Melatonin Nanoparticles for Neonatal Parenteral Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current melatonin formulations for parenteral administration are unstable, poorly soluble in water, and have low bioavailability, making it challenging to deliver effective doses for neonatal brain injury, particularly due to oxidative stress in neonates.
Innovation Solution
A pharmaceutical formulation comprising melatonin nanoparticles mixed with high-purity phospholipids and a cryoprotectant agent, such as mannitol and trehalose, is developed using micro jet reactor technology to create a stable and safe parenteral delivery system for neonates, ensuring high drug loading and stability during storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If melatonin is administered in aqueous solution, then it can be delivered via parenteral route, but it degrades quickly and loses potency due to instability in water
Solution Approach 1:
The patent uses phospholipids as intermediary substances to form nanoparticles that encapsulate melatonin. These phospholipid nanoparticles act as a mediator between the water-soluble parenteral route and the water-insoluble melatonin, allowing parenteral administration while protecting melatonin from degradation in aqueous environment.
Solution Approach 2:
The patent changes the physical state and solubility parameters of melatonin by forming nanoparticles. The melatonin is transformed from a water-insoluble crystalline form into a nanoscale particulate system with enhanced surface area and altered solubility characteristics, enabling parenteral administration while maintaining stability.
2Stability of the object's composition
If melatonin is formulated with stabilizers and preservatives to improve stability, then potency is maintained, but toxicological problems may occur especially in infants
Solution Approach 1:
The patent employs phospholipids that are naturally occurring, biocompatible, and rapidly metabolized by the body. These phospholipid nanoparticles serve as temporary delivery vehicles that degrade into safe, naturally occurring components after delivering melatonin, eliminating the need for long-term stabilizers or preservatives that could pose toxicological risks.
Solution Approach 2:
The patent changes the chemical composition parameters by selecting phospholipids with specific purity levels (≥99%) and specific types (phosphatidylcholines, phosphatidylglycerols, etc.), creating a formulation that is inherently stable and biocompatible without requiring additional stabilizing agents.
3Ease of operation
If oral melatonin is administered, then it is easier to administer, but bioavailability is low and very variable
Solution Approach 1:
The patent segments melatonin into nanoscale particles, increasing the surface area to volume ratio dramatically. This segmentation overcomes the poor solubility and variable absorption characteristics of oral melatonin by creating a formulation that can be directly delivered into the bloodstream via parenteral route, ensuring consistent bioavailability.
Solution Approach 2:
The patent transitions from oral (gastrointestinal) administration to parenteral (intravenous/intramuscular) administration, changing the dimensional route of delivery. This bypasses the variable absorption through the gastrointestinal tract and delivers melatonin directly into the systemic circulation, ensuring consistent and predictable bioavailability.
4Quantity of substance
If high doses of melatonin are administered to achieve therapeutic effect, then treatment efficacy improves, but formulation stability and safety become more challenging
Solution Approach 1:
The patent creates a composite material system consisting of melatonin encapsulated within phospholipid nanoparticles. This composite structure allows high concentrations of melatonin to be formulated stably by distributing the drug molecules within the phospholipid matrix, preventing crystallization and degradation even at therapeutic dose levels.
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 provides a stable and effective delivery of melatonin, achieving high drug loading and maintaining potency, suitable for the treatment of neonatal brain injuries like hypoxic-ischemic encephalopathy, with improved bioavailability and safety for neonates.
Implementation Method 1
wherein at least one of said phospholipid is adsorbed on melatonin surface
Implementation Method 2
25 to 80% by weight of a mixture of mannitol and trehalose as cryoprotectant agent
Data Source
AI summary
The present invention relates to a melatonin formulation suitable for parenteral administration to neonates. In particular, the present invention relates to a pharmaceutical formulation comprising nanoparticles of melatonin for use for the treatment of neonatal brain injury. The formulation could be in form of powder to be reconstituted before use or in form of ready-to-use suspension in a proper aqueous vehicle. The invention is also directed to a process of its preparation and to therapeutic uses thereof.