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Effect of Ultra-High Pressure Homogenization on the Interaction Between Bovine Casein Micelles and Ritonavir

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Abstract

Purpose

The aim of this work was to develop a milk-based powder formulation appropriate for pediatric delivery of ritonavir (RIT).

Methods

Ultra-high pressure homogenization (UHPH) at 0.1, 300 and 500 MPa was used to process a dispersion of pasteurized skim milk (SM) and ritonavir. Loading efficiency was determined by RP-HPLC-UV; characterization of RIT:SM systems was carried out by apparent average hydrodynamic diameter and rheological measurements as well as different analytical techniques including Trp fluorescence, UV spectroscopy, DSC, FTIR and SEM; and delivery capacity of casein micelles was determined by in vitro experiments promoting ritonavir release.

Results

Ritonavir interacted efficiently with milk proteins, especially, casein micelles, regardless of the processing pressure; however, results suggest that, at 0.1 MPa, ritonavir interacts with caseins at the micellar surface, whilst, at 300 and 500 MPa, ritonavir is integrated to the protein matrix during UHPH treatment. Likewise, in vitro experiments showed that ritonavir release from micellar casein systems is pH dependent; with a high retention of ritonavir during simulated gastric digestion and a rapid delivery under conditions simulating the small intestine environment.

Conclusions

Skim milk powder, especially, casein micelles are potentially suitable and efficient carrier systems to develop novel milk-based and low-ethanol powder formulations of ritonavir appropriate for pediatric applications.

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ACKNOWLEDGMENTS AND DISCLOSURES

Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under award number R21HD065170. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We acknowledge Abbott Laboratories for kindly donating the ritonavir used in this study.

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Authors and Affiliations

  1. Department of Food Science and Technology, The University of Tennessee, 2605 River Dr., Knoxville, Tennessee, 37996-4539, USA

    M. Corzo-Martínez & M. Mohan

  2. Division of Biology, The University of Tennessee, 1414 West Cumberland Ave., Knoxville, Tennessee, 37996-0830, USA

    J. Dunlap

  3. Department of Food Science, Pennsylvania State University, 331 Rodney A. Erickson Food Science Building, University Park, Pennsylvania, 16802, USA

    F. Harte

Authors
  1. M. Corzo-Martínez
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  2. M. Mohan
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  3. J. Dunlap
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  4. F. Harte
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Corresponding author

Correspondence to F. Harte.

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Corzo-Martínez, M., Mohan, M., Dunlap, J. et al. Effect of Ultra-High Pressure Homogenization on the Interaction Between Bovine Casein Micelles and Ritonavir. Pharm Res 32, 1055–1071 (2015). https://doi.org/10.1007/s11095-014-1518-9

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  • DOI: https://doi.org/10.1007/s11095-014-1518-9

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