(T1230-07-47) The Combination Use of Microcrystalline Cellulose and Lactose in Direct Compression

Purpose: Microcrystalline cellulose (MCC) is one of the most popular tableting excipients thanks to its outstanding dry binding properties, good powder flow, and disintegration properties. Lactose in various forms, including spray-dried, anhydrous, and granulated, are also widely used in direct compression given their excellent powder flow and good compaction characteristics[1] [2]. The synergistic advantage of MCC and lactose can be brought into full play when they are used together in tablet formulations. In the present study, the effects of MCC and lactose ratio on blend powder flow, compaction, and tablet disintegration were investigated.

Methods: MCC (Avicel^® PH-102) and lactose (SuperTab^® 11SD) were mixed in different proportions for 5 minutes at 20 rpm using Canaan Blender. Powder flow was measured using Hanson Flodex, Scott Volumeter, TDTF Tapped Density tester and Erweka Powder Flow Tester [3]. Final blends were prepared by adding 1% lubricant (Alubra^TMPG-100) and blending for 2 minutes at 20rpm. Tablets were compacted on a GYLongli 10 Stations Tablet Press fitted with 10mm round flat punches using 4, 7, 10, 15 and 20KN compaction force. Tensile strength (σ)^[4] was calculated using the Newton-Fell equation σ=2h/πtd where h is the tablet breaking force, t is tablet thickness, and d is tablet diameter. Tablet disintegration time was measured using TDTF Disintegration Tester. Design Expert (2-factor mixing design) was used for the design of experiments (DoE) to find the relationship between tensile strength and MCC/lactose ratio. Validation of this model formula with another MCC/lactose ratio not included in DOE was also attempted. Additionally, it was also attempted to extend this model formula to other MCC and lactose grades.

Results: Powder Flow: Three powder flow indicators, including Flodex™ Orifice Diameter (OD), Angle of Repose, and Carr's Index were tested (Figure 1). The powder flow of the blends with different MCC (Avicel^® PH-102) and lactose (SuperTab^® 11SD) ratios were acceptable among the three flow indices. Powder flow improved as lactose percentage increased. Compactibility: It was found that there was a linear relationship between tensile strength and MCC percentage(A) and lactose percentage (B) under different main compression forces. At the same time, the accuracy of this model was also well verified by another two MCC percentages (30%, 75%) (Figure 2). Additionally, this model was successfully extended to other MCC and lactose grades, Avicel^® PH-302 and SuperTab^® 24AN as an example (Figure 3). Disintegration: Disintegration time decreased with the increasing MCC level. When the tensile strength of tablet was between 1-2.5 MPa, the tablets showed very good disintegration performance as long as the MCC content was more than 25%.

Conclusion: The combination of MCC and lactose can be used in direct compression with required flowability and compactibility. The plastically deforming MCC in combination with the brittle lactose demonstrated synergy with compaction and powder flow. It can be speculated that the ratio between MCC and lactose can be optimized for the desired compactibility according to the model formula.

References: 1. Olufunke D. Akin-Ajani*, Oluwatoyin A. Odeku and Ololade Olumakinde-Oni. Evaluation of the mechanical and release properties of lactose and microcrystalline cellulose and their binary mixtures as directly compressible excipients in paracetamol tablets. J. Excipients and Food Chem. 11 (2), 42-52 (2020).
2. Zhang, Y., Law, Y. & Chakrabarti, S. Physical properties and compact analysis of commonly used direct compression binders. AAPS PharmSciTech 4, 62 (2003). https://doi.org/10.1208/pt040462
3. Lavoie, F., Cartilier, L. & Thibert, R. New Methods Characterizing Avalanche Behavior to Determine Powder Flow. Pharm Res 19, 887–893 (2002). https://doi.org/10.1023/A:1016125420577
4. Olsson, H., Nyström, C. Assessing Tablet Bond Types from Structural Features that Affect Tablet Tensile Strength. Pharm Res 18, 203–210 (2001). https://doi.org/10.1023/A:1011036603006

Acknowledgements: The authors would like to thank International Flavors and Fragrances Inc. (IFF) and DFE Pharma for providing excipient support and technical guidance.


Figure 1. DOE formulas and flowability results


Figure 2. Compactibility DOE Model Analysis and validation


Figure 3: Optimized model equations for Avicel® PH-302 and SuperTab® 24AN and corresponding validation