Design of an intravaginal ring for the controlled delivery of 17β-estradiol as its 3-acetate ester

A dynamic mechanical method for determining the silicone elastomer solubility of drugs and pharmaceutical excipients in silicone intravaginal drug delivery rings

“…These values are comparable with those obtained for cholesterol (35 mg/g, melting point 1311C) and progesterone (6 mg/g, melting point 1291C) using a related differential scanning calorimetry method [17]. Estradiol, whose exceptionally poor silicone solubility has prevented the development of an IVR capable of providing the clinically desired >50 mg/day release rate required for estrogen replacement therapy [1][2][3], shows a negative solubility value (À1.21 mg/g, Table 2) as determined by the dynamic mechanical method. Such a negative value demonstrates the difficulty in using this technique for substances with very poor silicone solubility.…”

“…In this study, a novel DMA method for determination of the silicone elastomer solubility of a range of drugs and pharmaceutical excipients at their melting point is reported. The drugs chosen represent examples of therapeutic agents currently being evaluated for IVR development [1][2][3][4][8][9][10], while the choice of excipients includes materials being investigated in our laboratory for modifying drug release from the rings.…”

“…1) designed to release drug(s) to the vagina [1][2][3]. The rings have, to date, been primarily developed for the systemic delivery of contraceptive steroids [1,[4][5][6][7] and the localized and systemic delivery of steroids for hormone replacement therapy [1][2][3][8][9][10], although it is likely they will in the future be exploited for a much wider range of applications within women's health care including the delivery of anti-infective agents and HIV microbicides. Unsurprisingly, the IVR, which was specifically designed for the intravaginal administration of drugs, overcomes many of the disadvantages associated with more traditional vaginal drug dosage forms, such as gels, tablets and pessaries, which are often difficult to apply, interfere with intercourse and are poorly retained within the vagina [1].…”

Strategies to Prolong the Intravaginal Residence Time of Drug Delivery Systems

“…Figure 13 showed the mean plasma concentration of 17b-estradiol 84-day period with an intravaginal ring (128).…”

Vaginal Microbicides for the Prevention of HIV Transmission

“…In order to provide protection, semisolid formulations are most likely to require application prior to every act of intercourse, which is also likely to lead to poor user compliance. A number of alternative formulations for the delivery of vaginal microbicides are currently being evaluated, such as controlled-rele ase intravaginal rings (Woolfson et a/., 1999(Woolfson et a/., , 2003Malcolm et aL., 2001Malcolm et aL., ., 2003aMalcolm, 2003), akin to those currently being marketed for contraception (Nuvaring4!) and hormone replacement therapy (Estring®, Femring®).…”