Nitroxoline Prodrug Composition for Stable Fast-Dissolving Delivery
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Solution Overview
Problem
There is no formulation available for the nitroxoline prodrug (S)-(5-nitroquinolin-8-yloxy)methyl 1-isopropionylpyrrolidine-2-carboxylate, which is needed to prolong its half-life and improve its pharmacokinetic properties.
Innovation Solution
A pharmaceutical composition comprising the nitroxoline prodrug with specific ratios of filler, disintegrant, binder, and lubricant, along with a conventional preparation method, is developed to enhance stability and dissolution properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If nitroxoline prodrug is developed to prolong half-life, then duration of action is improved, but formulation availability deteriorates
Solution Approach 1:
The patent applies parameter changes by systematically optimizing the formulation composition parameters (filler type, disintegrant, binder, lubricant ratios) to transform the prodrug into a manufacturable pharmaceutical composition. Specific parameter ranges are defined: filler 22.5-320 parts, disintegrant 0-40 parts, binder 0-95 parts, lubricant 2-30 parts per 100 parts prodrug, resolving the formulation availability issue while maintaining the prolonged half-life benefit
Solution Approach 2:
The patent creates a composite pharmaceutical material by combining the nitroxoline prodrug with multiple excipients (filler, disintegrant, binder, lubricant) in specific proportions. This composite formulation approach enables manufacturability and clinical application while preserving the pharmacokinetic advantages of the prodrug structure
2Stability of the object's composition
If prodrug formulation is developed, then stability is improved, but dissolution properties may deteriorate
Solution Approach 1:
The patent resolves the stability-dissolution contradiction by optimizing formulation parameters, specifically selecting filler types (starch, lactose, sucrose, mannitol, microcrystalline cellulose) and their ratios, along with disintegrant (0-40 parts) and binder (0-95 parts) concentrations. These parameter optimizations ensure both stability and rapid dissolution, with dissolution rates exceeding 80% within 15 minutes while maintaining prodrug stability
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 composition exhibits good stability, dissolution properties, and pharmacokinetic characteristics, suitable for clinical application and treatment of infectious diseases and cancers like bladder cancer.
Implementation Method 1
A prodrug is a compound obtained by chemical modification of an active drug, which is converted into the original drug in vivo by the action of enzymes to exert its efficacy.
Data Source
AI summary
A pharmaceutical composition containing a nitroxoline prodrug, and a preparation method and an application therefor. The pharmaceutical composition comprises the following ingredients in parts by weight: 100 parts of active pharmaceutical ingredient, 22.5-320 parts of filler, 0-40 parts of disintegrant, 0-95 parts of binding agent, and 2-30 parts of lubricant; relative to each 100 parts by weight of active pharmaceutical ingredient, the total content of the filler, the disintegrant, and the binding agent is 54-345 parts by weight; the active pharmaceutical ingredient is (S)-(5-nitroxoline-8-yloxy)methyl 1-isopropylpyrrolidine-2-carboxylate. The pharmaceutical composition has good stability, dissolution properties, and pharmacokinetic characteristics.