Modified Release Pharmaceutical Composition for Food-Independent Pharmacokinetics
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Solution Overview
Problem
Conventional formulations of (R)-2-(2-aminothiazol-4-yl)-4'-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide exhibit significant variations in pharmacokinetic data due to food intake, leading to reduced Cmax and AUC, necessitating a modified release formulation that is not affected by food consumption.
Innovation Solution
A pharmaceutical composition comprising (R)-2-(2-aminothiazol-4-yl)-4'-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide combined with a hydrophilic base and a hydrogel-forming polymer, designed to control the release rate of the drug, ensuring continuous drug release for 4 hours or more, thereby minimizing the impact of food on absorption and blood concentration profiles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a conventional formulation is used, then the formulation is simple to manufacture and administer, but the pharmacokinetic data varies significantly due to food intake, leading to reduced Cmax and AUC
Solution Approach 1:
The patent uses a composite formulation consisting of a hydrophilic base material and a hydrogel-forming polymer. The hydrophilic base (such as PEG or PVP) provides water penetration and swelling, while the hydrogel-forming polymer (such as HPMC or carbopol) forms a gel matrix that controls drug release. This composite structure creates a formulation that maintains reliable pharmacokinetics by controlling the release rate of the active ingredient, thereby reducing the impact of food intake on Cmax and AUC values.
2Object-affected harmful factors
If a modified release formulation with hydrogel-forming polymer and hydrophilic base is used, then the release rate of active ingredient is controlled and food effects are reduced, but the formulation complexity increases
Solution Approach 1:
The hydrophilic base acts as an intermediary substance that facilitates water penetration into the formulation and initiates hydrogel formation. The hydrogel-forming polymer then uses this water to create a gel matrix that mediates the controlled release of the active ingredient. This intermediary mechanism effectively blocks the harmful effects of food intake by creating a controlled release system that is independent of gastric conditions, thereby reducing variability in Cmax and AUC.
3Stability of the object's composition
If the release rate of active ingredient is controlled to reduce food effects, then Cmax and AUC become more stable, but the formulation requires specific ingredients and manufacturing processes
Solution Approach 1:
The patent controls the release rate by changing the physical and chemical parameters of the formulation system. The hydrophilic base and hydrogel-forming polymer create a system where water penetration, swelling, and gel formation parameters can be adjusted to achieve the desired release profile. By optimizing the types and amounts of these materials, the formulation achieves stable blood concentration profiles (reduced food effects on Cmax and AUC) while maintaining feasibility for manufacturing using conventional pharmaceutical equipment and processes.
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 achieves a significant reduction in the effects of food on Cmax and AUC, maintaining stable blood levels and reducing the rate of decrease in Cmax by 42% compared to conventional formulations, while maintaining efficacy and stability against environmental factors.
Implementation Method 1
an additive which ensures penetration of water into the pharmaceutical composition (hereinafter sometimes referred to as a hydrophilic base)
Implementation Method 2
a polymer which forms a hydrogel, in which the changes in AUC and Cmax caused by the intake of food can be decreased by controlling a releasing rate of the active ingredient
Data Source
AI summary
A pharmaceutical composition for modified release, comprising (1) (R)-2-(2-aminothiazol-4-yl)-4′-[2-((2-hydroxy-2-phenylethyl)amino]ethyl]acetic acid anilide, or a pharmaceutically acceptable salt thereof, (2) at least one additive which ensures penetration of water into the pharmaceutical composition and which has a solubility such that the volume of water required for dissolving 1 g of the additive is 10 mL or less, and (3) a hydrogel-forming polymer having an average molecular weight of approximately 100,000 or more, or a viscosity of 12 mPa's or more at a 5% aqueous solution at 25 C is disclosed.