(298b) Spray-Dried Nanocomposites and Amorphous Solid Dispersions with Identical Formulation for Comparative Assessment of Drug Dissolution Enhancement

The number of new drug candidates coming out of drug discovery having poor aqueous solubility has increased within the last few decades. Due to the poor aqueous solubility, intestinal absorption of these drugs turns out to be rate-limiting, leading to low bioavailability. Over the years, significant academic and industrial researches have been carried out and directed toward developing various formulation/processing strategies for efficient solubilization/dissolution rate enhancement of poorly water-soluble drugs. Among different approaches, two major platform approaches have gained prevalence both in the scientific literature and marketed products: nanoparticle-based dosage forms (nanocomposites) and amorphous solid dispersions (ASDs) [1]. Both nanoparticle-based dosage forms and amorphous solid dispersions (ASDs) can improve the dissolution rate and bioavailability due to very high surface area and higher saturation solubility, respectively, compared to the micron-sized crystalline drug particles. Although both drug nanocomposites and ASDs have been studied for decades, no head-to-head comparison of these two forms of drugs having identical formulation is available in the literature. Using a novel nanoextrusion process, a comparative assessment of relative dissolution enhancement capability of nanocomposites vs. ASDs was performed [2]. However, the nanoextrusion process requires the use of different polymers to produce nanocomposites or ASDs of a given drug via differing drug–polymer miscibility/interactions; thus, it is usually infeasible to produce nanocomposites and ASDs having identical formulation. Therefore, a direct and scientifically fair head-to-head comparison of drug dissolution performance of nanocomposites vs. ASDs having identical formulation is still lacking in the literature.

In this study, we aim to assess the dissolution enhancement of griseofulvin (GF, a poorly water-soluble drug) from nanocomposites vs. ASDs, both having identical formulations. GF nanocomposite was prepared by wet media milling (nanomilling) an aqueous GF suspension followed by spray drying. Two polymers, hydroxypropyl cellulose (HPC) and Soluplus®, with an anionic surfactant, sodium dodecyl sulfate (SDS), were used for the stabilization of drug nanoparticles. ASDs were prepared by spray-drying a solution of the respective drug–polymer in acetone–deionized water. Laser diffraction, XRPD, Raman spectroscopy, polarized light microscopy, and dissolution testing were used for characterization. XRPD confirmed that for both polymers, spray-drying of the aqueous nanosuspension led to drug nanocrystals dispersed in the polymeric matrix (nanocomposite), whereas that of the drug solution led to ASD. At supersaturating dissolution conditions (100 mg GF dose), both nanocomposites and ASDs significantly improved the dissolution performance as compared with the as-received GF and physical mixtures. For GF–Soluplus®, ASDs exhibited higher supersaturation generation than nanocomposites, whereas for GF–HPC, both dosage forms of the drug exhibited only slight supersaturation. Interestingly, regardless of the solid-state of the drug, higher extent of supersaturation was observed in the dissolution medium for GF–Soluplus® than GF–HPC. Overall, this study demonstrates how to produce both nanocomposites and ASD of the same drug with identical formulation using spray dryer as a tool and to perform a comparative assessment of their dissolution performance.

References:

[1] Brough, C., Williams, R., 2013. Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery. Int. J. Pharm. 453(1), 157–166.

[2] Li, M., Ioannidis, N., Gogos, C., Bilgili, E., 2017. A comparative assessment of nanocomposites vs. amorphous solid dispersions prepared via nanoextrusion for drug dissolution enhancement. Eur. J. Pharm. Biopharm. 119, 68–80.