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Drug Delivery and Translational Research

, Volume 9, Issue 1, pp 284–297 | Cite as

Domperidone nanocrystals with boosted oral bioavailability: fabrication, evaluation and molecular insight into the polymer-domperidone nanocrystal interaction

  • Stalielson Tatenda Ndlovu
  • Naseem Ullah
  • Shahzeb Khan
  • Pritika Ramharack
  • Mahmoud Soliman
  • Marcel de Matas
  • Muhammad Shahid
  • Muhammad Sohail
  • Muhammad Imran
  • Syed Wadood Ali Shah
  • Zahid Hussain
Original Article
  • 69 Downloads

Abstract

The aim of this study was to employ experimental and molecular modelling approaches to use molecular level interactions to rationalise the selection of suitable polymers for use in the production of stable domperidone (DOMP) nanocrystals with enhanced bioavailability. A low-energy antisolvent precipitation method was used for the preparation and screening of polymers for stable nanocrystals of DOMP. Ethyl cellulose was found to be very efficient in producing stable DOMP nanocrystals with particle size of 130 ± 3 nm. Moreover, the combination of hydroxypropyl methylcellulose and polyvinyl alcohol was also shown to be better in producing DOMP nanocrystals with smaller particle size (200 ± 3.5 nm). DOMP nanosuspension stored at 2–8 °C and at room temperature (25 °C) exhibited better stability compared to the samples stored at 40 °C. Crystallinity of the unprocessed and processed DOMP was monitored by differential scanning calorimetry and powder X-ray diffraction. DOMP nanocrystals gave enhanced dissolution rate compared to the unprocessed drug substance. DOMP nanocrystals at a dose of 10 mg/kg in rats showed enhanced bioavailability compared to the raw drug substance and marketed formulation. A significant increase in plasma concentration of 2.6 μg/mL with a significant decrease in time (1 h) to reach maximum plasma concentration was observed for DOMP nanocrystals compared to the raw DOMP. Molecular modelling studies provided underpinning knowledge at the molecular level of the DOMP-polymer nanocrystal interactions and substantiated the experimental studies. This included an understanding of the impact of polymers on the size of nanocrystals and their associated stability characteristics.

Keywords

Domperidone Nanocrystals Molecular modelling Polymers Dissolution Enhanced bioavailability 

Notes

Acknowledgments

The authors acknowledge Abdullah Jan at Central Research Laboratory, University of Peshawar for the scanning electron microscope, differential scanning calorimetry, and Fourier transform infrared spectroscopy instrumentation time and assistance by Mr. Saddiq Afridi at Pakistan Council of Scientific and Industrial Research Laboratory Peshawar KP. The authors also extend their thanks to Mr. Iqbal Central Research Laboratory Peshawar University for his contribution in carrying out the X-ray diffraction analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  1. 1.Discipline of Pharmaceutical Sciences, College of Health SciencesUniversity of KwaZulu-NatalDurbanSouth Africa
  2. 2.Department of PharmacyAbasyn UniversityPeshawarPakistan
  3. 3.Department of PharmacyUniversity of MalakandDir Lower ChakdaraPakistan
  4. 4.SEDA Pharmaceutical Development ServicesThe BioHub at Alderley ParkCheshireUK
  5. 5.Department of PharmacySarhad University of Science and Information TechnologyPeshawarPakistan
  6. 6.Department of PharmacyCOMSATS University IslamabadAbbottabadPakistan
  7. 7.HEJ, Research Institute of Chemistry, International Centre for Chemical and Biological SciencesUniversity of KarachiKarachiPakistan
  8. 8.Department of Pharmaceutics, Faculty of PharmacyUniversiti Teknologi MARA (UiTM) SelangorBandar Puncak AlamMalaysia

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