Optimization of S-Nitrosocaptopril Monohydrate Storage Conditions Based on Response Surface Method

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• S-nitrosocaptopril monohydrate (Cap-NO·H2O) is a novel crystal form with dual therapeutic actions: nitric oxide (NO) donation and angiotensin-converting enzyme inhibition (ACEI).
• Despite over two decades of research on S-nitrosocaptopril (Cap-NO) and its derivatives, a validated method for the long-term storage of Cap-NO·H2O has been notably absent.
• The inherent instability of previous crystal forms necessitates the development of stable storage protocols for Cap-NO·H2O to ensure its therapeutic efficacy and shelf-life.

Purpose of the Study:

• To establish optimal storage conditions for S-nitrosocaptopril monohydrate (Cap-NO·H2O) to ensure its stability and preservation.
• To identify critical factors influencing the stability of Cap-NO·H2O through experimental design.
• To determine a precise storage protocol that maximizes the preservation rate of Cap-NO·H2O over an extended period.

Main Methods:

• Plackett-Burman (PB) design was utilized to screen and identify the most significant factors affecting Cap-NO·H2O stability.
• Response Surface Methodology (RSM) was employed to optimize the storage conditions based on preliminary factor screening.
• A path of steepest ascent experiment was conducted to establish a suitable interval for RSM optimization.

Main Results:

• The Plackett-Burman design identified key factors influencing Cap-NO·H2O stability, guiding subsequent optimization efforts.
• Response Surface Methodology determined the optimal storage condition parameters: 97% nitrogen purity, a temperature of -10 °C, and 1.20 g of deoxidizer.
• Under these optimized conditions, a high final preservation rate of 97.91 ± 0.59% was achieved for Cap-NO·H2O.

Conclusions:

• The study successfully defined optimal storage conditions for S-nitrosocaptopril monohydrate (Cap-NO·H2O), significantly enhancing its stability.
• Cap-NO·H2O demonstrated stability for at least six months when stored under the determined optimal conditions in individual polyethylene (PE) packaging.
• These findings present a viable and potentially applicable strategy for the long-term storage and preservation of Cap-NO·H2O, facilitating its future clinical use.