(T1030-11-75) Simplified Formulation of Dietary Supplements Using High Functionality Clean Label Excipients – Case Studies

Purpose: In this study, two recently developed clean label, highly functional excipients have been investigated for their manufacturing of acceptable DS tablets. These novel excipients include a filler excipient blend, with filler and disintegrant properties and a second lubricant blend that achieves high tablet mechanical strength with lubricant and glidant properties. The applicability of these novel, clean label blends was investigated for a range of DS with varying powder properties and their tablet performance compared to two currently commercially available DS tablets containing either synthetic pharmaceutical excipients or clean label excipients. Three model dietary supplement ingredients were used: ashwagandha powder, ashwagandha granules and garlic powder.

Methods: The novel filler and lubricant blends are composed of simple, all plant-based ingredients. The powder properties determined were appearance, bulk density and particle size distribution (PSD) using Malvern Mastersizer Scirocco 2000. The flowability of the filler blend was characterized using Flodex™ instrument. The three model DS powders were characterized in terms of bulk density and PSD. They were formulated at 52% w/w DS, 45.5% filler and 2.5% lubricant blend into 450 mg, 10-mm round, biconvex tablets. They were manufactured at 50 rpm turret speed and 25 kN compression force. One unique advantage of the lubricant blend is that it is not prone to overmixing issues such as the case with synthetic lubricants (e.g., magnesium stearate) where reduced hardness, increased friability and prolonged disintegration times occur. The blends were made using either an all-in-one mixing with the three components mixed for 5 minutes or a traditional two-step mixing where the DS and the filler blend were mixed for 3 minutes in a V-blender, followed by adding the lubricant blend and mixing for a further 2 minutes. The properties of the clean label tablets were compared to the properties of two marketed products, one containing ashwagandha with all clean label excipients and the other containing garlic with synthetic excipients. Tablet appearance, tensile strength and disintegration time (DT) were determined. To compare the DT of clean label garlic tablets to the enteric coated marketed product, an enteric coating was applied. Appearance was characterized by placing the tablets on a white background with any visual defects recorded. Tensile strength was determined according to USP < 1217 >. Disintegration of n=6 tablets was performed in DI water at 37±2°C following USP < 701 >.

Results: The novel filler blend has an off-white color with a bulk density of 0.50 g/mL, average particle size of 97.5 µm and excellent flow with a flowability index of 9 mm. The novel lubricant blend had a light-brown appearance, free flowing powdery form with a bulk density of 0.26 g/mL and an average particle size of 14.9 µm. The three DS, ashwagandha powder, ashwagandha granules and garlic powder had an average bulk density of 0.53, 0.37 and 0.52 g/mL, respectively and average particle size of 26.1 µm, 246.0 µm and 35.7 µm, respectively. The composition and the tablet performance of the clean label tablets and the marketed products of ashwagandha and garlic are summarized in Table 1 and Table 2. The clean label formulations were simpler with less ingredients than the marketed ones. The marketed products had shiny, uniform-colored surfaces with clear logos and no visual defects (Figure 1). The clean label ingredients uncoated ashwagandha tablets using either powder or granular DS were significantly superior in terms of hardness and DT when compared to the marketed products as detailed in Table 1. They resulted in tablet hardness of >1.6MPa and DT of < 25 minutes, with the powder-based formulation giving harder tablets and slightly higher DT than the granular based tablets. Despite the garlic tablets with clen label ingredients being uncoated, they had higher tensile strength compared to the marketed ones with synthetic excipients as summarized in Table 2. The DT of both was comparable after enteric coating of our clean label tablets using nutrateric coating.

Conclusion: The novel clean label filler and lubricant blends resulted in simpler, clean label formulations and robust tablets for ashwagandha and garlic. The tablets formulations performed significantly better than existing marketed products.

References: 1. Sarah S. Aboelela, Robert Theisen, Manish Ghimire, Ali Rajabi-Siahboomi. The Effect of a Clean-label, Plant-based Natural Glidant on the Flow Properties of Multiple Model Powders compared to a Synthetic Glidant, AAPS 2022.

Figure 1: Appearance of Clean Label Tablets vs Marketed Products (a) Ashwagandha Powder Tablets; (b) Ashwagandha Granular Tablets; (c) Marketed Ashwagandha Tablets; (d) Garlic Tablets; (e) Marketed Coated Garlic Tablets

Table 1: Composition of Ashwagandha Tablets and Performance Compared to Marketed Product

Table 2: Composition of Garlic Tablets and Performance Compared to Marketed Product