Hydrophobic Upadacitinib Formulation for Moisture-Stable Dissolution
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Solution Overview
Problem
Existing upadacitinib formulations are sensitive to moisture, leading to changes in tablet appearance, decreased dissolution rates, and increased impurity profiles over time, necessitating improved moisture resistance and dissolution properties.
Innovation Solution
A pharmaceutical composition of upadacitinib using a hydrophobic polymer, such as glyceryl dibehenate or ethyl cellulose, combined with a pH modifier like tartaric acid, to create a stable and effective extended-release formulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If hydrophilic polymer and acidic pH modifier are used in upadacitinib formulation, then dissolution rate is improved, but moisture sensitivity increases leading to tablet mottling and impurity formation
Solution Approach 1:
The patent changes the fundamental parameter of polymer hydrophobicity from hydrophilic to hydrophobic. This parameter change fundamentally alters the formulation's moisture interaction profile while maintaining dissolution performance through the selection of specific hydrophobic polymers that provide controlled release capabilities.
Solution Approach 2:
The patent creates a composite formulation system combining hydrophobic polymer matrix with upadacitinib and pH modifiers. This composite approach allows the hydrophobic polymer to provide moisture protection while the pH modifiers maintain dissolution properties, achieving both moisture resistance and effective drug release.
2Stability of the object's composition
If storage time increases without moisture protection, then tablet appearance becomes mottled and dissolution rate decreases, but impurity profile increases
Solution Approach 1:
The patent converts the potentially harmful effect of moisture exposure into a beneficial protective feature by using hydrophobic polymers that actively repel moisture. The hydrophobic nature of the polymer matrix prevents moisture penetration that would otherwise cause mottling, dissolution rate decrease, and impurity formation during storage.
Solution Approach 2:
The hydrophobic polymer creates an inert, moisture-excluding environment around the upadacitinib drug substance. This protective matrix acts as a barrier that isolates the drug from harmful moisture in the external environment, thereby preventing degradation and maintaining formulation stability during storage.
3Reliability
If hydrophobic polymer is used to reduce moisture uptake, then moisture resistance is improved, but dissolution rate may be compromised
Solution Approach 1:
The patent applies local quality by incorporating pH modifiers at specific locations and concentrations within the hydrophobic polymer matrix. These localized modifications create microenvironments that facilitate drug dissolution and release while the bulk hydrophobic polymer maintains moisture protection, thus resolving the contradiction between moisture resistance and dissolution rate.
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 maintains dissolution properties comparable to commercial products, reduces moisture sensitivity, and ensures consistent drug release, with minimal impurities, demonstrating bioequivalence to the innovator product under varying conditions.
Implementation Method 1
the said release control polymer is hydrophobic polymer
Data Source
AI summary
The present invention is related to pharmaceutical composition of upadacitinib comprising upadacitinib or its pharmaceutically acceptable salt thereof, release controlling polymer, pH modifier and one or more pharmaceutical acceptable excipient; wherein the release controlling polymer is hydrophobic polymer.