Current State and Challenges of Physiologically Based Biopharmaceutics Modeling (PBBM) in Oral Drug Product Development.
Pharm Res
; 40(2): 321-336, 2023 Feb.
Article
em En
| MEDLINE
| ID: mdl-36076007
Physiologically based biopharmaceutics modeling (PBBM) emphasizes the integration of physicochemical properties of drug substance and formulation characteristics with system physiological parameters to predict the absorption and pharmacokinetics (PK) of a drug product. PBBM has been successfully utilized in drug development from discovery to postapproval stages and covers a variety of applications. The use of PBBM facilitates drug development and can reduce the number of preclinical and clinical studies. In this review, we summarized the major applications of PBBM, which are classified into six categories: formulation selection and development, biopredictive dissolution method development, biopharmaceutics risk assessment, clinically relevant specification settings, food effect evaluation and pH-dependent drug-drug-interaction risk assessment. The current state of PBBM applications is illustrated with examples from published studies for each category of application. Despite the variety of PBBM applications, there are still many hurdles limiting the use of PBBM in drug development, that are associated with the complexity of gastrointestinal and human physiology, the knowledge gap between the in vitro and the in vivo behavior of drug products, the limitations of model interfaces, and the lack of agreed model validation criteria, among other issues. The challenges and essential considerations related to the use of PBBM are discussed in a question-based format along with the scientific thinking on future research directions. We hope this review can foster open discussions between the pharmaceutical industry and regulatory agencies and encourage collaborative research to fill the gaps, with the ultimate goal to maximize the applications of PBBM in oral drug product development.
Palavras-chave
Texto completo:
1
Temas:
ECOS
/
Estado_mercado_regulacao
Bases de dados:
MEDLINE
Assunto principal:
Biofarmácia
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Desenvolvimento de Medicamentos
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos