GTN Stabilized Granules Using Non-Volatile Esters
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Solution Overview
Problem
Current pharmaceutical forms of glyceryl trinitrate (GTN) for oromucosal administration are unstable, volatile, and difficult to carry in emergency situations, with limited storage stability and rapid degradation, leading to challenges in providing rapid and reliable access to the medication.
Innovation Solution
A novel process combining GTN with non-volatile carboxylic acid esters as stabilizers, forming a stable GTN-containing slurry that can be processed into powders, granules, or tablets, using a carrier material and excipients to create a highly stable, non-liquid preparation that prevents volatilization and extends shelf life.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If GTN is prepared as solid commercially available medicinal product, then it provides rapid onset of action for angina pectoris treatment, but it exhibits volatility and limited storage stability leading to degradation
Solution Approach 1:
The patent changes the physical and chemical parameters of GTN by incorporating it into a solid matrix composed of excipients and stabilizers. This matrix formulation transforms GTN from a volatile liquid or solution into a stable solid preparation that maintains rapid onset of action while significantly improving storage stability and preventing degradation.
Solution Approach 2:
The patent creates a composite pharmaceutical preparation by combining GTN with multiple excipients (such as lactose, starch, cellulose) and stabilizers (such as antioxidants, chelating agents). This composite structure protects GTN from volatility and degradation while maintaining its therapeutic efficacy and rapid absorption properties.
2Reliability
If GTN is formulated in liquid phlegmatized solutions, then it allows safe preparation and handling, but it increases volume and complicates portability for emergency use
Solution Approach 1:
The patent utilizes phase transition by converting the liquid phlegmatized GTN solution into a solid preparation form. This phase change from liquid to solid dramatically reduces volume, eliminates the need for voluminous spray bottles, and enables easy portability in emergency situations while maintaining safe handling characteristics.
Solution Approach 2:
The patent develops single-dose solid preparations that can be individually packaged and carried without requiring patients to maintain large volumes of liquid medication. This approach replaces the need for carrying bulky spray bottles with compact, disposable solid doses that are ready for immediate use.
3Volume of moving object
If GTN tablets are made small for easy carrying, then portability improves, but removal of single tablets becomes difficult in emergency situations
Solution Approach 1:
The patent segments the GTN medication into individual single-dose solid preparations that are separately packaged. Each segment contains a complete therapeutic dose, allowing easy removal and administration without the need to handle or separate small tablets from a bulk container during emergency situations.
4Ease of operation
If GTN is administered in powder or granule form in stick packs, then single-dose portability and ease of dosing improve, but stabilization becomes more challenging due to larger total surface area
Solution Approach 1:
The patent introduces stabilizers and antioxidants as intermediary substances that protect GTN from degradation in powder and granule formulations. These stabilizers act as mediators between GTN and environmental factors (oxygen, moisture), preventing oxidation and hydrolysis that would otherwise be accelerated by the large surface area of particulate forms.
Solution Approach 2:
The patent creates a composite powder or granule system where GTN is combined with multiple excipients and stabilizers in a matrix structure. This composite formulation maintains the dosing advantages of stick packs while the stabilizer components protect against degradation despite the increased surface area exposure.
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 resulting solid pharmaceutical preparation is highly stable, allowing for comfortable carrying in single-dose forms like stick packs, maintaining efficacy and stability under various conditions, including elevated temperatures, and ensuring rapid absorption and action when needed.
Implementation Method 1
stabilized by addition of a stabilizer comprising a non-volatile ester
Implementation Method 2
GTN-containing powders or granules—with their substantially larger total surface area as compared with tablets
Implementation Method 3
GTN is readily hydrolyzed both in the acidic and alkaline pH range. Degradation reactions form 1,3- or 1,2-glyceryl dinitrate (GDN) and 1- or 2-glyceryl mononitrate (GMN)
Data Source
AI summary
Solid pharmaceutical preparation with the active substance glyceryl trinitrate for oromucosal or oral administration characterized in that it contains between 0.05 and 2 weight % glyceryl trinitrate, at least one carrier material, and at least one substance that reduces the volatility of the GTN, whereby this substance is a non-volatile ester stabilizer.