(M1330-03-17) Performance Evaluation of Different Diluents for the Direct Compression of Acetaminophen Tablets

Purpose: Microcrystalline cellulose is one of the most used diluents in direct compression (1). The present study aims to compare the performance of Microcrystalline cellulose, Tricalcium Citrate, and Lactose as different diluents for the direct compression of acetaminophen tablets.

Methods: Acetaminophen, a potent analgesic, was chosen as the active ingredient. Tricalcium Citrate (TCC), Silicified Microcrystalline cellulose (sMCC), and lactose (Lac) were used as different diluents for direct compression. Three formulations of 40% Acetaminophen (APAP) were prepared and defined as: F1(APAP + TCC), F2(APAP + sMCC), F3(APAP + Lac). Drug and excipient were mixed for 10 min at 25rpm using Maxi-blend^Ⓡ (Globe Pharma, NJ, USA). Bulk and tapped density were determined using flat-ground measuring cylinder with a volume of 250mL. Flowability was defined according to Hausner ratio, compressibility index and the angle of repose. Tablets of each formulation were compressed with force of 5, 8 and 10 kN. Theoretical weight of tablets is 1250 mg. Average tablet weight was determined by weighing 20 tablets individually using analytical balance (Ohaus Corporation, Florham Park, New Jersey). Tablet thickness was determined using a vernier caliper. Hardness was determined using tablet hardness tester and disintegration time was measured with DT2-IS disintegration tester. Tablet properties were correlated to applied compression force. Dissolution profiles were determined for tablets prepared with 10kN compression force using Erweka (Korsh –Erweka GmbH, Germany) dissolution tester, USP Dissolution Apparatus 2 – Paddle (37 °C), 50 rpm, pH 5.8 phosphate buffer.

Results: The three formulations exhibited poor to very, very poor flow properties according to the Hausner ratio and compressibility index: F1(1.42, 29.34), F2(1.61, 38.05), F3(1.94, 48.45). The angle of repose suggested good to poor flow properties: F1(31.59°), F2(36.01°), F3(46°). F1 showed better flow properties compared to the two other formulations. No tablet showed more or less than 5% deviation from average tablet weight. Therefore, all formulations met the specification of USP for weight variation. Tablet thickness was correlated to compression force as shown in Figure (1) and F1 showed the highest thickness at different compression forces. Tablet hardness was proportional to compression force as shown in Figure (2). Disintegration studies showed a slower disintegration for F3 (28min) compared to F1 and F2 which disintegrated in less than 1min. Compression force did not affect disintegration time in all formulations. Dissolution experiments are summarized in Figure (3). F2 showed the highest and most rapid drug release within 60 min.

Conclusion: For the direct compression of APAP tablets, TCC showed better powder flow properties compared to Lactose and sMCC and rapid drug release compared to lactose. However, sMCC showed the best performance in terms of tablet hardness and drug release.

References: Saigal, N., et al. "Microcrystalline cellulose as a versatile excipient in drug research." Journal of Young Pharmacists 1.1 (2009): 6.

Figure1. Relationship between compression force and APAP Tablet Thickness

Figure2. Relationship between compression force and APAP Tablet Hardness

Figure3. Release profile of APAP tablets compressed at 10 kN