Analysis of Swelling and Dissolution Dynamics of Xanthan Gum-Excipient Blends Using Dissolution Imaging

This research investigates how dissolution imaging can elucidate the impact of excipients with various solubility profiles (lactose, microcrystalline cellulose, and dicalcium phosphate) on the swelling and drug release properties of xanthan gum (XG) compacts using a dissolution imaging technique. Xanthan gum was mixed with the excipients in various ratios after which tablet surface characteristics and dissolution investigations were conducted to determine their impact on the swelling and drug release behaviours of the various compacts. The results from focus variation microscopy showed that the 1:3 XG:lactose compacts displayed lower Smr2 values, suggesting the greater likelihood of these compacts for initial wetting. The swelling studies from dissolution imaging revealed that the 3:1 XG:excipient, where there was a higher XG content, lead to the development of a more extensive gel layer. The incorporation of either lactose, microcrystalline cellulose or dicalcium phosphate into the XG compacts resulted in an increased rate of drug release when compared to the pure XG compacts. The amount of XG present in the compacts was therefore important in determining the drug retention capacity of the matrix. Such findings demonstrate the importance of dissolution imaging in providing qualitative and quantitative insights into the dissolution phenomena with value in the designing of drug delivery formulations with tailored release profiles.

Highlights

• Lactose, MCC and DCP used at different ratios within XG compacts influence drug release and swelling.
• The higher content of the lactose, MCC or DCP within the XG compacts displayed lower Smr2 values, indicating higher initial wetting.
• Compacts with higher XG concentration (3:1) ratios develop more extensive gel layers thus enhancing drug retention.
• The incorporation of the excipients into the XG compacts increased the rate and extent of drug release when compared to the pure XG compacts.
• Dissolution imaging shows important details about swelling behaviour and drug release.

Introduction

Natural polymers and their derivatives are promising for innovative drug delivery systems due to their easy accessibility, compatibility with biological systems, biodegradability, and potential for chemical modification. Their non-irritating nature, low toxicity, affordability, and abundant availability make them commonly employed in the pharmaceutical and medicinal industries. Natural gums consist of a number of sugar units linked by glycosidic bonds, which are called polysaccharides [1]. These biopolymeric materials enable controlled drug release. The drug is spread uniformly throughout the polymeric matrix prior to being compacted into tablet form. When in contact with physiological fluids or water, these polymeric materials swell. After that, the drug dissolves and is released in a controlled manner (Figure 1). Xanthan Gum (XG) serves as a matrix in tablets designed for regulated drug release [2].

XG is an extracellular heteropolysaccharide with a large molecular weight, typically ranging from 2 × 10⁶ to 2 × 10⁷ Da, made by pure culture fermentation of a carbohydrate with the bacterium Xanthomonas campestris 1, 3. XG is anionic in nature due to the occurrence of both pyruvic acid and glucuronic acid groups within the side chain [4] (Figure 2) and is commonly utilised as a stabilising or suspending ingredient in food and cosmetic products and in oral and topical preparations [5]. Due to its hydrophilic properties, XG is commonly used in producing hydrophilic matrix systems 6, 7.

When XG comes into contact with water, it swells into a hydrated glassy form. As the degree of swelling increases, it transforms into a more porous and rubbery form. Several factors, such as buffer solution concentration and the concentration of XG itself, have a major effect on the viscosity of the XG solution 8, 9. Previous studies investigated the compactibility, rheology and in vitro release from XG 10, 11, 12, 13, 14, 15. XG has also been used in alcohol resistant formulations [16], nanoparticle-loaded gels 17, 18, sustained-release pellets [19], microspheres [20], ophthalmic solutions [21], mucoadhesive patches 9, 22, mouth-dissolving films 23, 24, in situ ocular gels 25, 26 and hydrogel scaffolds [27].

Excipients have a key role in facilitating the manufacture, drug administration, absorption, and other functions of dosage forms. The effectiveness of a dosage form is determined by the characteristics of both its active component and excipients. Excipients have the potential to enhance the therapeutic benefits of the active pharmaceutical ingredient (API) in the dosage form by modifying factors such the stability, solubility, and absorption characteristics of the drug 28, 29. Evaluating the functionality of the excipient is essential [30]. In this work, three excipients are investigated, namely lactose, dibasic calcium phosphate (DCP), and microcrystalline cellulose (MCC), each with unique solubility properties. Lactose, a disaccharide, is frequently used as an excipient in the production of pharmaceutical tablets and capsules. It presents as a white crystalline powder that is easily dissolved in water 31, 32. MCC is a non-fibrous gum form of alpha-cellulose cellulose. While it can disperse in water and undergo swelling, it does not dissolve. MCC is predominantly employed as an excipient for direct compression. It also functions as a strong dry binder, lubricant, absorbent, diluent, and tablet disintegrant 33, 34. DCP is commonly used as a filler in tablet formulations. It is not soluble in water [35].

UV imaging, with its ability to provide rapid and spatially resolved absorbance values, is highly valued in pharmaceutical research. It has found application in many areas, including permeation across synthetic membranes [36], drug release and swelling behaviour of liquisolid compacts [37], swelling of hydrophilic compacts 38, 39, release from transdermal patches [40], dissolution of solid dispersions 41, 42, intrinsic dissolution rate events 43, 44, 45, 46 and buccal films [47]. Imaging techniques are increasingly employed within the pharmaceutical industry to establish links between dissolution rates and the structural and physical characteristics of dosage forms, such as the inclusion of excipients. This correlation of dissolution seeks to advance the comprehension of complex dissolution studies [48]. UV imaging was employed to analyse the behaviour of the commonly employed excipient, HPMC [49]. Additionally, UV imaging has been employed to assess the impact of drug-excipient interactions on drug release. Other observations reported include the identification of characteristics such as polymer entanglement, gel layer formation, diffusion layer, erosion front, and gel point 48, 50.

The key goal of this study was to investigate the impact of adding various excipients with different solubility profiles such as lactose, MCC, and DCP, at different ratios on the compaction and surface characteristics of XG compacts. This research also examined the effect of excipient type and ratio on surface parameters, wettability and initial liquid contact, and their connection to the swelling of the XG-based compacts. The dissolution behaviour of the highly soluble drug, propranolol hydrochloride (PPN) from the different XG compacts was also elucidated as a model drug using UV dissolution imaging. The novelty of this study lies in the application of UV dissolution imaging to simultaneously visualise and quantify swelling and drug dissolution dynamics, while also offering qualitative features such as channel formation. These findings make important contributions toward formulation optimisation and a mechanistic understanding of drug release.

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Materials

Xanthan Gum (XG) (Xanatural 75™) was a generously provided by CP Kelco, Atlanta GA, USA. Lactose was kindly donated by Meggle (Wasserburg, Germany). Dibasic calcium phosphate (DCP) was provided by Chemische Fabrik Budenheim KG (Budenheim, Germany). Microcrystalline cellulose (MCC) PH102 was supplied by JRS Pharma (Surrey, UK). The active ingredient, propranolol hydrochloride (PPN), was purchased from TCI Chemicals (UK). De-ionized water was used as the dissolution medium for hydration analysis to minimize the influence of ions on the hydration process. Potassium phosphate monobasic and sodium hydroxide, used to prepare the 0.2 M phosphate buffer dissolution media with a pH of 6.8, were acquired from Fisher (UK).

Haja Muhamad, Adam Ward, Rand Abdulhussain, James Williamson, Liam Blunt, Barbara Conway, Jesper Østergaard, Kofi Asare-Addo, Analysis of Swelling and Dissolution Dynamics of Xanthan Gum-Excipient Blends Using Dissolution Imaging, Journal of Drug Delivery Science and Technology, 2024, 106538, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2024.106538.

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