Abstract
Salvia miltiorrhizae (Danshen, the rhizome of Salvia miltiorrhiza Bge.) and Chuanxiong rhizome (Chuanxiong, the rhizome of Ligusticum chuanxiong Hort.) are two traditional Chinese medicines that have been widely used for the treatment
of cardiovascular and cerebrovascular diseases. However, formulation development is
difficult due to the complexity of the active ingredients, particularly the water-insoluble
tanshinones and volatile oil of Chuanxiong rhizome, which cannot be absorbed via oral
administration in conventional dosage forms. This study aimed to develop a self-stabilized
nanocrystal emulsion co-loading the water-soluble, insoluble, and volatile active
ingredients of Salvia miltiorrhizae and Chuanxiong rhizome to improve the bioavailability
of the drugs. In this work, a high-pressure homogenization method was used to prepare
a self-stabilizing nanocrystal emulsion. The emulsion was then spray-dried using hydroxypropyl-β-cyclodextrin.
The dispersibility and storage stability of the spray-dried emulsion, the particle
size and morphology of the emulsion droplets, and the drug content and phase distribution
of the reconstituted emulsion were evaluated. An everted intestinal sac model was
established, and high-performance liquid chromatography was used to determine the
concentration of six active components (ferulic acid, salvianolic acid B, senkyunolide
A, ligustilide, cryptotanshinone, and tanshinone IIA) and to assess the cumulative
uptake amount of the drug and the apparent permeability coefficient. A mixture of
the crude materials of tanshinones extract, total salvianolic acid, ferulic acid,
and volatile oil of Ligusticum Chuanxiong was used as a control. The results showed
that the spray-dried emulsion can be easily reconstituted into a uniform submicron
emulsion with no significant changes in particle size, morphology, and microstructure
of the emulsion droplets compared with the original emulsion before drying. The self-stabilizing
nanocrystal emulsion significantly improved the intestinal absorption of water-insoluble
components (tanshinone IIA, cryptotanshinone, and ferulic acid), and volatile oil
components (senkyunolide A and ligustilide). Overall, the spray-dried self-stabilizing
nanocrystal emulsion represents a potential oral formulation for Salvia miltiorrhiza
and Chuanxiong rhizoma.
Keywords
Salvia miltiorrhizae - Chuanxiong rhizome - nanocrystals - dry emulsion - oral delivery
- tanshinones - volatile oil
