Cystinuria Treatment Microtablet and Minitablet Formulation
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Solution Overview
Problem
Current pharmaceutical compositions for treating cystinuria, such as citrate-based and bicarbonate-based formulations, have limitations including poor gastric tolerance, frequent administration requirements, and inability to maintain urinary pH above 7 continuously, leading to suboptimal alkalization and patient compliance issues.
Innovation Solution
A solid oral pharmaceutical composition comprising microtablets with a Krebs cycle precursor salt and mini-tablets with a bicarbonate salt, both with sustained-release matrices and coatings, designed for simultaneous administration to provide prolonged alkalization and improved gastric tolerance, allowing for fewer daily administrations and maintaining urinary pH between 7.0 and 8.0 for several hours.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high doses of sodium bicarbonate (30-40 g/d) are administered to maintain urinary pH constantly above 7.0, then the alkalization efficacy is improved, but the gastric tolerance deteriorates to mediocre
Solution Approach 1:
The patent divides the bicarbonate dose into multiple small tablets (e.g., 4 tablets of 1 g each) to be administered simultaneously, distributing the total load and improving gastric tolerance while maintaining the required alkalization efficacy
Solution Approach 2:
The patent establishes a periodic administration schedule (every 2 hours including night) to maintain continuous alkalization, breaking down the total daily dose into periodic smaller administrations that are better tolerated by the stomach
2Reliability
If commercial pharmaceutical forms administer alkalizing agents every two hours including at night, then the urinary pH maintenance is improved, but the treatment complexity and patient compliance deteriorate
Solution Approach 1:
The patent prepares multiple small tablets in advance to be taken simultaneously at each administration time point, simplifying the patient's task at each moment while maintaining the frequent administration schedule needed for continuous pH control
Solution Approach 2:
By segmenting the total daily dose into many small individual tablets, the patent makes each administration act quicker and with less gastric burden, improving tolerability of the frequent dosing schedule
3Reliability
If citrate or bicarbonate doses are administered multiple times day and night, then the urinary pH alkalization is improved, but the treatment duration and frequency requirements worsen patient adherence
Solution Approach 1:
The patent implements a structured periodic administration regimen every 2 hours around the clock, creating a rhythm that maintains continuous alkalization while making the treatment schedule predictable and manageable for patients
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 long-acting urinary pH maintenance, improved gastric tolerance, and easier dose adjustment, ensuring better efficacy and patient compliance by distributing alkalizing agents gradually, avoiding abrupt alkaline overload and maintaining urinary pH throughout the day.
Implementation Method 1
a second pharmaceutical formulation for oral use in the form of at least one mini-tablet, the mini-tablet being constituted by a core comprising at least one bicarbonate salt as active ingredient, preferably as the only active ingredient, and at least one sustained-release matrix
Implementation Method 2
a coating comprising at least one coating agent... their pharmacokinetic and pharmacological effects are independently and temporally delayed
Data Source
AI summary
A solid oral pharmaceutical composition in the form of tablets including:—a first solid oral pharmaceutical formulation in the form of at least one micro-tablet, the micro-tablet consisting of a core including at least one Krebs cycle precursor salt as active ingredient, and of a coating including at least one coating agent, and—a second oral pharmaceutical formulation in the form of at least one mini-tablet, the mini-tablet consisting of a core including at least one bicarbonate salt as active ingredient and at least one prolonged-release matrix, and of a coating including at least one coating agent. The use thereof as a medicament, in particular in the treatment and/or prevention of cystinuria.