A new tool to determine end point for wet granulation using rheological and thermal effusivity measurements

Wet granulation has been widely used in pharmaceutical industry as a tablet manufacturing process. However end point determination of wet granulation process always remains a challenge for scientists. Though, there are many traditional methods available for end point determination, accuracy and reproducibility is always a challenge. Rheological and thermal property of a material is a very useful tool for determination of end point as well as for characterizing a proper lubrication mixing time to investigate the powder lubrication. In this research we have tried to develop a new method for determination of end point and lubrication time using freeman technology-4 (FT-4) rheometer and effusivity sensor probe. Micro crystalline cellulose (MCC-101/AVICEL 101), widely used excipient in pharmaceutical industry, was granulated in a cusinart mixer by addition of 200 g to 800 g of water. After addition of 800 g of water, granules are mixed with 1% of different lubricants like, magnesium strearate monohydrate (MG ST- M), magnesium strearate dihydrate (MG ST- D), SOW (SOW) and a mixture of MG ST- M (94%) + SLS (6%) to perform the time dependent study at different time interval. Specific energy (SE), permeability and basic flowability energy (BFE), were measured using ft-4 rheometer. Collected samples were measured at each data point for effusivity at room temperature using effusivity probe. Differential scanning colorimetry was also performed to study the water absorption characteristic of Avicel 101. In order to get the granules, wet mass was passed through sieve ;Basic flow energy (BFE) was dramatically increased at 800 g of water for wet granules while in case of dried granules it was decreased. Specific energy (SE) doubled at the end point while adding 600 g to 800 g of water while in case of dried granules it was decreased. Permeability decreased in linear fashion up to the end point for wet and dried granules. Effusivity data also suggested a dramatic increase in effusivity reading at the end point for wet granules while at end point % RSD of dried granules were lowest. So 53.53%w/w water was determined as end point of wet granulation.;Better flow of granules was observed in the presence of SOW, this observation was made from the values of BFE, SE and permeability which are lowest in case of SOW.;From the data we were able to quantify the changes occurring during wet granulation and accurately determine the end point. The developed method is easy to perform, reliable and has less scale up issues.