Category: Formulation and Quality
Purpose: As the pharmaceutical industry has adopted great changes in their quality system, selecting the right QbD paradigm that facilitates the economic and regulatory outcome is very critical. The objective of this work is to present the outcome of powder and tablet physical properties by using different types of fillers, such as cellulose and Polyvinylpyrrolidone. Those excipients present a possible binding activity which has a potential to improve the final product as well as robustness of pharmaceutical manufacturing processes, such as direct compression.
Methods: Formulation consists of Glucosamine-HCl and different ratios of fillers. Fillers that have been implemented in the formulation are MCC 101, MCC 102, MCC 105, HPC SSL-SFP, HPC SL-FP, and HPC L-FP, and Kollidon VA-64. The percentages of filler are 2.5%, 5%, 10%, and 15%. After the dispensing step, each dry powder was sieved on mesh # 25. Direct blend (DB) is prepared in V-blender for total of 15 mins at 20 RPM. Each batch then was pre-compressed at pre-determined compression loads of 30 LBS, then main-compressed at 6631 LBS via using 0.34 *0.75 oval shape faced punches in single tablet press NR-RD10A. Powder characteristics evaluated by Laser Diffraction Method (PSD), mDSC, powder rheology (FT-4), density tester (He Pycnometer-Mechanical tapper). Tablet characterization was performed using hardness tester (tensile strength from Normalization), electronic caliber and balance (weight and thickness).
Results: Using Different types of fillers has shown an increase and decrease in the tablet hardness. However, increasing the ratio of each type of filler has increased the hardness. In some cases, Tablet capping and lamination have been observed for some excipients which correlate to its incapacity to manufacture the desired tablets. HPC products have shown better hardness and processibility. On the other hand, microcrystalline cellulose produced tablets with proper hardness only under a certain grade (MCC-105); other grades (MCC 101-102) were not proper for this process. Data from other tests confirm the similarity in the trend of efficiency and optimization.
Conclusion: Chemically and physically interpretation about molecules helped in pre-selection the formulation components. In this work, Looking at the chemical structure of HPC, MCC, and Kollidon VA 64 has initialized the preference of selection a linear chains compounds. However, MCC is showing a micro-fibril weak internal bonding that results in weak segments which lead to capping based on physical and hardness inspection.