mid (20-60 MPa); for the compression and decompression phase of each material.
Material’s Modulus
The CM and DM can provide very important information about materials’ deformation, fragmentation and elastic properties under applied compression pressure. The rank order of CM and DM for all four model materials were observed as below:
Compression modulus (CM):
Starch 1500 > Tablettose 100 > Emcompress > Vivapur 101 (5-20 MPa)
Emcompress > Tablettose 100 > Starch 1500 > Vivapur 101 (20-60 MPa)
Decompression modulus (DM):
Emcompress > Tablettose 100 > Vivapur 101 > Starch 1500 (5-20 MPa and 20-60 MPa)
The rank of table mechanical strength (TMS) was observed as below:
Vivapur 101 > Emcompress ≥ Tablettose 100 > Starch 1500
Vivapur 101 exhibits lower CM and DM, which results in higher TMS. Starch 1500 exhibits high CM under low compression regions, low CM under mid compression regions and low DM under low and mid compression regions, which results into low TMS. Emcompress exhibited a lower compression modulus and a higher decompression modulus than the Tablettose 100. The higher moduli of fragmenting materials are due to their limited displacement or low strain in the loading and unloading of the compression pressure. Such stiff materials could mainly rely on the increasing bonding numbers by fragmentation into the smaller particles to provide a desired tablet strength.[3]
Proposed Material Classification System
Based on the data collected, the authors have proposed a new classification system to predict if material is going to produce strong or weak tablet. This system is the CDMCS described earlier (Fig. 2).
If CM and DM of the material lies in the green (Class-I) or light green colour (Class-II) region, then the material may result into robust tablets. If CM and DM of the material lies in the orange (Class-III) or red colour (Class-IV) region, then the material may result into poor tablets. High fragmenting materials will belong to Class-II and will form second strongest tablets after Class-I materials. Low fragmenting materials will fall into Class-III materials, and will form weaker tablets than Class-II materials. Predominately elastic materials will fall into Class-IV materials, which results in very weak tablets. The materials that fall into Class-IV have high potential for tablet capping and lamination issues.
Conclusion
The present investigation proves that the proposed compression behaviour parameterisation methodology and classification system could serve as a ‘first-hand tool’ in an early formulation development stage or as a ‘tableting problem diagnostic tool’ in the late development stage.
REFERENCES:
[1] Sonnergaard JM. 1999. A critical evaluation of the Heckel equation. Int J Pharm. 193(1):63–71. https://doi.org/10.1016/S0378-5173(99)00319-1
[2] Patel DB, Patel VD, Haware R, Sedlock R. 2022. Negative porosity issue in the Heckel analysis: A possible solution. [place unknown].
[3] Choi DH, Kim NA, Rok CH, Jung JY, Yoon J-H, Jeong SH. 2010. Material properties and compressibility using Heckel and Kawakita equation with commonly used pharmaceutical excipients. J Pharm Investig. 40(4):237–244. https://doi.org/10.4333/kps.2010.40.4.237.
Devang B. Patel, Vivek D. Patel, Robert Sedlock & Rahul V. Haware are with Natoli
