Comparative compression characterization of liquisolid systems prepared with mesoporous carriers

Abstract

1. INTRODUCTION Maintaining good compaction properties of liquisolid systems (LSS) is particularly challenging in the case of high-dose drugs [1]. High amount of liquid phase within LSS, required to dissolve/suspend higher amount of drug substance, while necessary for improvement of bioavailability, can cause difficulties during the tableting process, resulting in low tablet hardness or even inability of admixtures to be directly compressed. This has led to the development of new highly porous carriers, specifically designed for LSS, that can adsorb/absorb very high amount of liquid phase. The aim of this study was to investigate the compaction properties of LSS, prepared with three types of novel silica-based mesoporous carriers, using dynamic compaction analysis as a tool, with the focus on compressibility, compactibility and tabletability of these systems [2]. 2. MATERIALS AND METHODS 2.1. Materials Amorphous magnesium aluminometasilicate (Neusilin® US2, Fuji Chemical Industry Co, Ltd., Japan) and two types of amorphous mesoporous silicon dioxide (Syloid® XDP 3050 and Syloid® XDP 3150, Grace GmbH, Germany) were used as carriers. Colloidal silicon dioxide (Aerosil 200, Evonik Industries AG, Germany) was used as coating material and polyethylene glycol 400 (PEG 400, Fagron, Netherlands) was used as liquid phase. 2.2. Liquisolid Admixture Preparation LS admixtures (Table 1) were prepared using Mycrolab fluid bed processor (OYSTAR Hüttlin, Germany), with the operating temperature of 30°C, inlet air flow rate of 20 m3/h, and liquid feed rate of 12 g/min. Table 1. Composition of prepared LS admixtures Liquisolid admixturesa Rb Liquid load PEG 400 (%) S1 10 0.7 38.9 S2 30 0.7 40.4 S3 10 0.6 35.3 S4 30 0.6 36.7 N1 10 1.1 49.8 N2 30 1.2 54.7 a type of carrier used: S1, S2 - Syloid® XDP 3050, S3, S4 - Syloid® XDP 3150, N1, N2 - Neusilin® US2; bcarrier to coating material ratio 2.3. Powder density LS admixtures’ true densities were determined by helium pycnometer (AccuPyc 1330, Micromeritics, GA) while bulk and tapped densities were measured using a graduated cylinder and a volumeter (STAV 2003, J. Engelsmann AG, Germany). 2.4. Powder morphology The morphology of LS particles was examined using a scanning electron microscope (SEM, Supra 35VP, Carl Zeiss, Germany). 2.5. Dynamic compaction analysis Dynamic compaction analysis was performed on an instrumented tablet press (GTP D series, Gamlen Tableting Ltd, UK). 6 mm flat faced punches were used at a compaction speed of 60 mm/min, with compression load ranging from 250 to 500 kg, with a 50 kg increment. 3. RESULTS AND DISCUSSION 3.1. Compressibility of LS admixtures Regardless of the compaction pressure applied and differences in liquid load, very high values of solid fraction were observed in LS compacts with Neusilin® US2 (0.90-0.94). On the other hand, LS compacts with both Syloid® XDP carriers exhibited lower relative density (0.59- 0.89) that was affected by changes in the applied compaction pressure. Compressibility profiles suggest that carrier particle size and the amount of coating material used, had an effect on relative density. An increase in the amount of coating material used had a negative impact on compressibility and lower values of solid fraction were achieved. 3.2. Compactibility of LS admixtures Admixtures N1 and N2 could be considered as having good compactibility [3]. Compacts with Neusilin® US2 achieved higher tensile strength values compared to compacts with Syloid® XDP, even at low compaction pressures. Particle geometry and shape (Fig. 1) can affect the way particles interact during tableting and therefore may affect their mechanical characteristics. Differences in particle size could be a reason for lower values of solid fraction and tensile strength observed in compacts prepared with Syloid® XDP 3150 compared to compacts with Syloid® XDP 3050 as carrier. Figure 1. SEM micrographies of LS particles: admixture N1 (left) and S1 (right) 3.3. Tabletability of LS admixtures Despite the significantly higher liquid load, better tabletability was observed in LSS with Neusilin® US2 as carrier with tensile strength ranging from 1,68 to 2,55 and 1,61 to 2,11 for formulations N1 and N2, respectively. Although relatively similar values of tensile strength were achieved, tabletability profiles indicate that there are differences in compaction behavior between formulations N1 and N2. Higher values of tensile strength observed at the same compression pressure indicate better tabletability of LS admixtures with Syloid® XDP 3050 compared to those with Syloid® XDP 3150 as carrier. Interestingly, formulations with Syloid® XDP 3050 had higher liquid load which implies that this formulation factor had lesser influence on tabletability compared to the properties of the carrier itself (such as particle size and specific surface area). The lowest tabletability was observed in LS admixtures S3 and S4 with compact tensile strength lower than 1 MPa at all but highest compaction pressure applied. 4. CONCLUSION Out of the three investigated carriers, Neusilin® US2 showed the best compaction properties despite its high liquid load. LS admixtures with this carrier exhibited the highest values of tensile strength and solid fraction at relatively low compression pressures. Pronounced differences have been noticed between the two Syloid carriers, which indicates the effect of carrier particle size on compaction properties of LS admixtures.