Subcutaneous delivery of biotherapeutics: challenges at the injection site

ABSTRACT

Introduction: Biotherapeutics are primarily delivered subcutaneously due to better compliance and prolonged rate of absorption compared to other parenteral administration routes. Recent research has allowed for the development of biotherapeutic formulations for subcutaneous delivery that require a lower frequency of administration by increasing drug half-life. Formulations determine shelf-life stability as well as features and transient behaviors that influence stability once implanted in the subcutaneous space.

Areas covered: This review provides an overview of the factors affecting subcutaneous absorption with a focus on transient effects at the injection site following administration of biotherapeutics and the subsequent impact on absorption and stability.

Expert opinion: Advances have been made in understanding subcutaneous tissue and the complex interplay of factors that regulate its homeostasis. The issue of poor stability after injection has been neglected, and many biotherapeutics are hampered by low bioavailability. With the advent of new in vitro techniques that account for properties of the injection site, stability studies evaluating subcutaneous tissues and impacts on pharmacokinetics of biotherapeutics may be useful in the development of new formulations.

KEYWORDS:

• Bioavailability
• biotherapeutic
• formulation
• injection site
• stability
• subcutaneous delivery

Article highlights

• Protein biotherapeutics main advantages are their high specificity and potency. Currently, they are primarily delivered subcutaneously.

• Stability of protein biotherapeutics can be compromised during formulation development and after administration to the SC site, negatively impacting absorption.

• Formulation should account for the shelf-life stability and stability of the biotherapeutic following SC administration.

• New in vitro methods are being developed and can be used during research and development of new biotherapeutics to help understand the viability of selected formulation strategies.

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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

Joana A. D. Sequeira was supported by a PhD grant with Ref. [PD/BDE/135148/2017] from Fundacão para a Ciência e Tecnologia (FCT-Portugal) which was funded by Ministério da Ciência, Tecnologia e Ensino Superior of Portugal and Fundo Social Europeu and Tecnimede S.A.