Changing the pill: developments toward the promise of an ultra-long-acting gastroretentive dosage form

ABSTRACT

Introduction: The development of oral sustained release dosage forms has been a longstanding goal due to the potential for ease of administration, improved pharmacokinetics, reduced dosing frequency, and improved adherence. The benefits of multiday single-dose drug delivery are evident in the success and patient adoption of injected and implanted dosage forms. However, in the space of oral medications, all current commercially available gastric resident dosage forms, and most in development, are limited to gastric residence of less than 1 day.

Areas covered: Reviews of systems to extend gastric residence reveal that 1 day or more residence has been an unmet challenge. New dosage forms are in development that seek to address many of the key physiological and design challenges of long-term gastric retention beyond 24 h  and up to a week or longer. The present analysis highlights the design, material considerations and implications of unfolding dosage form systems with ultra-long-term gastric residence.

Expert opinion: The development of oral dosage forms providing sustained release of high potency medications over days or weeks could transform care, significantly decrease patient burden in chronic disease management and improve outcomes.

KEYWORDS:

• Gastric retentive dosage forms
• HIV
• malaria
• oral ultra-long-acting
• sustained release

Article highlights

• Description of currently marketed oral dosage forms which have achieved substantially extended, but <24 h, gastric residence

• Challenges of an oral dosage form with sustained release of medication over a week or longer with reference to recent advancements

• Design and material considerations of modular unfolding gastric retentive dosage forms (GRDFs)

• Challenges and potential sources of variability for GRDFs

• Challenges of in vitro to in vivo translation for GRDFs

• Applications where once-weekly dosing have the potential to improve medication adherence and health outcomes over once-daily oral dosing are presented with focus on pharmacokinetic advantages

This box summarizes key points contained in the article.

Declaration of interest

The authors are coinventors on multiple provisional patent applications describing various design and manufacturing aspects of gastric resident systems. D Altreuter, T Grant, C Kruger, G Traverso, and A Bellinger have a financial interest in Lyndra, Inc, a biotechnology company developing gastric resident drug delivery systems. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This authors were supported in part by NIH Grants AI131416, EB024484, TR001889, and the Division of Gastroenterology, Brigham and Women’s Hospital.