Utilization of poly-2-hydroxypropane-1,2,3-tricarboxylic carubin as a glidant in lactose granules

Abstract

Poly-2-hydroxypropane-1,2,3-tricarboxylic carubin (P-2HTCb) has characteristics as a glidant similar to talc and magnesium stearate (MgSt), such as irregular shape, wavy surface, difficulty dissolving in water, and hydrophobicity. The experiment’s purpose is to determine the effect and potential of P-2HTCb as a glidant in tablet dosage form with lactose granules (LG) as a filler model. The application of P-2HTCb as a glidant represents a novelty. P-2HTCb was used in each of mixture mass with contents of 0.5%, 1%, 2%, and 4%. Each mixture mass was tested for flow time, angle of repose, and Tap-Bulk, then tableted with a weight of 700 mg. The tablets were tested for hardness, friability, and disintegration time. Evaluation of the mixture mass with concentrations of 0.5%, 1%, 2%, and 4% for flow time 5.13-5.47 seconds; angle of repose 21.54-22.56^○; Tap-Bulk 0.070-0.078 g.mL^-1; tablet weight 699.7-702.0 mg; tablet hardness 7.9-8.4 kp; Tablet friability 0.70-0.86% and tablet disintegration time 0.52-1.63 minutes. The optimum concentration (2%) improves the flow time and angle of repose of the mixture mass. Increasing the concentration of P-2HTCb causes the Tap-Bulk value of the mixture mass and tablet friability to decrease, but increases tablet hardness. The optimum concentration (1%) provides the fastest disintegration time. P-2HTCb produces minimal dust when mixed with LG material. P-2HTCb can be recommended as an alternative glidant candidate in environmentally and health-friendly pharmaceutical formulations.

Introduction

2-hydroxypropane-1,2,3-tricarboxylic acid (2HT) reacts with carubin (Cb) under acidic conditions to form an ester polymer, poly(2-hydroxypropane-1,2,3-tricarboxylic carubin) (P-2HTCb) [1], [2]. The specific characteristics of P-2HTCb align with those of typical esterification products, including ester carbonyl groups, low solubility, and low viscosity. Characteristics derived from galactomannan that may appear in P-2HTCb include amorf, irregular particle shape, and a wavy surface [2], [3].

Glidant is a fine powder that coats particles, smoothing their surfaces and improving flow. It also fills the pores of filler granules, resulting in smoother surfaces and enhanced flowability [4]. Talc and magnesium stearate (MgSt) are commonly used glidants in the pharmaceutical industry due to their availability and low cost. Both have fine particle size, are hydrophobic, water-insoluble, and exhibit irregular shapes with wavy surfaces [5], [6], [7]. P-2HTCb shares similar characteristics with talc and MgSt, warranting evaluation of its glidant potential. Talc contains inorganic silicates that can slightly absorb humidity [8], [9]. MgSt is an organic compound derived from saturated fatty acid stearate, functioning as a envelop that renders particle surfaces slippery [10], [11], [12]. P-2HTCb is an ester of mannose-galactose and 2-hydroxypropane-1,2,3-tricarboxylic acid. Organoleptic tests indicate that P-2HTCb exhibits waxy properties.

This study aims to evaluate the effect and potential of P-2HTCb as a glidant in tablet formulations, using lactose granules (LG) as a filler model. P-2HTCb was used at concentrations of 0.5%, 1%, 2%, and 4%, similar to those applied for talc and MgSt as controls. These concentrations reflect typical usage levels of talc (1.00-10.00%) and MgSt (0.25-5.00%) in solid dosage formulations to facilitate particle flow [13], [14]. Each formulation was tested for flow time, angle of repose, and Tap-Bulk, then compressed into 700 mg tablets. The tablets were evaluated for hardness, friability, and disintegration time. LG was prepared from a lactose monohydrate solution by rapid wetting and spraying to form spherical agglomerates. It is commonly used as a filler in direct compression. LG characteristics include spherical or granular shape, porosity, water solubility, and hydrophilicity [6].

The application of P-2HTCb as a glidant represents a novelty. This study investigates the influence of increasing P-2HTCb concentrations on the flowability of the mixture mass and the quality of tablets to conventional glidants such as talc and MgSt. Both comparators generated visible dust during mixing due to their low bulk densities, approximately 0.56 g.cm-3 for talc and 0.16 g.cm-3 for MgSt [6], [15]. In contrast, P-2HTCb, synthesized from carubin (Cb) and 2-hydroxypropane-1,2,3-tricarboxylic acid (2HT), is estimated to possess a higher bulk density, given the densities of its precursors (0.63 g.cm-3 for Cb and 0.60 g.cm-3 for 2HT) [16], [17], [18]. This property suggests a potential reduction in dust formation during mixing. P-2HTCb was tested at concentrations ranging from 0.5% to 4.0% to assess potential as glidant. The results provide insight into its potential as an alternative glidant for solid dosage formulations.

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Raw materials and chemicals

The experimental ingredients were carubin (food grade, Viscogum, Cargill, France), 2-hydroxypropane-1,2,3-tricarboxylic acid (pro analytical, Merck KgaA, Darmstadt, Germany), hydrochloric acid (pro analytical, Sigma Aldrich Chemie, GmbH, USA), water for injection (sterile grade, PT. Otsuka Indonesia), aquadest (technical grade, Cawan Anugerah Chemika, Indonesia), acetone t.g (Cawan Anugerah Chemika, Indonesia), lactose granules (pharmaceutical grade, FlowLac 90, Meggle GmbH & Co. KG, Germany), talc (food grade, PT. Bratachem, Indonesia) and magnesium stearate (food grade, PT. Bratachem, Indonesia).

Wuryanto Hadinugroho, Stephanie Florencia Winarko, Echa Imanuela Sinta, Senny Yesery Esar, Jefri Prasetyo, Utilization of poly-2-hydroxypropane-1,2,3-tricarboxylic carubin as a glidant in lactose granules., Hybrid Advances, 2025, 100549, ISSN 2773-207X, https://doi.org/10.1016/j.hybadv.2025.100549.