Liquid Oral Formulation Balancing Dissolution and Suspension Stability
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Solution Overview
Problem
Existing technologies do not provide a stable, homogenous liquid oral formulation for netupitant and palonosetron suitable for oral administration, particularly for preventing chemotherapy-induced nausea and vomiting, and lack a suitable single unit dosage form for pediatric patients.
Innovation Solution
A mixed suspension/solution solvent system containing palonosetron or its pharmaceutically acceptable salt in a dissolved state and netupitant or its pharmaceutically acceptable salt in a solid suspended state, with specific particle size distribution and a solvent system comprising miscibilized wetting, suspending, and pH modifiers, ensuring stability and homogeneity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If a liquid oral formulation is prepared for netupitant and palonosetron, then the ease of administration is improved, but the formulation stability deteriorates due to solubility and suspension issues
Solution Approach 1:
The formulation is segmented into two distinct states: palonosetron is dissolved in the aqueous phase while netupitant is suspended as fine particles. This segmentation allows each drug to be optimized for its respective state, preventing instability while maintaining liquid oral form
Solution Approach 2:
The invention creates a composite suspension/solution system combining dissolved palonosetron and suspended netupitant in a single liquid formulation. This composite approach leverages the advantages of both solution and suspension dosage forms to achieve stability and ease of administration simultaneously
2Stability of the object's composition
If netupitant is suspended in solid state, then the formulation stability is improved, but the homogeneity deteriorates due to particle distribution
Solution Approach 1:
The particle size of suspended netupitant is controlled within specific ranges (d10: 0.5-5 μm, d50: 1-8 μm, d90: 2-24 μm) to optimize both stability and homogeneity. This parameter control prevents excessive aggregation while maintaining suspension stability
3Device complexity
If a single unit dosage form is created, then the device complexity is reduced, but the manufacturing precision deteriorates due to combining different dosage forms
Solution Approach 1:
The invention merges capsule and liquid dosage form characteristics into a single unit dosage form. The liquid suspension containing both dissolved and suspended drugs is filled into a capsule, creating a unified dosage form that combines the advantages of both forms while maintaining manufacturing precision
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 formulation remains stable without sedimentation, providing effective prevention of chemotherapy-induced nausea and vomiting, suitable for both adult and pediatric patients, with palonosetron and netupitant in a single liquid dosage form.
Implementation Method 1
one or more miscibilized wetting agents
Implementation Method 2
one or more miscibilized suspending agents
Data Source
AI summary
Orally administered liquid formulations of netupitant and palonosetron, and suitable pharmaceutical excipients, in a solvent system that allows for the netupitant to be suspended and the palonosetron to be dissolved, that are efficacious, chemically stable and physiologically balanced for safety and efficacy.