Mycophenolate Sodium Extended Release via pH-Sensitive Matrix
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Solution Overview
Problem
Current mycophenolate sodium formulations, such as enteric-coated delayed release systems, suffer from gastrointestinal side effects, incomplete absorption, and variability in drug release, leading to reduced bioavailability and patient compliance, especially in the treatment of immunosuppressant diseases like organ rejection and autoimmune disorders.
Innovation Solution
Development of extended release pharmaceutical compositions of mycophenolate sodium that provide a sustained release profile throughout the gastrointestinal tract, reducing gastrointestinal side effects and inter- and intra-patient variability, using hydrophilic or hydrophobic release controlling materials and pharmaceutically acceptable excipients to maintain therapeutic levels for an extended period.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If enteric-coated delayed release system is used, then release in stomach is prevented, but gastrointestinal side effects still occur and absorption is incomplete
Solution Approach 1:
The patent segments the gastrointestinal tract into multiple absorption zones by using a multiparticulate system (microspheres, granules, or pellets) rather than a single enteric-coated tablet. This segmentation allows the drug to be released and absorbed at multiple locations along the intestinal tract, improving overall absorption completeness while still avoiding stomach release.
Solution Approach 2:
The patent introduces an intermediary mechanism - a pH-sensitive matrix material that responds to the pH gradient along the gastrointestinal tract. This matrix gradually releases the drug as it moves through different pH zones, mediating between the need to avoid stomach release and the need for complete absorption throughout the intestine.
2Reliability
If immediate release formulation is used, then bioavailability is maintained, but gastrointestinal side effects increase
Solution Approach 1:
The patent applies local quality by creating different release characteristics at different locations. The pH-sensitive matrix provides immediate release in the alkaline environment of the intestine while preventing release in the acidic stomach environment. This spatial differentiation of release properties maintains bioavailability in the intestine while avoiding gastrointestinal side effects in the stomach.
3Productivity
If sustained release is implemented, then dosing frequency is reduced, but release profile variability increases
Solution Approach 1:
The patent utilizes parameter changes, specifically the pH parameter, to control drug release. The pH-sensitive matrix material changes its release characteristics based on the pH environment, providing sustained release in the intestine while preventing release in the stomach. This pH-dependent parameter change ensures consistent release profiles across different patients and conditions.
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 extended release compositions effectively alleviate gastrointestinal side effects, enhance bioavailability, and improve patient compliance by providing a predictable and sustained release of mycophenolate sodium, reducing the frequency of dosing and minimizing drug-related toxicity.
Implementation Method 1
not more than about 50% w/w of the active agent is released within 2 hours, when the composition is subjected to an in-vitro dissolution test
Data Source
AI summary
Extended release pharmaceutical compositions comprising mycophenolate sodium as the active agent, wherein the said composition exhibits a characteristic release profile when subjected to in-vitro dissolution study, and wherein said mycophenolate sodium is released in a sustained manner in-vivo for a prolonged duration in such quantities that substantially alleviates or at least reduces the chances of causing any associated gastrointestinal side effect(s) without compromising the bioavailability of the said active agent are provided. The present invention also provides process of preparing dosage form compositions and prophylactic and/or therapeutic methods of using such dosage form. The compositions of the present invention are useful for the management such as prophylaxis, amelioration and/or treatment of immunosuppressant indicated disease(s)/disorder(s) especially for the treatment or prevention of organ, tissue or cellular allograft or xenograft rejection, e.g. after transplant, or the management of immune-mediated diseases (autoimmune diseases).