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-9737530-B1
Publication Date
2017-08-22
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 abuse-deterrent extended-release drug products in the form of pharmaceutically acceptable solid microparticles and formulated microparticles. The process prepares a mixture comprising one or more drugs with one or more pharmaceutically acceptable waxes and one or more pharmaceutically acceptable fatty acids, or prepares one or more drugs as fatty acid salts with one or more pharmaceutically acceptable waxes. The mixture is heated to form a substantially homogeneous melt, and solid microparticles are formed from the homogeneous melt.
The formed solid microparticles, or formulated microparticles optionally further formulated with additional pharmaceutically acceptable excipients, 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. Curing within this range is used to stabilize dissolution after storage, including for dissolution-profile stability when compared to otherwise identical uncured formulated microparticles.
An inversion temperature behavior is described for dissolution, where dissolution decreases below an inversion temperature and increases above the inversion temperature for oxycodone with myristic acid and for oxycodone with stearic acid, respectively. The document further describes embodiments that optionally use a two-stage curing temperature profile with curing above then below the inversion temperature, and supports use of the cured microparticles in a capsule for treating pain.
Claims Coverage
The document provides two independent claims covering a process for making cured solid or formulated microparticles from a wax/drug/fatty-acid substantially homogeneous melt and the resulting cured solid microparticles or formulated microparticles themselves. The inventive content centers on curing at temperatures within 25°C up to and including an inversion temperature for at least about 48 hours, and on using waxes with drugs and fatty acids, or fatty acid salt forms, to obtain substantially homogeneous microparticles.
Cured microparticles formed from a substantially homogeneous wax/drug/fatty-acid melt
Preparing a mixture comprising one or more drugs, one or more pharmaceutically acceptable waxes, and one or more pharmaceutically acceptable fatty acids, or one or more drugs in the form of a fatty acid salt and one or more pharmaceutically acceptable waxes, at a temperature sufficient to form a substantially homogeneous melt; forming solid microparticles from the substantially homogeneous melt; optionally further formulating the solid microparticles with additional pharmaceutically acceptable excipients.
Curing within 25°C up to and including inversion temperature for at least about 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.
Substantially homogeneous cured solid microparticles from a wax/drug/fatty-acid melt
Pharmaceutically acceptable solid microparticles or formulated microparticles comprising a mixture prepared from a melt of one or more pharmaceutically acceptable waxes, one or more drugs or salts thereof with one or more fatty acids thereof, and a sufficient amount of the one or more fatty acids to provide said microparticles in substantially homogenous 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.
Overall, the claims focus on producing substantially homogeneous microparticles from a wax plus drug plus fatty acid, or fatty acid salt form, melt and maintaining dissolution stability by curing at temperatures from 25°C up to and including an inversion temperature for at least about 48 hours. Dependent claims refine the composition and the curing profile, and further include a method of treating pain via administering the defined microparticles.
Stated Advantages
Improves dissolution-profile stability after storage compared with uncured formulated microparticles.
Provides dissolution profile changes that are reported to be less than specified thresholds, including less than 15% change at a 4-hour timepoint after storage under defined conditions.
Documented Applications
Treating pain by administering a capsule containing the pharmaceutically acceptable microparticles or formulated microparticles described in the document to a patient who needs such treatment.
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