Drug Delivery Balloon Nucleation for Controlled Crystal Size
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Solution Overview
Problem
Paclitaxel-coated balloons do not provide predictable drug delivery to tissue sites, with issues of variable drug release rates and therapeutic levels over time, necessitating control over drug morphology and particle size for improved delivery characteristics.
Innovation Solution
A method for forming drug delivery balloons by applying a drug coating in amorphous form and annealing to produce crystalline form, utilizing nucleation sites on the balloon surface to control crystalline particle size, including vapor pretreatment to induce blooming of nucleating agents, resulting in high-density, small-sized crystalline drug particles for enhanced delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If paclitaxel is applied directly to the balloon or formulated with excipients, then the drug can be delivered to tissue, but the release rate and therapeutic levels are unpredictable
Solution Approach 1:
The invention changes the physical state parameter of paclitaxel from amorphous to crystalline form, and controls crystal size through nucleation. This parameter change transforms the unpredictable drug release into a controlled, predictable release profile with consistent therapeutic levels over time.
Solution Approach 2:
The invention performs preliminary nucleation of the balloon surface before applying paclitaxel. This preliminary action creates controlled nucleation sites that dictate subsequent crystal formation, ensuring predictable crystal size and drug release characteristics before the actual drug application occurs.
2Duration of action of moving object
If large crystalline paclitaxel particles are formed, then drug release may be sustained, but particle size becomes unsafe for vascular delivery
Solution Approach 1:
The invention changes the nucleation parameter by introducing nucleating agents that promote formation of numerous small crystals rather than few large ones. This parameter change achieves crystal sizes below 100 micrometers (safe for vascular delivery) while maintaining sufficient tissue residence time through controlled crystalline structure.
3Duration of action of moving object
If vapor annealing is used to form crystalline paclitaxel dihydrate, then longer tissue residence time is achieved, but control over crystal size and density is limited
Solution Approach 1:
The invention introduces nucleating agents as intermediaries between the amorphous paclitaxel coating and the final crystalline structure. These nucleating agents mediate the crystallization process, providing controlled nucleation sites that enable precise control over crystal size, density, and morphology while maintaining the beneficial dihydrate crystal form for extended tissue residence.
4Manufacturing precision
If amorphous drug coating is applied and annealed, then crystalline form is produced, but without nucleation sites crystal size is uncontrolled
Solution Approach 1:
The invention performs preliminary nucleation of the balloon surface using vapor pretreatment with nucleating agents before applying the amorphous paclitaxel coating. This preliminary action establishes controlled nucleation sites that will dictate subsequent crystal formation, enabling precise control over crystal size and density without adding significant complexity to the overall manufacturing process.
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 method achieves improved drug delivery characteristics, including predictable tissue residence time, minimized systemic loss, and safer particle size, leading to higher tissue uptake and prolonged therapeutic effects.
Implementation Method 1
annealing the coated balloon to produce a crystalline form of the drug in situ on the balloon
Implementation Method 2
produce a crystalline form of the drug in situ on the balloon
Implementation Method 3
vapor pretreatment of the balloon to induce blooming of a component of the balloon material as a nucleating agent
Implementation Method 4
nucleation sites on the balloon to control the crystalline particle size
Data Source
AI summary
Drug delivery balloons have densely packed crystals of small particle size of the drug thereon. An amorphous drug coating is applied to a balloon surface and annealed to provide the crystals. The balloon surface is nucleated to induce formation of drug crystals in the annealing step to provide the crystals in high density with small size.