(T0930-09-61) Enhancing the Tabletability of Fenofibrate-HPMCAS Amorphous Solid Dispersions Using Kollitab® DC 87 L: A Multifunctional Excipient Approach for Direct Compression

Purpose: Amorphous solid dispersions (ASDs) are widely used to enhance the solubility and bioavailability of poorly water-soluble drugs such as fenofibrate. However, their poor flow and compressibility, especially when formulated with hydrophilic polymers like HPMCAS pose significant challenges for direct compression tablet manufacturing. This study investigates the application of Kollitab® DC 87 L (Kollitab), a co-processed multifunctional excipient, to address the tableting limitations of HPMCAS-based ASDs and to enable direct compression without requiring dry granulation.

Methods: ASDs of Fenofibrate and HPMCAS were prepared via hot-melt extrusion (HME) at 25% drug loading, using a standard screw configuration at a barrel temperature of 90 °C, screw speed of 50 rpm, and feed rate of 9 g/min. Complete amorphization of Fenofibrate was confirmed by differential scanning calorimetry (DSC), and dissolution testing showed 100% drug release within 45 minutes. The ASDs were blended with Kollitab® DC 87 L at varying Fenofibrate–HPMCAS ASD to Kollitab ratios (1:0.5, 1:1, 1:1.5, 1:2, and 1:2.5) and compressed using 11.8 mm flat-faced TSM-B punches on a Styl’One Nano compaction simulator. A 1:2.5 ASD to Kollitab ratio (160 mg ASD and 400 mg Kollitab per 560 mg tablet) was selected for further evaluation across multiple compression forces. Tablets were characterized for weight variation, hardness, tensile strength, friability, disintegration, and in vitro dissolution. A comparative formulation was prepared using a lactose-based blend (LM blend) matching the Kollitab composition and tested under identical conditions.

Results: Tablets formulated with Kollitab (1:2.5 ratio) exhibited significantly enhanced mechanical properties, achieving a hardness of 9–16 kp, a friability of 0.4-0.8%, tensile strength (0.8-2.1 MPa) and a disintegration time of 130-300 seconds at 15 to 45 kN compression force. The tensile strength and disintegration data confirmed robust compactibility and rapid disintegration across a range of compression forces. While the dissolution profile indicated a marginally slower release during the initial 15 minutes, attributable to delayed disintegration due to compression and by the 30 to 45-minute interval, the performance of these tablets comparable to or exceeding that of ASD-filled capsules. In contrast, tablets prepared with the lactose-based blend failed to meet mechanical and friability specifications, demonstrating lower hardness (6–7 kp) and friability failure at maximum possible compression force. This highlights the crucial role of Kollitab in enhancing the tabletability of formulations.

Conclusion: This study highlights the advantages of using Kollitab as a multifunctional, co-processed excipient for the manufacturing of tablets from HPMCAS-based amorphous solid dispersions (ASDs), which are typically challenging to compress. Kollitab simplifies the formulation process through direct compression, offering an integrated solution with excellent compressibility, mechanical integrity without compromising dissolution performance. The findings demonstrate that Kollitab is a viable excipient platform for scaling up solid dosage forms of ASDs, resulting in improved efficiency and cost-effectiveness.

References: 1. Patil, H., Vemula, S.K., Narala, S. et al. Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation—Where Are We Now?. AAPS PharmSciTech 25, 37 (2024). https://doi.org/10.1208/s12249-024-02749-2
2. Triboandas H, Pitt K, Bezerra M, Ach-Hubert D, Schlindwein W. Itraconazole Amorphous Solid Dispersion Tablets: Formulation and Compaction Process Optimization Using Quality by Design Principles and Tools. Pharmaceutics. 2022 Nov 7;14(11):2398. doi: 10.3390/pharmaceutics14112398. PMID: 36365216; PMCID: PMC9693276.

Acknowledgements: The authors gratefully acknowledge BASF Corporation for providing Kollitab® DC 87 L as a gift sample for this research.

Figure 1: DSC study of fenofibrate, HPMCAS, physical mixture and extruded amorphous solid dispersion

Figure 2: Effect of compression force on tablet weight and hardness of ASD tablets with Kollitab and lactose-based blend

Figure 3: Tabletability and in-vitro dissolution comparison between ASD tablets with Kollitab and lactose-based blend