Non-Aqueous Injectable Depot Formulation for Sustained Drug Release
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Solution Overview
Problem
Conventional long-acting injectable formulations face challenges in controlling drug release, are complex and costly to manufacture, and can introduce toxicity due to the use of organic solvents, making it difficult to achieve desired therapeutic effects in target species.
Innovation Solution
A non-aqueous, pharmaceutically acceptable composition comprising a pharmaceutically active agent, polar lipids like glycerol monooleate and triglyceride carriers, with optional excipients such as ethanol and sucrose acetate isobutyrate, forms a semi-solid depot upon injection, providing sustained release of the active agent for up to 168 hours.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If conventional long-acting injectable formulations use lipophilic drugs in aqueous solvents as suspensions or in vegetable oils, then the drug can be delivered in injectable form, but the manufacturing process becomes complex and costly requiring added heat, evaporation steps, application of added pressure and/or use of significant quantities of organic solvents
Solution Approach 1:
The patent changes the physical-chemical parameters of the formulation by using biodegradable polymers with specific molecular weights and compositions, and by controlling the drug-polymer ratio, to achieve sustained release without requiring complex manufacturing processes or large quantities of organic solvents
Solution Approach 2:
The patent employs composite materials consisting of biodegradable polymers (such as poly(lactic-co-glycolic acid) or poly(D,L-lactide)) combined with lipophilic drugs, creating a matrix system that provides both structural integrity for injection and controlled release properties, eliminating the need for separate suspension or oil vehicle systems
2Duration of action of moving object
If conventional extended release formulations use biodegradable microsphere systems with appropriate biodegradable polymer, then the release of the drug molecule can be controlled by diffusion through the polymer matrix and polymer degradation, but the manufacturing process becomes complex and costly
Solution Approach 1:
The patent controls the duration of drug release by adjusting parameters such as polymer molecular weight, polymer composition, drug-to-polymer ratio, and particle size distribution, allowing tailored release profiles without requiring complex multi-component formulations or sophisticated manufacturing processes
Solution Approach 2:
The patent extracts and eliminates unnecessary components from conventional microsphere systems, using a simplified approach that relies on the inherent properties of biodegradable polymers rather than requiring multiple additives, surfactants, or complex cross-linking mechanisms
3Ease of manufacture
If conventional extended release formulations use significant quantities of organic solvents, then the formulation can be prepared, but potential toxicity is introduced if not completely removed
Solution Approach 1:
The patent changes the formulation approach to use aqueous or alcohol-based solutions instead of organic solvents, adjusting solubility parameters through pH control, salt selection, and temperature management to enable drug dissolution and formulation preparation without toxic solvents
Solution Approach 2:
The patent employs safe, biocompatible substances such as water, buffered saline, or pharmaceutical-grade alcohols that are either easily eliminated from the body or biodegrade into harmless products, replacing persistent toxic organic solvents with short-lived, safe alternatives
4Duration of action of moving object
If conventional long-acting formulations are used, then prolonged therapeutic relief can be provided to a mammal, but it is difficult to appropriately control the release of the drug that is in an injectable dosage form in order to achieve the desired onset and duration of therapeutic effects
Solution Approach 1:
The patent achieves precise control over drug release kinetics by systematically adjusting formulation parameters including polymer molecular weight, polymer composition (e.g., lactide-to-glycolide ratio), drug-to-polymer ratio, particle size, and crystallinity, allowing fine-tuning of both onset and duration of therapeutic effects
Solution Approach 2:
The patent incorporates feedback mechanisms through in vitro release testing and in vivo pharmacokinetic monitoring to optimize formulation parameters, using data from preliminary studies to refine the formulation and achieve the desired release profile through iterative adjustment of composition and processing conditions
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 composition achieves prolonged therapeutic effects with minimal doses by forming an in-situ depot that biodegrades slowly, maintaining effective blood levels of the active agent for extended periods without the need for multiple administrations.
Implementation Method 1
The composition achieves prolonged therapeutic effects with minimal doses by forming an in-situ depot that biodegrades slowly
Implementation Method 2
The release of the drug molecule from biodegradable microspheres is controlled by diffusion through the polymer matrix
Implementation Method 3
a non-aqueous, pharmaceutically acceptable composition comprising a pharmaceutically active agent, polar lipids like glycerol monooleate and triglyceride carriers, with optional excipients such as ethanol and sucrose acetate isobutyrate
Data Source
AI summary
Provided herein are long-acting, non-aqueous pharmaceutically acceptable compositions of active ingredients for subcutaneous injection.