Joseph M. Tobin

Comparison of fenofibrate–mesoporous silica drug-loading processes for enhanced drug delivery

Loading a poorly water-soluble drug onto a high surface area carrier such as mesoporous silica (SBA-15) can increase the drugs dissolution rate and oral bioavailability. The loading method can influence subsequent drug properties including solid state structure and release rate. The objective of this research was to compare several loading processes in terms of drug distribution throughout the mesoporous silica matrix, drug solid state form and drug release properties. A model poorly water-soluble drug fenofibrate was loaded onto SBA-15 using; (i) physical mixing, (ii) melt, (iii) solvent impregnation, (iv) liquid CO₂ and (v) supercritical CO₂ methods. Physical mixing resulted in heterogeneous drug-loading, with no evidence of drug in the mesopores and the retention of the drug in its crystalline state. The other loading processes yielded more homogeneous drug-loading; the drug was deposited into the mesopores of the SBA-15 and was non-crystalline. All the processing methods resulted in enhanced drug release compared to the unprocessed drug with the impregnation, liquid and SC-CO₂ producing the greatest increase at t=30 min.

Inclusion of fenofibrate in a series of mesoporous silicas using microwave irradiation

A selection of porous silicas were combined with a model drug using a recently developed, controlled microwave heating process to determine if the application of microwave irradiation could enhance subsequent drug release. Five mesoporous silica types were investigated (core shell, core shell rehydrox, SBA-15, silica gel, SYLOID®) and, for comparison, one non-porous silica (stober). These were formulated using a tailored microwave heating method at drug/excipient ratios of 1:1, 1:3 and 1:5. In addition, all experiments were performed both in the presence and absence of water, used as a fluidising media to aid interaction between drug and support, and compared with results obtained using more traditional heating methods. All formulations were then characterised using differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transformation infrared spectroscopy (FT-IR). Pharmaceutical performance was investigated using in vitro drug release studies. A significant enhancement in the release profile of fenofibrate was observed for formulations prepared using microwave heating in the absence of water for five of the six silica based formulations. Of all the formulations analysed, the greatest extent of drug release within the experimental 30 min was the 1:5 core shell rehydrox achieving a total of 86.6 ± 2.8%. The non-porous (stober) particles did not exhibit an increased release of the drug under any experimental conditions studied. This anomaly is thought to be a result of the comparatively small surface area of the silica particles, thus preventing the adsorption of drug molecules.

Microwave-assisted synthesis of icosahedral nickel nanocrystals

Nickel nanocrystals with icosahedral morphologies have been successfully synthesised using a microwave-assisted irradiation method. Nickel acetylacetonate was used as the metal precursor, while sodium formate and trioctylphosphine oxide were employed as the reducing agent and capping ligands, respectively. The nanocrystals, with a mean diameter of 237 ± 43 nm, exhibited enhanced ferromagnetic behaviour at room temperature compared to bulk nickel, with coercivities of up to 164 Oe and saturation magnetisation values of up to 46 emu g−1, due to their icosahedral morphologies.

Planarized and Nanopatterned Mesoporous Silica Thin Films by Chemical-Mechanical Polishing of Gap-Filled Topographically Patterned Substrates

Nanopatterning of mesoporous silica thin films is achieved by a simple chemical-mechanical polishing (CMP) process. Mesoporous silica thin films are deposited onto topographically patterned (rectangular cross-section channels) silicon substrates so that good gap fill is achieved within the topography. The straight-etched channels promote the ordering of the mesopores along the length of the channel. CMP can then be used to successfully remove excess film above the channels from the mesas, to leave only the material within the channels, without disrupting pore order. These results indicate the robustness of these mesoporous materials to damage during the CMP process making the prospect of integrating these materials into advanced circuitry a possibility.

Enhancing the dissolution of phenylbutazone using Syloid® based mesoporous silicas for oral equine applications

Three mesoporous silica excipients (Syloid® silicas AL-1 FP, XDP 3050 and XDP 3150) were formulated with a model drug known for its poor aqueous solubility, namely phenylbutazone, in an attempt to enhance the extent and rate of drug dissolution. Although other forms of mesoporous silica have been investigated in previous studies, the effect of inclusion with these specific Syloid® silica based excipients and more interestingly, with phenylbutazone, is unknown. This work reports a significant enhancement for both the extent and rate of drug release for all three forms of Syloid® silica at a 1:1 drug:silica ratio over a period of 30 min. An explanation for this increase was determined to be conversion to the amorphous form and an enhanced drug loading ability within the pores. Differences between the release profiles of the three silicas were 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. In addition, it has been confirmed that drug release can be carefully tailored based on the choice of Syloid® silica and desired release profile.