Inhaled Imatinib Formulation for Pulmonary Arterial Hypertension
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Solution Overview
Problem
Current therapies for pulmonary diseases such as interstitial lung disease and cancer, as well as viral infectious diseases, face challenges in efficacy, safety, and patient resistance, highlighting the need for improved pharmacokinetic and target organ dose delivery through inhalation methods.
Innovation Solution
Development of aqueous solutions for nebulized inhalation containing imatinib or its salts, phenylaminopyrimidine derivatives, or other kinase inhibitors, formulated with water, inorganic salts, and buffers to achieve concentrations between 0.1 mg/mL to 100 mg/mL, osmolality from 50 mOsmol/kg to 2000 mOsmol/kg, and pH between 4.0 and 8.0, for targeted delivery to lung, central nervous system, and systemic compartments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional systemic administration of kinase inhibitors is used, then therapeutic coverage is achieved, but systemic side effects increase and patient resistance develops
Solution Approach 1:
The invention divides the administration route into localized pulmonary delivery via inhalation, separating the therapeutic action at the target site from systemic circulation. This segmentation allows the drug to act locally in the lungs while minimizing systemic exposure, thereby maintaining efficacy while reducing side effects
Solution Approach 2:
The invention uses the pulmonary system as an intermediary pathway to deliver kinase inhibitors directly to the target tissue. By utilizing inhalation as the intermediary route, the drug bypasses first-pass metabolism and achieves direct local action, reducing the need for high systemic doses that cause side effects
2Quantity of substance
If conventional systemic administration is used, then broad therapeutic coverage is achieved, but target organ dose is insufficient
Solution Approach 1:
The invention applies local quality by concentrating the drug delivery at the specific target site (pulmonary tissue) through inhalation. This allows high local concentration at the target organ while maintaining lower systemic levels, improving the pharmacokinetic profile by achieving better target-to-plasma ratio
Solution Approach 2:
The invention transitions from systemic circulation (one-dimensional distribution) to localized pulmonary delivery (spatial dimensionality change). By delivering the drug directly to the lungs via inhalation, the patent achieves higher target organ dose through a different spatial dimension, bypassing the limitations of systemic distribution
3Duration of action of stationary object
If repeated systemic dosing is administered, then therapeutic effect is maintained, but patient resistance increases
Solution Approach 1:
The invention segments the treatment approach by using localized pulmonary delivery instead of repeated systemic dosing. This segmentation allows for sustained local therapeutic effect through less frequent inhalation administrations, reducing the selection pressure that leads to patient resistance while maintaining therapeutic duration
Data Source
AI summary
Disclosed herein are formulations of imatinib or a phenylaminopyrimidine derivative compound for aerosolization and use of such formulations for inhaled aerosol administration of imatinib or a phenylaminopyrimidine derivative compound for the prevention or treatment of various fibrotic, carcinogenic, vascular and viral infectious diseases, including diseases associated with the lung, heart, kidney, liver, eye, central nervous system and surgical sites. In some embodiments, formulations and delivery options described herein allow for efficacious local delivery of imatinib or a phenylaminopyrimidine derivative compound or salt thereof. Compositions include all formulations, kits, and device combinations described herein. Methods include inhalation procedures, indications and manufacturing processes for production and use of the compositions described. Also included are methods for identifying compounds and indications that may benefit by reformulation and inhalation administration.