Enteric Coated Peptide Formulation with Protease Inhibitor
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Solution Overview
Problem
Pharmaceutical or nutraceutical formulations with a core comprising an active ingredient, penetration promoter, and polymeric coating for gastrointestinal targeted release show promising in-vitro results but fail to deliver expected bioavailability in-vivo, particularly with peptides like desmopressin, due to enzymatic degradation in the gastrointestinal tract.
Innovation Solution
Incorporating a bioavailability promoting agent, such as a pharmaceutically acceptable inhibitor of proteolytic enzymes like Bowman-Birk inhibitor, to enhance the oral bioavailability of active ingredients by at least five times, combined with a multiparticulate formulation and enteric coating for controlled release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a polymeric coating for gastrointestinal targeted release is used, then the active ingredient is protected from premature release and degradation, but the formulation fails to deliver expected bioavailability in-vivo due to enzymatic degradation
Solution Approach 1:
The patent applies preliminary anti-action by incorporating proteolytic enzyme inhibitors (such as aprotinin, leupeptin, or EDTA) into the formulation before administration. These inhibitors preemptively counteract the harmful enzymatic degradation that would otherwise occur in the gastrointestinal tract, thereby protecting the active ingredient and enabling the formulation to achieve its intended bioavailability enhancement
2Productivity
If penetration promoters are used to enhance absorption, then cell penetration effects are improved in in-vitro assays, but the expected bioavailability is not achieved in-vivo
Solution Approach 1:
The patent employs composite materials by combining penetration promoters (such as aminoalkyl methacrylate copolymers) with proteolytic enzyme inhibitors in a single formulation. This composite approach allows the penetration promoter to facilitate cellular absorption while the enzyme inhibitor simultaneously protects against enzymatic degradation, thereby achieving both enhanced absorption rate and reliable bioavailability in-vivo
3Productivity
If high molecular weight active ingredients are used, then penetration promoter effects are more pronounced, but protease inhibitor combination is not well established
Solution Approach 1:
The patent applies universality by developing a multi-functional formulation that simultaneously addresses multiple needs: the penetration promoter enhances absorption for high molecular weight active ingredients, while the proteolytic enzyme inhibitor provides broad-spectrum protection against enzymatic degradation. This universal approach creates a versatile formulation platform that can be applied to various high molecular weight peptides and proteins without requiring separate optimization for each component
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 formulation significantly increases the oral bioavailability of active ingredients by protecting them from enzymatic degradation and ensuring targeted release in the gastrointestinal tract, as demonstrated by increased plasma concentration levels in minipigs, suggesting broader applicability beyond peptides.
Implementation Method 1
the outer coating is adjusted through the choice of the anionic polymer or copolymer or its formulation with excipients and its layer thickness such that the coating dissolves in pH ranges from 4.0 to 8.0 in the intestine within 15 to 60 min
Implementation Method 2
the active substance-containing, mucoadhesive matrix layer is exposed, and can bind to the intestinal mucosa and release the active substance there
Implementation Method 3
a bioavailability promoting agent, such as a pharmaceutically acceptable inhibitor of proteolytic enzymes like Bowman-Birk inhibitor, to enhance the oral bioavailability of active ingredients
Data Source
AI summary
The invention relates to a pharmaceutical or nutraceutical formulation comprising a core, comprising an active pharmaceutical or nutraceutical ingredient, a penetration promoter and a bioavailability promoting agent, and a polymeric coating for the gastrointestinal targeted release of the active ingredient, characterized in that the bioavailability promoting agent is a pharmaceutically acceptable inhibitor of proteolytic enzymes, which increases the oral bioavailability of the active ingredient by a factor of at least five, compared to a corresponding formulation without the bioavailability promoting agent.