Enteric Alkaline Phosphatase Powder for Intestinal Release
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Solution Overview
Problem
There is a need for novel formulations and therapeutic uses of alkaline phosphatases, particularly for oral administration, as existing formulations face challenges in stability and release in gastric fluid, and no AP-based drugs have been approved for clinical use.
Innovation Solution
Modified-release formulations of alkaline phosphatase-based agents, including powders dispersed in a solid matrix, resistant to compression and stable in gastric fluid, which transform into a gel form and release the agent in the intestinal tract, suitable for patients unable to take pills, and can be administered in sachets, tablets, or capsules with enteric agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If alkaline phosphatase is formulated for oral administration, then it can treat patients unable to receive pills, but the formulation becomes unstable in gastric fluid and releases agent prematurely
Solution Approach 1:
The formulation is divided into distinct functional components: an enteric coating layer that protects the alkaline phosphatase in gastric fluid, and an inner core containing the enzyme. This segmentation allows the formulation to survive stomach conditions while enabling controlled release in the intestine.
Solution Approach 2:
An enteric coating material acts as an intermediary barrier between the alkaline phosphatase and the harsh gastric environment. This coating selectively permits passage only in intestinal pH conditions, mediating the release process and protecting the enzyme from premature degradation.
2Ease of manufacture
If alkaline phosphatase is powderized for formulation, then it can be dispersed in solid matrix, but the protein structure becomes damaged and loses activity
Solution Approach 1:
The formulation process utilizes controlled parameter changes including low-temperature drying, protective atmosphere during powderization, and pH-controlled processing to maintain protein structure integrity while achieving the desired powder form for dispersion in solid matrices.
Solution Approach 2:
The alkaline phosphatase is formulated as a composite material where the enzyme is embedded in a protective solid matrix that provides structural support and protection during powderization. This composite structure allows mechanical processing while preserving biological activity.
3Reliability
If enteric coating is applied to protect from gastric fluid, then stability improves, but the coating may not release agent completely in intestinal tract
Solution Approach 1:
The enteric coating is designed to undergo a phase transition or structural change in response to intestinal pH conditions, transforming from a stable protective barrier in acid to a permeable or dissolving state in the intestine, ensuring complete release of the alkaline phosphatase agent.
Solution Approach 2:
The coating system employs periodic action through pH-responsive dissolution, remaining intact during the gastric phase and then dissolving/releasing in the intestinal phase, creating a temporal sequence that ensures both protection and complete delivery.
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 effective treatment for microbiome-related disorders, antibiotic-induced adverse effects, C. difficile infections, metabolic disorders, neurological diseases, and HIV-mediated gut dysbiosis, while maintaining stability and controlled release.
Implementation Method 1
the powders transform into a gel form in the presence of stomach acid
Implementation Method 2
Alkaline phosphatases are dimeric metalloenzymes that catalyze the hydrolysis of phosphate esters and dephosphorylate a variety of target substrates at physiological and higher pHs
Data Source
AI summary
The present invention provides, in part, formulations comprising an alkaline phosphatase (AP)-based agent. Particularly, modified-release powder formulations comprising an AP-based agent are provided which release a substantial amount of the AP-based agent in the intestines. Therapeutic uses of the formulations are also provided.