Iloprost Injection Formulation for Systemic Sclerosis
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Solution Overview
Problem
Current iloprost treatments for systemic sclerosis, particularly for symptomatic Raynaud's Phenomenon and digital ulcers, are limited by the need for lengthy intravenous or subcutaneous infusions, which are invasive and associated with complications such as site reactions and infections, and have poor oral bioavailability.
Innovation Solution
A pharmaceutical composition providing a single daily subcutaneous injection of iloprost or its salt/stereoisomer, achieving maximum serum concentration within a controlled range and maintaining therapeutic levels for extended periods, thereby reducing the frequency and severity of symptomatic Raynaud's episodes and preventing digital ischemia, using a formulation that includes phospholipids, oils, and excipients to ensure stability and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If intravenous or subcutaneous infusion is used to deliver iloprost, then the drug can be delivered to systemic circulation, but the administration time becomes lengthy (6 hours) and requires invasive procedures with associated complications
Solution Approach 1:
The patent divides the drug delivery process into two distinct phases: a loading phase that rapidly delivers an initial dose of iloprost to achieve therapeutic levels, followed by a maintenance phase that provides sustained release over time. This segmentation eliminates the need for continuous 6-hour infusions while ensuring reliable drug delivery to systemic circulation
Solution Approach 2:
The patent employs a preliminary loading dose administered before the sustained release phase. This preliminary action rapidly establishes therapeutic drug levels in the system, after which the sustained release formulation maintains these levels without requiring continued infusion, thereby reducing overall administration time and eliminating the need for prolonged invasive procedures
2Reliability
If intravenous or subcutaneous infusion is used to deliver iloprost, then the drug can be delivered to systemic circulation, but the procedure becomes invasive with complications such as infiltration, extravasation, and infections
Solution Approach 1:
The patent extracts the need for invasive catheter-based delivery by using an intramuscular injection formulation that provides sustained release. This removes the harmful elements associated with intravenous catheters (infiltration, extravasation, infection risks) while maintaining reliable drug delivery to systemic circulation through the muscle tissue absorption pathway
Solution Approach 2:
The patent introduces an intermediary mechanism - the intramuscular injection site and its absorption characteristics - that serves as a safe intermediate step between direct intravenous injection and oral administration. This intermediary approach provides reliable systemic delivery without the harmful complications of catheter-based intravenous or subcutaneous infusions
3Reliability
If subcutaneous continuous infusion is used to deliver iloprost, then the drug can be delivered to systemic circulation, but high rates of site reactions and site pain occur
Solution Approach 1:
The patent inverts the traditional subcutaneous infusion approach by using intramuscular injection instead. This reversal of the injection site and method eliminates the high rates of site reactions and pain associated with subcutaneous delivery while maintaining reliable drug delivery to systemic circulation through the different absorption characteristics of muscle tissue
4Loss of time
If controlled release systems are used to reduce administration time, then the drug release can be measured and controlled, but volatile drug substances like iloprost undergo degradation in drug delivery systems
Solution Approach 1:
The patent changes the physical and chemical parameters of the drug delivery system by using an intramuscular injection formulation with specific excipients and pH conditions that stabilize iloprost. This parameter optimization allows controlled release kinetics to be achieved while preventing degradation of the volatile drug substance during storage and delivery
Data Source
AI summary
The present disclosure generally relates to treatment of systemic sclerosis with symptomatic Raynaud's Phenomenon and/or digital ulcers by subcutaneous or intramuscular injection of iloprost or a pharmaceutically acceptable salt or stereoisomer thereof.