In vitro retinoid binding and release from a collagen sponge material in a simulated intravaginal environment

Four in vitro preparations were constructed to simulate the intravaginal release of two retinoids, all‐trans‐retinoic acid (t‐RA) and 13‐cis‐retinoic acid (c‐RA), from a 0.7% collagen sponge diaphragm insert. Four t‐RA concentrations, 0.019, 0.05, 0.1, and 0.15% in methanol were added to the sponge. The release into an artificial vaginal fluid was monitored serially over 72 h by serial analysis for t‐RA and c‐RA using high‐pressure liquid chromatography. In each preparation, retinoid release was immediate and noncontinuous. At 37°C, the retinoids were stable for at least 48 h. Trans‐retinoic acid was the predominant retinoid recovered. Only trace amounts of the cis‐isomer were released. Peak t‐RA levels were 20 μM after 0.01%, 60–80 μM after 0.05%, 100–200 μM after 0.1%, and 320 μM after 0.15%. When the vaginal fluid bath was changed after 5 h, no further significant retinoid release occurred. There was significant loss of up to 70% of the applied t‐RA into the collagen sponge. The retinoid binding was concentration dependent (higher binding with higher concentrations) and was maximal only after 24 h of co‐incubation. The discontinuous release of t‐RA and the high degree of binding to collagen would seem to preclude use of the diaphragm insert as a vaginal drug delivery system, at least for retinoids.