Posaconazole Granules With Enteric Polymer for Stable Dissolution
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing gastro-resistant unit dosage forms of posaconazole exhibit variability in dissolution behavior, leading to fluctuations in bioavailability.
Innovation Solution
A gastro-resistant, optionally film-coated tablet prepared from granules containing posaconazole molecularly dispersed in a mixture of enteric and non-enteric polymers, processed through hot-melt extrusion, with specific particle size distribution to ensure consistent drug release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If gastro-resistant unit dosage forms of posaconazole are used, then food effects are minimized and bioavailability is enhanced, but dissolution behavior variability occurs leading to fluctuations in bioavailability
Solution Approach 1:
The patent applies parameter changes by controlling the particle size distribution of granules (specifically, that at least 10 wt.% of granules have a particle size of 250 μm or more) and adjusting the molecular dispersion state of posaconazole in the polymer matrix. These parameter modifications ensure consistent dissolution behavior and minimize bioavailability fluctuations while maintaining gastro-resistance.
Solution Approach 2:
The patent applies local quality by creating specific regions within the tablet structure - granules with different particle sizes are distributed throughout the tablet matrix. This local variation in granule size creates zones with different dissolution rates, ensuring that the overall dissolution profile remains consistent and bioavailability is maintained reliably.
2Stability of the object's composition
If posaconazole is formulated with low aqueous solubility, then chemical stability is improved, but bioavailability is reduced unless coadministered with food
Solution Approach 1:
The patent uses an enteric polymer coating as an intermediary layer between the posaconazole granules and the gastrointestinal environment. This coating protects the drug from gastric acid degradation (maintaining chemical stability) while allowing controlled release in the intestinal environment (enhancing bioavailability) without requiring food administration.
Solution Approach 2:
The patent changes the physical state parameters of posaconazole by creating a molecular dispersion within the polymer matrix and controlling granule particle size. This transforms the drug from a purely crystalline low-solubility form to a formulation with enhanced dissolution characteristics while maintaining chemical stability through the protective polymer matrix.
3Stability of the object's composition
If crystalline forms of posaconazole are used, then chemical stability is enhanced, but water solubility is reduced compared to amorphous forms
Solution Approach 1:
The patent creates local variations in the physical state of posaconazole within the formulation. Crystalline posaconazole is used in granules with controlled particle sizes, while the enteric polymer coating provides a protective matrix that facilitates controlled dissolution. This local differentiation allows the formulation to maintain crystalline stability while achieving acceptable solubility through the polymer-mediated release mechanism.
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 solution provides a gastro-resistant tablet with stable drug dissolution profiles, minimizing food effects and enhancing bioavailability by maintaining consistent drug release in the intestinal fluid.
Implementation Method 1
posaconazole molecularly dispersed in a mixture of enteric and non-enteric polymers
Implementation Method 2
processed through hot-melt extrusion
Implementation Method 3
gastro-resistant tablet with stable drug dissolution profiles, minimizing food effects
Data Source
AI summary
The present invention relates to granules preferably prepared by subjecting a mixture containing posaconazole, an enteric polymer and optionally a non-enteric polymer to hot-melt extrusion, whereby the granules have a specific particle -size distribution and contain the drug in molecularly dispersed form, and a gastro-resistant, optionally film- coated tablet prepared from the granules.