Introduction: Intravaginal delivery is currently considered to be an important alternative
route for poorly-absorbed, rapidly metabolised oral drugs.
Objectives: The objective of this study was to evaluate (i) the preliminary feasibility of using the readyto-
use vehicle Pentravan® to compound dienogest, gestrinone, nimesulide and piroxicam and (ii) the
vaginal administration of theses formulations to patients with pelvic pain associated with endometriosis
Methods: Intravaginal creams were compounded containing the active pharmaceutical ingredients
(APIs) individually and with no addition of permeation enhancers (dienogest 0,2%, gestrinone 0,5%,
nimesulide 2,0% and piroxicam 2,0%). For quality control, pH, drug content and particle size were determined.
HPLC methods were developed and validated for each formulation. Vaginal permeation profiles
were determined using porcine vaginal mucosa on Franz-type diffusion cells and then kinetics parameters
Results: Quality control of the formulations showed that the products were convenient and easily prepared,
with narrow size distribution. Diffusion experiments demonstrated fluxes of 15.98 µg.cm-2.h-1
for dienogest, 3.91 µg.cm-2.h-1 for piroxicam, 3.72 µg.cm-2.h-1 for gestrinone and 2.26 µg.cm-2.h-1 for
nimesulide. Dienogest and gestrinone had permeation fluxes and quantities of drug absorbed hypothetically
compatible with therapeutic effect in vivo (fluxes to attempt in order to deliver the recommended
daily doses to treat PPRE were calculated as 0.87 µg.cm-2.h-1 for dienogest, 0.69 µg.cm-2.h-1 for gestrinone,
70.45 µg.cm-2.h-1 for nimesulide and 9.64 µg.cm-2.h-1 for piroxicam), whereas nimesulide and
piroxicam studies showed a great amount of these drugs retained in the vaginal mucosa. This could account
for a local effect for these two substances.
Conclusion: Pentravan®, which already has an established role for transdermal delivery of drugs,
seems to be a feasible intravaginal vehicle. Particularly in this study, we highlight its use for vaginal
delivery of dienogest and gestrinone for the treatment of PPRE. In vivo studies must now be conducted
to confirm these data.