SARS-CoV-2 Keto-Amide Composition for Stability and Rapid Dissolution
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Solution Overview
Problem
There is a lack of pharmaceutical compositions and preparations containing keto-amide derivatives with good anti-SARS-CoV-2 activity, and existing formulations lack feasibility, stability, and effective preparation methods.
Innovation Solution
A pharmaceutical composition comprising a compound of Formula I or its pharmaceutically acceptable salt, combined with specific excipients such as fillers, binders, glidants, disintegrants, and lubricants, optimized through non-wet granulation technology, ensuring high stability, feasibility, and rapid dissolution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If keto-amide derivatives are used as active ingredients, then anti-SARS-CoV-2 activity is improved, but pharmaceutical composition feasibility and stability are insufficient
Solution Approach 1:
The patent combines keto-amide derivative compounds with specific excipients (microcrystalline cellulose, lactose, hydroxypropyl methylcellulose, colloidal silica, cross-linked sodium carboxymethyl cellulose, magnesium stearate, sodium stearyl fumarate) to create a stable pharmaceutical composition. This composite formulation maintains the antiviral activity while ensuring compositional stability through proven compatibility among all ingredients.
Solution Approach 2:
The patent optimizes the mass ratios of active ingredient to excipients (e.g., 1:5 to 1:20 for fillers, 1:0.1 to 1:0.5 for binders) to achieve both high stability and rapid dissolution. By adjusting these parameters, the composition maintains structural integrity during storage while dissolving quickly in physiological conditions.
2Ease of manufacture
If traditional formulation methods are used, then preparation process is simple, but dissolution rate is slow
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation, including using microcrystalline cellulose with specific particle size distribution, optimizing binder concentration (1-5% w/w), and adjusting lubricant content (0.1-1% w/w) to achieve rapid dissolution without complex preparation processes. The composition dissolves 70% or more within 60 minutes in pH 6.8 buffer solution.
Solution Approach 2:
The inclusion of colloidal silica (0.1-5% w/w) and microcrystalline cellulose creates a porous structure in the tablet that facilitates rapid water penetration and drug dissolution, achieving 70% dissolution within 60 minutes while maintaining simple manufacturing processes.
3Duration of action of stationary object
If stability is optimized for long-term storage, then storage feasibility is improved, but dissolution performance may be compromised
Solution Approach 1:
The patent uses a composite excipient system where microcrystalline cellulose provides structural stability during storage, while hydroxypropyl methylcellulose and cross-linked sodium carboxymethyl cellulose maintain dissolution performance. This composite approach ensures both long-term stability and rapid dissolution of 70% or more within 60 minutes.
Solution Approach 2:
The patent applies different excipients with specific local functions: microcrystalline cellulose and lactose as fillers provide bulk and stability, hydroxypropyl methylcellulose as binder ensures tablet integrity, while cross-linked sodium carboxymethyl cellulose and colloidal silica create dissolution channels. This localized functional assignment achieves both stability and rapid dissolution.
Data Source
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AI summary
Provided is a pharmaceutical composition, comprising a compound of formula I or a pharmaceutically acceptable salt thereof and an auxiliary material. The auxiliary material comprises one or more of a filler, a binder, a glidant, a disintegrant and a lubricant. The pharmaceutical composition has the feasibility of preparation process, excellent properties of preparations, good stability and good dissolution, and meets the pharmaceutical standards.