Thermoreversible Bladder Gel Formulation for Sustained Drug Release
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Solution Overview
Problem
Current methods for delivering drugs to the urinary tract, bladder, and kidneys face challenges such as limited efficacy due to rapid dilution and washout, catheter obstruction, pain, and short retention time, necessitating repeated infusions and requiring improved formulations for prolonged drug release.
Innovation Solution
Liquid formulations containing an alcoholic solvent, polymers, and active agents that precipitate to form a mass in the urinary tract, bladder, or kidneys, providing extended release of active agents without obstructing the urethra, with the ability to modulate release duration and dose through formulation composition and instillation rate.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If drugs are instilled intravesically into the bladder via catheter, then high local concentrations of drug are achieved with minimal systemic effects, but the drug is diluted by urine and washed out during voiding, necessitating repeated infusions
Solution Approach 1:
The patent utilizes the phase transition of thermoreversible gelators that transition from liquid to gel state at body temperature. The formulation is instilled as a liquid at room temperature for easy administration, then transforms into a gel in the bladder to provide sustained drug release and prevent washout during voiding, thereby extending drug retention time while maintaining high local concentrations
Solution Approach 2:
The patent changes the physical state parameter of the drug formulation from liquid to gel by utilizing temperature-dependent gelation. This parameter change allows the formulation to be easily instilled as a liquid and then transform into a gel that resists dilution and washout, solving the contradiction between achieving high local concentration and maintaining prolonged retention
2Duration of action of moving object
If thermoreversible solutions are used for intravesical instillation, then prolonged drug release is achieved, but premature gelation occurs before reaching the bladder, obstructing the catheter
Solution Approach 1:
The patent introduces co-solvents (such as ethanol, isopropanol, or acetone) as intermediaries to modify the gelation behavior of the thermoreversible gelators. These co-solvents suppress premature gelation during catheter instillation by altering the solvent composition, allowing the formulation to remain liquid during administration and only gel after reaching the bladder where urine dilution triggers the phase transition
Solution Approach 2:
The patent modifies the gelation temperature and kinetics parameters by adjusting the co-solvent composition. This allows control over when and how quickly gelation occurs, ensuring the formulation remains fluid during instillation but transitions to gel state upon contact with urine in the bladder, thereby resolving the contradiction between prolonged release and ease of instillation
3Quantity of substance
If large volume of drug formulation is instilled to achieve therapeutic effect, then adequate drug dose is delivered, but micturition is urged and premature drug washout occurs due to short retention time
Solution Approach 1:
The patent utilizes gelation phase transition to increase the viscosity and structural integrity of the drug formulation in the bladder. The gel structure traps the drug and resists dilution by urine, allowing smaller volumes to be instilled while achieving adequate drug delivery and prolonged retention, thereby preventing premature washout during voiding
4Quantity of substance
If repeated and frequent bladder catheterization is performed for drug instillation, then adequate drug delivery is achieved despite dilution and washout, but the procedure becomes cumbersome and patient tolerability decreases
Solution Approach 1:
The patent employs thermoreversible gelation to create a sustained-release depot in the bladder that maintains high drug concentrations over extended periods. This eliminates the need for repeated catheterization and instillation procedures, as a single administration provides prolonged therapeutic effect, thereby reducing procedure complexity and improving patient tolerability while maintaining drug delivery efficacy
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 described formulations enable prolonged release of active agents over several days, reducing the need for frequent infusions and minimizing systemic side effects, while ensuring effective treatment of urinary tract disorders and diseases with improved patient tolerability.
Implementation Method 1
When in contact with urine, the one or more polymers precipitate from the formulation and entrap the one or more active agents, forming a mass
Implementation Method 2
Thermoreversible solutions turn into gels in a temperature range close to human body temperature
Data Source
AI summary
Polymeric liquid formulations for instillation into the bladder or kidney for prolonged release of an active agent and methods of treatment using the formulations are described. When in contact with urine, the formulation forms a mass in the bladder or kidney. The mass entraps the active agents and provides prolonged release of the active agents.