Formulation and Analysis of Drug-Silica and Drug-Polymer Based Systems

Three mesoporous silica excipients (Syloid®silicas AL-1 FP, XDP 3050 and XDP 3150) were formulated with three model drugs known for their poor aqueous solubility, namely phenylbutazone, indomethacin and imipramine in an attempt to enhance the extent and rate of their dissolution. Although other forms of mesoporous silica have been investigated in previous studies, the effect of inclusion with these specific Syloid® silica-based excipients with phenylbutazone, indomethacin and imipramineare unknown. This work reports a significant enhancement for both the extent and rate of drugs release for all three forms of Syloid® silica at 1:1, 2:1 and 1:3drug:silica ratios over a period of 45minutes. An explanation for this increase was determined to be conversion from crystalline to the amorphous form and an enhanced drug loading ability within the pores. Differences between the release profiles of the three silicas was concluded to be a consequence of the physicochemical differences between the three forms. Overall, this study confirms that Syloid® silica-based excipients can be used to enhance dissolution, and potentially therefore bioavailability, for compounds with poor aqueous solubility, such as phenylbutazone, indomethacin and imipramine. In addition, it has been confirmed that drug release can be carefully tailored based on the choice of Syloid® silica and desired release profile.

The second part of this study investigated the effect of microwave heating through the application of microwave differential thermal analysis to eight model pharmaceutical compounds and a set of four model excipients. Benzocaine, haloperidol, ibuprofen, indomethacin, ketoprofen, naproxen, imipramine and phenylbutazone were analysed, along with four excipients, namely β-cyclodextrin, D-mannitol, stearic acid and Syloid® silica (XDP 3050) using microwave differential thermal analysis. Samples were heated by microwave irradiation at 5 °C/min to a minimum of 160 °C, held isothermally and then slowly cooled to room temperature. Thermal profiles were analysed and compared with data obtained using differential scanning calorimetry (DSC), x-ray powder diffraction (XRD)and hot stage microscopy (HSM). Overall, it was found that the process of microwave heating produced different thermal profiles to those seen using traditional, conductive heating. Investigating differences in thermal profiles can be a useful way to consider the effect of microwave induced heating on formulations which can, in turn, help guide formulation choices.

The latter part of this study describes the analysis and characterisation of polyvinylalcohol (PVA)-based hydrogel polymer beads, developed for the embolisation of vessels, specifically focussing on the quantitative and qualitative aspects of water within such beads in the absence and presence of a model drug, namely imipramine. The utilisation of Microwave differential thermal analysis (MWDTA) for the characterisation of bound water within the polymer beads was unsuccessful because there was no cooling system and as a result, most of the water evaporated during the measurement. Following successful incorporation within the beads, thermogravimetric analysis (TGA) permitted determination of the total water content within the beads (96.8 %) and differential scanning calorimetry (DSC) indicated the water within the beads was apportioned as 15.8 % non-freezing, 25.1 % loosely bound and the remaining 55.9 % unbound. In the presence of drug, the size of the beads decreased with an average diameter reduction from 121.4 μm to 78.5 μm, coupled with a reduced total water content of 95.4 %, coupled with a reduced percentage of loosely bound water. This study confirms the ability of TGA and DSC to characterise the differing types of water within the beads and indicates the relative changes in water content in the presence of model drugs.