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AAPS PharmSciTech

, 20:75 | Cite as

Formulation and Evaluation of a Novel Oral Oil-Based Suspension Using Micro-environmental pH-Modifying Solid Dispersion

  • Shudong Zhang
  • Qiang Wan
  • Yidan Xing
  • Jiafeng Ding
  • Shizhuang Yang
  • Weiwei Sun
  • Mengmeng Lu
  • Baoliang PanEmail author
Research Article

Abstract

Drugs with pH-dependent solubility that have poor water solubility can be identified in the drug discovery pipeline. Some of them have poor oral absorption, which can result in insufficient efficacy. Micro-environmental pH-modifying solid dispersion (micro pHm SD) is a promising approach to overcome the poor oral absorption of these drugs. In the present study, toltrazuril (TOL), a weakly acidic drug with poor aqueous and pH-dependent solubility, was used as a model drug. Using micro pHm SD, a novel oral oil-based suspension of TOL SD (TSDS) was developed, and the stability of this formulation was evaluated based on particle size, settling volume ratio, redispersibility, thermal stability, and drug content. The optimized soybean oil-based TSDS (S-TSDS) had high physicochemical stability and good histocompatibility with common inflammatory reactions. The results of the in vitro dissolution analysis showed that S-TSDS rapidly and markedly released the drug and provided higher efficacy and longer persistence against coccidiosis (above 90.9%) in rabbits. This technique could increase the oral absorption and bioavailability of new drug candidates.

KEY WORDS

toltrazuril micro-environmental pH-modifying solid dispersion suspension oral 

Notes

Acknowledgments

This work was supported by the “National Key Research and Development Program of China” (2017YFD0501200 and 2018YFD0502305).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12249_2018_1222_MOESM1_ESM.docx (18 kb)
Supplemental Table I List of abbreviations and acronyms (DOCX 18 kb)
12249_2018_1222_Fig7_ESM.png (83 kb)
Supplemental Fig. 1

a DSC thermograms of raw TOL, PVPk30, TSD, and recovered TSD. b X-ray powder diffraction patterns of crystalline TOL, Ca(OH)2, PVPk30, TSD, recovered TSD suspensions. TSD (toltrazuril solid dispersion) was prepared at a ratio of 1:8:24 (Ca(OH)2/TOL/PVPk30, w/w/w); recovered TSD: TSD obtained from S-TSDS by repetitive washing (TIF 932 kb) (PNG 82 kb)

12249_2018_1222_MOESM2_ESM.tif (933 kb)
High resolution image (PNG 82 kb) (TIF 932 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Shudong Zhang
    • 1
  • Qiang Wan
    • 1
  • Yidan Xing
    • 1
  • Jiafeng Ding
    • 1
  • Shizhuang Yang
    • 1
  • Weiwei Sun
    • 1
  • Mengmeng Lu
    • 1
  • Baoliang Pan
    • 1
    Email author
  1. 1.The Department of Veterinary Parasitology, College of Veterinary MedicineChina Agricultural UniversityBeijingChina

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