Enteric Alkaline Phosphatase Tablets for pH-Targeted Intestinal Release
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Solution Overview
Problem
Formulating protein biologics, such as alkaline phosphatases, into stable and effective oral dosage forms that can target specific regions of the gastrointestinal tract for therapeutic use is challenging due to their sensitivity to degradation and the need for precise pH-dependent release.
Innovation Solution
Development of enteric-coated formulations comprising alkaline phosphatase-based agents, which are spray-dried and powderized with excipients, allowing for tablet formation that exhibits resilience to friability and pH-dependent solubilization in the intestines, ensuring targeted and effective delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If alkaline phosphatase is formulated as an oral dosage form, then it can be administered to patients, but the protein biologic is sensitive to degradation in the gastrointestinal tract
Solution Approach 1:
The alkaline phosphatase is spray-dried and powderized with excipients before tablet formation, creating a stable dry powder formulation that protects the protein from degradation during storage and handling prior to administration
Solution Approach 2:
The formulation utilizes pH-dependent solubilization properties, remaining stable in dry form at various pH levels but solubilizing at specific pH conditions in the intestines to release the active protein biologic
2Manufacturing precision
If the formulation is designed for pH-dependent release in intestines, then targeted delivery is achieved, but the tablet must remain stable in the stomach
Solution Approach 1:
The tablet formulation exploits pH as a critical parameter, designed to remain stable in the acidic environment of the stomach but undergo solubilization at the higher pH conditions found in the intestines, enabling site-specific drug release
Solution Approach 2:
Excipients are used as intermediary substances that facilitate the pH-dependent behavior of the tablet, mediating between the stable solid dosage form and the solubilized active ingredient at the target site
3Strength
If the tablet is compressed with high force to reduce friability, then mechanical strength is improved, but the dissolution profile may be affected
Solution Approach 1:
The compression force and resulting tablet hardness are optimized within specific ranges to achieve adequate mechanical strength without excessive compactness that would impede water penetration and dissolution at the target pH
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 formulations provide stable and targeted release of alkaline phosphatases in the intestines, enhancing therapeutic efficacy by promoting gut health and reversing dysbiosis, thus addressing the challenges of oral delivery for protein biologics.
Implementation Method 1
the tablet solubilizes in a pH-dependent manner and is suitable for releasing a substantial and therapeutic amount of the AP-based agent in the intestines
Implementation Method 2
the formulations are spray-dried and powderized with excipients in order to be compressed into tablets
Data Source
AI summary
The present invention provides for a formulation comprising an active alkaline phosphatase (AP)-based agent and an enteric agent, wherein the formulation is suitable for releasing a substantial amount of the active AP-based agent in the intestines.