Process of making stable abuse-deterrent oral formulations
Inventors
Saim, Said • Fleming, Alison B. • Varanasi, Ravi K.
Assignees
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Publication Number
US-9968598-B2
Publication Date
2018-05-15
Expiration Date
Abstract
The present disclosure relates to cured pharmaceutical compositions designed to reduce the potential for improper administration of drugs that are subject to abuse, the process of curing such composition in order to improve the dissolution stability, method of using the same for treatment of pain.
Core Innovation
The invention relates to an abuse-deterrent extended-release (ER) opioid microparticle platform in which solid microparticles, or formulated microparticles, are produced from a substantially homogeneous melt comprising oxycodone or oxycodone in the form of a fatty acid salt, myristic acid, beeswax, and carnauba wax. Solid microparticles are formed from the homogeneous melt and optionally further formulated with pharmaceutically acceptable excipients.
The solid microparticles or formulated microparticles are cured at a temperature within the range of 25°C up to and including the inversion temperature for a minimum of about 48 hours. The described behavior indicates that curing within this temperature range stabilizes dissolution after storage, including for formulations stored under defined conditions.
The document reports unexpected stability behavior for uncured oxycodone, myristic-acid, beeswax, and carnauba formulations, with inversion between about 30–40°C and an inflection around about 36°C. Dissolution improvements are described from single-stage curing at or under the inversion temperature and from two-stage curing above then below the inversion temperature.
Claims Coverage
The document includes two independent claims, a process claim and a microparticle composition claim. The main inventive features involve forming solid microparticles from a substantially homogeneous melt comprising oxycodone or a myristate salt, myristic acid, beeswax, and carnauba wax, and curing at temperatures from 25°C up to and including the inversion temperature for at least about 48 hours.
Curing microparticles within inversion temperature range for at least 48 hours
Curing the solid microparticles or formulated microparticles at a temperature within the range of 25°C up to and including the inversion temperature for a minimum of about 48 hours.
Forming solid microparticles from a substantially homogeneous melt of oxycodone, myristic acid, beeswax and carnauba wax
Preparing a mixture at a temperature sufficient to form a substantially homogeneous melt comprising oxycodone, myristic acid, beeswax and carnauba wax, or oxycodone in the form of a fatty acid salt, beeswax and carnauba wax, then forming solid microparticles from the substantially homogeneous melt.
Inversion-temperature cured pharmaceutically acceptable solid or formulated microparticles with myristic-acid-provided substantially homogeneous form
Providing pharmaceutically acceptable solid microparticles or formulated microparticles comprising a mixture prepared from a homogeneous melt comprising beeswax, carnauba wax, oxycodone or a myristate salt of oxycodone, and a sufficient amount of myristic acid to provide said microparticles in substantially homogeneous form, wherein said microparticles or formulated microparticles are cured at one or more temperatures within the range of 25°C up to and including the inversion temperature for a minimum of about 48 hours.
Across the independent claims, the inventive coverage centers on producing pharmaceutically acceptable solid or formulated microparticles from a homogeneous melt containing oxycodone or a myristate salt, myristic acid, beeswax, and carnauba wax, and curing them at temperatures from 25°C to the inversion temperature inclusive for at least about 48 hours.
Stated Advantages
Stabilizes dissolution after storage for cured microparticles.
Cured formulated microparticles show less change in dissolution profile after 6 months storage at 25°C and 60% RH than uncured formulated microparticles under the same storage conditions.
Documented Applications
Capsules containing the pharmaceutical composition recited in the claims.
Treatment of pain by administering the pharmaceutically acceptable microparticles or formulated microparticles to a patient in need of pain treatment.
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