Enteric Coated Tiopronin Tablet for Food-Independent Dosing
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Solution Overview
Problem
Current tiopronin tablet formulations for cystinuria treatment require administration on an empty stomach, leading to inconvenient dosing regimens and potential side effects like nausea, and there is a need for a formulation that can be taken with food to improve patient compliance and reduce stone formation risk.
Innovation Solution
A solid pharmaceutical composition comprising a core of tiopronin with an inner cellulose-based polymer coating and an outer enteric polymer coating, allowing for delayed release in the intestinal environment, enabling administration with food while maintaining effective plasma concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tiopronin is administered on an empty stomach to maintain drug efficacy, then chelation with food metals is avoided, but patient compliance decreases and dosing becomes inconvenient
Solution Approach 1:
The patent segments the release of tiopronin by using an enteric-coated tablet formulation that prevents drug release in the stomach and enables controlled release in the intestine. This segmentation allows the drug to bypass the chelation issue in the stomach while maintaining efficacy, thereby improving patient compliance without sacrificing reliability
Solution Approach 2:
The enteric coating acts as an intermediary barrier between the tiopronin drug and the gastric environment. This coating prevents direct contact between the drug and stomach contents that would cause chelation, while still allowing the drug to be released intact in the intestine where it can exert its therapeutic effect
2Reliability
If tiopronin tablet dissolves in the stomach to achieve rapid absorption, then drug efficacy is maintained, but gastrointestinal side effects like nausea and sulfur-like eructation increase
Solution Approach 1:
The patent extracts the dissolution step from the stomach environment and relocates it to the intestinal environment. By using enteric coating technology, the tablet is designed to remain intact during gastric passage and only dissolve in the more neutral pH environment of the intestine, thereby eliminating GI side effects while preserving drug efficacy through subsequent absorption
3Reliability
If complex dosing regimen with multiple daily doses is used to maintain therapeutic levels, then cystine stone prevention is optimized, but patient compliance and convenience decrease
Solution Approach 1:
The patent introduces dynamic controlled-release technology through enteric coating that adapts the drug release profile to the gastrointestinal transit conditions. The coating remains intact during gastric passage and dissolves in the intestine, providing sustained release of tiopronin that maintains therapeutic levels over time, potentially reducing the frequency of dosing while optimizing stone prevention
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 at least 70% of the fasted state maximum plasma concentration when taken with food, improving patient compliance and reducing gastrointestinal side effects, with tiopronin levels remaining stable during storage and exhibiting delayed release characteristics.
Implementation Method 1
the outer coating can include an enteric polymer, which helps to prevent the disintegration or dissolution of the composition in the gastric environment
Implementation Method 2
an inner coating surrounding the core, wherein the inner coating comprises a cellulose-based polymer
Data Source
AI summary
A solid pharmaceutical composition is provided that includes a core, an inner coating, and an outer coating. The core includes tiopronin as an active agent. Further, the inner coating, which includes a cellulose-based polymer, surrounds the core, and the outer coating, which includes an enteric polymer, surrounds the inner coating. As a result of the specific components of the solid pharmaceutical composition, the solid pharmaceutical composition exhibits a fed state Cmax of tiopronin that is at least 70% of a 12-hour fasted state Cmax of tiopronin after oral administration of the solid pharmaceutical composition when administered as a 300 milligram dose. As such, it is possible for the solid pharmaceutical composition to be administered orally with or without food (e.g., in a fed or fasted state) while still achieving a desired maximum plasma concentration of the tiopronin in a delayed release formulation.