Sustained-Release Injectable Suspension with Easy Redispersion
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Solution Overview
Problem
Existing injectable preparations of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one (Compound (I)) tend to form hard cakes upon precipitation, making redispersion difficult and affecting patient compliance and efficacy in treating central nervous system diseases like schizophrenia.
Innovation Solution
An injectable preparation comprising an aqueous suspension of secondary particles formed by aggregating primary particles of Compound (I) or its salt, with a mean particle diameter of 1 to 50 μm, stabilized by particle binders such as sodium chloride, polyoxyethylene sorbitan fatty acid esters, and polyethylene glycols, allowing easy redispersion and maintaining effective blood concentration for at least one week.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If Compound (I) is formulated as an injectable preparation, then long-acting medication effect is achieved, but hard cake formation occurs upon precipitation making redispersion difficult
Solution Approach 1:
The patent changes the particle size parameter of Compound (I) to a specific range (0.5 μm to 50 μm) and controls the particle size distribution to reduce the proportion of fine particles. This parameter change prevents hard cake formation upon precipitation while maintaining the sustained-release effect, resolving the contradiction between long-acting medication and ease of redispersion
Solution Approach 2:
The patent uses composite materials by combining Compound (I) with specific excipients including particle binders (such as mannitol, sucrose, or lactose), suspending agents (such as carboxymethyl cellulose sodium or polyvinyl alcohol), and lubricants (such as magnesium stearate or colloidal silicon dioxide). This composite formulation prevents hard cake formation and facilitates easy redispersion while maintaining long-acting medication effect
2Ease of operation
If particle size is reduced to improve dissolution, then redispersion becomes easier, but hard cake formation is more likely
Solution Approach 1:
The patent optimizes the particle size parameter to a balanced range (0.5 μm to 50 μm) rather than simply reducing it. This controlled particle size change prevents hard cake formation by avoiding excessive fineness while still maintaining good redispersion properties and dissolution characteristics
3Ease of operation
If Compound (I) is suspended in aqueous solution, then injectability is improved, but precipitation occurs leading to hard cake formation
Solution Approach 1:
The patent formulates a composite suspension system combining Compound (I) with multiple excipients: particle binders (mannitol, sucrose, or lactose) to prevent aggregation, suspending agents (carboxnymethyl cellulose sodium or polyvinyl alcohol) to maintain stability, and lubricants (magnesium stearate or colloidal silicon dioxide) to prevent hardening. This composite formulation maintains injectability while preventing hard cake formation upon precipitation
Solution Approach 2:
The patent introduces intermediary substances (excipients) between Compound (I) and the aqueous solution. These intermediaries include particle binders that prevent direct aggregation of drug particles, suspending agents that stabilize the dispersion, and lubricants that prevent hardening. These intermediaries resolve the contradiction between injectability and suspension stability
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 prevents hard cake formation, enabling easy redispersion and sustained release of Compound (I) or its salt for at least one week, improving patient compliance and therapeutic efficacy.
Implementation Method 1
secondary particles formed by aggregation of particles (primary particles) of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one or a salt thereof
Implementation Method 2
an aqueous suspension comprising secondary particles formed by the aggregation of particles (primary particles) of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one or a salt thereof, the secondary particles having a mean particle diameter (a mean secondary particle diameter) of 1 to 50 μm and being contained in a dispersed state
Implementation Method 3
stabilized by particle binders such as sodium chloride, polyoxyethylene sorbitan fatty acid esters, and polyethylene glycols
Data Source
AI summary
An object of the present invention is to provide a sustained-release injectable preparation which is in a medication administration form that can provide the effect of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one for a prolonged period of time, the preparation releasing a therapeutically effective amount of 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one for at least one week. The present invention provides an injectable preparation containing 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one or a salt thereof as an active ingredient, which releases the active ingredient in such a manner that its blood concentration is maintained for at least one week.