Tamper-Resistant Multiparticulate Dosage Form via Segmentation
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Solution Overview
Problem
Current opioid analgesic dosage forms, particularly controlled-release forms, are vulnerable to abuse due to ease of crushing and solvent extraction, which can lead to rapid drug release and misuse, and are difficult to formulate in high-strength, tamper-resistant, and cost-effective formats that maintain extended release profiles.
Innovation Solution
Melt-extruded particulates of opioid agonists incorporated into a matrix with a gel-forming agent, such as a copolymer of acrylic acid alkyl esters and methacrylic acid alkyl esters, provide crush resistance and resistance to alcohol extraction, forming a dosage form that is difficult to tamper with and maintains controlled drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high molecular weight polyethylene oxide (PEO) is used to control drug release rate and impart crush resistance, then the dosage form gains tamper resistance and crush resistance, but the dosage form becomes too large and heavy for easy administration
Solution Approach 1:
The dosage form is segmented into multiple small spherical multiparticulates (0.5-2.0 mm diameter) rather than a single large tablet. Each multiparticulate contains the opioid analgesic and PEO matrix, allowing the total drug dose to be distributed across many small particles that are easier to administer while maintaining the required PEO-to-drug ratio for tamper resistance
Solution Approach 2:
The invention changes the physical parameters of the dosage form by using spherical multiparticulates with controlled size distribution (0.5-2.0 mm diameter) instead of traditional large tablets. This parameter change maintains the effective PEO concentration for tamper resistance while reducing the overall dosage form size and weight for easier administration
2Duration of action of moving object
If high molecular weight polyethylene oxide (PEO) is used to control drug release rate, then the dosage form gains extended release capability, but the dosage form becomes too large and heavy for easy administration
Solution Approach 1:
The extended-release functionality is segmented across multiple small spherical multiparticulates, each containing the opioid and PEO matrix. The collective surface area and matrix structure of numerous small particles provide the required extended release duration (24 hours or more) while keeping individual particle size small for easy administration
Solution Approach 2:
The invention optimizes the size parameter of the multiparticulates (0.5-2.0 mm diameter) to achieve a balance between extended release duration and ease of administration. The controlled release is maintained through the PEO matrix structure across the multiparticulate system rather than requiring a single large formulation
3Strength
If melt extruded multiparticulates are used to provide crush resistance, then the dosage form gains some crush resistance, but the multiparticulates remain susceptible to abuse by alcohol extraction
Solution Approach 1:
The invention uses a composite material system where the PEO matrix (50-90% w/w of total formulation) is combined with the opioid analgesic. The PEO forms a gel structure upon contact with extraction solvents like alcohol, creating a viscous gel that physically resists syringing and injection while also providing the extended-release matrix. This composite approach simultaneously achieves crush resistance and alcohol extraction resistance
Solution Approach 2:
The invention converts the potential harm of alcohol extraction into a beneficial gel-forming response. When alcohol or other extraction solvents contact the PEO matrix, they trigger gel formation that increases viscosity and creates a physical barrier, transforming the extraction attempt into a self-defending mechanism that prevents rapid drug release
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 dosage form exhibits excellent alcohol-extraction resistance and crush resistance, ensuring consistent drug release over an extended period while deterring abuse, as it forms a viscous solution upon alcohol exposure and withstands physical tampering, maintaining therapeutic efficacy while minimizing misuse.
Implementation Method 1
The matrix in which the particulates are present provides resistance to alcohol extraction by forming a gel or viscous solution on exposure to alcohol that resists syringing or injection.
Implementation Method 2
Melt extruded multiparticulates comprising opioid analgesics
Implementation Method 3
Melt extruded multiparticulates comprising opioid analgesics are also known
Data Source
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AI summary
The present invention provides a dosage form, particularly a tamper resistant dosage form, comprising: melt-extruded particulates comprising a drug; and a matrix; wherein said melt-extruded particulates are present as a discontinuous phase in said matrix.