Vaginal, Rectal and GI Drug Delivery

Vaginal, Rectal, and GI Drug Delivery Notes

Learning Objectives

  • To understand the principles underlying vaginal, rectal, and gastrointestinal (GI) drug delivery.

  • To learn about physicochemical principles affecting rectal drug delivery.

  • To describe various types of vaginal, rectal, and GI dosage forms and drug delivery systems.

Vaginal Drug Delivery

Vaginal Douches

  • Definition: A vaginal douche is a method of washing the vagina with a solution.

  • Preparation:

    • The user adds a prescribed amount of powder to warm water and stirs until dissolved.

  • Components:

    • Boric Acid or Sodium Borate: Used for pH balancing and antiseptic properties.

    • Astringents: Such as potassium alum, ammonium alum, and zinc sulfate, which shrink tissues.

    • Antimicrobials: Examples include oxyquinolone sulfate and povidone iodine, utilized for infection control.

Additional Components of Vaginal Douches

  • Quaternary Ammonium Compounds: e.g., benzethonium chloride, which have antimicrobial properties.

  • Detergents: Such as sodium lauryl sulfate, that help in emulsifying and cleaning.

  • Oxidizing Agents: e.g., sodium perborate, contribute to disinfecting effects.

  • Salts: Sodium citrate and sodium chloride may be included for isotonicity.

  • Aromatics: e.g., menthol, thymol, eucalyptus, methyl salicylate, and phenol, used for their fragrance or additional medicinal properties.

Vaginal Aerosols

  • Definition: Automated foams used intravaginally for delivery of medications.

  • Contents: Usually contain estrogenic substances and contraceptive agents.

  • Usage: Applied similarly to creams, and designed to be water miscible and non-greasy.

  • Packaging: Comes in a canister with an inserter for application via plunger activation, resembling light creams.

Vaginal Creams, Ointments, and Gels

  • Types:

    • Products like Mycelex-7 vaginal cream for external use on the vulva.

    • Other examples include Gynazole-1® (butoconazole nitrate, 2%) for local treatment of vulvovaginal candidiasis, Cleocin (clindamycin phosphate) for bacterial vaginosis, Terazole 7 (terconazole) for antifungal treatment, and Ogen (estropipate) for hormonal management.

Clindesse Cream and Premarin Cream

  • Clindesse Cream: Contains clindamycin phosphate at 20 mg per gram, indicated for bacterial vaginosis.

  • Premarin Cream: Contains conjugated estrogens for atrophic vaginitis and kraurosis vulvae treatment.

Vaginal Inserts

  • Definition: Vaginal tablets more commonly used than suppositories due to ease of manufacturing, stability, and cleanliness.

  • Components:

    • Typically, they are ovoid and packaged with a plastic inserter for easy placement.

    • Ingredients include lactose as filler, starch as disintegrating agents, polyvinylpyrrolidone as dispersing agents, and magnesium stearate as lubricants.

  • Examples: Mycelex-G (500mg clotrimazole) and Semicid (100mg nonoxynol-9).

Dinoprostone (Cervidil)

  • Description: A thick, rectangular polymeric slab containing 10mg of dinoprostone.

  • Release Mechanism: Releases dinoprostone at a rate of 0.3mg/hr when placed in a moist environment.

  • Indications: Used for cervical ripening in labor induction.

Estring

  • Usage: A silicone polymer vaginal ring designed for the continuous release of estradiol (75 micrograms/24 hours) for 90 days, targeting postmenopausal vaginal atrophy.

  • Components: Comprised of silicone polymers and barium sulfate.

Progestasert

  • Description: A T-shaped intrauterine contraceptive system containing 38mg of progesterone, released at an average rate of 60 mcg/day for 1 year.

  • Replacement Frequency: Must be replaced annually.

Crinone Gel

  • Composition: Contains micronized progesterone and polycarbophil in an oil-in-water emulsion via a bioadhesive mechanism.

  • Indication: To assist in reproductive processes by allowing progesterone absorption through vaginal tissue over 25 to 50 hours.

Rectal Drug Delivery

Alprostadil Urethral Microsuppository (MUSE)

  • Description: A single-use transurethral system delivering alprostadil, formed into a pellet with dimensions of 1.4mm diameter and 3mm or 6mm in length.

  • Strengths Available: 125, 250, 500, and 1000 mcg, used for treating erectile dysfunction.

  • Application: Inserted via a translucent applicator and administered after urination.

Suppository Bases

Acid Number

  • Definition: The mass of potassium hydroxide (KOH) in milligrams needed to neutralize one gram of a substance, indicating the amount of carboxylic acid groups present.

Saponification Number

  • Definition: Measures the total free and combined acids in a fat or resin indicated by milligrams of KOH needed for full conversion into glycerin and potassium soap.

Iodine Number

  • Definition: The mass of iodine consumed by 100 grams of a substance; it helps determine the saturation of fatty acids, as unsaturated groups react with iodine.

Cocoa Butter

  • Characteristics: The most widely used suppository base, solid up to 32°C, melting around 34-35°C, composed of triglycerides (oleic, palmitic, stearic) and exhibits polymorphism.

Witepsol Bases

  • Description: Contain saturated fatty acid chains (C12-C18); does not exhibit polymorphism and solidifies rapidly without mold lubrication.

Weecobee Bases

  • Origin: Derived from coconut oil, comparable in action to Witepsol bases, and can incorporate emulsifiers.

Preparation of Suppositories

Methods of Preparation

  1. Hand-Rolling:

    • Involves molding with fingers after forming a plastic mass. Uses geometric dilution and levigation for even distribution.

  2. Compression:

    • Commonly used for cocoa butter bases, where a uniform mixture is placed into a compression device under pressure, producing suppositories efficiently.

  3. Fusion Method:

    • The primary method used for commercial production, suitable for cocoa butter, PEG, and glycerin-gelatin bases.

Example of Compression Method Calculation

  • For 12 suppositories each containing 300 mg of aspirin, with a cocoa butter density factor of 1.1, the calculation for total cocoa butter required is:

    • Total aspirin: 3.9g (i.e., 13x300mg)

    • Replaced cocoa butter: 3.55g

    • Total cocoa butter for 13 suppositories (2g each): 26g

    • Therefore, required cocoa butter: 26g - 3.55g = 22.45g.

GI Drug Delivery

Scored Tablets

  • Purpose: Allow for ease of splitting tablets to achieve varying dosages.

  • Examples: Extended-release medications like metoprolol (Toprol XL) and rosiglitazone (Avandia).

Rapidly Dissolving Tablets

  • Definition: Designed to dissolve within 1 minute or less to facilitate ease of administration, particularly beneficial for children and the elderly.

  • Example: Claritin redi-tabs (loratadine).

Fentanyl Lollipop (Actiq)

  • Description: A sugar-based lollipop containing fentanyl, designed for breakthrough cancer pain management.

  • Characteristics: Comes in various dosages and provides a controlled method for pain relief.

Oros System

  • Principle: An osmotic pump delivery system, composed of a tablet with a core and semipermeable membrane, allowing for sustained drug release.

  • Example: Concerta (methylphenidate), illustrating a delivery pattern over a 12-hour period through osmotic pressure.

  • Functionality: Initial rate of drug release and further release by expanded push layer after subsequent time intervals by osmotic pressure.