(M1230-07-44) Development of Directly Compressible Formulation of High Dose Calcium Citrate Tablets using Novel Clean Label Lubricant

Purpose: Calcium is known as an abrasive material when it comes to formulation development and tablet compression operation. The daily recommended dose of Calcium is approximately 1000 mg for adults¹. Given the abrasive nature of it and requirement for a high dose, this study aims to develop a directly compressible formulation of high-loading calcium citrate ( >95% w/w) using Nutracore™ – Label Friendly Lubricant. In this study, we have also investigated the impact of lubricant concentration and mixing time on tablet properties and compared the performance of Nutracore to the industry standard, magnesium stearate. Tablet coating is desired for many reasons, including calcium taste masking²; therefore, the tablet coating of the optimized Nutracore-based calcium citrate formulation was investigated to determine the impact on tablet properties.

Methods: High loading ( >95% w/w) calcium citrate tablet was formulated using Cab-O-Sil M-5P as a glidant at 0.5% w/w and Nutracore or magnesium stearate as lubricants. Nutracore lubricant concentration was studied at 2%, 3% and 4% w/w, and compared to a control formulation using magnesium stearate at 2% w/w. Both formulations were prepared by following a typical two-step mixing process: (i) mix calcium citrate with sieved silicon dioxide in a V-blender; (ii) add sieved lubricant and mix for 3 minutes. Furthermore, the effect of mixing time on tablet quality attributes was studied for the formulations with 2% w/w magnesium stearate at 3, 5 and 10 mins, and Nutracore lubricant at 3, 5, 10 and 20 mins. Formulations were tableted using a Piccola B/D rotary press at 30 rpm turret speed with 12.5 x 25.0 mm modulated caplet tooling and compression force in the range of 20-45 kN. Tablet quality attributes were analyzed in terms of appearance, weight variation, tensile strength, friability and disintegration. Optimized Calcium Citrate formulation using Nutracore were coated using Nutrafinish® Label-friendly coating at 3% weight gain in a fully perforated 12” pan at a target product bed temperature of 45°C and 10 g/min spray rate. Tablet properties in terms of appearance, tensile strength and disintegration time were analyzed for coated tablets.

Results: The study on tablet formulations using Nutracore lubricant and magnesium stearate revealed significant differences in performance. Tablets containing Nutracore exhibited acceptable appearance, < 1% w/w friability, and tensile strength of 1.69, 1.30, and 1.07 MPa at 40 kN compression force for 2%, 3%, 4% w/w concentration respectively, as depicted in Figure 1. In contrast, calcium citrate tablets containing magnesium stearate showed lower tensile strength as shown in Figure 1, failed friability, and capped at compression forces >35 kN, with severe capping at even higher forces. Disintegration time for tablets containing Nutracore at 2-4% w/w inclusion levels and compressed at 35-45 kN was less than 1 minute, meeting the USP monograph requirement of less than 15 minutes. Conversely, calcium citrate tablets containing magnesium stearate at 2% w/w inclusion level and 35 kN compression force failed disintegration criteria, requiring greater than 50 minutes to disintegrate. As expected, mixing time significantly impacted the robustness of tablets containing magnesium stearate, reducing tensile strength by almost 50% at 5 and 10 minutes, as observed from Figure 2, with all tablets failing tensile strength targets and capped when noted. Nutracore-based blends at 2% w/w were less affected by mixing time, maintaining robust tensile strength ( >1.2 MPa) at >40 kN and friability < 1% w/w, and disintegration time remained under 1 minute across all mixing times. Coating operations of optimized calcium citrate tablets with 2% w/w Nutracore lubricant made at 3 minutes mixing time and 45 kN compression force resulted in tablets with acceptable appearance, excellent tensile strength (3.0 MPa), and an acceptable disintegration time of 3.5 minutes.

Conclusion: Nutracore-Label Friendly Lubricant has proven to be a promising lubricant for producing robust, high-loading calcium citrate ( >97% w/w) tablets, outperforming magnesium stearate. Nutracore-based tablets were less susceptible to over-lubrication issues compared to those with magnesium stearate. Additionally, film coating enhanced the tensile strength of the tablets without adversely affecting their disintegration time.

References: 1. National Institute of Health. Calcium Fact Sheet for Consumers. https://ods.od.nih.gov/factsheets/Calcium-Consumer/. Accessed April 15, 2025.
2. Wenner, M., Scientific American. Like the Taste of Chalk? You're in Luck--Humans May Be Able to Taste Calcium. https://www.scientificamerican.com/article/osteoporosis-calcium-taste-chalk/. Accessed April 15, 2025.


Figure 1. Tabletability Profile of Nutracore Lubricant vs. Magnesium Stearate


Figure 2. Impact of Mixing Time on Tabletability Profile of Nutracore vs. Magnesium Stearate