Pirfenidone Granulate Formulation for Controlled Drug Release
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Solution Overview
Problem
Pirfenidone, a key anti-fibrotic drug, poses challenges in formulation due to poor powder flowability and sensitivity to particle size variations and moisture content, making it difficult to produce stable tablets with optimal drug release characteristics.
Innovation Solution
A granulate formulation of pirfenidone with an intragranular glidant and additional excipients, processed using fluid bed granulation, which improves flowability and stability, allowing for tablets with controlled solid fraction and thickness to achieve desired drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pirfenidone is formulated as a compressed tablet, then therapeutic effectiveness is achieved, but poor powder flowability and sensitivity to particle size variations make production difficult
Solution Approach 1:
The patent divides the tablet into granules with specific size ranges (d10, d50, d90 parameters) to improve powder flowability while maintaining therapeutic effectiveness. The granulation process segments the pirfenidone powder into controlled particle sizes that flow better during manufacturing.
Solution Approach 2:
The patent changes physical parameters of pirfenidone including particle size distribution, moisture content control, and granule density to transform the poor-flowing powder into manufacturable granules with improved flow characteristics while preserving drug efficacy.
2Ease of manufacture
If particle size is controlled to improve flowability, then manufacturing becomes easier, but sensitivity to particle size variations increases
Solution Approach 1:
The patent applies different quality requirements to different portions of the particle size distribution. Specific d10, d50, and d90 values are targeted to create a balanced granule population that flows well while accommodating normal manufacturing variations without excessive sensitivity.
Solution Approach 2:
The patent creates composite granules containing pirfenidone mixed with excipients in specific ratios. This composite structure improves flowability while the blend composition is designed to buffer against particle size variations, reducing manufacturing precision requirements.
3Ease of manufacture
If moisture content is increased to improve flowability, then manufacturing becomes easier, but stability of the formulation deteriorates
Solution Approach 1:
The patent optimizes moisture content to a specific range that provides sufficient flowability for manufacturing while maintaining formulation stability. This balanced parameter setting allows easy production without compromising drug stability or granule integrity.
Solution Approach 2:
The patent uses excipients as intermediary materials that improve powder flowability without requiring high moisture content. These intermediate substances act as flow aids while maintaining the stability of the pirfenidone formulation.
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 results in tablets with improved flowability, stability, and controlled drug release, capable of accommodating particle size variations and moisture content, providing a robust commercial-scale process with enhanced tensile strength and dissolution properties.
Implementation Method 1
mixing the 5-methyl-1-phenyl-2- (1H)-pyridone with intragranular excipients in a fluid bed granulator to form granules
Data Source
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AI summary
The disclosure relates to granulate formulations of pirfenidone and methods of making such formulations