A Novel Colon-Specific Osmotic Pump Capsule of Panax notoginseng Saponins (PNS): Formulation, Optimization, and In Vitro-In Vivo Evaluation
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In the current study, a novel colon-specific osmotic pump capsule of Panax notoginseng saponins was developed to achieve colon-specific release, a zero-order, thus to promote the efficacy of Panax notoginseng saponins. The capsule was assembled using a semi-permeable capsule shell with contents including Panax notoginseng saponins, sodium chloride (NaCl), and Ludipress. The semipermeable membrane was made of cellulose acetate (CA), along with polyethylene glycol (PEG) 6000 for flexibility and strength, and Eudragit® S100 for colon-specific targeting. The in vitro dissolution test showed an approximately zero-order release of Panax notoginseng saponins over 12 h at pH 7.8 through the pores on the membrane. Meanwhile, the drug release from the optimal formulation was found to be independent of equipment type or agitation speed. Rather, it depended on mainly the osmotic pressure of the dissolution media. The in vivo test in beagle dogs demonstrated that the relative bioavailability of the current system was 487.42% in comparison to that of the marketed product, yet with a prolonged retention time. The novel controlled delivery system for Panax notoginseng saponins in the current study utilizing colon-specific and osmotic pump system therefore offered the advantages of avoiding stomach and enteric irritation, reducing dosage frequency, minimizing the drug fluctuation in plasma, and improving its oral bioavailability.
KEY WORDSPanax notoginseng saponins colon-specific osmotic pump capsule pharmacokinetics
We thank Dr. Jun Shao of St. John’s University for his support in the design and writing of the thesis.
This project was supported by the National Natural Science Foundation of China (No.81573615, No.81274100) and Project of Scientific Research Fund of Anhui University of Chinese medicine (No. 2016zr009).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 6.Duan L, Xiong X, Hu J, Liu Y, Li J, Wang J. Panax notoginseng saponins for treating coronary artery disease: a functional and mechanistic overview. Front Pharmacol. 2017;8:1–18.Google Scholar
- 7.Chen YM, Li YW, Zhu GH. Panax notoginseng saponins injection induced 103 cases of adverse reactions analysis. Chin J Chin Mater Med. 2010;35(2):237–9.Google Scholar
- 17.Fang WY. Studies on oral colon-specific capsules of panax notoginsens saponins liposomes [master]: Anhui University of Chinese Medicine. 2015.Google Scholar
- 21.Wu L, LI HY, YIN XZ, LI Y, CHEN JX, HU RF, et al. Applicability of a natural swelling matrix as the propellant of osmotic pump tablets. Acta Pharm Sin. 2013;48(08):1319–24.Google Scholar
- 34.Guo Q, Li P, Wang Z, Cheng Y, Wu H, Yang B, et al. Brain distribution pharmacokinetics and integrated pharmacokinetics of panax notoginsenoside r1, ginsenosides rg1, rb1, re and rd in rats after intranasal administration of panax notoginseng saponins assessed by uplc/ms/ms. J Chromatogr B. 2014;969:264–71.CrossRefGoogle Scholar
- 35.Wu H, Liu H, Bai J, Lu Y, Du S. Simultaneous determination of notoginsenoside r1, ginsenoside rg1, ginsenoside re and 20(s) protopanaxatriol in beagle dog plasma by ultra high performance liquid mass spectrometry after oral administration of a panax notoginseng saponin preparation. J Chromatogr B. 2015;974:42–7.CrossRefGoogle Scholar