An abuse-deterrent, microsphere-in-capsule formulation of extended-release oxycodone: alternative modes of administration to facilitate pain management in patients with dysphagia

Abstract

Background: Patients with chronic pain may experience difficulty swallowing, in part due to worsening disease, comorbid conditions, iatrogenic etiology, or age. Patients or caregivers may manipulate extended-release (ER) opioid formulations to facilitate oral dosing due to a lack of therapeutic options that allow for sprinkle or enteral feeding tube administration. If crushed or broken, current oral ER opioids can be associated with adverse sequelae, including risk of potentially fatal overdose.

Objective: To review the safety, in vitro dissolution data, and in vivo pharmacokinetic data that support alternative modes of administration of oxycodone DETERx (Xtampza ER) via sprinkling onto soft foods for oral ingestion or via enteral feeding tubes.

Methods: A review of oxycodone DETERx data from in vitro and in vivo studies was conducted to demonstrate support for alternative routes and modes of administration.

Results: There was no difference in the dissolution profile when administered with various soft foods or when mixed with various liquid vehicles and administered via nasogastric (NG) or gastrostomy (G) tubes, based on in vitro studies. When sprinkled onto applesauce and administered orally, the microspheres were bioequivalent to the intact oxycodone capsules. When crushed or chewed, the formulation maintained its pharmacokinetic profile; no bolus dose of opioid was released. The sprinkle-dose study was limited by the single-dose study design, as well as the small sample size.

Conclusions: Oxycodone DETERx is the first ER oxycodone formulation that can be administered either intact, sprinkled onto soft foods, or via NG/G tubes, thereby providing options for treating pain in patients who have difficulty swallowing.

Keywords:

• Abuse-deterrent formulations
• Chronic pain
• Dysphagia
• Extended-release
• Opioids

Transparency

Declaration of funding

Funding for this study was provided by Collegium Pharmaceutical Inc., Canton, MA, USA. All costs associated with manuscript development and publication were met by the sponsor.

Declaration of financial/other relationships

B.H.M. has disclosed that he is an advisor for Pfizer, Collegium, Millennium, Salix, Takeda, Depomed, Janssen, Kaleo, AstraZeneca, and Teva. B.H.M. also has stock holdings with Johnson and Johnson, Protein Design Labs, Biospecifics Technologies, Nektar Therapeutics, Galena, and Collegium. E.A.K., M.O., A.M., R.K.V., C.T., and A.B.F. are full-time employees of Collegium Pharmaceutical Inc., Canton MA, USA and may hold Collegium stock/options.

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

Acknowledgments

This study was supported by Collegium Pharmaceutical Inc., Canton, MA, USA. Medical writing assistance was provided by Kelly M. Cameron PhD of The JB Ashtin Group Inc. who, on behalf of the authors, provided assistance in writing the first draft and implemented author revisions throughout the editorial process.