Process of making stable abuse-deterrent oral formulations
Inventors
Saim, Said • Fleming, Alison B. • Varanasi, Ravi K.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10646485-B2
Publication Date
2020-05-12
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 disclosure describes an abuse-deterrent extended-release opioid microparticle platform (DETERx) in which a hot-melt congealing approach is used to form solid microparticles, followed by a critical curing step. The platform uses oxycodone together with myristic acid and beeswax and carnauba wax, or oxycodone in the form of a myristic acid salt with beeswax and carnauba wax.
A key aspect is the use of an inversion (inflection) temperature, where dissolution behavior reverses. Curing at temperatures from about 25 °C up to and including the inversion temperature for at least about 48 hours stabilizes dissolution profiles during storage, including reduced change in mean % drug released at 4 hours after 6 months at 25 °C/60% RH versus uncured microparticles.
The curing regimes evaluated include single-stage curing and 2-stage curing, including heating above inversion and then cooling below inversion. The disclosure also describes capsules containing cured microparticles and includes an oral administration use for treating pain.
Claims Coverage
The claim coverage centers on one independent pharmaceutical composition claim with dependent claims refining curing temperatures and duration, specifying optional additional excipients and composition constraints, and adding downstream dosage form and therapeutic-use limitations. The core inventive features mainly define a melt-based microparticle formation using oxycodone and fatty acid/waxes, followed by curing solid or formulated microparticles for at least about 48 hours within a specified curing temperature range.
Melt-formed oxycodone/myristic acid wax microparticles cured at 26 °C to 38 °C for minimum 48 hours
A pharmaceutical composition comprising solid microparticles or formulated microparticles prepared by preparing a mixture at a temperature sufficient to form a melt comprising oxycodone, myristic acid, beeswax and carnauba wax, or oxycodone as a myristic acid salt with beeswax and carnauba wax; forming solid microparticles from the melt; optionally further formulating the solid microparticles with additional pharmaceutically acceptable excipients; and curing the solid microparticles or formulated microparticles at one or more curing temperatures from 26 °C to 38 °C for a minimum of about 48 hours to provide cured solid microparticles or cured formulated microparticles.
Optional additional excipient in the melt mixture
The pharmaceutical composition of the melt-based oxycodone/myristic acid wax microparticles includes stearoyl polyoxyl-32 glycerides as an additional component in the mixture from step (a).
Narrowed curing temperature range
The pharmaceutical composition of the melt-based cured microparticles is cured at one or more curing temperatures ranging from 28 °C to 36 °C for either solid microparticles or formulated microparticles.
Extended curing duration
The pharmaceutical composition containing solid or formulated microparticles is cured for approximately 3 days.
Quantitative composition constraints for oxycodone-equivalent and fatty acid and wax content
The pharmaceutical composition contains specified amounts of oxycodone (or an equivalent myristic acid salt), specified weight percentages of myristic acid, and specified weight percentages of a beeswax/carnauba wax combination, including about 30 wt.% to about 70 wt.% myristic acid, and about 20 wt.% to about 60 wt.% beeswax and carnauba wax combination, with about 9 mg to about 72 mg oxycodone dose equivalents.
Therapeutic use for treating pain by patient administration
A method for treating pain by administering the pharmaceutical composition to a patient in need.
Across the independent composition claim and its refinements, the coverage is directed to melt-based formation of oxycodone/myristic acid-wax solid microparticles (or formulated microparticles) and curing those microparticles at one or more curing temperatures from about 26 °C to 38 °C for a minimum of about 48 hours, with dependent claim refinements that narrow the curing window, extend curing duration, optionally add stearoyl polyoxyl-32 glycerides, specify quantitative composition constraints, and include administration for treating pain.
Stated Advantages
Stabilizes dissolution profiles during storage.
Reduces change in mean % drug released at 4 hours after 6 months at 25 °C/60% RH versus uncured microparticles.
Documented Applications
Treatment of pain by oral administration of capsules containing cured microparticles.
Interested in licensing this patent?