The vagina as a route for drug delivery: a review

Abstract

Overactive bladder (OAB) syndrome has a significant deleterious impact on quality of life. After conservative therapy and bladder retaining, antimuscarinic drugs remain the mainstay of OAB management. Oral therapy is associated with frequent side effects, leading to the development of alternative agents and formulations or the use of novel routes of drug administration, such as the vaginal route. The vagina is often ideal for drug delivery because it allows the use of lower doses, maintains steady drug administration levels, and requires less frequent administration than the oral route. With vaginal drug administration, absorption is unaffected by gastrointestinal disturbances, there is no first-pass effect, and use is discreet. The aim of this review is to provide a background overview of vaginal development, anatomy, and physiology and the effect this has on the use of this route for both local and systemic drug delivery, with special reference to OAB management. Vaginal therapy continues to be an underused route of drug delivery. Vaginal administration allows nondaily, low, continuous dosing, which results in stable drug levels and may, in turn, achieve a lower incidence of side effects and improve patient compliance. These benefits must be balanced against inherent patient or physician bias against using this route and the need to overcome cultural, personal, and hygiene-related barriers to this form of therapy. More sophisticated and programmable vaginal rings are being developed for systemic delivery of therapeutically important macromolecules, such as antimuscarinic therapy in OAB management.

Appendix

Medications currently available in the U.K. as vaginal therapy

• 1. Combined contraceptive vaginal ring:

  • NuvaRing® (vaginal ring, releasing ethinylestradiol approximately. 15 μg/24 h and etonogestrel approximately 120 μg/24 h; net price three-ring pack = £27.00. Counselling, administration dose 1 ring to be inserted into the vagina, removed on day 22; subsequent courses repeated after 7-day ring-free interval (during which withdrawal bleeding occurs)

• 2. Spermicidal contraceptives:

  • Gygel® gel, nonoxynol ‘9’ 2 %, net price 30 g = £4.25

• 3. Contraceptive pessaries:

  • Type A/B/C

• 4. Topical estrogens:

  • Gynest® intravaginal cream, estriol 0.01 %, net price 80 g with applicator = £4.67

  • Ovestin® intravaginal cream, estriol 0.1 %, net price 15 g with applicator = £4.45

  • Ortho-Gynest®, estriol 500 μg, net price 15 pessaries = £4.73

  • Vagifem® vaginal tablets, f /c, estradiol 10 μg in disposable applicators, net price 24-applicator pack = £16.72; estradiol 25 μg in disposable applicators, 15-applicator pack = £10.56

  • Estring® vaginal ring, releasing estradiol approximately 7.5 μg/24 h, net price 1-ring pack = £31.42. Label: 10, patient information leaflet; for postmenopausal urogenital conditions (not suitable for vasomotor symptoms or osteoporosis prophylaxis), to be inserted into upper third of vagina and worn continuously; replace after 3 months; maximum duration of continuous treatment 2 years

• 5. Nonhormonal preparations for vaginal atrophy:

  • Replens MD® and Sylk®; acidic, nonhormonal vaginal moisturizers; Replens MD® provides a high moisture content for up to 3 days

• 6. Preparations for vaginal and vulval candidiasis:

  • Imidazole drugs (clotrimazole, econazole, fenticonazole, miconazole) available as vaginal cream, pessaries, capsules, and tablets

  • Clotrimazole

  • Canesten®

  • Gyno-Daktarin®

  • Gyno-Pevaryl®

  • Gynoxin®

  • Nizoral®

• 7. Preparations for other types of vaginal infections:

  • Clindamycin cream and metronidazole gel; indicated for bacterial vaginosis

  • Dalacin®; clindamycin cream

  • Zidoval®; metronidazole gel

  • Relactagel® and Balance Activ Rx®; vaginal preparations intended to restore normal acidity may prevent recurrence of vaginal infections and permit the re-establishment of normal vaginal flora