Compound 1 Oral Tablet Formulation Balancing Hardness and Dissolution
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Solution Overview
Problem
There is a significant unmet need for effective treatments for cystic fibrosis, particularly for patients with the F508del-CFTR mutation, and existing drug formulations face challenges in ensuring consistent availability and efficacy.
Innovation Solution
Pharmaceutical compositions comprising 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (Compound 1) are developed, incorporating various excipients such as fillers, disintegrants, surfactants, lubricants, and glidants, in specific crystalline forms, to enhance stability and bioavailability, with processes like roller compaction, high shear granulation, and twin screw wet granulation for controlled production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing drug formulations are used for CFTR-mediated diseases, then treatment is provided, but consistent availability and efficacy cannot be ensured
Solution Approach 1:
The patent applies parameter changes by systematically varying formulation parameters including excipient types (fillers, disintegrants, surfactants, lubricants, glidants), crystalline forms of Compound 1, and processing parameters (roller compiction, high shear granulation, twin screw wet granulation) to optimize dissolution rates and tablet hardness, thereby ensuring consistent availability and efficacy
Solution Approach 2:
The patent employs composite materials by combining Compound 1 with multiple types of excipients (pharmaceutically acceptable fillers, disintegrants, surfactants, lubricants, and glidants) in specific formulations to enhance stability and bioavailability, creating optimized pharmaceutical compositions that address the reliability-adaptability contradiction
2Strength
If tablet hardness is increased to improve durability, then dissolution rate may be reduced
Solution Approach 1:
The patent resolves this contradiction by changing formulation parameters including selecting specific excipients (binders, disintegrants, lubricants) and optimizing their ratios, along with adjusting processing parameters (compression force, granulation conditions) to achieve a balance where tablets have sufficient hardness for durability while maintaining adequate dissolution rates through controlled porosity and surface area
Solution Approach 2:
The patent applies local quality by creating heterogeneous tablet structures with varying density and porosity distributions - the tablet exterior maintains sufficient hardness for handling while the interior structure is optimized for drug dissolution, achieving both durability and rapid release through spatial variation in physical properties
Data Source
AI summary
A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a disintegrant, a surfactant, a binder, and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Processes of preparing pharmaceutical compositions comprising Compound 1 are also disclosed.