Cured Microparticles for Stable Abuse-Deterrent Oral Formulations
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Extended-release opioid formulations are prone to misuse and abuse due to their manipulability, leading to unintended drug exposure and adverse consequences, and existing abuse-deterrent formulations lack sufficient stability during storage.
Innovation Solution
A manufacturing process involving the formation of microparticles from a homogeneous melt of drugs, waxes, and fatty acids, followed by curing at specific temperatures within a range up to the inversion temperature to enhance dissolution stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If extended-release opioid formulations are made manipulatable for ease of administration, then ease of operation is improved, but reliability deteriorates due to increased abuse potential and unintended drug exposure
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation by incorporating specific excipients (e.g., hydrophilic polymers, waxes, fatty acids) that modify the drug release characteristics. These parameter changes create formulations that maintain extended-release properties while resisting manipulation attempts, thus improving reliability without sacrificing ease of administration.
Solution Approach 2:
The patent uses composite materials combining multiple excipients with different properties (hydrophilic polymers, waxes, fatty acids, surfactants) to create a multifunctional formulation system. This composite approach provides both ease of administration through proper formulation and abuse deterrence through controlled release mechanisms that resist manipulation.
2Reliability
If abuse-deterrent formulations incorporate physical or chemical barriers, then reliability is improved, but manufacturing precision deteriorates due to complexity in maintaining consistent dissolution profiles
Solution Approach 1:
The patent applies preliminary action by pre-mixing excipients with the active ingredient before formulation, and by using a curing step in the manufacturing process. This preliminary preparation ensures consistent dissolution profiles and reduces variability during production, thereby improving manufacturing precision while maintaining abuse-deterrent properties.
Solution Approach 2:
The patent employs parameter changes by optimizing the curing temperature and time parameters during manufacturing. By controlling these parameters, the formulation achieves consistent dissolution profiles and improved manufacturing precision while maintaining the physical and chemical barriers necessary for abuse deterrence.
3Reliability
If curing is applied to improve dissolution stability, then reliability is improved, but loss of time increases due to extended curing duration
Solution Approach 1:
The patent applies parameter changes by optimizing the curing temperature and time parameters. By adjusting these parameters, the formulation achieves the required dissolution stability with reduced curing time, thus improving reliability while minimizing time loss during manufacturing.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The process results in pharmaceutical compositions with improved stability, maintaining consistent drug release profiles over six months, reducing changes in dissolution by up to 15% compared to uncured formulations.
Implementation Method 1
The fatty acid and active ingredient component of DETERx microspheres are selected such that they are associated via an ionic interaction (i.e., salt) in the solid microparticles
Implementation Method 2
This interaction allows the active component to be dissolved during the melt formulation process, and allows for the formation of a solid solution
Implementation Method 3
The process of making an abuse-deterrent formulation comprises the steps of: preparing a mixture comprising (i) one or more pharmaceutically acceptable waxes, one or more drugs, and one or more pharmaceutically acceptable fatty acids, or (ii) one or more drugs in the form of a fatty acid salt, one or more pharmaceutically acceptable waxes, at a temperature sufficient to form a substantially homogeneous melt
Implementation Method 4
curing the solid microparticles or formulated microparticles 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
Data Source
AI summary
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.