Nalfurafine Solid Formulation Without Light-Shielding Coating
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Solution Overview
Problem
Existing methods fail to improve the photostability of nalfurafine or its pharmaceutically acceptable acid addition salts, and large amounts of light-shielding coatings complicate production and reduce stability during storage.
Innovation Solution
A solid preparation comprising nalfurafine or its acid addition salt with stabilizing agents like n-propyl gallate, dibutylhydroxytoluene, butylhydroxyanisole, tocopherol, and D-isoascorbic acid, in specific ratios, without a light-shielding coating, to enhance photostability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a light-shielding coating is applied to improve photostability, then photostability is improved, but device complexity and manufacturing complexity increase
Solution Approach 1:
The invention extracts and eliminates the light-shielding coating layer from the pharmaceutical preparation, achieving photostability through the stabilizing agent system alone. This removes the complexity of coating application while maintaining protection against light-induced degradation.
Solution Approach 2:
The invention changes the chemical composition parameters by introducing specific stabilizing agents (sodium thiosulfate, saccharides, sugar alcohols, and low substituted hydroxypropyl cellulose) that chemically protect the active ingredient from light degradation, replacing the physical barrier approach of coatings.
2Reliability
If antioxidants and stabilizing agents are added to improve chemical stability, then chemical stability is improved, but manufacturing precision and formulation complexity increase
Solution Approach 1:
The invention creates a composite stabilizing system combining multiple components (sodium thiosulfate as antioxidant, saccharides and sugar alcohols as stabilizers, and low substituted hydroxypropyl cellulose as protective matrix) that work synergistically to protect the active ingredient, achieving enhanced stability through material composition rather than precise formulation control.
3Reliability
If large amounts of light-shielding coating are applied to ensure photostability, then photostability is improved, but productivity decreases due to complex production processes
Solution Approach 1:
The invention eliminates the time-consuming light-shielding coating process entirely by incorporating stabilizing agents directly into the preparation formulation, allowing for simpler manufacturing steps and improved production efficiency while maintaining photostability.
Solution Approach 2:
The stabilizing agents are incorporated into the preparation during the formulation stage rather than requiring post-manufacturing coating steps, performing the protective function in advance and eliminating subsequent processing steps that would reduce productivity.
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 preparation maintains high photostability, allowing easy handling and dosing without complex coatings, with the active ingredient retaining over 90% stability under light exposure.
Implementation Method 1
nalfurafine and pharmaceutically acceptable acid addition salts thereof, which are known to be compounds with remarkable antipruritic effects, are chemically unstable to, for example, heat, light, and oxygen
Implementation Method 2
The preparation maintains high photostability, allowing easy handling and dosing without complex coatings, with the active ingredient retaining over 90% stability under light exposure
Data Source
AI summary
An object of the present invention is to provide a solid preparation comprising a 4,5-epoxymorphinan derivative or a pharmaceutically acceptable acid addition salt thereof, which is stable to light even without light shielding coating. The present invention provides the solid preparation comprising an active ingredient composed of a 4,5-epoxymorphinan derivative as represented below or a pharmaceutically acceptable acid addition salt thereof, and one or more stabilizing agents selected from the group consisting of n-propyl gallate, sodium hydrogensulfite, dibutylhydroxytoluene, butylhydroxyanisole, tocopherol and D-isoascorbic acid, wherein the amount of the above active ingredient is 0.00001 to 0.01% by weight of the solid preparation, and the amount of the above stabilizing agent is 0.005 to 5% by weight of the solid preparation.