Trilaciclib Dihydrochloride Crystal Form for Stable IV Solubility
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Trilaciclib, a cyclin-dependent kinase inhibitor, has low solubility in water and is practically insoluble in DMSO, making it difficult to administer effectively in a concentrated form for therapeutic use, especially in the mildly basic environment of blood, which can lead to drug deposition and loss of activity.
Innovation Solution
Formulating trilaciclib as a dihydrochloride, dihydrate crystalline form (Pattern 1) for intravenous administration, which maintains stability and solubility, allowing for quick delivery in a concentrated IV solution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If trilaciclib is formulated in a concentrated form for therapeutic administration, then therapeutic efficacy is improved, but solubility problems arise leading to drug deposition and loss of activity
Solution Approach 1:
The patent applies parameter changes by converting trilaciclib from its free base form to a dihydrochloride salt form. This chemical parameter change fundamentally alters the solubility characteristics of the compound, enabling it to achieve both high concentration and stability in aqueous blood environment. The dihydrochloride salt form maintains therapeutic efficacy while preventing precipitation and drug deposition that would otherwise occur at therapeutic concentrations.
2Ease of operation
If trilaciclib is administered in water-based solution, then bioavailability is improved, but solubility is insufficient for effective delivery
Solution Approach 1:
The invention changes the chemical parameter of trilaciclib by forming a dihydrochloride salt, which dramatically improves water solubility. This allows the drug to be administered in water-based solutions at therapeutically effective concentrations, resolving the contradiction between administerability and solubility.
3Quantity of substance
If trilaciclib is given over a long period to achieve therapeutic dosage, then solubility constraints are relaxed, but treatment efficiency is reduced
Solution Approach 1:
By converting to the dihydrochloride salt form, the invention enables high concentrations of trilaciclib to be delivered in water-based solutions, allowing rapid administration over a short period (30-60 minutes) rather than requiring prolonged infusion times. This resolves the contradiction between achieving therapeutic dosage and minimizing administration time.
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 dihydrochloride, dihydrate form of trilaciclib ensures effective and stable delivery, maintaining therapeutic efficacy by preventing drug deposition and ensuring rapid administration.
Implementation Method 1
Formulating trilaciclib as a dihydrochloride, dihydrate crystalline form (Pattern 1) for intravenous administration, which maintains stability and solubility
Implementation Method 2
the dihydrochloride, dihydrate form of trilaciclib ensures effective and stable delivery, maintaining therapeutic efficacy by preventing drug deposition
Data Source
AI summary
An advantageous isolated morphic form of trilaciclib which is 2′-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)-7′,8′-dihydro-6′H-spiro[cyclohexane-1,9′-pyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyrimidin]-6′-one, for example in the form of a dihydrochloride salt or a dihydrochloride, dihydrate.