Stability of Latanoprost in Generic Formulations Using Controlled Degradation and Patient Usage Simulation Studies

Abstract

Purpose: To evaluate the stability of latanoprost in generic formulations by using controlled degradation and patient usage simulation studies

Methods: Standard latanoprost was subjected to controlled degradation studies. Latanoprost content was assessed by using MRM, and generated Degradation Products (DP) were analysed by using the Information Dependent Acquisition (IDA) protocol of positive ESI-LC-MS/MS. Latanoprost content and formation of DP were assessed in generic formulations and were compared with Xalatan® in a controlled patient usage simulation studies. The last few drops of latanoprost, present in containers used by patients were also evaluated.

Results: Extreme pH conditions, oxidation, light and heat were found to be the significant factors for high degree of latanoprost degradation. Systematic analysis of 7 selected generics revealed that the latanoprost content varied from 90–330%. Concentration of the latanoprost in Xalatan was found to be 97% of the label claim. Degradation studies showed the formation of 3 novel and 3 already known impurities. Upon simulated patient usage, 2 of the generic formulations showed significant degradation of latanoprost. Generic formulations having thermally sealed gas tight packing showed good stability during patient usage. Overage of latanoprost was observed in generics with other than thermal sealing. Latanoprost bottles used by patients showed concentrations ranging from 20 to 250% of label claim (144% median).

Conclusion: This study revealed the presence of overage of latanoprost in some generic formulations and formation of degradation products. Packaging with gas tight containers may be one of the important factors for latanoprost stability, along with its storage at low temperature during patient usage.

• Degradation
• generics
• glaucoma
• latanoprost
• stability

Acknowledgments

We appreciate the help rendered by the Residents of Glaucoma Unit and the help of Mr. A. Ghosh in the conduct of this study.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.