Modified-Release Oral Contraceptive Composition for Lower EE Doses
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing combined oral contraceptives (COCs) with low doses of ethinyl estradiol (EE) face issues of adverse events, irregular bleeding patterns, and reduced contraceptive efficacy, leading to non-compliance and increased pregnancy risk.
Innovation Solution
A prolonged-release oral contraceptive composition comprising 2 mg of dienogest and equal to or less than 0.02 mg of EE, with at least 80% of EE intended for slow release, providing a reliable contraceptive efficacy and acceptable bleeding pattern.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If the dose of ethinyl estradiol (EE) is reduced to decrease incidence of VTEs and adverse events, then safety and tolerability are improved, but contraceptive efficacy and cycle control deteriorate
Solution Approach 1:
The patent divides the release of dienogest into two distinct phases: a first phase with rapid release providing initial contraceptive protection, and a second phase with delayed slow release maintaining hormone levels during the hormone-free interval. This segmentation allows lower total EE doses while maintaining efficacy through optimized timing of progestogen release.
Solution Approach 2:
The invention implements a periodic release pattern where dienogest is released in pulses - an initial rapid release phase followed by a delayed slow release phase. This periodic action mimics physiological hormone patterns and maintains contraceptive efficacy with lower EE doses by ensuring adequate progestogen coverage at critical times.
2Object-affected harmful factors
If the dose of ethinyl estradiol (EE) is reduced to improve tolerability, then adverse events decrease, but bleeding patterns become irregular
Solution Approach 1:
The patent applies preliminary action by providing rapid release of dienogest at the beginning of the cycle (first phase) before the hormone-free interval starts. This initial progestogen surge prepares the endometrium and establishes stable bleeding patterns before the reduced EE dose takes effect during the hormone-free period, preventing irregular bleeding.
Solution Approach 2:
The invention changes the temporal parameters of hormone release rather than simply reducing doses. By shifting from continuous release to phased release (rapid then slow), the patent maintains endometrial stability and regular bleeding patterns even with lower EE doses, as the timing of progestogen availability is optimized.
3Object-affected harmful factors
If the dose of ethinyl estradiol (EE) is reduced to decrease adverse events, then safety improves, but compliance decreases due to non-compliance from adverse events and irregular bleeding
Solution Approach 1:
The patent segments the hormone release into two phases with different release rates, allowing the product to maintain efficacy and regular bleeding patterns at lower EE doses. This reduces adverse events that cause discontinuation, thereby improving compliance without sacrificing contraceptive protection.
4Reliability
If conventional rapid release formulation is used, then contraceptive efficacy is maintained, but peak fluctuations increase leading to more adverse events
Solution Approach 1:
The patent implements periodic action through phased release - an initial rapid release phase providing immediate contraceptive coverage, followed by a delayed slow release phase. This periodic pattern reduces peak fluctuations compared to continuous rapid release, decreasing adverse events while maintaining contraceptive efficacy throughout the cycle.
Solution Approach 2:
The invention changes the release rate parameters of dienogest over time, transitioning from rapid release to slow release. This temporal parameter change smooths out peak fluctuations in hormone levels, reducing adverse events associated with high peaks while maintaining adequate minimum levels for contraceptive efficacy.
Data Source
AI summary
The invention relates to a new modified release oral pharmaceutical form comprising 17α-cyanomethyl-17-ß-hydroxyestra-4,9-dien-3-one (dienogest) and 17α-ethinylestradiol (ethynyl estradiol), its method of production and its medical and non-medical uses, in particular its use in contraception.