Lipid Pre-Formulation for Sustained Peptide Release
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current controlled-release systems for bioactive agents, particularly peptides and proteins, face challenges due to poor bioavailability and rapid degradation, leading to inconvenient administration routes and irritation issues, with polymer-based depot compositions causing burst release profiles and irritation.
Innovation Solution
A lipid-based pre-formulation comprising a sorbitan ester, phospholipid, and a biocompatible organic solvent, eliminating the need for a liquid crystal hardener, which forms a non-lamellar liquid crystalline phase upon contact with aqueous fluids, providing a controlled release matrix with a non-burst release profile and improved bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If polymer-based depot compositions are used for controlled release, then sustained release over long period is achieved, but burst release profile and irritation at injection site occur
Solution Approach 1:
The patent changes the fundamental parameter of the release matrix from polymer-based to lipid-based pre-formulation. The lipid components (sorbitan ester, phospholipid, and biocompatible organic solvent) undergo phase transition upon contact with aqueous media to form a controlled release matrix, eliminating the burst release and irritation issues associated with polymer degradation products like acetic acid, lactic acid, and glycolic acid.
Solution Approach 2:
The lipid-based pre-formulation exploits phase transition phenomena where the lipid components spontaneously reorganize from an isotropic liquid state into a structured controlled release matrix (such as liquid crystalline phases or gel structures) upon contact with body fluids. This phase transition enables sustained release without the harmful effects of polymer degradation, providing a non-burst release profile while maintaining biocompatibility.
2Reliability
If peptides and proteins are administered to achieve therapeutic effect, then bioactivity is achieved, but rapid degradation by proteolytic enzymes reduces bioavailability
Solution Approach 1:
The lipid-based pre-formulation acts as a protective shell or matrix that encapsulates the peptide or protein bioactive agent. This lipid matrix protects the peptide from exposure to proteolytic enzymes in the body, thereby preventing enzymatic degradation and improving bioavailability. The flexible lipid structure allows for controlled release of the protected peptide over time.
3Reliability
If high concentration of bioactive agent is administered to overcome rapid clearance, then therapeutic level is maintained, but frequency of administration increases
Solution Approach 1:
The lipid-based pre-formulation enables a single administration to provide sufficient bioactive agent at therapeutic levels over an extended period. The controlled release matrix releases the bioactive agent gradually, maintaining therapeutic concentrations without requiring frequent dosing, thus reducing the time loss associated with repeated administrations.
4Reliability
If non-oral routes of administration are used for peptides, then bioavailability is improved, but self-administration becomes difficult and compliance decreases
Solution Approach 1:
The lipid-based pre-formulation changes the physical parameters of the formulation to enable easy self-administration. The pre-formulation has properties that allow it to be administered through smaller needles via subcutaneous injection, making self-administration feasible and improving patient compliance while maintaining the bioavailability benefits of non-oral routes.
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 allows for a controlled and sustained release of bioactive agents, reducing irritation and improving bioavailability, enabling self-administration through smaller needles and maintaining therapeutic levels without the need for frequent dosing.
Implementation Method 1
comprising lipids that upon exposure to water or aqueous media, such as body fluids, spontaneously undergo at least one phase transition, thereby forming a controlled release matrix
Implementation Method 2
forms a non-lamellar liquid crystalline phase upon contact with aqueous fluids
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to pre-formulations comprising low viscosity, non- liquid crystalline, mixtures of: a) at least one ester of a sugar or sugar derivative; b) at least one phospholipid; c) at least one biocompatible, oxygen containing, low viscosity organic solvent; wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with an aqueous fluid; with the proviso that the pre-formulation does not further comprise a liquid crystal hardener. The preformulations are suitable for generating parenteral, non-parenteral and topical depot compositions for sustained release of active agents. The invention additionally relates to a method of delivery of an active agent comprising administration of a preformulation of the invention, a depot composition formed by exposing pre-formulations of the invention to an aqueous fluid, a method of treatment comprising administration of a preformulation of the invention and the use of a preformulation of the invention.