Controlled Release Formulation Reducing Burst Release
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Solution Overview
Problem
Existing controlled release formulations for highly water-soluble active agents often exhibit undesirable initial burst release, leading to poor in vivo performance and manufacturing complexities, particularly when using hydrophilic polymers or waxes, which result in high costs and difficult production processes.
Innovation Solution
A controlled release formulation combining a non-polymeric release retardant with a pH-independent non-swelling release retardant, such as Kollidon SR, to achieve reduced initial burst release and sustained drug delivery independent of physiological pH, using melt granulation to produce granules that maintain consistent drug release rates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If hydrophilic polymers such as cellulose ethers and carbomers are used for controlled release, then sustained release is achieved, but high initial burst release occurs leading to poor in vivo performance
Solution Approach 1:
The patent employs a composite matrix system combining hydrophilic polymer (cellulose ether) with hydrophobic wax and polymer coating. This composite structure leverages the sustained release capability of hydrophilic polymers while the hydrophobic components suppress initial burst release, achieving both sustained delivery and reduced harmful initial release
Solution Approach 2:
The patent applies a polymer coating layer (thin film) over the core formulation containing hydrophilic polymer and wax. This coating acts as a barrier that modulates water penetration and drug release, reducing initial burst release while maintaining sustained release characteristics through controlled diffusion
2Object-generated harmful factors
If hydrophobic polymers and waxes are used to control initial burst release, then burst release is reduced, but manufacturing complexity and cost increase
Solution Approach 1:
The patent combines multiple functions into a single matrix formulation: the hydrophilic polymer provides sustained release, the hydrophobic wax suppresses burst release, and the polymer coating provides additional barrier protection. This merging of multiple control mechanisms into one formulation simplifies manufacturing compared to multi-layer coatings or complex multi-step processes
3Duration of action of moving object
If swelling polymers are used to retard drug release, then sustained release is achieved, but high initial burst release occurs due to delayed swelling
Solution Approach 1:
The patent changes the physical-chemical parameters of the release retardant by selecting non-swelling hydrophobic polymers and waxes with specific melting points and viscosities. These parameter adjustments ensure immediate effectiveness without relying on swelling time, thereby eliminating the delay that causes initial burst release while maintaining sustained release
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 combination of non-polymeric and pH-independent release retardants in the formulation significantly reduces initial burst release, providing a consistent and prolonged drug release profile with enhanced bioavailability and therapeutic effectiveness, while simplifying the manufacturing process and reducing costs.
Implementation Method 1
controlled release formulation comprising a combination of non-polymeric release retardant and pH independent non-swelling release retardant
Implementation Method 2
active agents having aqueous solubility of greater than 1 mg/ml
Data Source
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AI summary
The present invention provides a controlled release formulation comprising an therapeutically effective amount of pharmacologically active substance having high water solubility, at least one non-polymeric release retardant, and at least one pH independent non-swelling release retarding polymer. The said dosage form provides controlled release of the active agent with reduced initial burst release.