Plinabulin Hydrochloride Salt Forms for Stability and Bioavailability
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Solution Overview
Problem
There is a need for additional solid state forms and salts of Plinabulin, including hydrochloride, to improve processing properties, stability, and bioavailability for effective cancer treatment, as existing forms may have limitations in handling, storage, and dissolution profiles.
Innovation Solution
The development of crystalline forms of Plinabulin (Forms A-H, J-K, T, U) and its hydrochloride salt (Form Alpha), characterized by specific XRPD patterns and NMR spectra, which can be used to create pharmaceutical compositions for treating cancers such as breast, sarcoma, and prostate cancers, along with processes for their preparation and conversion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If existing solid state forms of Plinabulin are used, then the basic pharmaceutical function is achieved, but processing properties and handling characteristics are limited
Solution Approach 1:
The patent applies parameter changes by discovering and utilizing different solid state forms (polymorphs) of Plinabulin, each with distinct physical and chemical parameters such as crystal structure, melting point, and solubility. These parameter variations enable optimization of both manufacturing processing properties and handling characteristics without changing the chemical identity of the active ingredient.
Solution Approach 2:
The patent employs composite materials by creating salt forms of Plinabulin (such as hydrochloride salts) that combine the active ingredient with counterions. These composite salt forms exhibit improved processing and handling properties compared to the parent compound, while maintaining the desired pharmaceutical activity.
2Reliability
If existing solid state forms of Plinabulin are used, then the drug can be formulated, but stability and shelf-life are insufficient
Solution Approach 1:
The patent utilizes parameter changes by selecting specific solid state forms and salt configurations that exhibit enhanced chemical stability and resistance to degradation. The different crystal packings and intermolecular interactions in various polymorphic forms and salt structures provide improved stability profiles, directly extending shelf-life while maintaining reliability.
3Reliability
If existing solid state forms of Plinabulin are used, then the basic therapeutic effect is achieved, but bioavailability is limited
Solution Approach 1:
The patent applies parameter changes by exploiting variations in solubility and dissolution rate among different solid state forms and salt forms of Plinabulin. These parameter differences directly impact bioavailability, allowing selection of forms that enhance drug absorption and therapeutic effectiveness while maintaining the core therapeutic action.
Data Source
AI summary
The present disclosure relates to Plinabulin solid state forms, Plinabulin salts including hydrochloride and solid state forms thereof, processes for preparation thereof and pharmaceutical compositions thereof.