Setmelanotide Sustained Release via Lipid Liquid Crystals
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing pharmaceutical formulations of biological compounds, such as setmelanotide, result in rapid release, leading to short durations of action and undesirable pharmacokinetic and pharmacodynamic profiles.
Innovation Solution
A pharmaceutical product comprising setmelanotide or an MC4 receptor agonist, combined with lipid excipients, an alcohol, and a polar solvent, formulated to provide a sustained release through a non-lamellar liquid crystalline phase, optimizing pharmacokinetic and pharmacodynamic profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If setmelanotide is administered in standard formulations, then the compound is delivered to the subject, but the release is rapid resulting in short duration of action and undesirable pharmacokinetic profile
Solution Approach 1:
The patent applies parameter changes by modifying the physical and chemical parameters of the formulation system. Specifically, it changes the phase behavior of lipid excipients to form non-lamellar liquid crystalline phases (HII, V1, V2) instead of conventional lamellar phases. This phase change fundamentally alters the release kinetics, extending the duration of action from hours to days while improving the pharmacokinetic profile through controlled, sustained release of setmelanotide.
Solution Approach 2:
The patent employs composite materials by combining setmelanotide with specific lipid excipients that form non-lamellar liquid crystalline phases. The composite system includes lipids capable of forming HII, V1, or V2 phases in combination with aqueous buffers, creating a multi-phase composite formulation that provides sustained release. This composite approach allows the system to maintain structural integrity while enabling controlled drug release over extended periods.
2Loss of time
If setmelanotide is administered in standard formulations, then the compound is delivered to the subject, but the release is rapid leading to frequent dosing requirements
Solution Approach 1:
The patent utilizes phase transitions by employing lipid excipients that undergo transitions to form non-lamellar liquid crystalline phases (HII, V1, V2). These phase transitions create structured assemblies with controlled porosity and diffusion pathways, enabling sustained release of setmelanotide. The phase behavior of the lipids naturally regulates the release rate, extending the duration of action and reducing dosing frequency without requiring external control mechanisms.
3Object-affected harmful factors
If setmelanotide is administered in standard formulations, then the compound is delivered to the subject, but side effects increase due to rapid release
Solution Approach 1:
The patent applies parameter changes by fundamentally altering the release rate parameter through the use of non-lamellar liquid crystalline phases. The HII, V1, and V2 phase structures create controlled diffusion environments that slow down the release of setmelanotide, converting rapid release into sustained release. This parameter modification directly reduces peak concentrations and extends exposure time, thereby minimizing side effects associated with rapid drug delivery.
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 controlled and extended release of setmelanotide, providing a more desirable pharmacokinetic and pharmacodynamic profile, with improved duration of action and reduced side effects.
Implementation Method 1
formulated to provide a sustained release through a non-lamellar liquid crystalline phase
Data Source
AI summary
This disclosure provides, at least in part, a pharmaceutical product comprising: setmelanotide (also known as RM493); setmelanotide as sole active pharmaceutical ingredient formulated for injection; setmelanotide as the sole active ingredient; setmelanotide as the active pharmaceutical ingredient; setmelanotide as the active pharmaceutical ingredient for injection; or another pharmaceutical composition that has its primary mechanism of action at the MC4 receptor as an agonist (referred to herein as an MC4RAP), e.g., a lipid excipient, and/or a pharmaceutically acceptable carrier. The pharmaceutical product described herein provides a sustained release of setmelanotide or another pharmaceutical composition, which may result in a more desirable pharmacokinetic and pharmacodynamic profile upon administration.