Amorphous Solid Dispersion for Oral Antiviral Solubility
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Solution Overview
Problem
Heterocyclic compounds with potent antiviral activity against influenza virus A and B have low aqueous solubility, making it challenging to develop them into an effective oral drug formulation for treating influenza.
Innovation Solution
An amorphous solid dispersion of Cap-dependent endonuclease inhibitors or their pharmaceutically acceptable salts, combined with water-soluble polymers like polyvinylpyrrolidone or Eudragit, to enhance solubility and bioavailability for oral administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If heterocyclic compounds are used as Cap-dependent endonuclease inhibitors, then antiviral activity against influenza virus is improved, but aqueous solubility deteriorates
Solution Approach 1:
The patent transforms the crystalline compound into an amorphous form, changing the physical state from ordered crystal lattice to disordered molecular arrangement. This parameter change eliminates the rigid crystal structure that limits solubility, allowing the compound to dissolve more readily in aqueous environments while retaining its antiviral activity.
Solution Approach 2:
The patent creates a composite system by dispersing the heterocyclic compound within a polymer matrix (such as HPMC, PVP, or Eudragit). This composite structure combines the antiviral properties of the heterocyclic compound with the solubility-enhancing characteristics of the polymer, resolving the contradiction between maintaining antiviral activity and improving aqueous solubility.
2Quantity of substance
If amorphous solid dispersion is used to improve solubility, then oral bioavailability is improved, but formulation complexity increases
Solution Approach 1:
The patent introduces water-soluble polymers as intermediary substances that mediate between the poorly soluble heterocyclic compound and the aqueous environment. These polymers act as carriers that solubilize the compound through molecular dispersion, simplifying the formulation approach compared to other solubility enhancement techniques while improving oral bioavailability.
Solution Approach 2:
The patent utilizes the phase transition from crystalline to amorphous state as a key mechanism. By controlling the formulation process to produce an amorphous solid dispersion, the compound transitions from a low-solubility crystalline phase to a high-solubility amorphous phase, enhancing oral bioavailability without requiring complex formulation strategies.
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 amorphous solid dispersion formulation improves the solubility and bioavailability of Cap-dependent endonuclease inhibitors, enabling effective oral administration and treatment of influenza virus infections.
Implementation Method 1
an amorphous solid dispersion comprising a Cap-dependent endonuclease inhibitor or a pharmaceutically acceptable salt thereof, or a prodrug thereof
Implementation Method 2
combined with water-soluble polymers like polyvinylpyrrolidone or Eudragit, to enhance solubility and bioavailability
Data Source
AI summary
The present disclosure provides an amorphous solid dispersion containing a Cap-dependent endonuclease inhibitor or a pharmaceutically acceptable salt thereof for oral administration, wherein the Cap-dependent endonuclease inhibitor or a pharmaceutically acceptable salt thereof is dispersed in a matrix formed from the pharmaceutically acceptable polymer. Further disclosed are methods for preparing a above amorphous solid dispersion and a use thereof for treating virus infection and a pharmaceutical composition containing same.