Recent advances in solid dispersions and the formulation of poorly absorbed drugs

In this special issue, we have selected outstanding manuscripts that represent recent advances in the field of bioavailability enhancement. Specifically, the articles highlighted herein are focused on the improvement of the bioavailability of poorly water-soluble compounds through various formulation approaches with a focus on the creation of pharmaceutical solid dispersions. This field has been expanding rapidly, but many problems in prediction, stability, and applications to non-standard systems require alternative approaches. In the following special issue, advances in a variety of aspects of this maturing area of research are presented.

The issue begins with Piao et al.1, using a novel method for solid dispersion manufacture, namely, quasi-emulsion solvent diffusion. In this work the authors applied a surfactant free method to the goal of improving the bioavailability of paclitaxel. Hydroxypropyl methylcellulose acetate succinate and porous silicon dioxide were used in the development of their formulations. The authors found their approach lead to a bioavailability of almost 7 times that of the paclitaxel in the unprocessed form. Penkina et al.2 utilized solid dispersions to improve the solubility of poorly water-soluble compounds in their article using cryogenic co-grinding methods. Employing these methods, the authors report that as more milling energy was applied to the system, the defects on the crystalline surface lead to the complete amorphization of the system. Using stabilizing polymers, they report that the cryogenic co-ground solid dispersion prepared from polyvinylpyrrolidone enhanced the dissolution rate of their model drug prioxicam, while those prepared from a cellulose polymer system resulted in sustained release. Importantly, they note that the moisture content of the polymers may be a critical parameter to control.

Wong et al.3 utilized solid lipid microparticles for a poorly soluble model drug (ibuprofen) attained using spray congealing. They found that with this method, utilizing glyceryl dibehenate as the lipid matrix material, they could incorporate 20%, w/w of ibuprofen as a solid solution. They noted that physicochemical characterization of the formulations was necessary to understand the solid solutions and the stability of the material overtime, including the polymorphic changes to the lipid matrix itself. The addition of ethylcellulose allowed for the stabilization of the normally unstable alpha polymorph of the matrix for nearly a year. Oh, et al.4 also employed the process of spray congealing in this special issue. Their approach employed PEG as the matrix and is an excellent complementary paper to Wong et al.

Medarević et al.5, in their approach, used statistical design of experiments to develop solid dispersions. They then utilized artificial neural networks to allow for modeling of their obtained experimental data. They concluded that both techniques, used synergistically, provide advantages for pharmaceutical development of solid dispersions. Lang et al.,6 investigated the effects of hydrophilic additives on the in vitro and in vivo performance of itraconazole-enteric polymer amorphous solid dispersions. This study, important because solid dispersions are often hydrophobic and poorly wettable, showed that incorporating Vitamin E TPGS into amorphous solid dispersions significantly improved drug release and also enhanced the degree of drug supersaturation. In their in vivo studies, a prolonged half-life and increased drug absorption were obtained. Altamimi and Neau7 provided guidance on the use of Flory-Huggins Theory to predict drug solubility in polymers in their contribution to the issue. Cai and coworkers8 presented the use of a silica-supported solid dispersion to provide improved bioavailability.

Other approaches to increasing bioavailability are presented in a number of other manuscripts in this issue with relevance to different approaches in formulation design and applications. Hamdan et al9 assessed the in vivo bioavailability of diclofenac sodium from its cyclodextrin complexes and the importance of zinc in this system. Liu et al.10 presented their efforts to enhance the bioavailability of a drug that undergoes metabolism in the colon and rectum, Oxymatrine, by formulating alginate-chitosan floating beads prepared by the ionotropic gelation method to increase gastroretention. Their solid dispersion of oxymatrine had a sustained release for over 12 hours and were maintained in rabbit stomachs for 8.5 hours. Gao et al.11 explored the effects of the pore size of three-dimensionally ordered macroporous chitosan-silica systems on the solubility and oral bioavailability of the model drug nimodipine. The authors found that as the pore size of the matrix decreased, the drug crystallinity decreased and the aqueous solubility increased. The spatial confinement of the matrix and the wetting property of chitosan appear valuable for increasing solubility. Palem et al.12, characterized domperidone hot-melt extruded, controlled release films by central composite design for buccal delivery. The authors found that their optimized films had a bioavailability of 3.2 times higher than the standard oral dosage forms and were stable for 6 months. Lu et al.13, created amorphous solid dispersions using hot melt extrusion to improve the solubility and bioavailability of felodipine. The authors used an amphiphilic polymer (Soluplus®) and various techniques to characterize the solid state properties of their formulations. The authors found that in the 10% drug formulation, the drug was molecularly dispersed within the polymer matrix and had the highest solubility enhancement.

Mehanna and Allam14 formulated a controlled release formula of metformin using gellan gum microbeads through inotropic gelation. The authors found an in vitro release of up to 8 hours with their formulation and compared this to the marketed extended release formulation.

Jing et al.15, developed novel self-microemulsifying tablets to enhance the oral bioavailability of a poorly water-soluble drug, felodipine, using the wet granulation compression method. The authors found that in vitro dissolution performance of the liquid self-microemulsifying system and the tablets were similar, and both were higher than the commercially available tablet. They found that both the liquid and tablet SMEDDS had about a 2 -fold enhanced bioavailability compared to the commercially available tablets.

Collectively, these papers provide informative and novel solutions for increasing the solubility, and thereby bioavailability, of problem drugs. Readers will find the thematic links between these manuscripts synergistic and instructive in providing alternative approaches to this major problem facing researchers today. We thank the authors for their high quality work.