HPMCAS-Coated Multiparticulates for Stable Liquid Suspensions
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current oral pharmaceutical and probiotic delivery methods, particularly for patients who have trouble swallowing solid dosage forms, are limited by the lack of sustained-release liquid suspension products, which often require frequent dosing and can be unstable and costly to manufacture.
Innovation Solution
Development of modified-release multiparticulates in bead or granule form, comprising a core with a pharmaceutical or probiotic active ingredient and a functional coating, including hypromellose acetate succinate (HPMCAS), designed to provide a controlled release profile in acidic aqueous media, allowing for stability and extended release in a liquid suspension form.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If liquid dosage forms are used for patients who have trouble swallowing solids, then ease of operation is improved, but stability of the active ingredient is worsened due to lack of sustained-release formulations
Solution Approach 1:
The dosage form is segmented into multiple multiparticulate particles (beads or granules) suspended in liquid, where each particle contains the active ingredient. This segmentation allows the liquid to remain stable without requiring refrigeration while enabling easy administration to patients who cannot swallow solids.
Solution Approach 2:
The invention uses composite multiparticulate structures consisting of a core material containing the active ingredient coated with a sustained-release polymer layer. This composite structure provides both stability in liquid suspension and controlled release of the active ingredient, resolving the contradiction between ease of administration and stability.
2Reliability
If multiple doses are given throughout the day to maintain therapeutic levels, then reliability of therapeutic effect is improved, but loss of time and patient compliance are worsened
Solution Approach 1:
The sustained-release coating on the multiparticulates provides continuous release of the active ingredient over an extended period (e.g., 12-24 hours), maintaining therapeutic blood levels continuously without requiring multiple daily doses. This eliminates the need for patients to remember multiple dosing times while ensuring consistent therapeutic effect.
3Productivity
If large single doses are administered, then productivity of treatment is improved, but object-affected harmful factors are worsened due to gastrointestinal irritation
Solution Approach 1:
The multiparticulate formulation releases the active ingredient in a controlled periodic manner over time, delivering the total therapeutic dose in smaller incremental amounts rather than as a single large bolus. This periodic release pattern maintains treatment effectiveness while minimizing gastrointestinal irritation and side effects.
4Reliability
If solid dosage forms are used, then stability and ease of manufacture are improved, but ease of operation is worsened for patients with swallowing difficulties
Solution Approach 1:
The invention segments the solid dosage form into multiple small multiparticulate particles that can be suspended in liquid. This segmentation maintains the stability advantages of solid formulations while transforming them into a liquid suspension that is easy to administer to patients with swallowing difficulties.
Solution Approach 2:
The invention changes the physical state parameter from solid to liquid suspension, while maintaining the stability characteristics of solid formulations through the use of sustained-release coated multiparticulates. This parameter change enables easy administration without sacrificing shelf stability.
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 modified-release multiparticulates offer improved stability and reduced frequency of dosing, maintaining therapeutic levels with less patient compliance issues and minimizing side effects, while being stable in acidic media and cost-effective for large-scale production.
Implementation Method 1
a coating of hypromellose acetate succinate (HPMCAS) disposed on the one or more functional coatings and configured to impart multiparticulate stability in aqueous acidic media
Implementation Method 2
These reservoir and encapsulation multiparticulates can display a modified-release profile through a dissolution-based or diffusions-based delivery mechanism
Implementation Method 3
the active ingredient is typically either suspended or dissolved in a dispersion medium for delivery
Data Source
AI summary
Various embodiments of modified-release multiparticulates (in bead or granule from) are described. The modified-release multiparticulates can comprise a core including a pharmaceutical and/or probiotic agent, optionally with additional excipients or binders to aid in creation of the core, one or more functional coatings disposed on the core and configured to provide a modified-release profile of the pharmaceutical and/or probiotic agent when given orally, and a coating of hypromellose acetate succinate (HPMCAS) disposed on the one or more functional coatings and configured to impart multiparticulate stability in aqueous acidic media. Suspensions including the modified-release multiparticulates are also described.