High drug load, stable, manufacturable and bioavailable fenofibrate formulations in mesoporous silica: a comparison of spray drying versus solvent impregnation methods

Abstract

Encapsulation of drugs in mesoporous silica using co-spray drying process has been recently explored as potential industrial method. However, the impact of spray drying on manufacturability, physiochemical stability and bioavailability in relation to conventional drug load processes are yet to be fully investigated. Using a 2(3) factorial design, this study aims to investigate the effect of drug-loading process (co-spray drying and solvent impregnation), mesoporous silica pore size (SBA-15, 6.5 nm and MCM-41, 2.5 nm) and percentage drug load (30% w/w and 50% w/w) on material properties, crystallinity, physicochemical stability, release profiles and bioavailability of fenofibrate (FEN) loaded into mesoporous silica. From the scanning electronic microscopy (SEM) images, powder X-ray diffraction and Differential scanning calorimetry measurements, it is indicated that the co-spray drying process was able to load up to 50% (w/w) FEN in amorphous form onto the mesoporous silica as compared to the 30% (w/w) for solvent impregnation. The in vitro dissolution rate of the co-spray dried formulations was also significantly (p = 0.044) better than solvent impregnated formulations at the same drug loading. Six-month accelerated stability test at 40 °C/75 RH in open dish indicated excellent physical and chemical stability of formulations prepared by both methods. The amorphous state of FEN and the enhanced dissolution profiles were well preserved, and very low levels of degradation were detected after storage. The dog data for the three selected co-spray-dried formulations revealed multiple fold increment in FEN bioavailability compared to the reference crystalline FEN. These results validate the viability of co-spray-dried mesoporous silica formulations with high amorphous drug load as potential drug delivery systems for poorly water soluble drugs.

Extruded Soluplus/SIM as an oral delivery system: characterization, interactions,in vitroandin vivoevaluations

“…Many of these new chemical entities (NCEs) failed to be used in clinical therapy as they have poor bioavailability due to their limited solubility or slow dissolution rate in the gastrointestinal tract (Hong et al, 2014). Converting crystalline drugs into their amorphous counterparts is an efficient way to improve the dissolution rate and solubility of poorly water-soluble drugs, especially for biopharmaceutics classification system (BCS) Class II compounds (Srinarong, 2011).…”

“…With a Tg of 70.5 C, Soluplus had a wide extrusion temperature range (Zhang, 2013). Also its high flow-ability and excellent extrudability made it suitable for the extrusion process (Hong et al, 2014). Numerous studies based on Soluplus have shown that it can enhance the dissolution rates of poorly soluble drugs.…”

Porous Inorganic Drug Delivery Systems—a Review

“…This approach involves dispersing the carrier in a solution of the drug in a volatile solvent followed by spray drying of the dispersion. Compared to solvent based techniques, this method produces more stable amorphous state of the drug with considerably enhanced dissolution rate and oral bioavailability (182,183).…”

“…In addition these conventional methods have intrinsic disadvantages such as the use of organic solvents that will require a subsequent solvent elimination process; impacting on time and cost factors (129). Therefore, supplementary approaches have been proposed to load drug into mesoporous carriers without affecting active stability such as supercritical fluids method (129,181), co-spray drying (182,183) and microwave irradiation (184). The supercritical fluid method (e.g.…”

Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery

“…[12][13][14] In cellular systems, low toxicity and high uptake of MSNs have been well established in studies stemming from the past decade. 15 The ordered pore structure accompanied with the consequential high surface area and pore volume provides the nanocarriers with a high loading capacity 16 and offers efficient protection for the oligonucleotide cargo before reaching the point of release. 17,18 Furthermore, MSNs may facilitate slow, sustained and controlled release 19 owing to their design flexibility that enables multifunctionality as well as allows for sequential release.…”