RPL554 Inhalation Suspension Stability and Release
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Liquid pharmaceutical compositions for respiratory drugs, such as RPL554, face challenges in predictable toxicokinetic properties, stability, and patient comfort, particularly in inhalation forms, where solutions often degrade and require frequent administration.
Innovation Solution
A liquid pharmaceutical composition comprising a suspension of RPL554 particles with a particle size distribution of 0.2 µm to 5 µm, combined with a diluent and a phosphate buffer, offering improved stability and delayed release characteristics, allowing higher doses with reduced frequency of administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a solution formulation of RPL554 is used, then the drug can be administered by inhalation, but the composition shows degradation after storage and requires frequent administration
Solution Approach 1:
The patent changes the physical state parameter of the drug from dissolved (solution) to suspended (particles) form. This parameter change fundamentally alters the release characteristics, providing delayed release and improved stability without degradation during storage, while maintaining inhalable delivery.
Solution Approach 2:
The patent prepares RPL554 particles in advance with specific size distribution (Dv50 of 0.2-5 μm) and suspends them in the composition before administration. This preliminary preparation ensures the particles are ready for delayed release upon inhalation, extending duration of action without requiring frequent re-administration.
2Reliability
If a solution formulation of RPL554 is used, then the drug can be delivered to patients, but the toxicokinetic properties are unpredictable
Solution Approach 1:
The patent changes the formulation from solution to suspension with controlled particle size distribution (Dv50 of 0.2-5 μm). This parameter change makes the toxicokinetic properties predictable by controlling how the drug is released and absorbed after inhalation, while allowing accurate dosage control.
3Quantity of substance
If the dosage of RPL554 is increased, then the treatment efficacy is improved, but the administration frequency must be maintained
Solution Approach 1:
The patent prepares RPL554 in particle suspension form with specific size distribution before administration. This preliminary action creates a formulation that releases the drug slowly after inhalation, allowing higher doses to be administered with reduced frequency, thereby improving productivity.
Solution Approach 2:
The patent creates a dynamic release system where particles of different sizes (Dv50 of 0.2-5 μm) provide controlled, delayed release of the drug. This dynamic behavior allows the formulation to maintain therapeutic levels longer, reducing the need for frequent administrations even at higher doses.
4Duration of action of moving object
If a suspension formulation of RPL554 is used, then the release is delayed and dosage is increased, but the composition complexity increases
Solution Approach 1:
The patent changes the formulation from solution to suspension with controlled particle size distribution. While this increases composition complexity, it provides delayed release and extended duration of action, improving therapeutic efficacy.
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to a liquid pharmaceutical composition suitable for administration by inhalation which comprises a diluent and a suspension of particles of 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one (RPL554) or a pharmaceutically acceptable salt thereof, wherein the particles of RPL554 have a particle size distribution with a Dv50 (median particle size by volume) value of from about 0.2 µm to about 5 µm; and the composition comprises a phosphate buffer at a concentration of from 0 to 5 mg/mL. Also described is a liquid pharmaceutical composition according to the invention for use in the treatment of the human or animal body.