Week 9 Vaginal DDS

Vaginal Flora

• Vaginal and Urethral Drug Delivery Systems

  • Importance of maintaining a healthy vaginal pH (3.8-4.5), similar to that of a tomato.

  • Vaginal flora protect against reproductive system infections.

• Health Statistics

  • 42% of women report never being taught vaginal health care.

  • 45% of women use soaps, which can disrupt natural pH.

• Friendly Bacteria

  • L. reuteri RC-14® & L. rhamnosus GR-1®: Support vaginal health and balance flora.

• Imbalance in Flora

  • Over 50% of women with bacterial vaginosis experience recurrent infections.

Learning Objectives

1. Describe the physiology of the vagina and urethra.

2. Explain physiological challenges to vaginal/urethral drug delivery.

3. List ideal physicochemical properties for vaginal drug delivery systems (DDS).

4. Identify ideal formulation factors for vaginal DDS.

5. Compare different types of vaginal DDS.

6. Discuss special patient conditions benefiting from vaginal/urethral routes.

Physiology of the Vagina

• Vaginal Structure

  • Components: Ampulla, Isthmus, Infundibulum, Fimbriae, Ovary, Ovarian ligament.

• Uterine Layers

  • Perimetrium: Outer layer of uterus.

  • Myometrium: Muscular middle layer.

  • Endometrium: Inner lining.

Physiological Factors for Vaginal DDS

• Dimensions

  • Length: 8-10 cm; Width: 2 cm.

• Fluid Volume

  • Vaginal fluids: 2-3 mL.

• Vascularization

  • High vascular supply aiding absorption.

• Surface Area

  • Increased by rugae and microridges; varies cyclically with hormones affecting drug dissolution and permeability.

• Thickness of Epithelium

  • Thickness varies between menstruating (3.5-4.5) and non-menstruating (6-7) women; also affects buffering capacity.

• Enzymatic Activity

  • Generally low, influencing drug metabolism.

• Drug Transport

  • Primarily passive transcellular transport.

Physicochemical Factors for Vaginal DDS

• Drug Molecular Weight

  • Low molecular weight (< 1,000 Da) is preferred for absorption.

• Lipophilicity

  • Lipophilic drugs are absorbed more effectively than hydrophilic drugs.

Formulation Factors for Vaginal DDS

• Mucoadhesives

  • Increase contact time and prevent dripping, critical due to lack of sphincters in the vagina.

• Surfactants & Co-solvents

  • Aim to dissolve drugs slowly to avoid rapid leakage, which causes loss of dosage form.

• Dissolution pH

  • Menstruating women: acidic; non-menstruating women: neutral.

• Volume of Administration

  • Low

Dosage Forms for Vaginal DDS

• Types

  • Suppositories: PEG bases.

  • Ointments, Creams, Gels: Potentially messy.

  • Vaginal Tablets.

  • Vaginal Rings: For sustained release.

NuvaRing®

• Description

  • Non-biodegradable, flexible contraceptive vaginal ring.

  • Contains 0.12 mg etonogestrel and 0.015 mg ethinyl estradiol; releases drugs by diffusion.

• Usage

  • Worn for 3 weeks; 1-week removal required.

  • Total drug content: 11.7 mg etonogestrel, 2.7 mg ethinyl estradiol.

• Disposal

  • Must be discarded in waste, not in toilet.

Pharmacokinetic Profile of NuvaRing®

• Drug Concentration

  • Profiles for etonogestrel and ethinyl estradiol during 3-week use.

  • 

Insertion and Removal of NuvaRing®

• Insertion Steps

  • Remove from packaging, fold and insert gently into the vagina. Position is not crucial for effectiveness.

• Removal Steps

  • To be done 3 weeks post-insertion; dispose responsibly.

Advantages of Vaginal DDS

• Benefits

  • Large surface area, rich blood supply, low metabolic activity, and high permeability.

  • Easy administration and prolonged retention possible, enabling zero-order release.

• Limitations

  • Effective mainly for potent molecules; may irritate vaginal tissue; prone to leakage; epithelium changes with hormones; not applicable to half the population.

Urethral DDS

• Anatomy Overview

  • Male urethra ~20 cm; Female urethra ~4 cm.

• Functionality

  • Site of action for urine excretion and conditions like catheter infections.

Medicated Urethral System for Erection (MUSE®)

• Description

  • Trans-urethral suppository delivering alprostadil to erectile tissue.

  • Formulated in a pellet for easy insertion via an applicator.

  • Store in fridge

Advantages and Disadvantages of Urethral DDS

• Advancements

  • Offers local effects.

• Challenges

  • Unpopular and unsuitable for systemic delivery; requires different sizes for administration.

Review Quiz**

1. Determine if a weak base drug will be absorbed systemically or retained locally in the vagina based on the patient's reproductive status.