2021 FDA Science Forum
Interaction Studies of Tretinoin with Microspheres in Tretinoin Topical Gel
- Authors:
- Center:
-
Contributing OfficeOffice of the Commissioner
Abstract
BACKGROUND
Microparticle delivery systems such as porous microspheres have been used for more than two decades for the topical delivery of tretinoin. Due to the porous surface and correspondingly large surface area of microspheres, a relatively large amount of tretinoin can be loaded onto the microspheres. Our previous study showed that physicochemical properties, such as the particle size and drug loading of the microspheres, affected tretinoin release from the particles. However, the mechanism and kinetics of tretinoin release from microspheres are not well understood.
PURPOSE
The purpose of this study is to elucide the potential interactions between tretinoin and the microspheres, which provides insights into the mechanism(s) controlling the release of tretinoin from the microspheres.
METHODOLOGY
Tretinoin was loaded onto Microsponges® 5640, a commercial microspheres product, at a loading efficiency of 0.5%, 1% and 2% w/w. The in-house prepared drug-loaded microspheres, and microspheres that were separated from Retin-A® Micro (tretinoin) topical gel, 0.1% were studied by Microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transformed infrared (FTIR) spectroscopy.
RESULTS
The XRD diffractograms of raw and processed tretinoin exhibited a series of intense sharp peaks, which disappeared in the drug-loaded microspheres and the separated microspheres. The FTIR spectra showed a strong and broad stretch of the hydroxyl group at 2800-3200 cm?1 for tretinoin, and a strong stretching vibration of the carbonyl group at 1790–1710 cm?1 for blank microspheres. The characteristic bands observed with microspheres disappeared, and the hydroxyl band of tretinoin shifted by 8-12 cm?1, for drug-loaded microspheres and separated microspheres, indicating that there was a molecular interaction between tretinoin and the polymeric matrix of the microspheres, via hydrogen bonding.
CONCLUSION
Tretinoin presented in an amorphous dispersion state within the microspheres in Retin-A® micro gel, 0.1%, and when tretinoin was loaded into Microsponges® 5640. It was molecularly dispersed within the pore structure of the microspheres and interacted with the acrylate matrix of microspheres through hydrogen bonding. The study suggested that the release of tretinoin from the microspheres may involve the dissociation of the hydrogen bonds between tretinoin and the acrylate polymer, before tretinoin diffuses out from the pores of microspheres.
