Iloperidone Depot Injection Prevents Needle Clogging

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Solution Overview

Problem

The challenge in administering depot formulations of antipsychotic drugs like iloperidone is the clogging of needles during intramuscular injection, particularly with pre-mixed or pre-constituted formulations.

Innovation Solution

A method for preparing and administering an injectable depot formulation of crystalline iloperidone by suspending it in a vehicle, characterized by specific particle sizes and concentrations, and injecting it intramuscularly in a single, fast push, using a syringe, to prevent clogging and ensure effective delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If depot formulations are pre-mixed or pre-constituted, then patient compliance is improved through controlled release, but needle clogging occurs during intramuscular injection

Engineering Contradiction:
Improvepatient complianceVSAvoidinjection process
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The depot formulation is divided into two separate components: a lyophilized powder containing crystalline iloperidone and a separate sterile vehicle solution. This segmentation allows each component to be optimized independently - the crystals can be properly formed for controlled release while the vehicle remains free-flowing, eliminating needle clogging when mixed immediately before injection

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The iloperidone is pre-processed into specific crystal forms with controlled particle size distributions (Dv50 between 5-50 μm) and lyophilized in advance. This preliminary action ensures the crystals are ready for suspension without requiring extensive mixing or processing during the injection procedure, preventing clogging while maintaining compliance

Inventive Principle:
Principle #10Preliminary action

2Ease of operation

If crystal size is reduced to prevent needle clogging, then injection ease is improved, but controlled release performance deteriorates

Engineering Contradiction:
Improveinjection processVSAvoidcontrolled release
Core Design Contradiction:
Ease of operationVSDuration of action of moving object

Solution Approach 1:

The invention specifies precise particle size parameters (Dv50 between 5-50 μm, with preferred ranges of 7-20 μm or 10-20 μm) that optimize both injectability and release characteristics. This parameter optimization ensures crystals are small enough to pass through needles without clogging while maintaining sufficient mass and surface area properties for controlled release over the desired time period

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The formulation combines crystalline iloperidone particles with specific excipients (mannitol, sodium chloride, polysorbate 80) in a sterile aqueous vehicle. This composite system provides a suspension medium that keeps crystals dispersed and prevents aggregation, ensuring both smooth injection and consistent controlled release performance

Inventive Principle:
Principle #40Composite materials

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 method allows for the successful administration of crystalline iloperidone without needle clogging, ensuring proper reconstitution and delivery of the drug in a controlled manner, improving patient compliance and treatment efficacy for schizophrenia.

Implementation Method 1

combining crystalline iloperidone with a suspension vehicle to produce a suspension having a concentration of 166.67 mg to 200 mg of crystalline iloperidone per mL of vehicle solution. The crystalline iloperidone may be suspended in the vehicle, e.g., by agitating, vortexing, or manually shaking.

Methodology Applied
Scientific EffectSuspension: Suspension

Data Source

PatentUS20240252479A1Depot administration of iloperidone
Publication Date: 2024.08.01 VANDA PHARMACEUTICALS INC

AI summary

Methods of preparing and administering an injectable depot formulation of crystalline iloperidone are disclosed herein.