Non-Extractable Oral Solid Dosage Form via Polymer Matrix
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Solution Overview
Problem
Current abuse-deterrent opioid formulations are inadequate in preventing oral abuse, as they can be extracted using solvents or physically tampered with, leading to misuse and potential overdose, highlighting the need for a non-extractable dosage form that maintains the antagonist's sequestration and releases the agonist only upon intact administration.
Innovation Solution
A non-extractable oral solid dosage form (NEOSD) comprising a tacky amorphous polymer and a crystalline polymer curing agent, combined with an agonist and antagonist, where the agonist is releasable and the antagonist is non-releasable unless the dosage form is tampered with, utilizing a tackifying agent to re-tackify the polymer and prevent solvent extraction and physical manipulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If conventional abuse-deterrent formulations are used, then mechanical resistance is improved, but they can still be extracted using solvents or physically tampered with
Solution Approach 1:
The patent employs a composite material system consisting of an amorphous polymer matrix combined with a crystalline polymer. The amorphous polymer provides solvent resistance while the crystalline polymer provides structural integrity and mechanical strength. This composite approach creates a formulation that simultaneously resists both physical tampering and solvent extraction, resolving the contradiction between mechanical resistance and solvent extraction vulnerability.
Solution Approach 2:
The patent utilizes the glass transition temperature (Tg) of the amorphous polymer as a critical parameter. By selecting an amorphous polymer with a Tg below body temperature but above solvent temperatures, the formulation maintains a rubbery, flexible state during normal physiological conditions (allowing drug release) while remaining resistant to solvent extraction. This parameter-based approach enables the formulation to exhibit different properties under different thermal conditions, simultaneously achieving mechanical resistance and solvent resistance.
2Reliability
If the dosage form is made resistant to physical tampering, then abuse deterrence is improved, but the agonist release may be compromised
Solution Approach 1:
The patent exploits temperature-dependent parameter changes in the amorphous polymer. At physiological temperature (37°C), the polymer is above its glass transition temperature, placing it in a rubbery state that allows drug diffusion and release. However, at lower temperatures (room temperature or solvent temperatures), the polymer remains in a glassy state that provides mechanical strength and solvent resistance. This temperature-dependent parameter change enables the formulation to be both abuse-deterrent and therapeutically effective.
Solution Approach 2:
The patent creates a dynamic material system where the physical properties of the amorphous polymer change based on environmental conditions. The polymer transitions between glassy and rubbery states depending on temperature, allowing the formulation to dynamically adapt its properties: rigid and resistant during storage and abuse attempts, but flexible and permeable during physiological administration. This dynamic behavior resolves the contradiction between abuse deterrence and drug release.
3Reliability
If the antagonist is sequestered to prevent abuse, then abuse deterrence is improved, but separation from agonist becomes difficult
Solution Approach 1:
The patent merges the antagonist and agonist into a single homogeneous amorphous polymer matrix rather than using separate compartments or layers. Both drugs are dispersed at the molecular level within the same polymer phase, making them difficult to separate physically or chemically. This merging approach ensures that any extraction attempt retrieves both drugs together, maintaining the therapeutic ratio and preventing abuse, while eliminating the complexity of multi-component structures.
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 NEOSD formulation effectively reduces the potential for opioid misuse by ensuring the antagonist remains sequestered unless the dosage form is compromised, thereby deterring abuse and maintaining therapeutic release of the agonist, even under conditions of physical tampering or solvent exposure.
Implementation Method 1
form a polymeric matrix with a glass transition temperature below body temperature and above the temperature of any solvent that could be used to extract the drugs from the dosage form
Implementation Method 2
The curing agent may be a crosslinking agent or a polymer that is crystalline at room temperature
Implementation Method 3
The particles may further comprise a channelizer that facilitates release of the agonist but not the antagonist
Implementation Method 4
a polymeric matrix with a glass transition temperature below body temperature
Data Source
AI summary
This invention relates to abuse-deterrent pharmaceutical compositions and dosage forms and manufacturing processes thereof, the compositions comprising an agonist and antagonist that are difficult to separate visually, physically, or chemically. The compositions comprise a tacky amorphous polymer and a crystalline polymer curing agent for the amorphous polymer such that the agonist is releasable and the antagonist is non-releasable unless the dosage forms are tampered with. The non-extractable dosage forms reduce the potential for prescription drug abuse.