A Self-microemulsifying Drug Delivery System (SMEDDS) for a Novel Medicative Compound Against Depression: a Preparation and Bioavailability Study in Rats
Journal Title: AAPS PharmSciTech - Year 2015, Vol 16, Issue 5
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 Cmax 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 and Affiliations
Lan Wu, Yanli Qiao, Lina Wang, Jiahua Guo, Guocheng Wang, Wei He, Lifang Yin, Jinhua Zhao
Keywords
Related Articles
- EP ID EP682286
- DOI 10.1208/s12249-014-0280-y
- Views 88
- Downloads 0
Influence of Hydroxypropyl Methylcellulose on Metronidazole Crystallinity in Spray-Congealed Polyethylene Glycol Microparticles and Its Impact with Various Additives on Metronidazole Release
The purpose of this study was to investigate the effect of a hydrophilic polymer, hydroxypropyl methylcellulose (HPMC), on the crystallinity and drug release of metronidazole (MNZ) in spray-congealed polyethylene glycol...
Effect of Acetate and Carbonate Buffers on the Photolysis of Riboflavin in Aqueous Solution: A Kinetic Study
The photolysis of riboflavin (RF) in the presence of acetate buffer (pH 3.8–5.6) and carbonate buffer (pH 9.2–10.8) has been studied using a multicomponent spectrophotometric method for the simultaneous a...
Solid-State Interactions at the Core-Coat Interface: Physicochemical Characterization of Enteric-Coated Omeprazole Pellets Without a Protective Sub-Coat
Conventionally, scanning electron or transmission microscopy, Raman and near infrared (NIR) spectroscopy, terahertz, florescence, and nuclear magnetic resonance imaging have been used to characterize functional coating s...
A Novel Approach in Distinguishing Between Role of Hydrodynamics and Mechanical Stresses Similar to Contraction Forces of GI Tract on Drug Release from Modified Release Dosage Forms
The objective of this study was to determine the influence of mechanical stresses simulating gastrointestinal contraction forces of 2.0 N (stomach) and 1.2 N (intestine) on the gel properties and drug release characteris...
The Influence of Ionizing Radiation on Itraconazole in the Solid State
The aim of this study was to investigate the ionizing radiation effects, in the form of an electron beam, on itraconazole (ITR) in the solid phase. It was found that the ITR, under the influence of a standard 25 ...