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A Self-microemulsifying Drug Delivery System (SMEDDS) for a Novel Medicative Compound Against Depression: a Preparation and Bioavailability Study in Rats

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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.

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ACKNOWLEDGMENTS

This work was financially supported by the National Key Subject of Drug Innovation (grant no. 2013ZX09402-202) and the Key Projects in the Tianjin Science and Technology Pillar Program (grant no. 12ZCZDSY01200).

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Authors and Affiliations

  1. School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Lan Wu, Wei He & Lifang Yin

  2. Chem-Pharm R&D Institute, Tasly Holding Group Company, Tianjin, 300402, People’s Republic of China

    Lan Wu, Yanli Qiao, Lina Wang, Guocheng Wang & Jinhua Zhao

  3. Pharmacology and Toxicology Institute, Tasly Holding Group Company, Tianjin, 300402, People’s Republic of China

    Jiahua Guo

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  1. Lan Wu
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  2. Yanli Qiao
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  6. Wei He
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Correspondence to Wei He, Lifang Yin or Jinhua Zhao.

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Wu, L., Qiao, Y., Wang, L. et al. A Self-microemulsifying Drug Delivery System (SMEDDS) for a Novel Medicative Compound Against Depression: a Preparation and Bioavailability Study in Rats. AAPS PharmSciTech 16, 1051–1058 (2015). https://doi.org/10.1208/s12249-014-0280-y

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