Suppositories

• Much work has been conducted in recent years as evidenced by the literature citations; in the past 50 years, there have been over 4,000 citations in Medline
• Urethral administration of suppositories has become more acceptable with urethral suppositories in the treatment of male erectile dysfunction (Muse-Vivus)
• Suppositories are used more routinely in southern European countries and in Latin American countries, as compared to northern European and Anglo-Saxon countries
• In the past 5 to 10 years in the United States, progesterone vaginal inserts have become much more widely used by postmenopausal women
• Hormone replacement therapy in postmenopausal women using bioidentical hormones, or those that are identical to those hormones produced by the body as compared to synthetic or semisynthetic hormones, is more popular in the treatment of postmenopausal symptoms (flushing, night sweats, mood swings, etc.)
• Although suppositories are not very popular as a mode of administering drugs, this dosage form will probably always have a place in medicine
• Reasons suppositories have been employed

  • To promote defecation
  • To introduce drugs into the body
  • To treat anorectal diseases
• Rectal administration is not often the first route of choice, but it becomes a good alternative when the oral route is inadvisable
• A suppository is also an excellent dosage form for those patients to whom one does not want to administer numerous injections daily
• They are also a dosage form that can be administered to avoid nausea and vomiting caused by certain medications upon oral administration, and it is a dosage form that can often result in a fast onset of action
• Suppository


  Solid dosage form in which one or more active pharmaceutical ingredients (APIs) are dispersed in a suitable base and molded or otherwise formed into a suitable shape for insertion into the rectum to provide local or systemic effect
• Suppository


  Upon administration, suppositories melt, soften, or dissolve and exert local or systemic effects
• Suppository


  The derivation of the word suppository is from the Latin supponere, meaning "to place under," as derived from sub (under) and ponere (to place)
• Suppository


  Meant both linguistically and therapeutically to be placed under the body, as into the rectum
• Rectal suppositories


  • Usually about 32 mm (1.5 inch) long, are cylindrical, and have one or both ends tapered
  • Some are shaped like a bullet, a torpedo, or the little finger
  • Adult rectal suppositories weigh about 2 g when cocoa butter (theobroma oil) is employed as the base
  • Rectal suppositories for use by infants and children are about half the weight and size of the adult suppositories and assume a more pencil-like shape
• Inserts


  Solid dosage form that is inserted into a naturally occurring (nonsurgical) body cavity other than the mouth or rectum, including the vagina and urethra
• Vaginal inserts


  • Also called pessaries
  • Usually globular, oviform, or cone shaped and weigh about 5 g when cocoa butter is the base
• Urethral inserts


  • Also called bougies
  • Slender, pencil-shaped suppositories intended for insertion into the male or female urethra
  • Male urethral suppositories may be 3 to 6mm in diameter and approximately 140 mm long, weighing about 4 g when cocoa butter is the base
  • Female urethral suppositories are about half the length and weight of the male urethral suppository, being about 70 mm long and weighing about 2 g when made of cocoa butter
• Medication sticks


  • Convenient form for administering topical drugs
  • Cylindrical in shape and generally range from 5 to 25 g
  • Packaged in an applicator tube for topical administration, and the applicator can be adjusted to continually expose new, fresh stick from inside the tube
• Drugs that are intended to be absorbed into the general circulation to provide systemic effects

  • Aspirin - pain
  • Ergotamine tartrate - migraine headaches
  • Theophylline - smooth muscle relaxant in treating asthma
  • Chloropromazine and prochlorperazine - antiemetics and tranquilizers
• Other examples of suppositories given for systemic results

  • Diazepam
  • Metronidazole
  • Progesterone
  • Aminophylline
  • Morphine
  • Prochlorperazine
  • Chlorpromazine
  • Thiethylperazine
  • Indomethacin
  • Diclofenac
  • Ketoprofen
  • Naproxen
  • Ondansetron

  
• Rectal administration provides for a rapid and, in many cases, extensive absorption of the active ingredient. The rapidity, intensity, and duration of action are three parameters that must be considered during formulation for rectal administration and, in many cases, can be altered to meet the needs of the individual patient
• The factors that affect the rectal absorption of a drug administered in the form of a suppository may be divided into two main groups: (a) anatomic and physiologic factors and (b) physicochemical factors of the drug and the base
• Local action


  Once inserted, the suppository base melts, softens, or dissolves, distributing its medicaments to the tissues of the region
• Rectal suppositories intended for local action

  • Most frequently used to relieve constipation or the pain, irritation, itching, and inflammation associated with hemorrhoids or other anorectal conditions
• Glycerin suppositories


  • Promote laxation by local irritation of the mucous membranes, probably by the dehydrating effect of the glycerin on those membranes
• Vaginal suppositories or inserts intended for local effects


  • Employed mainly as contraceptives, as antiseptics in feminine hygiene, and as specific agents to combat an invading pathogen
• Drugs used in vaginal suppositories or inserts

  • Nonoxynol 9 for contraception, trichomonacides to combat vaginitis caused by Trichomonas vaginalis, antifungals to treat Candida (Monilia) albicans, and anti-infectives/ antibiotics directed at other microorganisms
• Urethral suppositories


  • May be antibacterial or a local anesthetic preparative for a urethral examination
• Medication sticks


  • Commonly used for local effect and include hydration/emollient, antibacterial, sunscreen, antipruritic, and other uses
• Systemic action


  The mucous membranes of the rectum and vagina permit the absorption of many soluble drugs
• Drugs absorbed rectally for systemic effects

  • Prochlorperazine, Chlorpromazine - nausea, vomiting, tranquilizer
  • Morphine, Oxymorphone - opioid analgesia
  • Ergotamine tartrate - migraine syndrome
  • Indomethacin - non-steroidal anti-inflammatory analgesic, antipyretic
  • Ondansetron - nausea, vomiting
• The dose of a drug administered rectally may be greater than or less than the dose of the same drug given orally, depending on such factors as the constitution of the patient, the physicochemical nature of the drug and its ability to traverse the physiologic barriers to absorption, and the nature of the suppository vehicle and its capacity to release the drug and make it available for absorption
• Physiological factors affecting drug absorption from the rectum

  Circulation route, colonic contents, and the pH and lack of buffering capacity of the rectal fluids
• Circulation route


  • Drugs absorbed rectally can bypass the portal circulation during their first pass into the general circulation, enabling drugs that are otherwise destroyed in the liver to exert systemic effects
  • The lower hemorrhoidal veins surrounding the colon receive the absorbed drug and initiate its circulation throughout the body, bypassing the liver
  • Lymphatic circulation also assists in the absorption of rectally administered drugs
• pH and lack of buffering capacity of the rectal fluids


  The pH of the rectal fluid is generally in the range of 7.2 to 7.4, and it has negligible buffer capacity
• Rectal absorption


  1. Absorption can occur via one pathway or another or a combination

  2. At least 50% to 70% of the active ingredients administered rectally take the direct pathway, bypassing the liver and avoiding the first-pass effect

  3. Possibility of absorption into the lymphatic vessels
• Vagina


  • Specialized organ whose primary function is reproduction
  • Highly elastic muscular tube, located between the urethra and the rectum
  • Has three tissue layers: epithelial tissue, loose connective tissue, and muscle tissue
  • Upper, middle, and lower vaginal sections have separate blood supplies
  • pH is in the range of about 4 to 4.5
  • Moistened and cleansed daily by secretions that also serve to lubricate the vaginal tract
• Urethra


  • Epithelium begins as transitional cells as it exits the bladder
  • Further along the urethra, there are stratified columnar cells and then stratified squamous cells near the external meatus
  • Small mucus-secreting urethral glands help protect the epithelium from the corrosive urine
  • Female urethra is supplied by the internal pudendal and vaginal arteries
  • Male urethra is supplied by the inferior vesical and middle rectal arteries, with the nerve supply via the pudendal nerve
• When systemic effects are desired from the administration of a medicated suppository, greater absorption may be expected from a rectum that is void than from one that is distended with fecal matter