Effervescent Pramipexole Formulation for Stable Neutral pH
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Solution Overview
Problem
Current pramipexole formulations, particularly tablets and capsules, face challenges with patient compliance due to difficulty in swallowing and stability issues, as well as unpleasant taste and potential gastrointestinal damage from acidic or alkaline environments, necessitating the development of an effervescent formulation that is stable, non-hygroscopic, and has a controlled disintegration time.
Innovation Solution
An effervescent formulation comprising pramipexole or its pharmaceutically acceptable salt, solvate, or hydrate, combined with a specific ratio of acidifying and alkalizing agents, such as fumaric acid and sodium glycine carbonate, along with other excipients like fillers, binders, and sweeteners, to create a stable, rapidly dissolving, and neutrally tasting tablet or sachet that maintains drug efficacy and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If effervescent formulations are designed to dissolve quickly in water, then ease of administration is improved, but stability problems occur due to hygroscopic porous structure
Solution Approach 1:
The patent changes the chemical composition parameters by selecting specific acidifying agents (citric acid, fumaric acid, ascorbic acid) and alkalizing agents (sodium glycine carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, sodium bicarbonate, sodium carbonate) in controlled ratios to create a formulation that dissolves quickly while maintaining stability. The specific combination and ratio of these agents modify the physical and chemical properties of the effervescent tablet to achieve both rapid dissolution and resistance to humidity.
Solution Approach 2:
The patent uses composite materials by combining multiple excipients including acidifying agents, alkalizing agents, fillers, disintegrants, binders, lubricants, antioxidants, aromatic agents, and sweeteners in a specific formulation. This composite approach creates an effervescent tablet that leverages the properties of each component to achieve both rapid dissolution and stability, with the composite structure providing both porosity for dissolution and resistance to hygroscopic effects.
2Stability of the object's composition
If acidifying agent - alkalizing agent couple is used to buffer water-active solution, then active ingredient stability is improved, but disintegration time and taste become problematic
Solution Approach 1:
The patent optimizes the ratio parameter of acidifying agents to alkalizing agents to achieve the desired balance between stability and disintegration time. By controlling this critical parameter, the formulation maintains neutral pH without excessive buffering, allowing rapid disintegration while preventing premature reaction that would extend dissolution time.
Solution Approach 2:
The patent applies local quality by using specific types of acidifying agents (citric acid, fumaric acid, ascorbic acid) and alkalizing agents (sodium glycine carbonate, ammonium carbonate, potassium carbonate, calcium carbonate, sodium bicarbonate, sodium carbonate) with different reaction characteristics. This selective combination creates localized zones of acid-base reaction within the tablet structure, enabling controlled disintegration timing while maintaining overall stability.
3Stability of the object's composition
If high amount of acidifying agent is used, then pH control is improved, but gastrointestinal damage occurs
Solution Approach 1:
The patent converts the potentially harmful effect of strong acidifying agents into a beneficial buffering system by combining them with alkalizing agents in controlled ratios. The acid-base reaction neutralizes the harsh effects of high concentrations of either agent, creating a mild, controlled pH change that protects the gastrointestinal system while still achieving the desired stability and disintegration effects.
Solution Approach 2:
The patent uses the acidifying agent-alkalizing agent couple as an intermediary buffering system that mediates between the need for pH control and the avoidance of gastrointestinal damage. This intermediary reaction system provides controlled pH adjustment without the extreme acidity or alkalinity that would directly harm the gastrointestinal tract, effectively translating a potentially harmful parameter into a protective mechanism.
4Stability of the object's composition
If high amount of alkalizing agent is used, then pH control is improved, but precipitation and gastrointestinal damage occur
Solution Approach 1:
The patent converts the harmful effect of high alkalizing agent concentrations into a beneficial buffering system by pairing them with acidifying agents in controlled ratios. This combination prevents the extreme alkalinity that would cause precipitation and gastrointestinal damage, while still achieving the desired pH control and stability effects through the balanced acid-base reaction.
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 achieves a neutral pH solution without precipitation, desired disintegration time, and improved gastric absorption, while being non-hygroscopic and non-damaging to the gastrointestinal system, enhancing patient compliance and stability.
Implementation Method 1
They generally contain acidifying agents and alkalizing agents which react rapidly in the presence of water by releasing carbon dioxide such as carbonates or bicarbonates. Carbon dioxide emitted by the effervescent reaction can induce enhanced active-ingredient permeability due to an alteration of the paracellular pathway.
Implementation Method 2
Acidifying agent - alkalizing agent couples, however, can buffer the water-active solution so that the stomach pH increases and thus prevent the degradation or inactivation of the active ingredient.
Implementation Method 3
Carbon dioxide emitted by the effervescent reaction can induce enhanced active-ingredient permeability due to an alteration of the paracellular pathway.
Data Source
AI summary
The present invention relates to an effervescent formulation comprising pramipexole or a pharmaceutically acceptable salt, solvate or hydrate thereof and one or more pharmaceutically acceptable excipients.