Most new drug candidates under development are poorly soluble in water, which are related to multiple pharmaceutical issues, increasing the bioavailability of these drugs by the improvement of solu...

Different from previously reported co-amorphous systems, a co-amorphous curcumin-magnolol (CUR-MAG CM) system, as compared with its crystalline counterparts, exhibited decreased dissolution due to its aggregation during dissolution. The main purpose of the present study is to deaggregate CUR-MAG CM to optimize drug dissolution and explore the deaggregation mechanism involved. Herein, a small amount of polymer (HPMC, HPC, and PVP K30) was co-formulated at 5% (w/w) with CUR-MAG CM as ternary co-amorphous systems. The polymer addition changed the surface properties of CUR-MAG CM including improved water wettability enhanced surface free energy, and hence exerted a deaggregating effect. As a result, the ternary co-amorphous systems showed faster and higher dissolution as compared with crystalline CUR/MAG and CUR-MAG CM. In addition, the nucleation and crystal growth of dissolved CUR and MAG molecules were significantly inhibited by the added polymer, maintaining a supersaturated concentration for a long time. Furthermore, polymer addition increased the T_g of CUR-MAG CM, potentially involving molecular interactions and inhibiting molecular mobility, resulting in enhanced physical stability under 25 °C/60% RH and 40 °C/75% RH conditions. Therefore, this study provides a promising strategy to optimize the dissolution and physical stability of co-amorphous systems by deaggregation and crystallization inhibition via adding small amounts of polymers.

The present study aims to develop cubosomes with surface cross-linked chitosan for sustained drug delivery and enhanced oral bioavailability of vinpocetine (VPT). GMO based liquid cubosomes with VPT loading were prepared by the high pressure homogenization method. In order to enhance the anti-digestion effect, chitosan was cross-linked on cubosomes by the Schiff reaction, followed by solidification via spray drying. The obtained spray-dried cubosomes (chito-cubosomes) are spherical microspheres with nano-sized holes on the surface. After reconstitution, the particle size and zeta potential of chito-cubosomes were determined to be ∼250 nm and +35.9 mV, respectively. In comparison to unmodified liquid cubosomes, chito-cubosomes exhibited a significant anti-digestion effect with a typical sustained release profile. In comparison to a VPT suspension, liquid cubosomes showed a 2.5-fold higher C_max and 3.0-fold higher AUC_0–∞, while chito-cubosomes further enhanced bioavailability (5.0-fold) with prolonged MRT (2.2-fold) and delayed T_max (2.8-fold). The results suggested that chito-cubosomes could be a promising drug carrier for enhancing oral absorption with sustained release behavior.