Solid-Core Oil Marble Compositions for Poorly Soluble Drugs

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing pharmaceutical formulations of poorly water-soluble active ingredients face challenges in mechanical stability, storage stability due to humidity and temperature sensitivity, and patient compliance issues with soft gelatin capsules, necessitating a method for solid dosage forms with controlled or immediate release of active ingredients while improving patient comfort.

Innovation Solution

A pharmaceutical composition based on oil marbles with a solid core containing an active ingredient, pharmaceutically acceptable wax, and a shell of solid particles, allowing for controlled release rates and improved mechanical strength, suitable for hard capsules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If liquid marbles are used for poorly water-soluble active ingredients, then solubility and bioavailability are improved, but mechanical strength and stability are insufficient

Engineering Contradiction:
Improvesolubility and bioavailabilityVSAvoidmechanical strength
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The invention uses a composite shell structure comprising solid particles (such as sugars, polymers, or inorganic materials) that form a mechanically strong yet flexible barrier around the liquid core. This composite approach combines the solubility-enhancing properties of liquid marbles with the mechanical strength of solid particulate matrices, resolving the contradiction between reliability in dissolution and mechanical integrity.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The shell formed by solid particles creates a flexible yet mechanically robust barrier that maintains the liquid core's integrity while allowing controlled interaction with the environment. This flexible shell structure prevents premature rupture under mechanical stress while maintaining the liquid marble's dissolution properties, thereby improving both mechanical strength and reliability.

Inventive Principle:
Principle #30Flexible shells and thin films

2Quantity of substance

If soft gelatin capsules are used for liquid preparations, then loading of active ingredient is achieved, but size and weight increase making them difficult to swallow

Engineering Contradiction:
Improveloading of active ingredientVSAvoidease of swallowing
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The invention segments the active ingredient into multiple small liquid marble units, each containing a portion of the total dose. These miniaturized units (ranging from micrometers to millimeters in size) can be easily swallowed individually or in small groups, eliminating the difficulty of swallowing large soft gelatin capsules while maintaining the required total loading of active ingredient through aggregation of multiple segments.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from macroscopic soft gelatin capsules to microscopic or millimeter-scale liquid marbles, effectively moving the dosage form to a smaller dimensional scale. This dimensional reduction allows the active ingredient to be delivered in forms that are easily ingestible while maintaining therapeutic efficacy through controlled release mechanisms at the microscale.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Ease of manufacture

If gelatin shell is used for soft gelatin capsules, then liquid preparation is encapsulated, but sensitivity to humidity and temperature increases storage restrictions

Engineering Contradiction:
Improveencapsulation of liquid preparationVSAvoidstorage stability
Core Design Contradiction:
Ease of manufactureVSStability of the object's composition

Solution Approach 1:

The invention changes the material parameters of the encapsulation shell from gelatin-based (which is hygroscopic and temperature-sensitive) to solid particles with controlled properties such as sugars, polymers, or inorganic materials. These alternative materials exhibit superior stability across a broader range of humidity and temperature conditions, reducing storage restrictions while maintaining encapsulation functionality.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The solid particle shell provides a disposable, single-use encapsulation structure that protects the liquid core during storage and administration. These shells are designed to be stable under various storage conditions and to dissolve or disintegrate under controlled conditions in the body, eliminating the need for complex storage infrastructure required by gelatin capsules.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Duration of action of moving object

If liquid marbles are used, then controlled release is achieved, but irreversible deformation and destruction occur under compression force

Engineering Contradiction:
Improvecontrolled releaseVSAvoidstructural integrity under force
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

The composite shell structure made of solid particles provides enhanced mechanical strength that can withstand compression forces during handling, filling, and administration. The particulate matrix acts as a reinforcing framework that maintains structural integrity while allowing the liquid core to maintain its controlled release properties, preventing premature rupture or deformation.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The solid particle shell serves as a protective cushioning layer that absorbs and distributes mechanical stresses before they can reach the liquid core. This beforehand protection prevents irreversible deformation and destruction of the liquid marble structure under compression, ensuring reliable delivery of the controlled release function.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

Data Source

PatentEP3666256B1Pharmaceutical composition for solid dosage forms
Publication Date: 2025.10.01 ZENTIVA AS
  • EP3666256B1 patent drawingFigure 1~2
  • EP3666256B1 patent drawingFigure 3~4
  • EP3666256B1 patent drawingFigure 5

AI summary

The present invention provides oil marbles for pharmaceutical compositions, comprising: - a core containing an active ingredient which is dissolved, suspended or dispersed in a pharmaceutically acceptable solvent, said core further comprising at least one component selected from the group comprising a pharmaceutically acceptable polymer, a pharmaceutically acceptable wax, a pharmaceutically acceptable solid polymer matrix; and - a shell containing or comprised of solid particles, said solid particles comprising at least one pharmaceutically acceptable filler or binder. These solid-core oil marbles are suitable for preparation of pharmaceutical formulations, in particular for poorly soluble active ingredients, and namely for decreasing the size of the pharmaceutical form and influencing the release rate of the active ingredient.