Biopredictive tools for the development of injectable drug products

ABSTRACT

Introduction

Biopredictive release tests are commonly used in the evaluation of oral medicines. They support decision-making in formulation development and allow predictions of the expected in-vivo performances. So far, there is limited experience in the application of these methodologies to injectable drug products.

Areas covered

Parenteral drug products cover a variety of dosage forms and administration sites, including subcutaneous, intramuscular, and intravenous injections. In this area, developing biopredictive and biorelevant methodologies often confronts us with unique challenges and knowledge gaps. Here, we provide a formulation-centric approach and explain the key considerations and workflow when designing biopredictive assays. Also, we outline the key role of computational methods in achieving clinical relevance and put all considerations into context using liposomal nanomedicines as an example.

Expert opinion

Biopredictive tools are the need of the hour to exploit the tremendous opportunities of injectable drug products. A growing number of biopharmaceuticals such as peptides, proteins, and nucleic acids require different strategies and a better understanding of the influences on drug absorption. Here, our design strategy must maintain the balance between robustness and complexity required for effective formulation development.

KEYWORDS:

• Biopredictive performance assay
• biorelevant dissolution testing
• depot injectable suspension
• Dissolution
• drug release
• intravenous (IV)
• liposomes
• Long-acting injectables (LAI)
• Physiologically based biopharmaceutics modeling (PBBM)
• Physiologically based pharmacokinetic modeling (PBPK)
• subcutaneous (SC) microparticle formulations

Article highlights

• Future perspectives of biopredictive methods for injectables.

• Key considerations regarding small molecules and biotech drugs.

• Snapshot of the common terminology and practices.

• A systematic approach to developing and validating biopredictive release assays.

• Case studies to support the readers’ understanding.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Matthias G. Wacker and Kennard Gan acknowledge the National Research Foundation (A-0000065-09-00) and the Ministry of Education of Singapore (Tier1 Grant A-0004337-00-00, Startup Grant A-0004627-00-00) for financial support.