Guanfacine Extended Release Liquid Compositions
Solution Overview
Problem
Current solid dosage forms of guanfacine are not suitable for patients with swallowing difficulties and lack convenience in chronic therapy, and existing liquid formulations face challenges in maintaining extended release profiles and stability, leading to inconsistent drug release and potential medical complications.
Innovation Solution
Development of extended release liquid compositions of guanfacine that are bioequivalent to marketed tablet compositions, using a pharmaceutically acceptable carrier with specific release-controlling agents and pH management to maintain stability and consistent drug release over time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If guanfacine is formulated in liquid composition, then patient compliance and convenience are improved, but drug leaching into carrier during storage occurs
Solution Approach 1:
The patent uses an osmotic agent as an intermediary substance that creates an osmotic gradient to prevent guanfacine from leaching into the liquid carrier during storage, while still allowing controlled release in the gastrointestinal tract. This mediator resolves the contradiction by enabling liquid formulation for better compliance without sacrificing compositional stability.
Solution Approach 2:
The patent modifies the osmolality parameter of the liquid composition by adding specific osmotic agents to match or exceed the osmolality of the extended release units. This parameter change prevents leaching during storage while maintaining the ability to provide extended release when administered, thus improving patient compliance without compromising stability.
2Duration of action of moving object
If extended release units are used in liquid composition, then prolonged plasma levels are achieved, but release consistency deteriorates due to leaching
Solution Approach 1:
The osmotic agent acts as a mediator that maintains the integrity of extended release units in the liquid composition, preventing premature drug release during storage while ensuring consistent extended release performance in the gastrointestinal tract, thus maintaining both prolonged duration and release consistency.
Solution Approach 2:
By adjusting the osmolality of the liquid composition through osmotic agents, the patent ensures that the extended release units maintain their release characteristics during storage, preventing leaching that would compromise release consistency while preserving the prolonged plasma level duration.
3Adaptability or versatility
If liquid carrier is used, then dosing flexibility is improved, but drug stability deteriorates
Solution Approach 1:
The patent changes the osmolality parameter of the liquid carrier by incorporating osmotic agents, which creates an environment that stabilizes guanfacine during storage while preserving the dosing flexibility advantages of liquid formulations. This parameter modification allows the liquid form to maintain both versatility and stability.
Solution Approach 2:
The osmotic agent serves as a protective intermediary in the liquid carrier that prevents degradation and leaching of guanfacine, enabling the formulation to maintain drug stability while retaining the dosing flexibility and patient compliance benefits of liquid administration.
4Ease of operation
If conventional liquid formulation is used, then ease of administration is improved, but extended release performance deteriorates
Solution Approach 1:
The osmotic agent acts as a mediator that preserves the extended release mechanism within the liquid formulation, allowing the composition to be easily administered while maintaining prolonged plasma levels and extended release performance that would otherwise be lost in conventional liquid formulations.
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 extended release liquid compositions provide consistent and prolonged plasma levels of guanfacine, ensuring bioequivalence, stability, and improved patient compliance with a pleasant mouth feel, while preventing leaching and maintaining stability for extended periods.
Implementation Method 1
The liquid composition comprises an osmotic agent capable of preventing leaching of the extended release units into the liquid carrier
Implementation Method 2
U.S. Pat. No.'s. 6,287,599 and 6,811,794 describe sustained release tablet compositions of guanfacine, comprising at least one non-pH dependent sustained release agent, and at least one pH dependent agent that increases the rate of release of guanfacine from the tablet at a pH in excess of 5.5
Data Source
AI summary
The present invention relates to extended release liquid compositions of guanfacine. The extended release liquid compositions of the present invention are bioequivalent to marketed extended release tablet compositions of guanfacine. Said extended release liquid compositions provide substantially similar in-vitro dissolution release profile upon storage for at least seven days. Further, the extended release liquid compositions are stable. The extended release liquid compositions are in the form of ready-to-use liquid compositions or reconstituted liquid compositions. It also relates to processes for the preparation of said extended release liquid compositions.