GLP-2 Analogue One-Pot Formulation to Reduce Foaming
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Solution Overview
Problem
The existing manufacturing process for GLP-2 analogues, such as ZP1848 and ZP1846, faces issues with excessive foaming, lump formation, and difficulty in scaling up due to the amphiphilic nature of these peptides, leading to poor visual process control and stability challenges.
Innovation Solution
A one-pot formulation process where excipients and the GLP-2 analogue are added sequentially in a single tank, minimizing stirring and adjusting pH and volume to create a stable liquid formulation suitable for industrial scale-up, reducing foaming and lump formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If traditional two-pot formulation process is used, then dissolution of excipients and drug substance can be controlled separately, but excessive foaming and lump formation occur leading to poor visual process control
Solution Approach 1:
The patent merges the separate dissolution processes into a single-pot formulation process. The excipients and drug substance are dissolved together in one vessel, eliminating the interface between separate solutions where foaming and lump formation occur. This single-pot approach maintains the benefit of controlled dissolution while removing the visual control problems associated with two-pot mixing.
2Ease of manufacture
If manual stirring is used to dissolve drug substance, then dissolution can be achieved, but the process cannot be scaled up to industrial production
Solution Approach 1:
The patent replaces manual stirring with automated mechanical stirring systems suitable for industrial scale. The single-pot formulation process is designed to work with standardized mechanical stirrers and mixing equipment, enabling seamless transition from laboratory to industrial production without relying on manual operations.
3Adaptability or versatility
If GLP-2 analogues are formulated in liquid form, then they can be used in delivery devices, but they form oligomers and show stability issues
Solution Approach 1:
The patent optimizes formulation parameters including pH, buffer composition, and excipient ratios to minimize oligomer formation. By carefully controlling the chemical environment and using specific buffer systems, the liquid formulation maintains stability while remaining compatible with delivery devices like pre-filled syringes and infusion pumps.
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 process enables the production of stable liquid formulations with reduced oligomer formation and improved scalability, allowing batches of up to 50 liters with enhanced stability for at least 18 months at 2-8°C, suitable for delivery devices like pre-filled syringes and infusion pumps.
Implementation Method 1
excessive foaming, lump formation, and difficulty in scaling up due to the amphiphilic nature of these peptides
Implementation Method 2
adjusting pH and volume to create a stable liquid formulation suitable for industrial scale-up
Implementation Method 3
reduced oligomer formation and improved scalability
Data Source
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AI summary
Processes for producing a stable liquid pharmaceutical formulation comprising a glucagon-like peptide 2 (GLP-2) analogue, and in particular to processes for producing formulations that comprise ZP1848 (glepaglutide) or ZP1846 (elsiglutide) based on one- pot formulation.