Tamper-resistant pharmaceutical compositions of opioids and other drugs
Inventors
Rariy, Roman V. • Fleming, Alison • Hirsh, Jane C. • Saim, Said • Varanasi, Ravi K.
Assignees
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Publication Number
US-10668060-B2
Publication Date
2020-06-02
Expiration Date
Abstract
Tamper-resistant pharmaceutical compositions have been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opioids. The tamper-resistant compositions retard the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is passes through the GI tract.
Core Innovation
The invention relates to abuse-deterrent tamper-resistant oral pharmaceutical compositions for opioids, including oxycodone. The compositions include multiparticulates or microparticles in which oxycodone is present as a myristic acid salt together with myristic acid, beeswax, and carnauba wax. The formulation is designed to retard drug release after physical damage such as chopping or crushing and exposure to water or other misuse routes.
The invention also addresses maintaining sustained gastrointestinal release when administered as directed. The compositions are constructed to provide controlled release over an extended period in the GI tract, while reducing extractability associated with tampering and misuse.
The disclosure includes specification of particle-size distributions for the solid particles, including D[0.50] and D[0.90] ranges, and characterizes particle morphology, including embodiments with substantially spherical particles. The disclosure also includes optional multi-layer coatings to reduce extractability, including water-insoluble diffusion barrier coatings, enzymatically degradable coatings, and enteric coatings.
To support the lipophilicity and salt strategy, the disclosure includes characterization of the oxycodone-myristic acid ionic salt or complex formation using FTIR and solid-state and solution NMR. The invention also includes comparative in vitro release results showing substantially lower % oxycodone release after crushing compared with OxyContin®.
Claims Coverage
The claims cover multiple inventive features centered on solid particles containing oxycodone as a myristic acid salt with myristic acid, beeswax, and carnauba wax, together with specified particle-size distribution limits. Additional claim features include particle morphology, a D[0.10] constraint, a myristic acid to oxycodone molar ratio, a method for treating pain in a human, and a spinning disc atomization process.
Oxycodone as myristic acid salt with specified wax excipients
A pharmaceutical composition comprising a plurality of solid particles, each particle comprising oxycodone, myristic acid, beeswax, and carnauba wax, wherein the oxycodone is in the form of a myristic acid salt.
Controlled particle-size distributions D[0.50] and D[0.90]
The particles have a D[0.50] from 200 microns to 400 microns and a D[0.90] from 400 microns to 700 microns.
Substantially spherical particle morphology
The particles are substantially spherical.
Additional D[0.10] particle-size constraint
The particles have a D[0.10] size between 50 microns and 250 microns.
Myristic acid to oxycodone molar ratio
Myristic acid and oxycodone have a molar ratio of about 6:1 to about 15:1.
Administering to treat pain in a human
A method for treating pain in a human by administering a therapeutically effective amount of the composition.
Spinning disc atomization in manufacture
The method includes a spinning disc atomization process.
The claim coverage centers on solid particles that contain oxycodone as a myristic acid salt combined with myristic acid, beeswax, and carnauba wax, together with specified particle-size distribution limits and optional refinements such as substantially spherical morphology and D[0.10] limits, plus treatment and manufacturing features.
Stated Advantages
Retarded drug release even after physical damage such as chopping or crushing.
Retarded drug release upon exposure to water or other misuse routes.
Sustained GI release when administered as directed.
Reduced extractability associated with tampering and misuse.
Substantially lower % oxycodone release after crushing compared with OxyContin®.
Documented Applications
Treating pain in a human by administering a therapeutically effective amount of the composition.
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