Citrate Salt Tablet Coating for Gastric Tolerance and Urinary Alkalization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current citrate salt pharmaceutical compositions for treating urinary lithiasis have limitations, including low gastric tolerance, unpleasant taste, and unsuitable administration forms, particularly for children, which restrict their use and effectiveness.
Innovation Solution
A solid pharmaceutical composition in the form of tablets with a core of Krebs cycle precursor salt and a coating that releases the salt in a controlled manner, masking the taste and optimizing absorption, featuring a core comprising 40-80% Krebs cycle precursor salt, coated with a polymer film to control release kinetics and maintain efficacy across varying pH levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If citrate salt is administered in immediate-release liquid formulations, then rapid alkalization of urine is achieved, but gastric tolerance is low and unpleasant taste occurs
Solution Approach 1:
The patent divides the citrate salt administration into multiple small doses throughout the day rather than single large doses. This segmentation reduces the burden on the gastric system at any one time, improving tolerance while maintaining cumulative alkalization effect. The formulation is designed to be taken with meals, further distributing the impact across multiple dining occasions.
Solution Approach 2:
The patent introduces food as an intermediary medium to deliver citrate salt. By formulating the medication to be taken with meals, food acts as a carrier that masks the unpleasant taste and reduces gastric irritation. The dietary context provides a beneficial environment for absorption while minimizing direct contact between citrate salt and the gastric mucosa.
2Ease of operation
If citrate salt is administered in sustained-release formulations, then administration convenience is improved, but dissolution profile in vivo matches immediate-release with low gastric tolerance
Solution Approach 1:
The patent creates a dynamic release profile where the formulation adapts its dissolution characteristics based on the gastric environment. The coating system is designed to dissolve rapidly in the acidic gastric environment, providing immediate citrate salt release in the stomach and duodenum where it is most needed for protection, while maintaining sustained release characteristics in the more neutral intestinal environment.
Solution Approach 2:
The patent modifies the physical-chemical parameters of the citrate salt formulation by adjusting the coating composition and thickness. These parameter changes enable the formulation to exhibit different dissolution rates at different locations in the gastrointestinal tract, optimizing both gastric tolerance and therapeutic efficacy simultaneously.
3Quantity of substance
If large amounts of citrate salt are absorbed in single administration, then therapeutic efficacy is improved, but gastric tolerance decreases
Solution Approach 1:
The patent implements periodic administration of citrate salt in divided doses throughout the day. This periodic action allows the gastrointestinal system to process and tolerate smaller amounts at each occasion while maintaining cumulative therapeutic effect. The rhythm of administration with meals creates predictable absorption patterns that optimize both tolerance and efficacy.
Solution Approach 2:
The patent ensures continuous therapeutic action through multiple daily administrations. Rather than relying on a single large dose, the formulation provides continuous protection through repeated smaller doses taken with each meal. This continuous action maintains stable citrate levels in the urine and gastrointestinal tract, improving overall tolerance while sustaining efficacy.
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 provides sustained release of citrate salt for up to four hours, improving gastric tolerance and maintaining effective urinary alkalization, reducing side effects, and making it suitable for long-term use, including in children, by ensuring consistent and controlled absorption.
Implementation Method 1
Another advantage of citrate is that it complexes with calcium in the urine. Thus, it is one of the ions most used for preventing the formation of calculi from calcium phosphate, calcium oxalate, uric acid and cystine
Implementation Method 2
leading to alkalization of the urine... owing to its capacity for alkalizing the urine and for eliminating supersaturation of the urine with calcium oxalate ions
Implementation Method 3
said composition being able to release the Krebs cycle precursor salt in vitro, both in a dissolution medium of purified water at pH 7 and in a dissolution medium of solution buffered at pH 1.3
Data Source
AI summary
A solid oral pharmaceutical composition in the form of a tablet consisting of a core including a Krebs cycle precursor salt as active ingredient, and of a coating including a coating agent, the composition including from 40% to 80% by weight of this precursor salt on the basis of the total weight of the composition, the composition being able to release this salt in vitro, both in purified water at pH 7 and in a solution buffered at pH 1.3, with a dissolution device in accordance with the European Pharmacopoeia, at a rate of from 2 to 15% in 15 minutes, from 15 to 25% in 30 minutes, and from 30 to 50% in one hour. The composition is a usefeul medicament, in particular in the treatment and/or prevention of urinary lithiasis occurring at a physiological pH and/or during urinary acidosis and/or during hypocitraturia and/or during hypercalciuria and/or during hyperoxaluria.