Tamper-Resistant Opioid Multiparticulates via Segmentation
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Solution Overview
Problem
Traditional sustained release formulations of opioid analgesics like oxycodone are vulnerable to abuse due to their susceptibility to crushing and dissolution, leading to rapid bioavailability when tampered with, which poses challenges for law enforcement and patient safety.
Innovation Solution
Development of abuse-deterrent pharmaceutical compositions in the form of multiparticulates with modified lipophilic drugs dispersed within water-insoluble excipients, which slow down drug release even when the dosage form is compromised, using processes like spray congealing and coating with water-insoluble layers to prevent easy extraction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional sustained release formulations are used, then therapeutic efficacy is maintained over an extended time period, but the formulations become vulnerable to abuse through crushing and dissolution
Solution Approach 1:
The formulation is divided into multiple separate particles (multiparticulates) rather than a single monolithic tablet. This segmentation makes the formulation more difficult to crush effectively while maintaining sustained release properties, as each particle must be individually compromised to release drug rapidly
Solution Approach 2:
The formulation combines multiple materials with different properties: water-insoluble excipients provide structural integrity and resistance to crushing, while water-soluble excipients enable controlled dissolution and drug release. This composite approach creates a formulation that resists tampering while maintaining therapeutic function
2Object-affected harmful factors
If the formulation is made more resistant to crushing, then abuse potential is reduced, but the formulation may become more difficult to administer properly
Solution Approach 1:
Different regions of the formulation have different properties: the water-insoluble excipients provide mechanical strength and crush resistance in the bulk, while water-soluble excipients are distributed throughout to enable controlled dissolution. This local differentiation allows the formulation to be both tamper-resistant and easily administrable when intact
Solution Approach 2:
The formulation utilizes changes in solubility parameters - materials that are insoluble in water provide structural resistance to crushing, while soluble materials enable controlled release. This parameter-based differentiation allows the same formulation to resist tampering while maintaining ease of oral administration
3Object-affected harmful factors
If water-insoluble excipients are used to prevent dissolution, then abuse is deterred, but drug release may be excessively slowed
Solution Approach 1:
The formulation merges water-insoluble and water-soluble excipients in a single multiparticulate system. The water-insoluble materials provide structural integrity and resistance to crushing/dissolution, while the water-soluble materials create controlled dissolution pathways. This combination achieves both abuse deterrence and controlled release at appropriate rates
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 multiparticulate formulation effectively reduces the potential for improper administration by slowing down drug release, maintaining therapeutic efficacy while deterring abuse, and is less prone to tampering, ensuring safe and controlled drug delivery.
Implementation Method 1
multiparticulates with modified lipophilic drugs dispersed within water-insoluble excipients, which slow down drug release even when the dosage form is compromised
Implementation Method 2
using processes like spray congealing and coating with water-insoluble layers to prevent easy extraction
Data Source
AI summary
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.