Ospemifene Solid Dispersion Amorphous State Solubility

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Poorly water-soluble drugs like ospemifene face challenges in bioavailability and absorption due to low solubility, leading to delayed therapeutic effects and increased dosages, which are costly and inefficient.

Innovation Solution

The development of solid dispersions comprising ospemifene combined with hydrophilic carriers such as polyvinylpyrrolidine, copovidone, and surfactants, which enhance solubility and bioavailability by forming amorphous states that prevent crystallization during dissolution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If ospemifene is administered in conventional oral dosage form, then manufacturing and administration are simplified, but solubility and bioavailability are poor

Engineering Contradiction:
Improveease of manufactureVSAvoidbioavailability
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent applies parameter changes by transforming ospemifene from its conventional crystalline solid state into an amorphous solid dispersion state. This phase change from crystalline to amorphous form fundamentally alters the drug's solubility parameters, enabling significantly improved dissolution and bioavailability while maintaining the benefits of oral dosage forms.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite material system by dispersing ospemifene molecules within a hydrophilic carrier matrix. This composite structure combines the lipophilic drug with hydrophilic polymers, forming a new material system that leverages the carrier's solubility-enhancing properties to overcome the drug's poor water solubility.

Inventive Principle:
Principle #40Composite materials

2Reliability

If higher dosages are used to compensate for poor absorption, then therapeutic effect is achieved, but cost increases and treatment efficiency decreases

Engineering Contradiction:
Improvetherapeutic effectVSAvoiddosage
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

By changing the physical state parameter from crystalline to amorphous, the patent dramatically improves the dissolution rate and extent of ospemifene. This enables achieving therapeutic plasma concentrations with lower dosages, as the amorphous form provides more rapid and complete absorption compared to conventional crystalline formulations.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If solid dispersion technology is applied to improve solubility, then bioavailability increases, but manufacturing complexity and cost increase

Engineering Contradiction:
ImprovebioavailabilityVSAvoidmanufacturing complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs self-service principles by utilizing the inherent properties of the hydrophilic carrier to stabilize ospemifene in an amorphous state during processing. The carrier's molecular structure naturally prevents drug crystallization through molecular interactions, reducing the need for complex external stabilization mechanisms or specialized manufacturing equipment.

Inventive Principle:
Principle #25Self-service

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 solid dispersion formulation significantly increases the solubility and bioavailability of ospemifene, allowing for reduced dosages and improved therapeutic effects, with enhanced absorption and stability across various pH levels.

Implementation Method 1

forming amorphous states that prevent crystallization during dissolution

Methodology Applied
Scientific EffectAmorphous state formation: Vitrification

Implementation Method 2

amorphous states that prevent crystallization during dissolution

Methodology Applied
Scientific EffectCrystallization prevention: Metastability

Implementation Method 3

solid dispersions comprising ospemifene combined with hydrophilic carriers such as polyvinylpyrrolidine, copovidone, and surfactants, which enhance solubility

Methodology Applied
Scientific EffectSurfactant action: Surfactant

Data Source

PatentEP3270696B1Solid dispersions comprising ospemifene
Publication Date: 2023.09.06 SHIONOGI INC
  • EP3270696B1 patent drawingFigure 1
  • EP3270696B1 patent drawingFigure 2~3
  • EP3270696B1 patent drawingFigure 4~5

AI summary

An ospemifene solid dispersion for enhancing solubility and bioavailability,, and methods of preparation thereof are disclosed. The solid dispersion comprises an active pharmaceutical ingredient, such as ospemifene, and a hydfophilie carrier, such as copovidone, hypromellose acetate succinate, polyvinylpyrrolidine, a polyvinylpyrrolidine/vinyl acetate co-polymer, hydroxy! propyl methylcellulose, hypromellose acetate succinate, a Eudragit® compound, hydroxypropylcellulose, a polyvinyl caprolactam-polyvinyl acetate polyethylene glycol graft co-polymer, hydroxypropyl methylcellulose phthalate, and mixtures thereof, and optionally a surfactant The ospemifene solid, dispersions can be used in methods of treating a symptom related, to menopause, such as vaginal dryness or sexual dysfunction, or in methods of treating osteoporosis.