ALP001E Pharmaceutical Composition Stability via Spray Drying
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Solution Overview
Problem
The glucagon receptor antagonist ALP001E has poor aqueous solubility and is sensitive to hydrolytic degradation, acid, and basic environments, making it challenging to develop stable pharmaceutical compositions with desirable in vitro and in vivo performance.
Innovation Solution
A novel pharmaceutical composition comprising ALP001E with a specific formulation of 8-30 wt% active ingredient, 70-92 wt% excipients including a dispersant and solubilizer, such as hypromellose acetate succinate and Macrogol 15 Hydroxystearate, which enhances stability and bioavailability through spray drying methods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ALP001E is formulated as a conventional pharmaceutical composition, then it can be administered to patients, but it exhibits poor aqueous solubility and hydrolytic degradation leading to poor stability
Solution Approach 1:
The patent uses a composite material system consisting of ALP001E combined with specific excipients including dispersants and solubilizers. This composite formulation resolves the contradiction by integrating multiple components that collectively improve both solubility and stability, with the active ingredient present at 8-30 wt% and excipients at 70-92 wt%
Solution Approach 2:
The patent applies parameter changes by optimizing the concentration ranges of the active ingredient (8-30 wt%) and excipients (70-92 wt%), and by controlling processing parameters such as spray drying conditions. These parameter optimizations enable the formulation to achieve both improved solubility and enhanced stability
2Object-affected harmful factors
If ALP001E is formulated to improve solubility through excipients, then aqueous solubility improves, but the formulation complexity increases
Solution Approach 1:
The excipients selected in the formulation serve multiple functions simultaneously: they act as dispersants to improve solubility, provide stabilization to prevent degradation, and facilitate the spray drying process. This multi-functionality reduces formulation complexity despite the need for improved solubility
3Reliability
If ALP001E is stabilized against hydrolytic degradation, then chemical stability improves, but manufacturing process complexity increases
Solution Approach 1:
The patent incorporates stabilizing excipients and protective measures into the formulation before the manufacturing process. The spray drying method is designed to rapidly remove moisture and stabilize the compound against hydrolytic degradation, preventing degradation rather than addressing it after formation
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 composition achieves chemical and polymorphic stability, improved solubility, and increased oral absorption, enabling effective administration and bioavailability, suitable for clinical use in reducing glycemic levels and treating glucagon-related disorders.
Implementation Method 1
a dispersant and a solubilizer present in an amount of 70 wt% to 92 wt%
Implementation Method 2
a dispersant and a solubilizer present in an amount of 70 wt% to 92 wt%
Implementation Method 3
spray drying methods
Data Source
AI summary
Disclosed is a pharmaceutical composition comprising: an active ingredient of the following formula (I) or a pharmaceutically acceptable salt or solvate thereof present in an amount of 8 wt% to 30 wt%: and two or more excipients at least including a dispersant and a solubilizer present in an amount of 70 wt% to 92 wt%.. Also disclosed are methods for reducing the glycemic level and treating disorders associated with glucagon with the aforesaid pharmaceutical composition.