Yes, lipid oxidation is a major stability issue associated with use of lipid as excipients. Cholesterol is another major ingredient in lipid-based drug delivery systems and susceptible to oxidation as we observed.
https://www.sciencedirect.com/science/article/pii/S0378517319306209
I observed most recently approved intravenous liposomal formulations use fully saturated lipids and it minimize oxidation and most oxidation occurs in unsaturated lipids as double bonds are more susceptible to oxidation. In addition to oxidation lipid degradation is another stability issue.
https://www.sciencedirect.com/science/article/pii/S0378517320300612
------------------------------
Thilak Mudalige Ph.D.
Research Chemist
US Food and Drug Administration
Jefferson AR
[email protected]Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
------------------------------
Original Message:
Sent: 02-26-2024 06:20
From: Dimple Modi
Subject: Challenges associated with lipids and lipid based excipients
I have experience with utilizing lipids in both topical and parenteral dosage forms. A significant challenge encountered is the oxidation of lipids, as they tend to oxidize and degrade when exposed to air if not managed correctly. This can lead to overall degradation of the drug product and a decrease in pH.. This oxidative degradation can result in changes to the drug's chemical structure, impacting its safety, effectiveness, and overall quality.
To prevent lipid oxidation in pharmaceutical products, incorporating antioxidants is a common strategy, as they can neutralize free radicals and halt the oxidation process. Additionally, storing products under inert atmospheres, such as nitrogen purging, can significantly reduce oxygen exposure and thus lipid oxidation. Ensuring products are kept away from direct light and at appropriate temperatures also plays a critical role in minimizing oxidative degradation.
------------------------------
Dimple Modi
Investigator
GlaxoSmithKline
Gilbertsville PA
[email protected]
Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
Original Message:
Sent: 02-22-2024 14:06
From: Masumi Dave
Subject: Challenges associated with lipids and lipid based excipients
Hello Lipid-based Drug Delivery Systems Community,
I want to ask the LBDDS community about the challenges you face using lipids/ lipid based excipients in your drug product development process and if you could share your insights on how you have overcome these challenges.
------------------------------
Masumi Dave
Lab Manager
Gattefosse Corporation
Paramus NJ
[email protected]
Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
------------------------------