Maribavir Polymorph Formulations to Minimize In Vivo Isomerization
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Solution Overview
Problem
Maribavir isomerizes under in vivo conditions to other compounds with potentially lower biological activity, leading to reduced efficacy and failure to meet clinical trial endpoints, particularly in varying dosing protocols.
Innovation Solution
Formulations and dosing strategies are developed to mitigate isomerization, including fasted dosing, combination with antacids or antibiotics, and controlled release formulations, along with monitoring methods to adjust treatment protocols.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If maribavir is administered under in vivo conditions, then the drug can treat viral infections, but the drug isomerizes to compounds with lower biological activity, reducing therapeutic efficacy
Solution Approach 1:
The patent applies preliminary action by pre-formulating maribavir in stable crystalline forms (Polymorphs A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, X, Y, Z) that resist isomerization before administration. These pre-stabilized forms prevent in vivo isomerization, ensuring the drug maintains its biological activity throughout treatment.
Solution Approach 2:
The patent changes the physical and chemical parameters of maribavir by establishing specific crystalline polymorphs with distinct properties (melting points, solubilities, stabilities). Each polymorph represents a different parameter state that provides enhanced stability against isomerization while maintaining therapeutic efficacy.
2Ease of operation
If dosing protocols are varied to improve patient compliance, then ease of operation improves, but isomerization increases, reducing bioavailability
Solution Approach 1:
The patent pre-stabilizes maribavir in crystalline forms that are resistant to isomerization under various dosing conditions. This preliminary stabilization allows flexible dosing protocols (fasted, fed, with antacids, with antibiotics) without compromising bioavailability, as the crystalline structure prevents isomerization regardless of in vivo conditions.
3Reliability
If fasted dosing is used to minimize isomerization, then therapeutic efficacy is improved, but patient compliance and ease of operation deteriorate
Solution Approach 1:
The patent changes the physical state of maribavir to stable crystalline polymorphs that maintain low isomerization rates regardless of fasting or fed conditions. This parameter change allows patients to take the drug with or without food without affecting therapeutic efficacy, greatly improving dosing convenience.
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
Enhances maribavir bioavailability and therapeutic efficacy by minimizing isomerization, ensuring effective treatment of viral infections such as CMV and EBV.
Implementation Method 1
maribavir may isomerize under in vivo conditions to one or more configurational stereoisomers or constitutional isomers
Data Source
AI summary
The invention relates to novel compositions and methods of using maribavir which enhance its effectiveness in medical therapy, as well as to maribavir isomers and methods of use thereof for counteracting the potentially adverse effects of maribavir isomerization in vivo in the event it occurs.