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Controlled Release of the Nimodipine-Loaded Self-Microemulsion Osmotic Pump Capsules: Development and Characterization

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Abstract

The present study was intended to develop a controlled released osmotic pump capsule based on Nimodipine (NM)-loaded self-microemulsifying drug delivery systems (SMEDDSs) in order to improve the low oral bioavailability of NM. To optimize the NM-loaded SMEDDS composition, the experiments of NM solubility in different oils, the pseudo-ternary phase diagram experiments and the different drug loading experiments were conducted in the preliminary screening studies. Controlled release of NM required an osmotic pump capsule comprising a coated semi-permeable capsule shell, plasticizer, and pore-forming agent. NM release follows zero-order kinetics after oral administration. Polyethylene glycol content, used as a pore-forming agent, coating mass, and drug release orifice size were key factors affecting drug release behavior according to the single methods and were optimized through response surface methodology. The NM-loaded SMEDDS droplet size and the 1H NMR mass spectrogram of the novel capsule were determined. The droplet size of the reconstituted microemulsion was 39.9 nm and 1H NMR analysis showed NM dissolution in the microemulsion. The dissolution test performed on three batches of NM-SMEDDS capsules—prepared using optimal preparation methods—indicated the capsule to deliver a qualified drug delivery with a zero-order release rate. The results demonstrated that NM-loaded SMEDDSs were successfully developed and displayed a qualified release rate in vitro.

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Acknowledgements

The authors are thankful to Prof. Li Ning from Guangdong Pharmaceutical University, for providing equipment used in this project and for consultation on analytical methods.

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Authors and Affiliations

  1. Guangzhou Higher Education Mega Center, Guangdong Pharmaceutical University, No. 280 Waihuandong Road, Guangzhou, China

    Yaping Huang, Sisi Zhang, Huifen Shen & Jinqing Li

  2. Department of Pharmaceutics, School of Pharmacy, Guangzhou Higher Education Mega Center, Guangdong Pharmaceutical University, No. 280 Waihuandong Road, Guangzhou, 510006, China

    Chongkai Gao

Authors
  1. Yaping Huang
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  2. Sisi Zhang
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Correspondence to Chongkai Gao.

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The authors declare that they have no conflicts of interest.

Novelty Statement

The use of self-microemulsifying drug delivery system (SMEDDS) solves the water insolubility problem of Nimodipine. Besides, osmotic pump systems (OPSs) can be used as a method to control formulation release by oral administration, whereby the drug release follows zero-order kinetics.

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Huang, Y., Zhang, S., Shen, H. et al. Controlled Release of the Nimodipine-Loaded Self-Microemulsion Osmotic Pump Capsules: Development and Characterization. AAPS PharmSciTech 19, 1308–1319 (2018). https://doi.org/10.1208/s12249-017-0936-5

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