In Vitro Assessment of New Formulations of Nonoxynol-9 (N-9) Coprecipitated With Polyvinylpyrrolidone (PVP) as Possible Vaginal Contraceptives

¹P. M. Zavos, ¹J. R. Correa, ²D. Noskova, ²F. Mohammadi, ²G. A. Digenis. ¹Dept. of Animal Sciences and ²Dept. of Medical Chemistry and Pharmaceutics, University of Kentucky, Lexington, KY

Objectives: Nonoxynol-9 (N-9), the most commonly used active ingredient in over-the-counter spermicidal contraceptives, is a nonionic detergent that inactivates sperm via membrane disruption. We have previously shown in rabbits that some of the selected oligomers representing the high, medium and low molecular weight fractions of N-9 could be as spermicidal as the parent N-9 mixture (Pharm. Res., 8(3):403). The objective of this study was to evaluate the spermicidal qualities of various combinations of N-9 (whole molecule=oligomers 1-18) and its isolated fractions (oligomers 8-10, 4-6 and 1-3; Pharm. Res., 8(3):409), coprecipitated with polyvinylpyrrolidone (PVP) as possible vaginal contraceptives. The coprecipitation of PVP and N-9 is a necessary step to alter the chemical state of N-9 (liquid to powder) for spermicidal delivery purposes.

Design: Minimal spermicidal lethal dose (LD) concentrations were determined via a modified Sander-Cramer test (SCT) and a standardized cervical mucus penetration test (CMPT).

Materials and Methods: Semen samples were obtained from healthy donors via masturbation and randomly pooled (2 to 3 specimens) each time the assays were performed. Spermicidal qualities of known equimolar concentrations of various combinations of PVP/N-9 were tested using human spermatozoa via a modified SCT and a standardized CMPT (Serono Diagnostics, Allentown, PA). For the performance of the SCT, various concentrations of each spermicide were obtained by serial dilutions of the spermicide preparations. A solution containing the spermicide was added 1:1 (v/v), mixed with semen and immediately evaluated for sperm viability. Spermicidal activity was reported as the minimal LD concentration (\mug/mL) of spermicide capable of killing all spermatozoa within 20 sec after exposure to the spermicide. The CMPT was performed as previously described (Fertil Steril, 36(2):201). For the CMPT, equal volumes of semen were mixed with LD's and sub-LD's of the various spermicides. The minimal dose of spermicide that prevented sperm penetration of the cervical mucus was reported as the LD.

Results: LD concentrations (\mug/mL) of PVP/N-9 coprecipitates for the SCT and CMPT were 1) whole molecule: 167 and 138, 2) oligomers 8-10: 183 and 160, 3) oligomers 4-6: 432 and 216, and 4) oligomers 1-3: 367 and 70, respectively. Control preparations consisting of N-9 alone for the SCT and CMPT yielded lethal doses of 194 and 166 \mug/mL, respectively. Also PVP alone, was used as a vehicle and did not show any spermicidal qualities and, in this study, it was used merely as a vehicle. The results indicate that the PVP/N-9 (whole molecule and oligomer 8-10) preparations for the SCT showed similar spermicidal qualities with some deviation exhibited by the PVP/N-9 spermicides containing oligomers 4-6 and 1-3 (P<0.05). Different patterns of spermicidal qualities were noted with the CMPT. When contrasting the two test employed, lower LD concentrations of N-9 were required for the CMPT. Furthermore, significantly lower LD's of PVP/N-9 oligomers 4-6 and 1-3 were necessary for the CMPT (P<0.05).

Conclusions: PVP was proven to be an effective vehicle in this study. Oligomer 8-10 when tested via the SCT was similar to the whole molecule. Oligomers 4-6 and 1-3 showed inferior results (P<0.05). However, when the CMPT was applied to the same PVP/N-9 preparations it was found to be more discriminatory than the SCT. In the CMPT, overall lower LD's of PVP/N-9 were established especially for oligomers 4-6 and 1-3 (P<0.05) which was in contrast to the results generated via the SCT. Cur- rent findings could be of clinical significance when pre- paring and delivering those selected coprecipitates vaginally.

National Institute of Child Health and Human Development; contract #NO1-HD-3-3184.

Source: 1995 ASRM Meeting