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A Dual-Biotic System for the Concurrent Delivery of Antibiotics and Probiotics: In Vitro, Ex Vivo, In Vivo and In Silico Evaluation and Correlation

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Abstract

Purpose

A delayed release bio-polymeric Dual-Biotic system has been extensively evaluated in this study to overcome the therapeutic issue of probiotic killing due to incorrect administration with the antibiotic.

Methods

In vitro and ex vivo release and characterization studies have been undertaken on the Dual-Biotic system. In vivo analyses utilizing a Large White pig model were also performed with commercial products used as a comparison. Intestinal fluid for probiotic quantification was aspirated using a surgically implanted intestinal cannula with Lactobacillus acidophilus cell counts determined through luminescence and inoculation onto Lactobacilli-specific agar. Plasma amoxicillin concentrations were determined through Ultra-Performance Liquid Chromatography. The reactional profile and crosslinking mechanism of ovalbumin and genipin was elucidated using molecular mechanic energy relationships in a vacuum system by exploring the spatial disposition of different concentrations of genipin with respect to ovalbumin with ovalbumin/genipin ratios of 1:1, 1:5 and 1:10.

Results

In vivo evaluation of the Dual-Biotic system detailed maximum Lactobacillus viability (~455% baseline viability) 6 h after oral administration. Concurrent administration of the commercial products revealed a 75% decrease in bacterial viability when compared to the controls analyzed. A level A in vitro-in vivo correlation was also established with 96.9% predictability of amoxicillin release ascertained. The computational results achieved corroborated well with the experimental findings and physicochemical data.

Conclusions

Evaluation and correlation of the Dual-Biotic system has detailed the success of the formulation for the concurrent delivery of an antibiotic and probiotic.

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Abbreviations

DBioS:

Dual-biotic system

GMS:

Glyceryl monostereate

MMER:

Molecular mechanic energy relationships

MPCT:

Minimum probiotic concentration time

PE:

Prediction error

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Acknowledgments and Disclosures

This research work was funded by the National Research Foundation (NRF) of South Africa.

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Authors and Affiliations

  1. Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa

    Mershen Govender, Yahya E. Choonara, Pradeep Kumar, Lisa C. du Toit & Viness Pillay

  2. Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa

    Sandy van Vuuren

  3. School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa

    Kennedy Erlwanger

Authors
  1. Mershen Govender
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  2. Yahya E. Choonara
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  3. Sandy van Vuuren
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  4. Pradeep Kumar
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  5. Lisa C. du Toit
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  6. Kennedy Erlwanger
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  7. Viness Pillay
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Corresponding author

Correspondence to Viness Pillay.

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Ethics Approval

Ethical clearance for this study was obtained from the Animal Ethics Screening Committee (AESC) of the University of the Witwatersrand, South Africa (Ethics Clearance no. 2012/26/05).

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Govender, M., Choonara, Y.E., van Vuuren, S. et al. A Dual-Biotic System for the Concurrent Delivery of Antibiotics and Probiotics: In Vitro, Ex Vivo, In Vivo and In Silico Evaluation and Correlation. Pharm Res 33, 3057–3071 (2016). https://doi.org/10.1007/s11095-016-2030-1

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  • DOI: https://doi.org/10.1007/s11095-016-2030-1

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