Stabilized Prostaglandin E Non-Aqueous Formulation
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Solution Overview
Problem
Prostaglandins of the E group, such as PGE1, are relatively insoluble in water and unstable, leading to short shelf life and inconvenience in aqueous solutions, limiting their practical utilization for treatments like sexual erectile dysfunction.
Innovation Solution
Stabilizing prostaglandin E compounds in non-aqueous compositions that include a (C1-C4)-alkyl(C8-C22)carboxylic ester, like ethyl laurate, and optionally a viscosity enhancing agent, without C1-C4 alcohols, to create a room temperature stable formulation for topical application.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If prostaglandin E compounds are dissolved in aqueous solutions for injection, then they can be administered topically or intracavemously, but they exhibit relatively short shelf life and are unstable
Solution Approach 1:
The patent changes the solvent parameter from aqueous to non-aqueous (oil-based) formulation. Specifically, it uses a composition containing a long-chain carboxylic acid ester (C8-C22) as the solvent medium, which fundamentally alters the chemical environment to stabilize the prostaglandin E compound and extend shelf life while maintaining biological activity
Solution Approach 2:
The patent creates a composite formulation combining prostaglandin E compound with specific excipients including long-chain carboxylic acid esters, cyclodextrins, and other stabilizing agents in a non-aqueous medium. This composite system provides synergistic stabilization effects that extend shelf life while preserving therapeutic efficacy
2Ease of operation
If prostaglandin E compounds are formulated as aqueous solutions, then they can be easily administered, but they are relatively insoluble in water and require preparation shortly prior to use
Solution Approach 1:
The patent changes the formulation parameter from aqueous-based to non-aqueous oil-based composition. This allows the prostaglandin E compound to be stored in a stable, pre-prepared form that can be administered immediately without requiring recent preparation, thereby eliminating the time loss associated with fresh preparation while maintaining ease of topical or intracavernous administration
3Reliability
If cyclodextrin complexes are used to stabilize PGE1 in aqueous systems, then some stability improvement is achieved, but the shelf life remains relatively short
Solution Approach 1:
The patent employs a composite stabilization system that combines cyclodextrin complexes with long-chain carboxylic acid esters and other excipients in a non-aqueous medium. This multi-component composite formulation provides enhanced stabilization compared to aqueous cyclodextrin complexes alone, achieving both improved reliability and extended shelf life through synergistic effects of multiple stabilizing agents working together in an oil-based matrix
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 non-aqueous compositions enhance the stability of prostaglandin E compounds while maintaining bioavailability, allowing for a longer shelf life and convenient topical administration in the form of creams or gels for treating sexual dysfunctions.
Implementation Method 1
Prostaglandin E (PGE) group compounds are stabilized as non-aqueous compositions that are substantially free from C1-C4 alcohols and include the prostaglandin E compound together with a (C1-C4)-alkyl(C8-C22)carboxylic ester
Implementation Method 2
about 0.025 to 40 percent by weight of a N,N-di(C1-C8)alkylamino substituted, (C4-C18)alkyl(C2-C18)carboxylic ester skin permeation enhancer, such as dodecyl 2-(N,N-dimethylamino)-propionate
Implementation Method 3
a viscosity enhancing agent such as a polysaccharide, a modified polysaccharide, a cellulose derivative, a cross-linked polyacrylic acid, or a salt thereof
Data Source
AI summary
A prostaglandin E composition comprises are substantially free from C1-C4 alcohols and include the prostaglandin E compound together with a (C1-C4)-alkyl(C8-C22)carboxylic ester (e.g., ethyl laurate), an N,N-di(C1-C8)alkylamino substituted, (C4-C18)alkyl(C2-C18)carboxylic ester and/or a pharmaceutically acceptable addition salt thereof, and optionally, a viscosity enhancing agent such as guar gum. The prostaglandin E composition can be combined with an aqueous alcoholic diluent to form a pharmaceutical composition for topical application to a patient, for example, to treat sexual dysfunction. The prostaglandin E compositions are stable for prolonged periods of storage at room temperature.