Bictegravir Sodium Polymorphs for Solubility and Stability
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Solution Overview
Problem
Current polymorphic forms of Bictegravir, an HIV integrase inhibitor, exhibit variations in stability, solubility, and bioavailability due to differences in physicochemical properties, affecting the quality and performance of HIV treatment formulations.
Innovation Solution
Development of novel crystalline forms of Bictegravir sodium, specifically Forms C2 to C9, characterized by unique X-ray powder diffraction patterns, along with processes for their preparation, including dissolution in solvents and treatment with alcoholic sodium solutions, to enhance stability and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If different polymorphic forms of Bictegravir are used, then solubility and dissolution rate may be improved, but stability and bioavailability become unpredictable
Solution Approach 1:
The patent applies parameter changes by systematically varying crystallization conditions (solvent type, temperature, pH, additives) to produce specific polymorphic forms of Bictegravir sodium. Each polymorphic form (Forms C2-C9) has distinct crystal lattice parameters and physical properties, allowing optimization of both solubility and stability through controlled parameter selection during manufacturing.
2Speed
If various polymorphic forms are developed to improve dissolution rate, then manufacturing complexity increases
Solution Approach 1:
The patent employs preliminary action by pre-determining the optimal polymorphic form (Forms C2-C9) for each specific application through advance characterization and selection. Once a particular polymorphic form is selected based on desired dissolution rate, the manufacturing process is standardized around that specific form, eliminating the need to manage multiple polymorphic forms simultaneously and thereby reducing manufacturing complexity.
3Stability of the object's composition
If novel polymorphic forms are created to enhance stability, then characterization and detection difficulty increases
Solution Approach 1:
The patent replaces complex manual characterization methods with advanced analytical techniques including X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and nuclear magnetic resonance (NMR). These instrumental methods automatically detect and characterize the polymorphic forms, reducing the difficulty of analysis while providing comprehensive stability data for each form (Forms C2-C9).
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 novel polymorphic forms of Bictegravir sodium improve stability, solubility, and bioavailability, leading to more effective HIV treatment formulations with predictable pharmacokinetic profiles and reduced impurities.
Implementation Method 1
The crystalline nature of forms according to the present invention is characterized by X-ray powder diffraction pattern
Implementation Method 2
processes for their preparation, including dissolution in solvents and treatment with alcoholic sodium solutions
Data Source
AI summary
Novel crystalline forms of Bictegravir sodium, pharmaceutical compositions containing said crystalline forms and the use of said crystalline forms in the treatment of HIV infection are disclosed. The present invention is further directed to the processes for the preparation of the novel crystalline forms.