Type of Posting: General Chapter Prospectus
Posting Date: 23-Feb-2024
Input Deadline: 24-Mar-2024
Proposed GC Title: <1785> Osmolality / Osmolarity – Practical Considerations
Expert Committee: General Chapters-Physical Analysis
Suggested audience: Suppliers and manufactures of excipients, drug substances, drug products, veterinary products; Regulatory agencies; Manufacturers of water activity instruments.
Estimated proposal PF: 50(5)
Background and objectives:
The purpose of this chapter is to provide additional guidance regarding whether an osmolality instrument is suitable for use with certain pharmaceutical formulations. This chapter will discuss how to assess the ideal behavior of a solution , how to determine what non-ideal behaviors dominate in a solution, and how to evaluate whether a freezing point measurement is suitable for an undiluted sample. Additionally, this chapter also provides suggestions on conditions when the procedure needs to be verified due to the test condition changes. This chapter briefly discusses the correlation and difference between tonicity and osmolality to add clarification for users.
Description of scope and application: The new chapter is intended to provide guidance for the correct application of <785> to various dosage forms, a discussion of the types of non-idealities samples may exhibit and what instrument factors may affect the accuracy of a freezing-point method. Additionally, recommendations are provided regarding how to assess if a freezing-point measurement is providing reliable results for a particular sample, and recommendations on method verification and method transfer.
Preliminary outline:
- - Introduction
- Background.
- Discuss instrumental factors that may affect accuracy of a freezing-point measurement.
- Discuss samples that may be difficult to measure (e.g., high-concentration protein solutions, high-concentration polymer solutions).
- Calculations of osmolality and osmolality coefficients.
- Discuss types of non-idealities exhibited by real solutions.
- Non-electrolytes exhibit primarily solute-water interactions.
- Electrolytes exhibit primarily solute-solute interactions. Zwitterions also exhibit solute-solute interactions.
- How to model solutions with mixtures or unknown solutes
- Experimental determination of the (approximate) ideal behavior for mixtures or unknown solutes and calculation of the osmotic coefficients.
- Recommendations for assessing reliability of osmolality for a particular sample using the osmolality coefficient.
- Case Study/Example: an example of when the osmolality coefficient plot indicates a problem with the osmolality measurement for a particular solution.
- Recommendations for transferring an osmolality method or comparing an osmolality measurement between two different instruments.
- Relevance of osmolality to pharmaceutical development and production.
- Tonicity and Osmolality
- Glossary
- References
Contact: Margareth Marques, Senior Principal Scientist (mrm@usp.org)