Relating mechanical properties of dry and granulated pharmaceutical powder formulations with tablet quality parameters.

摘要

Mechanical properties of powders are very important to understand various unit operations such as storage, flow, granulation, compaction, and mixing. Pharmaceutical tablets are formed by compressing powder formulations consisting of ingredients such as filler, binder, lubricant, disintegrant, and active pharmaceutical ingredient (API). These powder formulations are sometimes granulated to improve flow and compression property as well as to prevent segregation of ingredients specially the API. The goal of this research was to predict the tablet quality based on the mechanical behavior of the powder formulations prior to manufacturing of the tablet with an emphasis on the effect of binder.;The formulations used for the research were composed of Avicel (filler), Methocel (binder), Magnesium stearate (lubricant), Ac-Di-Sol (disintegrant), and Acetaminophen (active pharmaceutical ingredient). Three different levels of methocel (binder): 0 (none), 5, and 10%, were used in powder formulation.;For dry blended formulations, at 10 MPa/min loading rate, the bulk modulus increased with increase in the isotropic pressure and binder content in all cases. At 20 MPa/min, the bulk modulus was maximum at 0% binder followed by those at 10 and 5% binder content. Increase in bulk modulus with increase in the binder content was also observed for granulated formulations at both loading rates of 10 and 20 MPa/min. In case of dry formulations, the compression index value increased with pressure; whereas, for granulated formulations, at 10 MPa/min loading rate, the compression index values at 10% binder content increased with pressure. At 5% binder, the compression index decreased and then increased. At 20 MPa/min loading rate, the compression index decreased and then increased for both binder contents. In all cases, the spring-back index value increased with pressure. In case of dry blended formulations at 10 MPa/min loading rate, the spring-back index value decreased with binder content. At 20 MPa/min, the spring-back index value for dry powder formulations was lowest at 0% binder content followed by 10 and 5% binder contents. In case of granulated formulations, at both loading rates, the spring back index for 10% binder content was higher than for 5% binder content. The shear modulus increased with increase in the confining pressure in all cases including dry and granulated formulations. In case of 20 MPa/min loading rate also, the shear modulus increased with increase in the confining pressure in all cases.;Various tablet quality parameters such as diametral strength, axial penetration strength, indentation hardness, and friability were evaluated. Diametral strength, axial penetration strength, and indentation hardness, values were higher at 90 MPa than at 70 MPa compression pressure for all binder contents. These parameters increased upto 5% binder content; thereafter, very little or no change was observed when binder content increased from 5 to 10%. This shows that increase in binder after 5% only had marginal effect on tablet quality parameters. Furthermore, binder content of around 5% appears to be optimum for tablet formation for ingredient and proportions used in this study. In case of granulated formulations, the friability decreased when binder content increased from 5 to 10%. The friability for granulated formulations was less than for dry blended formulations.;Statistical relations were developed between tablets' quality parameters and the powder mechanical properties at different binder contents and loading conditions. The regression equations between each tablet quality and powder property having r2 value more than 0.8 were selected for prediction. For dry formulations, spring-back index and compression index were found most suitable for predicting diametral strength, indentation hardness, and friability. In case of axial penetration strength, compression index, spring-back index, and shear modulus at higher loading rate had good relation (r2 > 0.8) for tablets formed at 90 MPa. For tablets formed using granulated formulations, compression index, spring-back index, and bulk modulus were found most suitable for predicting diametral strength, axial penetration strength, indentation hardness, and friability. An elastic energy-based approach was successfully used to explain the relationship of tablet quality parameters with spring-back index.;In summary, the mechanical properties of dry and granulated pharmaceutical powder formulations at different loading conditions and binder contents were determined. Tablets were formed using the same formulations and quality parameters were quantified. (Abstract shortened by UMI.)