Solid Cyclodextrin Eye Drop Complexes for Ocular Drug Solubility
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Solution Overview
Problem
Current ophthalmic drug delivery methods face challenges in delivering effective doses of drugs to target tissues in the eye due to low solubility, rapid drug concentration decrease, and slow permeation through membrane barriers, leading to limited bioavailability and systemic side effects.
Innovation Solution
The preparation of ophthalmic compositions involving solid complexes of active pharmaceutical ingredients with cyclodextrins, utilizing controlled heating and cooling processes to form microparticles with tailored diameter and viscosity, enhancing solubility and precorneal half-life while preventing impurity formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If topical eye drops are administered for drug delivery to the eye, then convenience and safety are improved, but drug solubility and permeation through membrane barriers deteriorate
Solution Approach 1:
Cyclodextrins are used as intermediary molecules that form inclusion complexes with hydrophobic drugs, enabling them to dissolve in the aqueous environment of eye drops. The cyclodextrin cavity encapsulates the drug molecule, acting as a mediator between the hydrophobic drug and hydrophilic tear fluid, thereby resolving the solubility contradiction while maintaining topical administration convenience
2Ease of operation
If topical eye drops are administered for drug delivery to the eye, then convenience and safety are improved, but drug permeation through membrane barriers deteriorates
Solution Approach 1:
The invention changes the physical-chemical parameters of the drug delivery system by forming cyclodextrin inclusion complexes, which modify the drug's solubility, stability, and permeation characteristics. This parameter transformation enables effective drug delivery through ocular membranes while preserving the convenience of topical administration
3Quantity of substance
If heating is applied to form solid cyclodextrin complexes, then complex formation and solubility enhancement are improved, but impurity formation may worsen
Solution Approach 1:
The invention utilizes phase transition by heating the cyclodextrin and drug mixture to dissolve components and form complexes in the molten state, then cooling to precipitate the solid inclusion complex. This controlled phase transition enables effective complex formation and solubility enhancement while the cooling process can be optimized to minimize impurity formation
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 method provides a 10- to 100-fold increase in dissolved active pharmaceutical ingredient concentration, improved bioavailability, and reduced impurities, thereby overcoming the obstacles of passive drug diffusion in the eye.
Implementation Method 1
Cyclodextrins are well-known to enhance the solubility and bioavailability of hydrophobic compounds. In aqueous solutions, cyclodextrins form inclusion complexes with many active pharmaceutical ingredients.
Implementation Method 2
The suspension is heated for a sufficient time at a sufficient temperature until the active pharmaceutical ingredient and the cyclodextrin are dissolved in the aqueous eye drop solution
Implementation Method 3
The resulting solution is cooled at a rate sufficient to produce a microparticle active pharmaceutical ingredient/cyclodextrin complex
Implementation Method 4
Cyclodextrins are well-known to enhance the solubility and bioavailability of hydrophobic compounds
Implementation Method 5
The method provides a 10- to 100-fold increase in dissolved active pharmaceutical ingredient concentration, improved bioavailability, and reduced impurities
Data Source
AI summary
The present disclosure relates to ophthalmic compositions containing solid complexes of active pharmaceutical ingredient and cyclodextrin, to their method of preparation and their uses. The compositions can include an active agent drug/cyclodextrin complex substantially dissolved in an aqueous eye drop vehicle. The ophthalmic composition is generally in the form of a microsuspension including an active agent complex having a diameter of less than about 100 μm.