(357f) The Effect of Excipient Viscoelastic Properties On Predicting the Tensile Strength of Pharmaceutical Compacts

Powder compaction is a complex process involving rate dependent effects such as friction, temperature increase, entrapped air removal and viscoelasticity. Currently, elastoplastic and elasto-viscoplastic models are used to explain powder densification. These models predict permanent deformation to occur once the compaction pressure exceeds yield pressure. However, in our experiments, we have observed significant permanent deformation of Microcrystalline Cellulose (MCC) at compaction pressures much lower than the yield pressure. This observation can be explained due to the presence of viscoelastic properties of excipients used in tablet making. Unlike plastic deformation, the presence of a viscous component results in the onset of permanent deformation upon immediate application of a deforming force. Since viscosity is deformation rate dependent, the final deformation in powder compacts is rate dependent as well, as demonstrated by higher densities and tensile strengths for lower compaction speeds (Nokodchi et al. 1996). Hence, it is critical to incorporate viscoelastic properties while developing models that predict the final compact properties.

The contact area between two particles is an important property in wet and dry granulation that influences the final granule properties. Due to compaction, there is an increase in the contact area between two particles which is also concomitant to an increase in tensile strength. The amount of contact area formed is dependent on the particle deformability, which in turn depend on process variables such as contact time and pressure as well as the particle viscoelastic properties. The viscoelastic properties in turn, depend on raw material attributes such as moisture and drug content. The final tensile strength of a pharmaceutical compact has been shown to depend on both raw material properties and process variables (Almaya and Aburb (2008), Narayan and Hancock (2005)). For a given material, it has been found that larger the at-rest contact area, the stronger the bonding (Sebhatu and Alderborn (1999), Hiestand (1997a)). Viscoelastic properties increase the strength because of the effects on the work done during the separation of surfaces and on the radius of curvature of the surfaces in contact (Hiestand, 1997b).

The overall goal of this research is to predict tensile strength as a function of viscoelastic properties. The specific objective was to explore the role of viscoelastic contact area to predict tensile strength of Microcrystalline Cellulose (MCC) and acetaminophen (APAP) mixtures. Powders used for experiments were composed of 0, 25 and 50% APAP (rest MCC PH200). Magnesium stearate (0.5%) and Silicon Dioxide (0.2%) were used as lubricant and flow aide respectively. Moisture content of each drug composition corresponded to 40 and 70% RH. The powders were compressed in a Uniaxial testing machine at a punch velocities of 2 mm/min to final pressures in the range of 12.5 to 85 MPa. The diametral tensile strength was measured based on breakage force at 2 mm/min. The compaction response and stress relaxation of the uniaxial compact so formed were measured on the same machine. The small deformation contact area was calculated using equation by Lum and Duncan-Hewitt (1999) by using the median particle size of MCC, compaction and relaxation properties. The stress relaxation response was found to fit well to Maxwell model with two Maxwell elements and a spring in parallel (R²>0.99). The compaction curves were modeled using an exponential model (R²>0.99). It was found that stress relaxation and compaction parameters and hence the contact area, depended on the APAP composition, moisture content and on compact pressure. The viscoelastic contact area and final compact tensile strength were found to increase with increasing compaction pressure, moisture content and MCC. A unified model that expresses the compact tensile strength as a function of viscoelastic contact area was successfully developed. Thus, viscoelastic properties, which are dependent on important raw material properties and process variables, were incorporated in predicting the tensile strength of pharmaceutical compacts.

References:

1. Nokhodchi, A., Ford, J., Rowe, P. and Rubinstein, M. The effects of compression rate and force on the compaction properties of different viscosity grades of hydroxypropylmethylcellulose 2208. International Journal of Pharmaceutics 129 (1996) 21-31
2. Almaya, A. and Aburb, A. Effect of Particle Size on Compaction of Materials with Different Deformation Mechanisms with and without Lubricants. AAPS Pharm Sci Tech, 9 (2), 414-418.
3. Narayan, P and Hancock, B. The influence of particle size on the surface roughness of pharmaceutical excipient compacts. Materials Science and Engineering A 407 (2005) 226–233.
4. Sebhatu, T. and Alderborn, G. Relationships between the effective interparticulate contact area and the tensile strength of tablets of amorphous and crystalline lactose of varying particle size. European Journal of Pharmaceutical Sciences 8 (1999) 235 –242
5. Hiestand, E. Principles, tenets and notions of tablet bonding and measurements of strength. European Journal of Pharmaceutics and Biopharmaceutics 44 (1997a) 229- 242
6. Hiestand, E. Mechanical Properties of Compacts and Particles that Control Tableting. Journal of Pharmaceutical Sciences 86(9) (1997b) 985-990.
7. Lum, S. K. and Duncan-Hewitt, W.C. (1999). Powder Densification. 1. Particle-Particle Basis for Incorporation of Viscoelastic Material Properties. Journal of Pharmaceutical Sciences 88(2): 261-276.