Preparation and in vitro/in vivo evaluation of anastrozole reservoir‐type intravaginal ring

Abstract

This report details the preparation of anastrozole (ATZ) reservoir‐type intravaginal ring (IVR) and the detection of the concentration of ATZ in beagle dog plasma by liquid chromatography–tandem mass spectrometry (LC–MS/MS). An ATZ reservoir‐type IVR which included ATZ silicone elastomer core and a nonactive silicone layer was manufactured by reaction injection moulding at 80°C for 20 min. An in vitro release experiment was performed under sink conditions and the samples were determined by high‐performance liquid chromatography. A bioanalytical method was developed and validated for determination of ATZ in beagle dog plasma for IVR development. The analytical method consisted of the extraction of plasma samples and determination of ATZ by LC–MS/MS using buspirone as the internal standard. Separation was achieved on a Kinetex‐C18 110A column (3 × 30 mm, 2.6 μm, Phenomenex) using step‐gradient mobile phase and an isocratic flow rate consisting of formic acid. Protonated ions formed by a turboion spray in the positive mode was used to detect the analyte (ATZ) and internal standard. The MS–MS detection was performed on a triple quadrupole mass spectrometer equipped with electrospray ionization source. The mass spectrometer was operated in the multiple reaction monitoring mode. The mass transition ion‐pair was followed as m/z from 294.10 to 225.08 for anastrozole and m/z from 386.23 to 122.11 for buspirone. The results proved that the correlation between in vitro and in vivo analyses was relatively good.

Evaluation of Pharmacokinetics and Safety With Bioequivalence of Anastrozole in Healthy Chinese Volunteers: Bioequivalence Study Findings

“…Then, the RSABE approach is used to demonstrate BE. According to the literature, 18,19 the intrasubject variability of anastrozole is <14%. Accordingly, in the present study, the ABE approach was used to demonstrate the BE of anastrozole.…”

In Vitro Methods for Evaluating Drug Release of Vaginal Ring Formulations—A Critical Review

“…The least complex medium used for QC purposes is water. Due to its lacking buffer capacity in pharmaceutical dissolution, testing water is also one of the least reliable media for dissolution testing, and its use in in vitro drug release testing of IVRs is not very common [46,48,50,61,66,67]. Sink conditions are an essential prerequisite for in vitro dissolution test methods used in QC.…”

“…However, as possible, daily release should be determined over the entire release period, since information on the release rates during different time periods (for example, day 1, 2–7 days, 8–14 days, 15–21 days, etc.) can be helpful for both developing discriminative QC methods or estimating in vivo drug release [44,57,67,71,83].…”

A novel anastrozole intravaginal ring for endometriosis: Pharmacokinetic characteristics and mucosal irritation

“…Compared with cynomolgus monkeys, beagles, rabbits and other experimental animals, mini pigs are very similar to humans in anatomical and physiological structure, metabolic processes, pathological diagnostic indicators, etc., especially in vaginal size, menstrual cycle length and ovulation interval (Svendsen, 2006). At present, rabbits (Li et al, 2016), beagles (Xia et al, 2019), monkeys (Rotgeri et al, 2015) and other experimental animals are mostly used in the study of the pharmacokinetics of vaginal rings in vivo . Because of their small size and narrow vagina, the complete ring cannot be used for the experiment, and the release data closest to the whole ring cannot be obtained.…”

“…HPLC and LC-MS/MS methods of light spray ion source are commonly used in mice (Shavi et al, 2011). A liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the analysis of ATZ concentration in beagle dogs has recently been developed (Xia et al, 2019), providing a reference for the analysis of ATZ concentration in large mammals.…”