(T1130-07-45) Formulation of Acetaminophen Chewable Tablets Using Carrageenan

Purpose: Oral solid dosage forms, such as tablets and capsules, are a convenient and widely accepted method of drug administration for most patients. Additionally, oral formulations are generally less expensive to design, and manufacture compared to other routes of drug delivery. However, solid formulations have limitations and disadvantages, particularly for patient populations like pediatrics and geriatrics who may have difficulty swallowing¹. Chewable tablets are gaining popularity due to their ease of administration and safety. These tablet formulations can be produced using various pharmaceutical methods and excipients, but the simplest and most economical method is direct compression. Texture and drug release are amongst critical properties that can be modulated by multipurpose excipients like carrageenan to improve patient acceptance and drug performance. Carrageenan, a naturally occurring anionic sulphated polysaccharide derived from red seaweed, is widely utilized in the pharmaceutical industry for its gelling, thickening, and stabilizing properties. It serves various functions, such as a polymer matrix in oral controlled release tablets, an extrusion aid in pellet manufacturing, and a carrier/stabilizer in micro/nanoparticle systems. In chewable tablets, carrageenan functions primarily as a gelling agent, providing a firm, cohesive texture and acting as a binder to ensure the tablet holds together with a chewable consistency and facilitates fast drug release. This study aimed to assess the impact of carrageenan's water gel strength (WGS) on the properties of chewable tablets. Four robust chewable tablet formulations were created using a direct compression method. Acetaminophen was chosen as the model drug, with a commercially available acetaminophen children's chewable tablet as the control. The study evaluated how the WGS of carrageenan influenced the tablet properties.

Methods: Chewable tablet formulations consisted of 12.8% w/w acetaminophen as model drug targeting 160 mg dose was prepared. Each formulation included 2% w/w carrageenan with four different water gel strengths ranging 700g-1150g/cm2 (Gelcarin^® GP 911 NF) as binder, 29.2% w/w silicified microcrystalline cellulose (Avicel® SMCC 90), 40% Mannitol (Perlitol^® 100SD) as filler, 11% co-processed microcrystalline cellulose/guar gum (Avicel® CE-15) as texture modifier, 0.25% w/w colloidal silica (SiO2, Cab-O-Sil^®) as anti-adherent, 0.25% w/w sodium stearyl fumarate (Alubra^®) as lubricant, 1% sucralose (Spectrum) as sweetener, 0.25% strawberry flavor and 0.25% Red 40 color. Each formulation blend was evaluated for blend properties and compressed into 1.25 g tablets on a compaction simulator using a standard round concave punch tooling. The resulting tablets were evaluated for physical properties and drug release. Tablets with tensile strength (TS) of approximately 0.5 MPa to 1 MPa were selected for further study. Dissolution testing was carried out on n=6 tablets using USP apparatus 2 at 50 rpm in 900 mL of pH 5.8 phosphate buffer.

Results: Formulation Properties: Tabletability of formulation blends containing Gelcarin^® GP 911 with lowest water gel strength of 752 g/cm2 and a sample of Gelcarin^® with the highest gel strength 1148 g/cm2 are shown in Figure 1. As shown, 50% increase in the gel strength did not significantly affect the tablet compaction profile. Chewing Difficulty Index: Tablet chewing difficulty index (CDI) is measured by multiplying tablet hardness (Newtons) by thickness (millimeters) in units of Newton-millimeters (Nmm). This index represents the force required to break a tablet and provides a measure of its chewability based on mechanical properties where a higher CDI value indicates greater chewing difficulty. The CDI of tablets ranging from 52-62 (Nmm) were comparable regardless of the water gel strengths of the binder. Drug Release Figure 2 shows comparative release profiles of chewable acetaminophen tablets containing 2% carrageenan with a wide range of water gel strength (WGS). The release profiles were similar across all formulations, indicating comparable tablet performance. The release profiles of chewable acetaminophen tablets prepared in this study were faster than the marketed product, as shown in Figure 3. This indicates one of the advantages of using carrageenan as binder, which creates a robust, fast dissolving tablet without negatively impacting drug release.

Conclusion: Four robust chewable tablet formulations for acetaminophen, a pain relief model drug, were studied and compared with a marketed product. All acetaminophen chewable formulations demonstrated similar blend flow properties, tablet properties, and dissolution performance regardless of the wide range of water gel strengths of carrageenan tested in the study. The release profile of chewable acetaminophen tablets was faster than that of the marketed product. It was demonstrated that carrageenan, a natural polysaccharide polymer, with a wide range of water gel strengths, may successfully be used in chewable tablets.

References: 1. Homayun B, Lin X, Choi HJ. Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals. Pharmaceutics. 2019 Mar 19;11(3):129. doi: 10.3390/pharmaceutics11030129. PMID: 30893852; PMCID: PMC6471246.


Figure 1. Impact of carrageenan gel strength on the tabletability of acetaminophen formulations


Figure 2. Comparative release profiles of acetaminophen chewable tablets containing carrageenan with varying gel strengths


Figure 3. Comparative release profiles of acetaminophen chewable tablets with marketed product