BIBW 2992 MA2 Compacted Intermediate for Solid Dosage
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Solution Overview
Problem
BIBW 2992 MA 2 exhibits challenging physico-chemical properties such as susceptibility to moisture, poor flowability, low compressibility, and electrostatic charging, leading to instability and variability in pharmaceutical formulations, which complicates the production of solid oral dosage forms with consistent bioavailability and pharmacokinetic profiles.
Innovation Solution
A compacted intermediate form of BIBW 2992 MA 2 is created through roller compaction and subsequent sieving, followed by blending with excipients, to achieve a uniform particle size distribution and improved flowability, resulting in a stable and efficient immediate release pharmaceutical dosage form with consistent bioavailability across various dosage strengths.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If BIBW 2992 MA 2 is used in solid oral dosage forms, then pharmacological activity is achieved, but poor flowability and low compressibility lead to manufacturing difficulties
Solution Approach 1:
The patent applies parameter changes by modifying the physical state and particle characteristics of BIBW 2992 MA 2 through compaction and size reduction. The active ingredient is compacted to form denser particles with improved flowability and compressibility, transforming the material properties to enable successful tablet manufacturing while maintaining pharmacological activity.
Solution Approach 2:
The patent uses an intermediary approach by introducing a compaction step as an intermediate process between the raw material preparation and final tablet formation. This compaction intermediate form serves as a bridge, improving the manufacturability of BIBW 2992 MA 2 without altering its essential pharmacological properties.
2Reliability
If BIBW 2992 MA 2 is used in pharmaceutical formulations, then therapeutic effect is achieved, but susceptibility to moisture and electrostatic charging cause instability
Solution Approach 1:
The patent changes the physical parameters of BIBW 2992 MA 2 through compaction and particle size reduction, creating a denser, more stable form that is less susceptible to moisture absorption and electrostatic charging. This parameter transformation improves formulation stability while preserving the therapeutic effect.
3Productivity
If conventional dissolution testing is used for BIBW 2992 MA 2, then dissolution rate is measured, but variability in bioavailability and pharmacokinetic profiles occurs
Solution Approach 1:
The patent changes the physical state and particle size parameters of BIBW 2992 MA 2 through compaction and size reduction, creating a more uniform and predictable dissolution profile. This parameter transformation reduces variability in bioavailability and pharmacokinetic profiles, achieving consistent dissolution rates across different formulations.
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 process ensures an immediate release dissolution profile across the physiologically relevant pH range, maintaining bioavailability and pharmacokinetic consistency, with over 85% dissolution in 60 minutes or less, and dose-proportional increases in plasma concentration and area under the curve, suitable for commercial-scale production.
Implementation Method 1
The rate and extent to which the active ingredient is absorbed from a pharmaceutical dosage form and becomes available at the site of action is defined as bioavailability... dissolution of the solid oral dosage form
Data Source
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AI summary
The present invention relates to a pharmaceutical dosage form containing the active substance BIBW 2992 as the dimaleate salt, providing an immediate release profile of the active substance, further, the invention relates to compacted intermediates comprising BIBW 2992 dimaleate salt (BIBW 2992 MA2) in form of a powder prepared using a combined roller compaction and sieving step from BIBW 2992 MA2, intermediate blends prepared from said compacted intermediate as well as solid oral formulations providing an immediate release profile of the active substance, made from said compacted intermediate or from said intermediate blends ready for use/ingestion, e.g. capsule and tablet formulations such as uncoated or film-coated tablets prepared by direct-compression, and methods for their production.