Abuse Deterrent Immediate Release Egg-Shaped Tablet (Egglets) Using 3D Printing Technology: Quality by Design to Optimiz
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Research Article Theme: NIPTE on Current Topics in Abuse Deterrent Science Guest Editors: Heather Boyce, Steve R. Byrn, and Stephen W. Hoag
Abuse Deterrent Immediate Release Egg-Shaped Tablet (Egglets) Using 3D Printing Technology: Quality by Design to Optimize Drug Release and Extraction Pavan Kumar Nukala,1 Siddhant Palekar,1 Manali Patki,1 and Ketan Patel1,2
Received 26 October 2018; accepted 26 December 2018 Abstract.
Opioid abuse is a growing problem and has become a national health crisis over the past decade in the USA. Oral ingestion, snorting, and injection are the most commonly employed routes of abuse for an immediate release product. To circumvent these issues, we have developed an egg-shaped tablet (egglet) using fused deposition modeling (FDM) 3D printing technology. Drug-loaded polymeric filaments (1.5 mm) were prepared using hot melt extrusion (HME) followed by printing into egglets of different sizes and infill densities. Based on printability and crush resistance, polyvinyl alcohol (PVA) was found to be the most suitable polymer for the preparation of abuse deterrent egglets. Further, egglets were evaluated and optimized for mechanical manipulation using household equipment, milling, particle size distribution, solvent extraction, and drug release as per the FDA guidance (November 2017). A multifactorial design was used to optimize egglets for solvent extraction and drug release. Extreme hardness (> 500 N) and very large particle size (> 1 mm) on mechanical manipulation confirmed the snorting deterring property while less than 15% drug extraction in 5 min (% Sext) demonstrated the deterrence for injection abuse. Quality target product profile D85 < 30 min and % Sext < 15 was achieved with egglets of 6 mm diameter, 45% infill density, and 15% w/w drug loading. Dose of drug can be easily customized by varying dimension and infill density without altering the composition. HME coupled with FDM 3D printing could be a promising tool in the preparation of patient-tailored, immediate release abuse deterrent formulation. KEY WORDS: 3D printing technology; abuse deterrent dosage form; quality by design; dose customization; hot melt extrusion.
INTRODUCTION Generally, non-steroidal anti-inflammatory (NSAID) and opioid drugs are used to treat or reduce pain. NSAID is responsible for blocking the function of the enzyme cyclooxygenase which leads to prostaglandins synthesis. However, opioid analgesics work as an agonist on opioid receptors located in central and peripheral nervous system. Based on the differences in their mechanisms of action, opioid analgesics are more effective than NSAID in treating the most severe cases of pain (1). Commonly used opioid drugs include
Guest Editors: Heather Boyce, Steve R. Byrn, and Stephen W. Hoag 1
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, St. Albert Hall, B18B, 8000 Utopia Parkway, Queens, New York 11439, USA. 2 To whom correspondence should be addressed. (e–mail: [email protected])
morphine, codeine, oxymorpho
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