Non-Aqueous Carrier Sustained Release Formulations
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Solution Overview
Problem
Existing injectable sustained release formulations face issues with short-term stability, require separate packaging and storage, and often result in an undesirable initial burst release of active pharmaceutical ingredients, which can lead to toxic side effects.
Innovation Solution
A one-component injectable formulation comprising microspheres suspended in a non-aqueous pharmaceutically acceptable carrier, specifically a poly(lactide-co-glycolide) polymer with exenatide and sucrose, using a medium chain triglyceride carrier that provides long-term stability and controlled release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If aqueous carrier is used in injectable sustained release formulations, then the formulations can be prepared and administered, but they do not offer long term stability and require separate packaging and storage
Solution Approach 1:
The patent changes the fundamental parameter of the carrier from aqueous to non-aqueous (oil-based). This parameter change enables long-term stability of the formulation while allowing single-container packaging, as the non-aqueous carrier prevents degradation and maintains formulation integrity over extended periods without requiring separation into multiple packages
2Duration of action of moving object
If presently available injectable microsphere formulations are used, then sustained release is achieved, but a large burst release occurs following injection causing undesirable in vivo release
Solution Approach 1:
The patent uses a composite system combining non-aqueous carrier with biodegradable polymer microspheres. This composite approach modifies the release mechanism by eliminating the aqueous environment that causes rapid initial dissolution, thereby reducing burst release while maintaining sustained release properties through the polymer degradation mechanism
Solution Approach 2:
The patent changes the carrier parameter from aqueous to non-aqueous, which fundamentally alters the release kinetics. This parameter change prevents the immediate dissolution and rapid release characteristic of aqueous formulations, thereby reducing burst release while preserving the sustained release function through controlled polymer degradation
3Duration of action of moving object
If two-component formulations are used, then sustained release formulations can be provided, but the patient must mix the formulation with carrier prior to injection reducing ease of use
Solution Approach 1:
The patent merges the carrier and microsphere components into a single integrated formulation. The non-aqueous carrier serves as both the suspension medium and the sustained release matrix, eliminating the need for separate mixing steps and allowing patients to administer the therapy directly from a single container without complex preparation procedures
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 offers extended stability, reduced burst release, and convenient self-administration, maintaining therapeutic levels of the active ingredient within a therapeutic window, thereby enhancing safety and efficacy while simplifying patient use.
Implementation Method 1
Injectable sustained release formulations comprising a non-aqueous carrier and microspheres
Data Source
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AI summary
The disclosure provides one-component, injectable, sustained release formulations which comprise microspheres containing active pharmaceutical ingredients (e.g., exenatide), wherein the microspheres are suspended in a non-aqueous carrier. The non-aqueous carrier can be an oil, a fractionated oil, triglycerides, diglycerides, monoglycerides, propylene glycol fatty acid diesters, and the like. The formulations offer distinct advantages of long shelf life for the stability and potency of the formulation and sustained release of active pharmaceutical ingredients to reduce the frequency of medication dosing and to increase patient compliance.