Regorafenib Coated Composition Low-Temperature Stability
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Solution Overview
Problem
The challenge is to develop a coated pharmaceutical composition of regorafenib that maintains high purity, both immediately after coating and during storage, due to its limited solubility and potential for degradation.
Innovation Solution
A pharmaceutical composition comprising regorafenib, a hydrate, solvate, or pharmaceutically acceptable salt thereof, coated with a polyvinyl alcohol-based polymer and optional excipients, which enhances stability and bioavailability, and is administered orally in the form of a solid dispersion, particularly using polyvinylpyrrolidone as a matrix agent, with a coating process conducted at controlled low temperatures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If regorafenib is administered as a solid formulation requiring coating, then oral convenience and mechanical stability are improved, but drug degradation during coating and storage increases
Solution Approach 1:
The patent changes the critical parameter of coating temperature from conventional high temperatures to low temperatures (≤40°C, preferably ≤35°C). This parameter change prevents thermal degradation of regorafenib while still achieving effective coating formation, thereby resolving the contradiction between maintaining drug stability and providing oral convenience through coating.
Solution Approach 2:
The patent introduces an intermediary approach by using a multi-component coating system comprising polyvinyl alcohol, polyethylene glycol, and titanium dioxide. This coating composition acts as a protective intermediary layer that shields the regorafenib from degradation during storage and handling, allowing the drug to maintain stability while still providing the mechanical protection and oral convenience of a coated formulation.
2Productivity
If conventional coating temperatures are used, then coating efficiency and film formation are improved, but regorafenib degradation increases
Solution Approach 1:
The patent fundamentally changes the temperature parameter from conventional coating temperatures (typically 45-65°C or higher) to low temperatures (≤40°C, preferably ≤35°C). This parameter change maintains adequate coating efficiency through optimized coating composition and process control while dramatically reducing regorafenib degradation, thus resolving the contradiction between productivity and substance loss.
Solution Approach 2:
The patent employs a composite coating material system consisting of polyvinyl alcohol as the film-forming polymer, polyethylene glycol as a plasticizer and solubility enhancer, and titanium dioxide for opacity and protection. This composite material system achieves effective coating formation at low temperatures, resolving the contradiction between coating efficiency and drug stability.
3Reliability
If regorafenib is formulated with improved solubility, then bioavailability is improved, but manufacturing complexity increases
Solution Approach 1:
The patent uses a composite material approach where regorafenib is formulated with polyethylene glycol and other excipients in a solid dispersion system. This composite formulation improves solubility and bioavailability through the synergistic effects of the components while using conventional solid dispersion manufacturing techniques, thereby avoiding excessive manufacturing complexity.
Solution Approach 2:
The patent changes the physical state and solubility parameters of regorafenib through solid dispersion technology, transforming the drug into a more soluble form. This parameter change improves bioavailability while the process uses established solid dispersion manufacturing methods, keeping manufacturing complexity at acceptable levels.
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 composition achieves reduced degradation of regorafenib, maintaining its potency and stability for extended periods, including during storage, with minimal generation of side products, and ensures effective pharmacological activity when administered.
Implementation Method 1
the pharmaceutical composition is coated by a coating comprising a polyvinyl alcohol based polymer
Implementation Method 2
a coating process conducted at controlled low temperatures
Data Source
AI summary
Abstract The present invention relates to a coated pharmaceutical composition containing regorafenib, a hydrate, solvate, metabolite or pharmaceutically acceptable salt thereof or a polymorph thereof and its process of preparation and its use for treating disorders.