A Novel Physical Model and Mathematical Equation for Pre-process Wet granulation Endpoint Prediction
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In this study we propose a mathematical formula to estimate the amount of granulating liquid needed in the wet granulation process, which saves time, money and minimizing errors during formulation. The end point of wet granulation can be defined as the uncritical granulating liquid amount that is needed to produce the intended granular size distribution. Most frequently, this end point is determined during the process of wet granulation and, until today, there are no pre-process methods for its determination. Our equation is a modification of Washburn equation, where he described the flow of liquids in powders stacked in a column. The modification of the equation depended on the wetting characterization of the powder bed and sucking saturation level. Moreover, in order to validate the equation, lactose monohydrate, corn starch and mixtures of different percentages of starch and lactose were granulated using the amount of PVP solution calculated for each case. Drop on powder test was used to measure the level of saturation of pores of the powder bed by the PVP solution. The amount of liquid used was according to the calculated porosity, or according to the amount calculated by the modified Washburn equation. The resulting granules proved to have good flow properties. The normality of the granular size distributions curves was confirmed by linear normal probability Q-Q plots, as was shown by the values of R2. The narrowness of the distribution was characterized by the mean, median, standard deviation and span for starch, lactose, and their mixtures. A narrow size distribution was obtained, indicating that the calculated volume of the granulating liquid succeeded in reaching the optimum end point. The three end points used resulted in similar granular properties, indicating the potential advantage of using the amount calculated by the modified Washburn equation. Our results indicate also the ability of this equation to take into account the effect of physicochemical properties of the inactive materials used in tableting on the amount of granulating liquid. In conclusion, this new physical model can be proposed to estimate the amount of granulating liquid depending on: the wetting characterization of the powder bed and sucking saturation level. List of abbreviations used throughout the text:I: is the height of penetrating liquid in the cylinder, r: Pore effective radius, γ: the liquid surface tension, t: is the time needed by the liquid to reach the front of the powder bed, µ: The liquid viscosity, cosθ: is the cosine of the contact angle between solid and liquid, ε: porosity, Vb: powder bulk volume , Vfp: the liquid amount calculated with considering porosity determined by liquid displacement method, Vfe: the experimental value of porosity that represents the value of liquid interring the column in the classical Washburn method ,Vfw: the value calculated by equation 15.