The Increase in the Plasticity of Microcrystalline Cellulose Spheres’ When Loaded with a Plasticizer

Abstract

Compaction pressure can induce an undesirable solid-state polymorphic transition in drugs, fragmentation, loss of coated pellet integrity, and the decreased viability and vitality of microorganisms. Thus, the excipients with increased plasticity can be considered as an option to decrease the undesirable effects of compaction pressure. This study aims to increase the plasticity (to reduce the mean yield pressure; Py) of dried microcrystalline cellulose (MCC) by loading it with a specially selected plasticizer. Diethyl citrate (DEC), water, and glycerol were the considered plasticizers. Computation of solubility parameters was used to predict the miscibility of MCC with plasticizers (possible plasticization effect). Plasticizer-loaded MCC spheres with 5.0 wt.% of water, 5.2 wt.% of DEC, and 4.2 wt.% glycerol were obtained via the solvent method, followed by solvent evaporation. Plasticizer-loaded formulations were characterised by TGA, DSC, pXRD, FTIR, pressure-displacement profiles, and in-die Heckel plots. Py was derived from the in-die Heckel analysis and was used as a plasticity parameter. In comparison with non-plasticized MCC (Py = 136.5 MPa), the plasticity of plasticizer-loaded formulations increased (and Py decreased) from DEC (124.7 MPa) to water (106.6 MPa) and glycerol (99.9 MPa), and that was in full accordance with the predicted miscibility likeliness order based on solubility parameters. Therefore, water and glycerol were able to decrease the Py of non-plasticized MCC spheres by 16.3 and 30.0%, respectively. This feasibility study showed the possibility of modifying the plasticity of MCC by loading it with a specially selected plasticizer.

Introduction

Being non-invasive and, in most cases, not requiring medical assistance, tablets for oral administration are the most widespread and the most popular pharmaceutical and nutraceutical dosage forms. Despite the rising topic of individualised/personalised medicine, including individualised dosing, drug release, and customer properties, national healthcare systems worldwide are highly dependent on the mass-market production of tablets and their usage following treatment protocols.
In the vast majority of cases, pharmaceutical substances cannot be converted into tablets via tableting with high-speed rotary tablet presses [1]. To achieve the desirable mechanical and biopharmaceutical properties, specific excipients are required. Appropriate mechanical properties, such as tablet hardness (or tensile strength) and abrasion resistance (friability) should ensure tablet applicability to transportation, coating, and packaging processes without losing their appearance, dose, and biopharmaceutical properties. Moreover, the intrinsic properties of tablet excipients and the structural-mechanical properties of the tablets formed eventually affect the disintegration and drug release behaviour of the dosage form, and so, can be deliberately selected to achieve the desired release profile [2].
Upon tableting, the compaction pressure and tableting speed (dwell time) induce elastic and plastic deformation, or fragmentation, and affect the extent of these deformations [3]. The tableting cycle can be described with a force–displacement profile: the distance between punches, which is plotted against the compaction pressure or force. This can be determined with state-of-the-art equipment, such as compaction simulators containing hi-tech sensors and sophisticated user-friendly software [4,5] (Figure 1).

Considering the true density of the material, an in-die Heckel plot can be built: ln(1/porosity) is plotted against the compaction pressure. The greater the slope of the linear region (K), the greater the degree of plasticity of the material [6]. The mean yield pressure (Py) of the solid is reciprocal to K [7] and describes the point after which the deformation is irreversible (pointed out in Figure 1). It should be stressed that the mean yield pressure from the in-die Heckel analysis can be used as a reliable plasticity parameter: the lower the Py, the greater the degree of plasticity of the material [8].

Possessing information about the Py of each ingredient in the blend allows predicting the sequence of the events of the material irreversible deformations upon tableting cycle. Consequently, the targeted composition of a tableting blend based on excipients’ Py can predetermine the deformation (the extent of deformation) of the specific ingredients in this blend upon tableting at a specific compaction pressure [9]. Considering the possibility of undesirable solid-state polymorphic transition of the drug [10,11], particle fragmentation, the loss of coated pellet integrity [12,13], and the decreased viability and vitality of microorganisms [14,15] as a function of compaction pressure, the above-mentioned circumstances are of particular interest.
Microcrystalline cellulose (MCC) is a partially depolymerised, naturally occurring polymer in the form of crystalline powder or spheroids composed of porous particles [16], and it is one of the most commonly used excipients in tablet formulations [17]. MCC is used for direct compression (up to 90 wt.%), dried granulation/roll-compaction, and wet granulation to achieve tablets with desirable mechanical and biopharmaceutical properties [3,10,16]. MCC is recognised as an excipient with relatively low Py that undergoes plastic deformation at relatively low compression forces [3].

The effect of water on the plasticization of the MCC as well as its effect on the compaction properties upon tableting has been previously reported [18,19,20]. To the best of our knowledge, the information regarding MCC plasticization with other solvents or excipients in order to influence the compaction properties upon tableting is lacking. Nevertheless, the practice of modulating cellulose derivatives plasticity for film forming [21,22], hot-melt extrusion, and/or fusion deposition modelling 3D-printing [23,24] is common practice. While solubility parameters were found to be a useful instrument for plasticizer pre-screening [24,25].

This study aims to increase the plasticity (to reduce the Py) of MCC by loading it with a specially selected (based on the solubility parameters) plasticizer. It was assumed that a lower Py of the MCC could enable tablets to be prepared at lower compaction pressure and decrease the undesirable effect of compaction pressure.

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Materials

Cellets^® 500 MCC cores (lot# 21E1034; IPC, Process-Center GmbH & Co KG, Grunaer Weg, Germany) were used as the starting cores. The rest of the chemicals used for the experiment, such as diethyl citrate (DEC), glycerol, and methanol were of Pharmacopeia grade and used as received.

Paulausks, A.; Kolisnyk, T.; Mohylyuk, V. The Increase in the Plasticity of Microcrystalline Cellulose Spheres’ When Loaded with a Plasticizer. Pharmaceutics 2024, 16, 945. https://doi.org/10.3390/pharmaceutics16070945

Read also our introduction article on Microcrystalline Cellulose here:

excipients formulation