Drospirenone Particle Size and Dosing for Contraceptive Reliability

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Solution Overview

Problem

Current progestogen-only contraceptives (POCs) have low reliability, alter bleeding patterns, and are not well-tolerated due to high plasma concentration peaks of drospirenone, leading to side effects and poor compliance.

Innovation Solution

Development of pharmaceutical compositions and kits with novel dosing regimens for drospirenone that allow for skipped doses and a pharmacokinetic profile with reduced Cmax and delayed Tmax, ensuring effective contraception with reduced side effects and improved tolerance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional progestogen-only contraceptives are used, then contraception is provided, but reliability is low and bleeding patterns are altered

Engineering Contradiction:

Improvecontraceptive reliabilityVSAvoidaltered bleeding patterns

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the particle size parameter of drospirenone from conventional micronized form to a specific size range (d10≥5μm, d50≥15μm, d90≤50μm) to modify dissolution rate and achieve smoother plasma concentration profile, thereby improving reliability while reducing harmful bleeding patterns

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces a dosing regimen with periodic skipped doses (taking the pill every other day or skipping up to 2 doses per cycle) to create intentional fluctuations in plasma concentration that maintain contraceptive efficacy while reducing side effects and improving bleeding patterns

Inventive Principle:

Principle #19Periodic action

2Reliability

If high plasma concentration peaks of drospirenone are achieved, then contraceptive efficacy is ensured, but side effects increase and tolerance decreases

Engineering Contradiction:

Improvecontraceptive efficacyVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the particle size parameter of drospirenone to control dissolution rate, achieving a pharmacokinetic profile with reduced Cmax (peak concentration) while maintaining adequate AUC (area under curve), thereby ensuring contraceptive efficacy with reduced side effects

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies a coating or formulation approach that cushions the release of drospirenone, preventing sudden high plasma concentration peaks and reducing associated side effects while maintaining overall exposure and contraceptive efficacy

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

3Ease of manufacture

If drospirenone is micronized to promote rapid dissolution, then oral bioavailability is improved, but plasma concentration peak becomes too high

Engineering Contradiction:

Improveoral bioavailabilityVSAvoidplasma concentration peak

Core Design Contradiction:

Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent optimizes the particle size parameter within a specific range (not too fine, not too coarse) to achieve a balance between dissolution rate (affecting bioavailability) and peak plasma concentration, avoiding both poor absorption and excessive peaks

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS11439598B2Synthetic progestogens and pharmaceutical compositions comprising the same

Publication Date: 2022.09.13 LAB LEON FARMA

AI summary

Described herein are synthetic progestogens, such as 6β,7β:15β,16β-Dimethylene-3-oxo-17α-pregn-4-ene-21,17-carbolactone, as well as pharmaceutical compositions comprising the same. Also described are methods of use.