Pediatric ASBTI Liquid Formulations for Cholestatic Liver Disease
Solution Overview
Problem
Current treatments for pediatric cholestatic liver diseases are invasive and costly, and there is a lack of effective, less invasive therapies suitable for children, with existing medications posing challenges such as unpleasant taste, swallowing difficulties, and side effects like diarrhea and intestinal discomfort.
Innovation Solution
Non-systemic administration of Apical Sodium-dependent Bile Transporter Inhibitors (ASBTIs) in pediatric dosage forms, designed to minimize systemic absorption and target the distal gastrointestinal tract, reducing bile acid recycling and associated symptoms like pruritis and hypercholemia.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If oral solid dosage forms are used for pediatric patients, then adult medication can be administered, but swallowing difficulties and compliance issues arise
Solution Approach 1:
The patent changes the physical form of the medication from solid tablets to liquid formulations (syrups, suspensions, solutions), fundamentally altering the administration parameters to suit pediatric patients who cannot swallow solid dosage forms. This parameter change enables effective medication delivery while avoiding swallowing difficulties.
2Reliability
If adult medication formulations are used, then treatment efficacy can be achieved, but unpleasant taste and side effects increase
Solution Approach 1:
The patent modifies the formulation parameters by using liquid vehicles instead of solid matrices, adding flavoring agents to mask unpleasant tastes, and adjusting concentration levels to reduce gastrointestinal side effects while maintaining therapeutic efficacy in pediatric patients.
Solution Approach 2:
The patent introduces flavoring agents and palatable liquid vehicles as intermediaries between the active pharmaceutical ingredient and the pediatric patient, masking the unpleasant taste of the medication and improving compliance without affecting treatment efficacy.
3Reliability
If invasive treatments like liver transplantation are used, then severe cholestatic liver diseases can be treated, but healthcare costs and treatment complexity increase
Solution Approach 1:
The patent employs bile acid sequestrants that work locally in the gastrointestinal tract to bind and eliminate excess bile acids, providing a self-contained therapeutic mechanism that reduces bile acid accumulation and its toxic effects without requiring invasive surgical interventions or complex medical procedures.
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
Significantly decreases serum and hepatic bile acid levels by up to 50%, ameliorates symptoms like pruritis and hypercholemia, and protects liver and intestinal integrity by increasing intraluminal bile acid concentrations, thereby reducing the need for invasive treatments.
Implementation Method 1
Apical Sodium-dependent Bile Transporter Inhibitors (ASBTIs)... reducing bile acid recycling... decreases serum and hepatic bile acid levels by up to 50%
Data Source
AI summary
Provided herein are methods of treating or ameliorating a pediatric cholestatic liver disease by non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a pediatric liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an ASBTI or a pharmaceutically acceptable salt thereof.