Oral Biologic Dosage Form With Protective Microenvironment
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Solution Overview
Problem
When biomacromolecules are orally administered, they are digested in the gastrointestinal tract, losing their native conformation and effectiveness due to digestive processes, and achieving a high surface area-to-volume ratio increases exposure to these mechanisms, counterintuitively increasing digestion.
Innovation Solution
A pharmaceutical solid dosage form with multiple single units, each containing therapeutically active biomacromolecules, water-soluble polymers, and small-molecule weak acids, with a high surface area-to-volume ratio and density, forming a microenvironment that protects biomacromolecules from digestion while maintaining contact with gastrointestinal luminal folds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Area of stationary object
If the surface area to volume ratio is increased to enhance contact with GIT luminal folds, then the contact surface area and delivery efficacy are improved, but the exposure to digestive mechanisms (pH, enzymes, microbes) increases, leading to greater digestion of the biomacromolecule API
Solution Approach 1:
The dosage form is divided into multiple small single units (minitablets) with high surface area to volume ratio, each containing the biomacromolecule API. This segmentation allows the formulation to achieve greater overall contact surface area with GIT luminal folds while each individual unit maintains protective characteristics
Solution Approach 2:
A weak acid (WA) or weak acid surfactant (WAS) is introduced as an intermediary substance that creates a protective microenvironment around the biomacromolecule API. This intermediary layer protects the API from digestive mechanisms (pH, enzymes, microbes) while allowing the dosage form to maintain high surface area contact with the GIT mucosal membrane
2Object-affected harmful factors
If a standard-sized larger tablet is used, then the biomacromolecule is better protected from digestion, but the surface area to volume ratio is reduced, limiting contact surface area with GIT luminal folds
Solution Approach 1:
Instead of using a single large tablet, the invention segments the dosage form into multiple small single units (minitablets). Each unit has high surface area to volume ratio for enhanced contact with GIT luminal folds, while collectively providing sufficient protection through the weak acid/WAS microenvironment
Solution Approach 2:
The invention changes the physical parameters of the dosage form by creating multiple small units with surface area to volume ratio greater than 1.0 mm-1 and single-unit density greater than 1.0 g/cm3. This parameter change enables both high contact surface area and protection from digestion through the formulated microenvironment
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 dosage form maintains biomacromolecular integrity and effectiveness by protecting them from digestion, allowing for localized or systemic absorption with enhanced contact surface area without increased susceptibility to digestive mechanisms.
Implementation Method 1
forming a microenvironment that protects biomacromolecules from digestion while maintaining contact with gastrointestinal luminal folds
Implementation Method 2
Ideally, the composition exhibits high surface area-to-volume (SA/Vol) ratio for greater contact surface area with the GIT luminal folds
Data Source
AI summary
The present invention relates to pharmaceutical dosage forms suitable for gastrointestinal delivery, as well as to methods for the treatment of conditions suitable for treatment by gastrointestinal delivery.