title: A Self-microemulsifying Drug Delivery System (SMEDDS) for a Novel Medicative Compound Against Depression: a Preparation and Bioavailability Study in Rats.
abstract: AJS is the code name of an untitled novel medicative compound synthesized by the Tasly Holding Group Company (Tianjin, China) based on the structure of cinnamamide, which is one of the Biopharmaceutics Classification System (BCS) class II drugs. The drug has better antidepressant effect, achieved by acting on the 5-hydroxytryptamine receptor. However, the therapeutic effects of the drug are compromised due to its poor water solubility and lower bioavailability. Herein, a self-microemulsifying drug delivery system (SMEDDS) was developed to improve its solubility and oral bioavailability. AJS-SMEDDS formulation was optimized in terms of drug solubility in the excipients, droplet size, stability, and drug precipitation using a pseudo-ternary diagram. The pharmacokinetic study was performed in rats, and the drug concentration in plasma samples was assayed using the high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-MS/MS) method. The optimized formulation for SMEDDS has a composition of castor oil 24.5%, Labrasol 28.6%, Cremphor EL 40.8%, and Transcutol HP 2.7% (co-surfactant). No drug precipitation or phase separation was observed from the optimized formulation after 3 months of storing at 25°C. The droplet size of microemulsion formed by the optimized formulation was 26.08 ± 1.68 nm, and the zeta potential was -2.76 mV. The oral bioavailability of AJS-SMEDDS was increased by 3.4- and 35.9-fold, respectively, compared with the solid dispersion and cyclodextrin inclusion; meanwhile, the C max of AJS-SMEDDS was about 2- and 40-fold as great as the two controls, respectively. In summary, the present SMEDDS enhanced oral bioavailability of AJS and was a promising strategy to orally deliver the drug.
authors: School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China.|Chem-Pharm R&D Institute, Tasly Holding Group Company, Tianjin, 300402, People's Republic of China.
authors: Lan
authors: L
authors: Wu
authors: Chem-Pharm R&D Institute, Tasly Holding Group Company, Tianjin, 300402, People's Republic of China.
authors: Yanli
authors: Y
authors: Qiao
authors: Chem-Pharm R&D Institute, Tasly Holding Group Company, Tianjin, 300402, People's Republic of China.
authors: Lina
authors: L
authors: Wang
authors: Pharmacology and Toxicology Institute, Tasly Holding Group Company, Tianjin, 300402, People's Republic of China.
authors: Jiahua
authors: J
authors: Guo
authors: Chem-Pharm R&D Institute, Tasly Holding Group Company, Tianjin, 300402, People's Republic of China.
authors: Guocheng
authors: G
authors: Wang
authors: School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. weihe@cpu.edu.cn.
authors: Wei
authors: W
authors: He
authors: School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. lifangyin_@163.com.
authors: Lifang
authors: L
authors: Yin
authors: Chem-Pharm R&D Institute, Tasly Holding Group Company, Tianjin, 300402, People's Republic of China. zhaojinhua@tasly.com.
authors: Jinhua
authors: J
authors: Zhao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D002934:Cinnamates / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D053758:Nanoparticles; D017208:Rats, Wistar; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization; D013501:Surface-Active Agents / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D013696:Temperature; D014783:Viscosity
chemical_list: D000928:Antidepressive Agents; D002934:Cinnamates; D004337:Drug Carriers; D004655:Emulsions; D013501:Surface-Active Agents
keywords: HPLC-MS/MS; bioavailability; self-microemulsifying drug delivery system; solubilization; stability
references: J Control Release. 2011 Jan 20;149(2):168-74
references: 20951749
references: AAPS PharmSciTech. 2010 Jun;11(2):672-8
references: 20405254
references: J Affect Disord. 2013 Aug 15;150(1):96-103
references: 23643106
references: Int J Nanomedicine. 2011;6:521-33
references: 21468355
references: J Control Release. 2013 Aug 28;170(1):15-40
references: 23648832
references: Eur J Pharm Sci. 2013 Nov 20;50(3-4):420-8
references: 23981338
references: Adv Drug Deliv Rev. 2011 Sep 10;63(10-11):923-42
references: 21689702
references: Pharm Res. 2013 Dec;30(12):3077-87
references: 23636839
references: Drug Discov Today. 2010 Nov;15(21-22):958-65
references: 20727418
references: Eur J Pharm Biopharm. 2014 Apr;86(3):418-26
references: 24184672
references: Nat Rev Drug Discov. 2007 Mar;6(3):231-48
references: 17330072
references: Int J Pharm. 2013 Aug 16;452(1-2):241-8
references: 23680730
references: Int J Pharm. 2011 Jan 17;403(1-2):162-9
references: 20937370
references: Adv Drug Deliv Rev. 2008 Mar 17;60(6):625-37
references: 18068260
references: Int J Pharm. 2009 Jul 6;376(1-2):153-60
references: 19394416
references: AAPS PharmSciTech. 2011 Dec;12(4):1234-40
references: 21948306
references: Eur J Pharm Biopharm. 2006 Jul;63(3):288-94
references: 16527467
references: Int J Pharm. 2013 Mar 10;445(1-2):69-78
references: 23396257
references: Int J Pharm. 2012 Nov 15;438(1-2):123-33
references: 22850296
references: Neuropharmacology. 2013 Jul;70:338-47
references: 23499664
references: AAPS PharmSciTech. 2009;10(1):81-7
references: 19148759
references: AAPS PharmSciTech. 2015 Apr;16(2):435-43
references: 25367002
references: Eur J Pharm Sci. 2013 Nov 20;50(3-4):459-66
references: 23973887
references: Biomed Pharmacother. 2004 Apr;58(3):173-82
references: 15082340
references: Int J Pharm. 2009 Jun 5;374(1-2):66-72
references: 19446761
references: Eur J Pharm Biopharm. 2011 Sep;79(1):171-80
references: 21303694
references: Drug Discov Today. 2007 Dec;12(23-24):1068-75
references: 18061887
references: Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
references: 11259830
references: Int J Pharm. 2015 Jan 15;478(1):297-307
references: 25434592
references: ISRN Pharm. 2013 Dec 26;2013:848043
references: 24459591
references: Eur J Pharm Sci. 2006 Jun;28(3):233-42
references: 16650738
references: N Engl J Med. 2008 Jan 3;358(1):55-68
references: 18172175
references: AAPS PharmSciTech. 2009;10(3):906-16
references: 19609837
references: AAPS PharmSciTech. 2010 Sep;11(3):1287-93
references: 20717759
references: AAPS PharmSciTech. 2008;9(2):628-34
references: 18473177
references: J Pharm Biomed Anal. 2013 Sep;83:141-8
references: 23732534
references: AAPS PharmSciTech. 2009;10(1):276-81
references: 19283492