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. 2022 Jun;30(1):229-243.
doi: 10.1007/s40199-021-00423-7. Epub 2022 Jan 30.

Assessment of the predictive capability of modelling and simulation to determine bioequivalence of inhaled drugs: A systematic review

Juliet Rebello  1 , Bill Brashier  2 , Sharvari Shukla  3
Affiliations

Assessment of the predictive capability of modelling and simulation to determine bioequivalence of inhaled drugs: A systematic review

Juliet Rebello et al. Daru. 2022 Jun.

Abstract

Objectives: There are a multitude of different modelling techniques that have been used for inhaled drugs. The main objective of this review was to conduct an exhaustive survey of published mathematical models in the area of asthma and chronic obstructive pulmonary disease (COPD) for inhalation drugs. Additionally, this review will attempt to assess the applicability of these models to assess bioequivalence (BE) of orally inhaled products (OIPs).

Evidence acquisition: PubMed, Science Direct, Web of Science, and Scopus databases were searched from 1996 to 2020, to find studies that described mathematical models used for inhaled drugs in asthma/COPD.

Results: 50 articles were finally included in this systematic review. This research identified 22 articles on in silico aerosol deposition models, 20 articles related to population pharmacokinetics and 8 articles on physiologically based pharmacokinetic modelling (PBPK) modelling for inhaled drugs in asthma/COPD. Among all the aerosol deposition models, computational fluid dynamics (CFD) simulations are more likely to predict regional aerosol deposition pattern in human respiratory tracts. Across the population PK articles, body weight, gender, age and smoking status were the most common covariates that were found to be significant. Further, limited published PBPK models reported approximately 29 parameters relevant for absorption and distribution of inhaled drugs. The strengths and weaknesses of each modelling technique has also been reviewed.

Conclusion: Overall, while there are different modelling techniques that have been used for inhaled drugs in asthma and COPD, there is very limited application of these models for assessment of bioequivalence of OIPs. This review also provides a ready reference of various parameters that have been considered in various models which will aid in evaluation if one model or hybrid in silico models need to be considered when assessing bioequivalence of OIPs.

Keywords: Asthma and COPD; Computational fluid dynamics; Inhalation; PBPK; Population pharmacokinetics.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart for identification of articles as per the keywords
Fig. 2
Fig. 2
Role of in silico modelling in generic OIP development
See this image and copyright information in PMC

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