Fabrication of multicomponent amorphous bufadienolides nanosuspension with wet milling improves dissolution and stability

Abstract

Multicomponent formulations have attracted increasing attention because of their favourable patient compliance and greater therapeutic effect. The aim of this study was to develop a multicomponent nanosuspension formulation of bufadienolides, the antitumor components of a traditional Chinese medicine, toad venom, using a wet-milling technique to improve its dissolution behaviour. Croscarmellose sodium (CCS) and sodium lauryl sulfate (SLS) were chosen as the combined stabilizers of the nanosuspension. A Taguchi orthogonal array design was used for this study to optimize the formulation and process parameters. The optimized nanosuspension was characterized by its particle size distribution, zeta potential, morphology, crystallinity, molecular interactions, stability and dissolution. The results showed that the nanosuspension was a homogeneous amorphous system with average particle sizes of <100 nm and significantly improved dissolution behaviour. It was also physically stable for at least 2 months; steric and kinetic stabilization were its main stability mechanisms. These findings suggested that the use of wet milling to fabricate nanosuspensions is a promising method for achieving the fast and synchronized dissolution of multicomponent formulations, presumably increasing the bioavailability of poorly water-soluble drugs.

Effect of Shape on Mesoporous Silica Nanoparticles for Oral Delivery of Indomethacin

“…However, there are still limitations to this form of delivery, and the challenge remains to improve oral bioavailability of Biopharmaceutical Classification System (BCS) II molecules, owing to their low solubility and poor stability in the gastrointestinal tract (GI tract). In recent years, many strategies have been proposed to improve the dissolution and bioavailability of poorly water-soluble drugs, including spray drying [4,5,6], solid dispersions [7,8,9], nanosuspensions [10,11], cryogenic technologies [12,13], and prodrug approaches [14]. For example, Xu et al prepared hydrophilic polymer-based solid dispersions by a freeze-drying technique, and enhanced the dissolution rate and oral bioavailability of valsartan [15].…”

Nanosuspension-Based Drug Delivery Systems for Topical Applications

“…In the quest for creating a nanosuspension suitable for parenteral administration and capable of withstanding autoclaving, lecithin has emerged as the preferred stabilizer. 16 , 47 …”

Evolving Roles of Natural Terpenoids From Traditional Chinese Medicine in the Treatment of Osteoporosis

“…In addition, other problems, such as poor water solubility, short half-life, poor stability, and low bioavailability, severely limit the development and clinical use of TCM. The application of modern technologies (nanotechnology and co-crystallization) can overcome these short comings ( 175 – 177 ). Hence, for those terpenoids with perfect anti-OP efficacy but poor water solubility, we can apply nanoparticles in the drug delivery.…”