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Preparation and Evaluation of Mosapride Citrate Dual-Release Dry Suspension

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Abstract

In this paper, a novel formulation of dual-release dry suspension of mosapride citrate (DRDS-MC) was designed which can be quickly released in the stomach while having sustained-release effect. Co-grinding mixture of mosapride citrate (MC) together with L-HPC as hydrophilic excipient was prepared in order to improve the solubility of MC. The co-grinding mixture was characterized by solubility studies, DSC, X-RD, SEM, FTIR, and size distribution before the preparation of the DRDS-MC. Then, the co-grinding mixture was used to prepare DRDS-MC via wet granulation method. The evaluation of DRDS-MC was focused on physicochemical properties, intestinal absorption, and pharmacokinetics. The results of DSC, X-RD, SEM, FTIR, and size distribution indicated that MC resides in co-grinding mixture with no crystalline changes, hydrogen bonds made L-HPC greatly improving the solubility of MC. Then, the dissolution of DRDS-MC reached 70% in pH 1.2 within 2 h, and the 12-h dissolution of MC in pH 6.8 was nearly 80%. The sedimentation volume after 3 h was 0.94 and redispersibility was good. The linear regression equation between in vitro release of DRDS-MC and intestinal absorption fraction in rats was: Y = 29.215 + 47.535*X (r = 0.952). At last, pharmacokinetic studies in beagle dogs demonstrated that DRDS-MC has prolonged effect compared with commercial formulation Gasmotin as a reference. All results indicated that the DRDS-MC could be quickly released in the stomach while having sustained-release effect.

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Funding

This work was financially supported by the Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture (Nos.XTD1820) and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (Nos.KYCX18_1104, KYCX18_1115).

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Author notes

  1. Kuntang Liu and Zhengjie Meng contributed equally to this work.

Authors and Affiliations

  1. College of Pharmacy, Nanjing Tech University, No. 30, Puzhu South Road, Nanjing, 211816, People’s Republic of China

    Kuntang Liu, Yonglu Wang & Xueming Li

  2. Nanjing Bestform Pharmaceutical Technology Co., Ltd., Nanjing, China

    Kuntang Liu, Yang Li & Yonglu Wang

  3. College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, 211816, China

    Zhengjie Meng, Jiwei Liu & Yan Xu

Authors
  1. Kuntang Liu
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  2. Zhengjie Meng
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  4. Jiwei Liu
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  5. Yan Xu
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Correspondence to Yonglu Wang or Xueming Li.

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Highlights

• Co-grinding mixture was prepared by mosapride citrate (MC) and L-HPC, and hydrogen bonds may be the reason for enhancing the hydrophilic of L-HPC which greatly improved the water solubility of MC.

• Dual-release dry suspension of mosapride citrate (DRDS-MC) was prepared.

• The dissolution of DRDS-MC reached 70% in pH1.2 within 2 h and the 12 h dissolution of MC in pH6.8 was nearly 80%. DRDS-MC could quickly release in acid medium and has sustained-release effect in pH6.8.

• The linear regression equation between in vitro release of DRDS-MC and intestinal absorption fraction in rats was: Y=29.215+47.535*X (r=0.952).

• Pharmacokinetic results proved that DRDS-MC had long-term sustained-release effect compared with commercial formulation Gasmotin in beagle dogs.

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Liu, K., Meng, Z., Li, Y. et al. Preparation and Evaluation of Mosapride Citrate Dual-Release Dry Suspension. AAPS PharmSciTech 20, 155 (2019). https://doi.org/10.1208/s12249-019-1343-x

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