Injectable Ropinirole Composition pH Control

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Solution Overview

Problem

Current treatments for Parkinson's disease, particularly oral formulations, suffer from peak-trough blood level fluctuations leading to side effects and poor patient compliance due to gastric motility issues, necessitating a non-gastrointestinal tract dependent and stable injectable ropinirole formulation.

Innovation Solution

Development of injectable ropinirole compositions with low impurities, stable for extended periods, achieved by controlling pH between 3.0 and 6.5, using antioxidants, and manufacturing in reduced oxygen environments, allowing for continuous infusion and bypassing gastrointestinal absorption.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If oral formulations are used to treat Parkinson's disease, then the treatment can be administered easily, but the blood levels fluctuate between peaks and troughs causing side effects and poor compliance

Engineering Contradiction:

Improveease of administrationVSAvoidblood level stability

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent replaces the gastrointestinal absorption mechanism (oral administration) with direct parenteral injection to deliver ropinirole into the bloodstream, thereby eliminating the peak-trough fluctuations caused by gastric emptying and intestinal absorption variability while maintaining ease of administration through simple injection routes

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Ease of operation

If sustained release oral formulations are used, then patient compliance improves, but gastric motility dysfunction delays absorption and onset of symptom relief

Engineering Contradiction:

Improvepatient complianceVSAvoiddelayed onset of symptom relief

Core Design Contradiction:

Ease of operationVSLoss of time

Solution Approach 1:

The patent replaces the gastrointestinal tract-dependent sustained release mechanism with direct parenteral injection, bypassing the dysfunctional gastric motility and intestinal absorption barriers that delay onset, while maintaining compliance benefits through reduced dosing frequency achievable via injection

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If ropinirole is formulated for injection, then gastrointestinal dependence is eliminated, but the composition becomes unstable and forms impurities during manufacturing and storage

Engineering Contradiction:

Improveindependence from gastrointestinal tractVSAvoidcomposition stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent introduces antioxidants (such as ascorbic acid, sodium metabisulfite, or citric acid) as intermediary substances that chemically scavenge oxygen and prevent oxidative degradation of ropinirole during manufacturing and storage, thereby stabilizing the injectable composition without compromising its therapeutic efficacy

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs inert atmosphere techniques during manufacturing processes, replacing oxygen-containing air with nitrogen or other inert gases in the manufacturing environment and in the headspace of storage containers, thereby preventing oxidation of ropinirole and maintaining composition stability throughout the product lifecycle

Inventive Principle:

Principle #39Inert atmosphere (Inert environment)

4Manufacturing precision

If oxidation is prevented by adding antioxidants, then impurity formation is reduced, but the manufacturing process becomes more complex

Engineering Contradiction:

Improveimpurity controlVSAvoidmanufacturing process complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent optimizes the pH of the injectable composition to fall within the range of 3.0 to 6.5, a parameter change that inherently reduces the rate of ropinirole oxidation and impurity formation, thereby achieving impurity control through simple pH adjustment rather than complex manufacturing processes or multiple antioxidants

Inventive Principle:

Principle #35Parameter changes

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 injectable ropinirole compositions provide stable and effective dopaminergic symptom relief with reduced fluctuations, improving patient compliance and maintaining potency over time, even after sterilization and lyophilization.

Implementation Method 1

reducing or preventing oxidation of the ropinirole by adding an antioxidant

Methodology Applied

Scientific EffectOxidation: Oxidation

Implementation Method 2

manufacturing in a reduced oxygen environment

Methodology Applied

Scientific EffectOxidation: Oxidation

Implementation Method 3

lyophilizing the pH-adjusted ropinirole so as to form the injectable lyophilized ropinirole composition

Methodology Applied

Scientific EffectLyophilization: Freeze Drying

Data Source

PatentUS9155695B2Injectable ropinirole compositions and methods for making and using same

Publication Date: 2015.10.13 MEDTRONIC INC

AI summary

Compositions and methods are provided that utilize an injectable ropinirole having a therapeutically effective amount of ropinirole in an aqueous solvent, the composition having a pH of from about 3.0 to about 6.5. The compositions and methods provided contain less than 3% by weight of impurities and are suitable for administration by infusion pumps. In some embodiments, the compositions are made in an oxygen free environment and/or are made with an antioxidant to reduce impurities and improve stability. In some embodiments, the compositions provided are utilized to treat Parkinson's disease.