Rectal, Vaginal, and Urehtra Drug Delivery Systems PDF

RECTAL, VAGINAL AND URETHRAL DRUG DELIVERY SYSTEMS Wan Maznah Wan Ishak Rectal, Vagina and Urethral Drug Delivery Systems Objectives To explain the structure of rectum, vagina and urethra To describe the different types of commonly used delivery s...

RECTAL, VAGINAL AND URETHRAL DRUG DELIVERY SYSTEMS Wan Maznah Wan Ishak Rectal, Vagina and Urethral Drug Delivery Systems Objectives To explain the structure of rectum, vagina and urethra To describe the different types of commonly used delivery systems for rectal and vagina administration To evaluate the factors influencing drug delivery and absorption of rectal, vagina and urethra To compare advantages and disadvantages of rectal and vagina drug delivery RECTAL DDS Rectal Drug Delivery The rectal used is used alternatively for patient having nausea, vomiting or convulsions, uncooperative patient or oral intake is restricted Mechanism of drug absorption from rectum is passive diffusion Rectal pH range in adult is 7.2, children is 9.6 (range 7.2 – 12.1) Absorption of drug administered in an aqueous or alcoholic solution occur very rapidly Absorption of drug from suppository is slower and depends on the nature of suppository base, the presence of other additives and the physicochemical properties of the drug Advantages and Disadvantages Rectal Drug Delivery Advantages Alternative to intravenous route Painless and convenient to use High concentration of drugs can be achieved, so this route is useful for local action Avoid first-pass hepatic metabolism Disadvantages Absorption maybe delayed or rapid as with IV bolus dose, therefore create inter-subject and intra-subject variability in absorption Diarrhea and disease affect absorption Non patient compliance because of a reluctance to use rectal formulations Can cause mucosal irritation in sensitive tissues Rectal Formulations Suppository Solid delivery system in which drug is incorporated into a base with or without additional excipients The base either melts at body temperatures or dissolved in the mucous secretions, releasing the drug Use directly to the site of action to facilitate emptying of lower bowel provide local anti-inflammatory and anesthetic effects Deliver the drug to the rectum to produce systemic effect. Rectal Formulations Suppository Base The base should be solid at room temperatures but either melt or soften at body temperatures or dissolve in body fluids It should be stable, nonirritating, chemically compatible and inert Classified into i) Fatty or oleaginous bases. ii) Water-soluble or water-miscible bases. Rectal Formulations Fatty or Oleaginous Base Examples: cocoa butter, hydrogenated vegetable oils, waxes A lipophilic drug released slowly from oleaginous base Less irritating to sensitive tissue Water-Soluble Base Example: polyethylene glycol, glycerinated gelatin Cause some irritation because they are hygroscopic and take up water from surrounding tissues May produce slight desiccation of the rectal mucosa VAGINAL DDS Vaginal Drug Delivery System pH of vagina fluid ranges from 3.5 to 4.5. This acidity maintained by lactobacilli which convert glycogen to lactic acid The ionization state of weakly acidic and basic drugs can be altered by changes in pH At acidic pH, the drug is in protonated and trapped in the vagina If the pH increases to neutral or slightly basic pH, the drug becomes nonionized and is able to cross the membranes of the vagina Vaginal Drug Delivery System The vaginal mucosa composed of epithelium and highly vascularized The surface area is appx 60 cm2 Large surface area and highly vascular surface of mucosa enable rapid absorption of low-molecular weight and lipophilic drugs Delivery systems such as solutions, foams, gels, and tablets are removed quickly The contact time with epithelial surface is increased if the drug is delivered in a ring or along with mucoadhesive or bioadhesive gel Vaginal Formulations i) Tablets Stable and less messy to handle than cream or ointments Intended to be easily dissolve, dissolve or melt, disintegrate and release drugs Ease of manufacture and insertion Mainly for local anti-inflammatory and sterilizing effects, and sex hormone drugs Vaginal Formulations ii) Suppositories Vaginal suppositories also called as pessaries Oviform or cone in shaped Melt in body temperature or dissolve in body fluids and absorb directly into the bloodstream PEG is most common vaginal suppository base Treatment for vaginal yeast infection, bacterial vaginosis or spermicide Vaginal Formulations iii) Creams, Ointments, Gels and Foams Used for delivery of spermicides, antibacterial drugs, hormones and for cervical ripening Messy to use and uncomfortable because they tend to leak out of the vagina Vaginal foams contain propellants that aid in the delivery of drug Drug concentration can only be maintained for a very short time, thus repeated administration is required Vaginal Formulations iv) Rings Circular delivery systems roughly 5.5 cm in diameter Ring is flexible and nonirritating Not messy to use Release predetermined amount of drug per day for an extended period (sustained- release) Made by ethylene vinyl acetate copolymers or polymeric materials such as silicone Polymer is nonbiodegradable, therefore rings must be removed after use Used for treatment for sexual transmitted disease like HIV Advantages and Disadvantages Vagina Drug Delivery Advantages Rich in vasculature of mucosa is attractive route for systemic drug delivery Not affected by GIT, so first-pass metabolism is avoided Convenience for self-administration Painless Lower dose of hormones can be delivered to achieve local effect Disadvantages Thickness of vaginal epithelium and pH vary with age, hormonal activity and menstrual cycle influences permeability and absorption of drug The systemic absorption can be erratic and unpredictable Formulation may leak or slip out from the formulation resulting in soiling of clothing The drug or ingredients in the formulations can cause local irritation Some patient reluctant to use vaginal drug delivery URETHRAL DDS Urethral Drug Delivery Urethral is the tube that connects urinary bladder to the outside of the body Function of urethra is for passing urine in both males and females Urethral suppository also referred as bougies Only one urethral suppository is commercially available marketed under the name Muse® Use for the treatment of erectile dysfunction helps to create and maintain an erection The suppository is administered using intraurethral applicator device provided by manufacturer