Route of Synthesis (ROS) In Pharmaceutical Development: Interview Questions

Route of Synthesis (ROS) In Pharmaceutical Development: Interview Questions

What is the API route of synthesis?

he API Route of Synthesis refers to the detailed sequence of chemical reactions and processes used to produce the Active Pharmaceutical Ingredient (API) from basic starting materials or intermediates.

Key Points:

• It outlines each step, including reagents, conditions, purification methods, and yields.
• It is developed to ensure efficiency, safety, cost-effectiveness, and scalability.
• Often involves retrosynthetic analysis to design the most effective pathway.
• Must meet regulatory standards for quality, reproducibility, and impurity control.

What is a route scouting?

Route scouting is the process of exploring and evaluating different possible synthetic pathways to produce a target compound, such as an Active Pharmaceutical Ingredient (API), during early drug development.

Key Points:

• It involves identifying multiple routes to synthesize the same compound.
• Each route is assessed for efficiency, safety, cost, yield, purity, and scalability.
• It often uses retrosynthetic analysis to break down the target molecule into simpler precursors.
• The goal is to find the best route for lab-scale and eventual commercial manufacturing.
• Helps in minimizing waste, hazards, and process complexity.

In short, route scouting helps select the most practical and economical synthetic method for drug development.

What are the applications of ROS?

Applications of the Route of Synthesis (ROS) in Pharmaceutical Development:

1. Development of Active Pharmaceutical Ingredients (APIs):
   Helps in designing efficient and scalable methods to synthesize drug molecules.
2. Process Optimization:
   Enables improvement in yield, purity, and cost-effectiveness of the synthesis.
3. Impurity Profiling:
   Identifies and controls potential impurities formed during synthesis.
4. Regulatory Submissions:
   Detailed ROS is required in documents like DMF (Drug Master File) and CMC sections of regulatory filings.
5. Technology Transfer:
   Provides a clear process for transferring synthesis from R&D to manufacturing.
6. Patent Strategy:
   Novel ROS can be patented to protect intellectual property.
7. Green Chemistry:
   Aids in selecting environmentally friendly and sustainable synthetic routes.
8. Troubleshooting and Quality Control:
   Understanding ROS helps in identifying process issues and ensuring consistent product quality.

What are the principles/concepts of deciding the route of synthesis?

The principles/concepts of deciding a Route of Synthesis (ROS) in pharmaceutical development are based on scientific, economic, and regulatory considerations to ensure the process is efficient, safe, and scalable.

Key Principles/Concepts for Deciding ROS:

These principles are often balanced together to find the most practical and robust synthetic route for a given pharmaceutical compound.

What are examples of Routes of Synthesis (ROS) used for Active Pharmaceutical Ingredients (APIs)?

1. Paracetamol (Acetaminophen)

• Starting material: Phenol
• Steps:
  1. Phenol to 4-nitrophenol
  2. 4-nitrophenol to p-aminopheno
  3. Acetylation of p-aminophenol using acetic anhydride
  4. Crystallization and purification
• Reaction type: N-acylation
• Outcome: Produces paracetamol with high yield and purity

2. Ibuprofen

• Original route (Boot process): Involved 6 steps and used toxic reagents
• Modern route (Green synthesis):
  1. Friedel-Crafts acylation of isobutylbenzene
  2. Rearrangement and hydrolysis
  3. Oxidation to form carboxylic acid (ibuprofen)
• Advantages: Fewer steps, higher atom economy, environmentally friendly

Related:

• What is Custom API Synthesis in Pharma R&D and Why Is It Important
• CRO And CMO in Pharma: Key Differences, Roles, FAQs and What is CDMO