Ocular Sustained Release Formulations Using Eutectic Liquid Excipients
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Solution Overview
Problem
Current drug delivery methods for ocular treatments often result in high and low blood concentrations and shortened half-life, requiring large doses that can lead to toxic side effects, and there is a need for more economical and efficient sustained release formulations for biologics in the eye.
Innovation Solution
The development of biocompatible and biodegradable injectable pharmaceutical formulations using a combination of non-polymeric liquid excipients such as citrate esters and a small amount of poly(D, L-lactide) or poly(D,L-lactide-co-glycolide) polymer, which maintains a liquid state and releases active agents for a sustained period, allowing for controlled kinetics and prolonged delivery of therapeutic proteins to the eye.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional drug delivery methods (topical application, oral delivery, intramuscular, intravenous, subcutaneous injection) are used, then drugs can be administered to patients, but the drugs result in high and low blood concentrations and shortened half-life, requiring large doses that may result in toxic side effects
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation by using a eutectic mixture of cyclic carbonate and cyclic carbamate, which fundamentally alters the release profile of the drug. This eutectic system enables sustained release at the injection site, transforming the pharmacokinetic parameters from rapid clearance to prolonged local availability, thereby maintaining therapeutic efficacy while avoiding toxic side effects associated with large doses
Solution Approach 2:
The eutectic mixture of cyclic carbonate and cyclic carbamate acts as an intermediary vehicle that carries the biologic drug (such as PEG interferon) and controls its release. This intermediary system provides a controlled interface between the administered drug and the body, enabling sustained release kinetics and preventing the rapid fluctuations in blood concentration that lead to toxicity
2Reliability
If large doses of medications are administered to achieve therapeutic efficacy, then therapeutic goals can be met, but toxic side effects may result
Solution Approach 1:
The eutectic formulation provides continuous release of the biologic drug at the injection site over an extended period. This continuous action maintains steady therapeutic levels without the peaks and troughs of conventional administration, ensuring reliable therapeutic efficacy while avoiding the toxic side effects that result from administering large doses to compensate for rapid clearance
3Productivity
If standard injection methods are used, then drugs can be delivered systemically, but the drugs result in shortened half-life in the blood
Solution Approach 1:
The patent segments the drug delivery process into two distinct phases: an initial loading dose that establishes therapeutic levels, followed by sustained release from the eutectic formulation at the injection site. This segmentation eliminates the need for repeated systemic dosing and extends the effective half-life by maintaining local reservoirs of the drug that release continuously, thereby improving delivery efficiency while extending duration of action
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
These formulations provide a sustained release of active agents for at least 14 days, maintaining therapeutic concentrations and minimizing side effects, while being injectable through small needles and maintaining monolithic integrity in the eye, suitable for various ocular applications.
Implementation Method 1
comprising: at least one active agent; at least one non-polymeric liquid excipient... and a small amount (e.g., less than 10% ± 1%) of a poly(D, L- lactide) (PLA) or poly(D,L-lactide-co-glycolide) (PLGA) polymer... upon initial injection the composition maintains its monolithic integrity in a liquid state
Implementation Method 2
at least one biodegradable, biocompatible poly(D, L- lactide) (PLA) or poly(D,L-lactide-co-glycolide) (PLGA) polymer... wherein the composition releases the active agent for a period of at least about 14 days
Data Source
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AI summary
The present invention provides for injectable pharmaceutical sustained release formulations for delivery of active agents, particularly therapeutic proteins, to the eye. The formulations are biocompatible, biodegradable sustained release formulations comprising low- solubility liquid excipients and relatively small amounts (less than about 10%) of biocompatible, biodegradable polymer such as PLA or PLGA polymers. A unit dose of 5 muL to 100 muL of the formulation provides for sustained release of the agent for at least 14 days.