title: Improved Oral Bioavailability Using a Solid Self-Microemulsifying Drug Delivery System Containing a Multicomponent Mixture Extracted from Salvia miltiorrhiza.
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.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, China. bxl77@126.com.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Bi
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, China. ptziye@163.com.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, China. diliuqingbox@126.com.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Di
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, China. zuqiang1975@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D016503:Drug Delivery Systems; D004355:Drug Stability; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry*; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051381:Rats; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D012995:Solubility
chemical_list: D004365:Drugs, Chinese Herbal; D004655:Emulsions
keywords: bioavailability; dissolution rate; oral drug delivery; salvia extract; solid self-microemulsifying drug delivery system