(200ab) Extrudability Analysis of Drug Loaded Pastes for 3D Printing of Modified Release Tablets

Authors: 
Alayoubi, A., U.S. Food and Drug Administration
Zidan, A., U.S. Food and Drug Administration
Coburn, J., FDA
Cruz, C. N., U.S. Food and Drug Administration
Ashraf, M., Office of Testing and Research, U.S. Food and Drug Administration
The rheological characteristics of 3D printing pastes cannot be fully described by the traditional rheological tests suitable for other pastes. In the present study, extrudability testing of carbopol based 3D printing pastes was performed to establish a constitutive rheological model for micro-extrusion. This model was developed for pastes that follow a plasto-viscoelastic constitutive relationship and the associated generalized Herschel–Bulkley flow rule. An analytical model was then applied to the extrudability data obtained by extrusion through nozzle of 400 and 600 µm diameters. For this purpose, nineteen paste formulations were prepared per a fractional factorial design using various concentrations of the active ingredient and soluble and insoluble excipients. Critical constitutive material parameters including uniaxial yield flow stress (σ₀), uniaxial flow consistency index (k); and uniaxial flow index (n) related to viscosity of pastes were then calculated. This was performed by interpreting extrudability data into mathematical equation relating flow rate, nozzle and cartridge diameters, printing pressure and slip-flow angle. The accuracy of the constitutive model to predict yield stress, consistency and flow indices were evident by low RMSE values of 0.0691 bar, 0.034 and 6.3 bar/sn, respectively. The percent loading of soluble and swellable excipients was found to significantly affect the rheology of various pastes. However, nozzle diameter was found to affect significantly the flow index rather than consistency index. Hence, this study helped develop a mechanistic model to interpret data for characterizing the complex intrinsic rheological behavior of various pastes, for 3D printing, by employing the micro-extrusion process.