Amorphous-Crystalline Solid Dispersion for Hepatitis C Drug Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current hepatitis C treatments with velpatasvir, sofosbuvir, and voxilaprevir, when used in combination, lack understanding of their therapeutic benefits and face challenges related to stability and side effects.
Innovation Solution
A fixed dosage composition of sofosbuvir, velpatasvir, and voxilaprevir is developed, where velpatasvir is substantially amorphous, sofosbuvir is substantially crystalline, and voxilaprevir is substantially amorphous, formulated with polymers like hypromellose and copovidone to enhance stability and dissolution profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If three antiviral compounds (velpatasvir, sofosbuvir, and voxilaprevir) are co-formulated into a fixed dosage composition, then therapeutic benefits are improved and side effects are reduced, but stability and dissolution profiles become challenging to maintain
Solution Approach 1:
The patent applies local quality by assigning different physical states to different active ingredients within the same formulation. Velpatasvir and voxilaprevir are formulated in amorphous state to enhance dissolution, while sofosbuvir is maintained in crystalline form to ensure stability. This differentiated approach allows each compound to contribute its optimal properties to the combination product, resolving the contradiction between therapeutic benefit and stability.
Solution Approach 2:
The invention employs composite materials by creating a multi-phase solid dispersion system where amorphous velpatasvir and voxilaprevir are dispersed in a polymer matrix alongside crystalline sofosbuvir. This composite structure enables the formulation to simultaneously achieve improved dissolution (from amorphous phases) and enhanced stability (from crystalline phase), directly addressing the technical contradiction.
2Speed
If velpatasvir and voxilaprevir are formulated as amorphous solids in a polymer matrix, then dissolution profile is improved, but manufacturing complexity increases
Solution Approach 1:
The patent uses pharmaceutically acceptable polymers as intermediary materials to disperse and stabilize the amorphous velpatasvir and voxilaprevir. These polymer matrices act as mediators that prevent recrystallization of the amorphous compounds while facilitating their dissolution. Common polymers used include hydroxypropyl methylcellulose, polyvinylpyrrolidone, and ethyl cellulose, which simplify the manufacturing process by providing a ready-made dispersing medium.
Data Source
AI summary
Disclosed are pharmaceutical compositions comprising three antiviral compounds. In particular, the pharmaceutical compositions comprise an effective amount of velpatasvir, an effective amount of sofosbuvir, and an effective amount of voxilaprevir. Also disclosed are methods of use for the pharmaceutical composition.