Improved Oral Bioavailability Using a Solid Self-Microemulsifying Drug Delivery System Containing a Multicomponent Mixture Extracted from Salvia miltiorrhiza

Abstract

Abstract:The active ingredients of salvia (dried root of Salvia miltiorrhiza) include both lipophilic (e.g., tanshinone IIA, tanshinone I, cryptotanshinone and dihydrotanshinone I) and hydrophilic (e.g., danshensu and salvianolic acid B) constituents. The low oral bioavailability of these constituents may limit their efficacy. A solid self-microemulsifying drug delivery system (S-SMEDDS) was developed to load the various active constituents of salvia into a single drug delivery system and improve their oral bioavailability. A prototype SMEDDS was designed using solubility studies and phase diagram construction, and characterized by self-emulsification performance, stability, morphology, droplet size, polydispersity index and zeta potential. Furthermore, the S-SMEDDS was prepared by dispersing liquid SMEDDS containing liposoluble extract into a solution containing aqueous extract and hydrophilic polymer, and then freeze-drying. In vitro release of tanshinone IIA, salvianolic acid B, cryptotanshinone and danshensu from the S-SMEDDS was examined, showing approximately 60%-80% of each active component was released from the S-SMEDDS in vitro within 20 min. In vivo bioavailability of these four constituents indicated that the S-SMEDDS showed superior in vivo oral absorption to a drug suspension after oral administration in rats. It can be concluded that the novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of both lipophilic and hydrophilic constituents of salvia. Thus, the S-SMEDDS can be regarded as a promising new method by which to deliver salvia extract, and potentially other multicomponent drugs, by the oral route.

Lipid-based nanosystem of edaravone: development, optimization, characterization andin vitro/in vivoevaluation

“…Solid lipid-based nanoformulation could offer the superior stability and patient compliance. Therefore various water-soluble carriers such as mannitol and lactose, and water-insoluble carriers including silicon dioxide were used previously to convert liquid to solid lipid-based nanoformulation (Bi et al., 2016 ). The water-insoluble carrier was preferred over water-soluble carriers because of possible inadequacy related to water-soluble carriers such as significantly low oil absorbing capacity and being relatively hygroscopic in nature which tends to recrystallize during the storage and deteriorate the quality features of liquid lipid-based nanoformulation (Yeom et al., 2016 ).…”

“…The commercial success of liquid lipid-based nanoformulations is limited due to stability concern including the interaction of components with gelatin capsules, the interaction between the components and/or issues related to oxidation of the oil (Bi et al., 2016 ). By converting liquid to solid lipid-based nanoformulations using solid adsorbents, it is possible to overcome issues including stability and handling problems.…”

Extraction of Tanshinones Rich Extract of Danshen (Salvia Miltiorrhiza Bunge) Root Using Adsorptive (Non-Ionic) Macroporous Resins

“…X. Bi và cộng sự (2016) nghiên cứu chiết xuất cao rễ đan sâm giàu tanshinon bằng CO2 siêu tới hạn với các điều kiện: đồng dung môi EtOH 95%, áp suất 30 MPa, nhiệt độ 45 °C và thời gian chiết 2 giờ. Cao chiết thu được có hàm lượng TAN và CRYP lần lượt là 30,9 và 19,1% [9]. Quy trình chiết xuất bằng CO2 siêu tới hạn có thể cho sản phẩm có hàm lượng hoạt chất cao, tuy nhiên hiệu suất chiết trong quy trình đó không được công bố cụ thể.…”

A New Self Microemulsifying Mouth Dissolving Film

“…The small droplet size provides a large surface area for drug release and absorption. 13 SMEDDS enhances drug dissolution and improves stability of drug. 14 SMEDDS has great ability to enhancing oral bioavailability of poorly water soluble drugs.…”