(M1530-10-57) Innovative Moisture Activated Dry Granulation (MADG) with Mesoporous Silica vs Wet Granulation: A Comparative Study

Purpose: The study explores the performance of Moisture Activated Dry Granulation (MADG) using mesoporous silica compared to a traditional wet granulation unit operation in pharmaceutical processing. The intent is to assess any advantages of MADG process on the final blend, tableting, and overall performance of the pharmaceutical granulation process.

Methods: Two granulation techniques were compared in this examination.  The MADG method involved the use of mesoporous silica in the formulation to facilitate moisture activation and granule formation during water addition. Key steps in both processes included blending, granulation, drying (only for wet granulation), milling (only for wet granulation), and lubrication before compression into tablets. MADG Process: Dispensed and dry mixed ingredients in a high shear granulator. Added small amounts of water (4%) to activate the binder to form bridges between the particles and initiated granule formation [1] [2]. Added mesoporous silica to the activated wet mass for moisture absorption/distribution making the blend dry. Disintegrant and lubricant were then added to make the final blend ready for compression. Wet Granulation Process: Dispensed and dry mixed ingredients in a high shear granulator. Addition of large amounts of water (15%) to prepare a wet mass and ensure the endpoint of granule formation. Dried the wet mass until a desired loss on drying (LOD) was obtained.  The dried granules were milled to reduce particle size of the coarse material for further processing. Disintegrant and lubricant were then added to make the final blend ready for compression.

Results: Physical characterization assessments of blend properties such as bulk density, tapped density, powder flow, and particle size distribution were measured for both MADG and wet granulation. The MADG blend exhibited superior flow properties and uniform particle size distribution compared to the wet granulation blend. Compressibility Index falls in FAIR range for MADG and PASSABLE range for Wet Granulation. Flodex result proves that MADG (6 mm) has better flow compared to wet granulation (18 mm). The particle size of MADG falls in the range of 125 µm whereas for wet granules they fall in the range of 250 µm.  In comparison, the MADG demonstrated better flow properties with the lower particle size. In terms of tablet compression parameters, tablets produced via MADG showed steady hardness, lower friability, and consistent weight compared to those produced by wet granulation. As an amorphous material, mesoporous silica absorbs moisture and dissolved caffeine in the blend, potentially leading to loss of crystallinity. Similar results are shown by DSC as the endotherm is absent in the MADG batch with mesoporous silica. Conversely, the endotherm is present in the wet granulation batch. PXRD data confirms loss of crystalline peaks and may indicate form conversion during wet granulation or caffeine entrapment during MADG which can be established by a retarded caffeine release profile in dissolution for MADG while disintegration results were comparable for the two processes.

Conclusion: The study demonstrates that MADG with mesoporous silica offers significant advantages over traditional wet granulation. These advantages include improved blend properties, enhanced tableting performance, and reduced number of steps in preparation. The findings suggest that MADG can be a viable alternative to wet granulation, providing a robust and efficient method for producing high-quality pharmaceutical tablets.

References: Sharma, D., Godbole, M. D., Lanewar, A., & Burle, S. (2017). Formulation and Evaluation of Tabletw Containing Poorly Water Soluble Drug by MADG Method. World J Pharm Res, 6, 1523-37.
Sharma, D., & Lanjewar, A. (2018). Optimization and Evaluation of Ibuprofen Tablets by MADG Method. PharmaTutor, 6(1), 56-71.

Figure 1: Comparison of Blend Properties for MADG and Wet Granulation

Figure 2: Comparison of Tablet Properties and Release Profiles for MADG and Wet Granulation

Figure 3: Comparison of Caffeine Crystalline Properties for MADG and Wet Granulation