Oral API Formulation Particle Size Control
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Solution Overview
Problem
Current composite formulations for oral administration with high content of 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazol-4-carboxylic acid lack excellent physical properties and dissolution rates, leading to increased manufacturing time and cost, and reduced patient acceptability due to lower bioavailability.
Innovation Solution
A composite formulation with an API particle size range of 80 μm to 300 μm, achieving a dissolution rate of 70% at 15 minutes, 85% at 30 minutes, and 89% at 60 minutes, using a pH 6.8 buffer, and containing 30-50% API by weight, which maintains physical stability and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high content of API is used in composite formulation, then bioavailability and dissolution rate are improved, but physical properties such as hardness and tableting properties deteriorate
Solution Approach 1:
The patent applies parameter changes by controlling the particle size distribution of API within specific ranges (D10: 45-80 μm, D50: 80-150 μm, D90: 150-300 μm) and adjusting the content ratio of API to excipients (5:1 to 1:1). By optimizing these parameters, the formulation achieves both high bioavailability and acceptable physical properties without requiring additional excipients or complex granulation processes.
2Strength
If granulation process is used to improve physical properties of high content API formulation, then tableting properties are improved, but manufacturing time and production cost increase
Solution Approach 1:
The patent extracts the granulation process from the manufacturing workflow by directly compressing the API-excipent mixture without preliminary granulation steps. This elimination of the granulation stage significantly reduces manufacturing time and complexity while maintaining acceptable tableting properties through optimized particle size control and direct compression formulation design.
3Strength
If amount of excipients is increased to decrease API ratio, then physical properties are improved, but production cost increases and patient acceptability is lowered
Solution Approach 1:
The patent changes the particle size parameters of API to achieve better flowability and compressibility, allowing for reduced excipient content (5:1 to 1:1 API to excipient ratio). This parameter optimization enables high API content formulations to maintain physical properties without requiring excessive excipients, thereby reducing production cost and improving patient acceptability.
4Speed
If high content of API is used, then dissolution rate should be improved, but physical properties are generally lowered
Solution Approach 1:
The patent optimizes particle size distribution parameters (D10, D50, D90) and content ratio to achieve a balance where high API content (improving dissolution rate) coexists with acceptable physical properties. The specific particle size ranges ensure adequate surface area for dissolution while maintaining flowability and compressibility necessary for tablet formation.
Data Source
AI summary
The present invention relates to a composite formulation for oral administration comprising an active pharmaceutical ingredient (API) selected from 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazol-4-carboxylic acid or a pharmaceutically acceptable salt thereof, wherein the API has a particle size of granules corresponding to 90% of the maximum particle size in the cumulative particle size distribution (D(0.9)) of 80 μm or more and 300 μm or less.The composite formulation for oral administration according to the present invention has a low friability and an increased dissolution rate even if a high content of API is included, by regulating the particle size of the API to a certain range.