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In vitro Dissolution Testing of Rifampicin Powder Formulations For Prediction of Plasma Concentration–Time Profiles After Inhaled Delivery

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Abstract

Purpose

The purpose of this study was to evaluate the in vitro lung dissolution of amorphous and crystalline powder formulations of rifampicin in polyethylene oxide (PEO) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), and to predict the in vivo plasma concentration–time profiles using the in vitro data.

Methods

The in vitro dissolution and permeation profiles of respirable rifampicin particles were studied using a custom-made dissolution apparatus. Data from the in vitro dissolution test were used to estimate the parameters to be used as the input for the simulation of in vivo plasma concentration–time profiles using STELLA® software. For prediction of in vivo profiles, a one-compartment model either with a first order elimination or with a Michaelis–Menten kinetics-based elimination was used.

Results

Compared to the crystalline formulation, the amorphous formulation showed rapid in vitro dissolution suggesting their possible faster in vivo absorption and higher plasma concentrations of rifampicin following lung delivery. However, the simulations suggested that both powder formulations would result in similar plasma-concentration time profiles of rifampicin.

Conclusions

Use of an in vitro dissolution test coupled with a simulation model for prediction of plasma-concentration time profiles of an inhaled drug was demonstrated in this work. These models can also be used in the design of inhaled formulations by controlling their release and dissolution properties to achieve desired lung retention or systemic absorption following delivery to the lungs.

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Data Availability

All data generated or analysed during this study are included in this published article and its supplementary information files.

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Acknowledgements

The authors would also like to acknowledge Nicole Wood for her help in running the in vitro dissolution experiments.

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Authors and Affiliations

  1. School of Pharmacy, University of Otago, Adams Building, 18 Frederick Street, P.O. Box 56, Dunedin, 9054, New Zealand

    Prakash Khadka, Ian G. Tucker & Shyamal C. Das

Authors
  1. Prakash Khadka
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  2. Ian G. Tucker
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  3. Shyamal C. Das
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Contributions

Conceptualization: Prakash Khadka, Ian G. Tucker, Shyamal Das.

Methodology: Prakash Khadka, Ian G. Tucker, Shyamal Das.

Data curation: Prakash Khadka.

Formal analysis: Prakash Khadka, Ian G. Tucker, Shyamal Das.

Writing, review and editing: Prakash Khadka, Ian G. Tucker, Shyamal Das.

Project administration: Shyamal Das.

Corresponding author

Correspondence to Shyamal C. Das.

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Khadka, P., Tucker, I.G. & Das, S.C. In vitro Dissolution Testing of Rifampicin Powder Formulations For Prediction of Plasma Concentration–Time Profiles After Inhaled Delivery. Pharm Res 40, 1153–1163 (2023). https://doi.org/10.1007/s11095-022-03439-z

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