Zeolites – tabletting ibuprofen with and without zeolites as an excipient
Authors: Martin C J , Ikechukwu O O , Richards D , Smith J C 
Published: November 2024

Introduction

Drug delivery via the oral route is a patient and industry-preferred approach. However, maintaining plasma concentrations of the active pharmaceutical ingredient (API) within the therapeutic window can be challenging with immediate-release (IR) tablets. To avoid the plasma peaks and troughs associated with IR tablets, sustained release (SR) formulations have been investigated.

Zeolites are microporous aluminosilicate minerals that represent a novel tabletting material with the potential for modifying drug release due to their unique adsorption and ion exchange properties1.

Aim

This study will investigate the potential for inclusion of zeolites within orally disintegrating tablets (ODTs) and assessment of their ability to modify API release.

Methods

In-house, 50%w/w ibuprofen (IBU)-loaded ODTs (IHODTs) were prepared from Pearlitol® Flash, magnesium (Mg) stearate and 2 different zeolites (CP814C and CP814E), incorporated at 5%w/w each, using a manual tablet press. Formulations were prepared and mixed for 10 minutes in a cube mixer prior to direct compression (DC) into tablets. Physical characteristics of the tablets were assessed by hardness and friability measurements. Tablet quality was assessed by disintegration and dissolution analysis to British Pharmacopeia (BP) standards2. Release profiles were assessed against various models to determine the effect of zeolites on the release of IBU. Formulations were further examined and characterised using scanning electron microscopy (SEM) and energy-dispersive x-ray (EDX) spectroscopy. An ethics evaluation was completed, and the study was identified as not having any ethical considerations by the University of South Wales.

Results

The mean weight of blank ODTs was found to be 225.3mg, with a mean thickness of 3.65mm, diameter of 8.10mm, hardness of 43.9±9.2N (mean±SD, n=5) and friability of 0.2±0.2% (mean±SD, n=3). The hardness of IHODTs was found to be 59.98±1.6N, reducing to 54.9±4.3N and 43.4±0.7N (mean±SD, n=3) with the inclusion of CP814C and CP814E, respectively. The friability of IHODTs containing zeolites was 1.76±0.4% and 1.91±0.9N (mean±SD, n=3), for CP814C and CP814E, respectively; conforming to BP specification2. The disintegration time for all in-house tablets, both with and without a zeolite included, was found to be an order of magnitude greater than commercial ODTs (CT) controls, but all remained within the BP specification2. The release of IBU from IHODTs and CTs showed good correlation to the first-order release model (R2 = 0.96 and 0.98, respectively), indicating IR behaviour. Similarly, the release of IBU from IHODTs containing zeolites was shown to correlate best with the first-order release model, R2 = 0.91 for CP814C and R2 = 0.90 for CP814E, respectively. SEM analysis suggested a homogeneous blend of components within IHODTs, whilst EDX analysis indicated the presence of silicon and aluminium from zeolites, and Mg and carbon from Mg stearate and IBU, respectively.

Discussion / Conclusion

This study investigated the effect of zeolite inclusion on the release properties of ODTs containing IBU. Although the quality of ODTs containing zeolites was not compromised, this study suggests that inclusion of a zeolite by DC only, does not significantly modify the release profile. Future studies are required to ascertain whether zeolites can achieve SR from ODTs using alternative API loading approaches, such as solvent loading1.

References

1. Khodaverdi E, Honarmandi R, Alibolandi M, Rafatpanah BR, Hadizadeh F, Gholamhossein Z. Evaluation of synthetic zeolites as oral delivery vehicle for anti-inflammatory drugs. Iran J Basic Med Sci, 2014; 17:337-343.

2. British Pharmacopoeia Commission. British Pharmacopoeia 2016. London: TSO; 2016.