Acetaminophen Cyclodextrin Formulation to Limit Hydrolysis Byproducts
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Solution Overview
Problem
Acetaminophen is susceptible to hydrolysis, forming p-aminophenol, which degrades into quinoneimine, and existing stabilization methods using buffers or free-radical scavengers can cause irritant, allergenic, and/or carcinogenic effects.
Innovation Solution
A pharmaceutical formulation comprising acetaminophen and sulfoalkyl ether cyclodextrin with a molar ratio of 0.01 to 2, without N-acetylcysteine, L-methionine, or cysteine derivatives, stabilizes acetaminophen and reduces p-aminophenol formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If buffers or free-radical scavengers are used to stabilize acetaminophen, then degradation is reduced, but irritant, allergenic and/or carcinogenic effects occur
Solution Approach 1:
Sulfoalkyl ether cyclodextrin acts as an intermediary substance that forms an inclusion complex with acetaminophen, protecting it from degradation without introducing harmful side effects. The cyclodextrin molecule encapsulates the acetaminophen, creating a stable complex that prevents hydrolysis and oxidation while being biocompatible and non-toxic.
Solution Approach 2:
The invention changes the chemical environment by introducing sulfoalkyl ether cyclodextrin, which modifies the local microenvironment around acetaminophen molecules. This alters the degradation kinetics and stability characteristics without requiring traditional buffers or scavengers, thereby avoiding their associated harmful effects.
2Stability of the object's composition
If acetaminophen is stabilized through conventional methods, then degradation is reduced, but potential irritant and allergenic effects are introduced
Solution Approach 1:
Sulfoalkyl ether cyclodextrin serves as a benign intermediary that mediates between acetaminophen and the aqueous environment, preventing direct contact with water that would cause hydrolysis. This intermediary approach stabilizes the formulation while avoiding the introduction of harmful substances.
Solution Approach 2:
The invention creates a composite system where acetaminophen is combined with sulfoalkyl ether cyclodextrin in a specific molar ratio. This composite formulation leverages the protective cavity structure of cyclodextrin while maintaining the therapeutic properties of acetaminophen, resulting in a stable and safe pharmaceutical product.
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 formulation effectively mitigates acetaminophen degradation and minimizes potential adverse effects, maintaining stability and safety.
Implementation Method 1
sulfoalkyl ether cyclodextrin, wherein the molar ratio of sulfoalkyl ether cyclodextrin to acetaminophen is in the range of about 0.01 to about 2
Data Source
AI summary
Pharmaceutical formulations containing acetaminophen and sulfoalkyl ether cyclodextrin are described. The formulation includes acetaminophen; and sulfoalkyl ether cyclodextrin, wherein the molar ratio of sulfoalkyl ether cyclodextrin to acetaminophen is in the range of about 0.01 to about 2. The formulations can be prepared in an injectable form for mitigating or treating fever or alleviating pain in a patient.