Anatomy and Physiology of the Vagina

The vagina is a organ capable of absorbing drugs systemically, with various compounds administered vaginally including sodium salicylate, quinine hydrochloride, and hormones.
The vagina's large surface area and high blood supply facilitate easy absorption of active substances into the bloodstream.
The vaginal epithelium is composed of squamous cells with gaps in their connecting links, allowing for the movement of molecules and electrolytes and the absorption of certain drugs.
The vaginal epithelium acts as a physical barrier, with a thickness that varies with age and hormonal changes.

Vaginal drug delivery systems can be optimal for treating and preventing vaginal infections, cervical intraepithelial neoplasia, and delivering hormones for hormone replacement therapy.
The most common drugs administered vaginally are related to the treatment of vaginal infections, spermicides or contraceptive agents, and induction of labor or interruption of pregnancy.
Avoiding the hepatic first-pass effect and minimizing systemic exposure can lead to lower dosing and reduced side effects.

Physiological factors: menstrual cycle, age, pregnancy, and menopause can affect drug absorption and distribution.
Physicochemical properties of drugs: molecular weight, lipophilicity, ionization, and surface charge can influence drug absorption.
Vaginal microflora: Lactobacillus species play a crucial role in defining the environment and can influence drug absorption.
Enzyme activity: proteases, aminopeptidases, and dipeptidyl peptidases can degrade peptide and protein drugs.

Vaginal pH ranges from 3.5 to 5, maintained by the production of lactic acid by Lactobacillus.
pH affects drug ionization potential, with many drugs being weak electrolytes.
Changes in vaginal pH can affect the release profiles of pH-sensitive drugs.

The rectal route offers a non-invasive, useful route of drug administration when systemic or local effects are required.
Advantages over the oral route: avoiding hepatic first-pass metabolism, improving bioavailability, and decreasing side effects.
The rectal route is useful for patients with nausea, vomiting, objectionable taste, or difficulty in swallowing.

The rectum is a temporary storage area for defecation, with a pH of 7.2-7.4 and a fluid volume of 1-3 mL.
The rectum epithelium is similar to that of the upper GI tract, with a predominant mechanism of transcellular passage across the cell membrane.
The rectum has a much lower surface area, but is potentially beneficial for drugs with poor gastrointestinal absorption or low solubility.

Physiological and pathological factors: stool presence, motility, and bowel movements can affect drug absorption.
Physicochemical factors: dissolution, stability, and drug contact with the mucosal wall.
Formulation factors: dosage form and drug-associated factors can influence drug absorption.
Pathological conditions: inflammatory bowel disease, hemorrhoids, and gastro-intestinal infections can influence drug absorption and efficacy.### Factors Affecting Rectal Absorption of Drugs
Proctitis (inflammation) can alter drug absorption from the rectum
Ionized drugs have a higher degree of ionization, leading to higher absorption
Particle size affects absorption, with smaller particles having a greater surface area to volume ratio, leading to faster dissolution and absorption

The type of formulation used influences the absorption of drugs
Aqueous and alcoholic solutions can lead to rapid absorption, which is therapeutically valuable in acute convulsive attacks
Suppositories have slower absorption, dependent on the nature of the suppository base, use of surfactants, and particle size of the active ingredient

LogP measures the lipophilicity or hydrophobicity of the drug molecule
The lipophilicity of the drug affects its absorption through the transcellular route, with higher lipophilicity leading to greater absorption
A balance between lipophilicity and hydrophilicity is necessary for effective rectal drug administration

The existence of a drug in its ionized or unionized form affects drug absorption
Unionized drugs are more lipophilic and show higher absorption through the transcellular route
Basic drugs with a pKa near or above the physiological pH of the rectum exist more in the unionized form and show higher absorption

Smaller particles have a faster dissolution rate and solubility, leading to faster absorption
Drugs with a particle size of 50-100 µm show maximum absorption through the rectal route
Liquid formulations have a faster drug release and solubilization, leading to faster absorption and greater spreading capacity

Solid formulations undergo disintegration, liquefaction, and dissolution before drug release and absorption
Solid formulations have a longer time to obtain a therapeutic effect compared to liquid formulations
Semi-solid formulations provide better retention time in the rectum, reduce patient compliance issues, and increase drug release