Atomoxetine Oral Solution Taste Masking with Peppermint Orange Viscosity
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Solution Overview
Problem
Current formulations of atomoxetine, used to treat ADHD, are challenging due to its intensely bitter taste and numbing effect, which leads to non-compliance and ineffective therapy, especially in children and elderly patients, as existing taste masking methods are inadequate for high concentrations and do not effectively address the prolonged aftertaste.
Innovation Solution
A taste-masked liquid carrier comprising peppermint flavor, orange flavor, and a viscosity agent, which provides a synergistic effect that masks the bitter taste, numbness, and aftertaste of atomoxetine, creating a palatable oral solution with improved swallowability and minimal aftertaste, functioning at a slightly higher pH than traditional atomoxetine solutions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If atomoxetine is formulated as a high concentration oral solution, then the therapeutic efficacy is improved, but the bitter taste and numbness become more intense making it unbearable for patients
Solution Approach 1:
The patent employs multiple intermediary substances including cyclodextrins, flavoring agents (peppermint, orange, strawberry), sweeteners, and viscosity agents that act as mediators between the atomoxetine drug and the patient's sensory system. These intermediaries mask the bitter taste and numbness through physical encapsulation (cyclodextrins) and sensory overwriting (flavors), enabling high concentration formulation while maintaining patient acceptability
Solution Approach 2:
The patent creates a composite liquid formulation system combining atomoxetine with multiple functional components: cyclodextrins for solubilization and taste masking, flavoring agents for sensory masking, sweeteners for taste modification, and viscosity agents for texture improvement. This composite approach allows the formulation to simultaneously achieve high drug concentration, stability, and palatability
2Object-affected harmful factors
If traditional taste masking agents such as ethanol and mannitol are used, then some bitter taste suppression is achieved, but the prolonged aftertaste and numbness remain unresolved
Solution Approach 1:
The patent modifies the chemical and physical parameters of the formulation system by using cyclodextrins to change the solvation environment of atomoxetine, thereby altering its taste properties. The pH is adjusted to optimize drug solubility and stability while minimizing taste issues. Flavoring agents are selected and combined in specific ratios to create a synergistic masking effect that extends through the entire duration of drug dissolution and absorption
3Object-affected harmful factors
If high concentrations of taste masking agents are used to mask the bitter taste, then the taste improvement is achieved, but the solubility of the drug decreases sharply
Solution Approach 1:
Cyclodextrins serve as molecular intermediaries that form inclusion complexes with atomoxetine, increasing its apparent solubility in aqueous media. This allows high drug concentrations to be achieved without requiring excessive amounts of flavoring or sweetening agents, as the cyclodextrin-atomoxetine complex itself contributes to taste masking while maintaining solubility
Solution Approach 2:
The patent optimizes the pH of the formulation to enhance atomoxetine solubility, using buffer systems to maintain pH in a range that maximizes both drug dissolution and stability. This parameter optimization reduces the need for large quantities of taste masking agents that would otherwise be required to achieve adequate drug concentration
4Stability of the object's composition
If atomoxetine is formulated as solid dosage form, then the stability is improved, but the swallowability and compliance become problematic for children and elderly patients
Solution Approach 1:
The patent transitions from solid to liquid dosage form, utilizing the fluid properties of liquid formulations to improve ease of administration. The liquid formulation can be easily swallowed by children and elderly patients who have difficulty with capsules or tablets. The formulation includes viscosity agents to provide a smooth, syrup-like consistency that is pleasant to take and reduces the sensation of bitterness during swallowing
Data Source
AI summary
Disclosed herein is an oral pharmaceutical composition in the form of an aqueous solution of atomoxetine as an active ingredient. The aqueous solution of atomoxetine comprises a taste-masked liquid carrier comprising peppermint, orange flavor and a viscosity agent. The combined flavors successfully masked atomoxetine hydrochloride's bitter smell and/or taste which makes it a novel palatable pharmaceutical composition. The viscosity agent improves the oral pharmaceutical composition's consistency and provides a smooth texture which makes it easy to swallow. More specifically, the oral pharmaceutical composition comprises effective amounts of: (a) atomoxetine or the pharmaceutically acceptable salts thereof; and (b) a taste-masked liquid carrier. Also provided is a method for making the aqueous solution of atomoxetine. The present disclosure also provides methods of using oral pharmaceutical composition for the treatment of a subject having a disorder treatable by the administration of atomoxetine. In one embodiment, the disorder is attention deficit hyperactivity disorder (ADHD).