Oseltamivir Phosphate Granules Stability via Impurity Control
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Solution Overview
Problem
Oseltamivir phosphate formulations in granule form lack preservation stability against humidity, temperature, and exhibit coloring and aggregation issues during storage, with no reported studies on the influence of additives.
Innovation Solution
A pharmaceutical composition comprising oseltamivir phosphate with specific excipients such as erythritol, D-mannitol, and sucrose, along with optional components like water-soluble polymers, high-intensity sweeteners, and anti-caking agents, which maintains stability and prevents coloring by controlling water content and impurity levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If granules and the like are used as a dosage form for convenience of pediatric use, then ease of operation is improved, but preservation stability against humidity and temperature deteriorates
Solution Approach 1:
The patent changes the physical and chemical parameters of the excipients by strictly controlling the content of reducing sugars (glucose and mannose) to be not more than 0.01% by weight each. This parameter control prevents Maillard reaction with oseltamivir phosphate, thereby maintaining preservation stability while keeping the granule dosage form convenient for pediatric use.
2Duration of action of stationary object
If granules and the like are stored in the storage environment, then duration of action is extended, but harmful factors (coloring, coagulation, aggregation) increase
Solution Approach 1:
The patent applies preliminary anti-action by pre-controlling the excipient composition to contain not more than 0.01% by weight of glucose and mannose before storage. This preventive measure counteracts the potential Maillard reaction that would otherwise cause coloring, coagulation, and aggregation during storage, allowing extended storage duration without harmful effects.
3Ease of manufacture
If excipients with reducing sugars (glucose, mannose) are used in granules, then ease of manufacture is improved, but object-generated harmful factors (coloring) increase
Solution Approach 1:
The patent modifies the chemical composition parameters of the excipients by limiting reducing sugar content (glucose and mannose) to not more than 0.01% by weight each. This parameter change eliminates the Maillard reaction pathway that causes coloring, while still allowing the use of sugar-based excipients for ease of manufacture.
Data Source
AI summary
The present invention provides a pharmaceutical composition comprising: one or more excipients selected from sugars and sugar alcohols in which equilibrium water content is 1% by weight or less at 25°C and at 70% relative humidity; and oseltamivir phosphate, wherein an amount of each of glucose and mannose contained in the sugars and sugar alcohols as impurities is 0.01% by weight or less.