Rectal and Vaginal Drug Delivery

• Rectal and Vaginal Drug Delivery


  Although oral route is the most common route of drug administration, it might be difficult to use in some cases
• Reasons oral route may be difficult

  • Patient could have problems with GIT
  • Patient could be nauseous or postoperative
  • Patient could be unconscious
  • Patient could be very old or young or mentally disturbed
• Rectum


  Part of the colon and forms the final 150-200 mm of GIT, consists of anal canal and ampulla
• Rectum


  • Separated from the outside environment by a circular muscle called the anus
  • Hollow organ with a smooth surface due to absence of villi, limiting surface area to around 300 cm2
  • Has only three folds that represent rectal valves
  • Rectal wall composed of one thick epithelium layer containing cylindrical and globlet cells that secrete mucus
  • Mucus volume is around 3 ml and has a pH of 7.5
• Drug Absorption From Rectum


  • Absorption takes place mainly by passive diffusion
  • Rate and extent of absorption through rectal route is lower than oral route because of the small absorption surface area
• Veins that supply the rectum with blood


  • Inferior and middle haemorrhoidal (take blood into the interior vena cava)
  • Superior haemorrhoidal (takes blood to the liver via the portal vein, resulting in low bioavailability due to first pass metabolism)
• Drug Release From Rectal Dosage Forms

  1. After full insertion, the dosage form will either melt or dissolve in the rectal fluid, depending on the base used

  2. Bases that are butter in nature will melt at body temperature and release the drug

  3. Other bases can dissolve or absorb the surrounding water and then dissolve and release the drug

  4. Rectal fluid volume is small and the suppository vehicle attracts water by osmosis from the surroundings

  5. Drug will leave the vehicle by the rectum movement and then dissolve in rectal fluid
• Physiological Factors Affecting Rectum Absorption

  • Quantity of fluid available
  • Properties of rectal mucus
  • Contents of rectum
  • Motility of rectal wall
• Rectum Absorption

  Suitable for peptide-like drugs due to absence of esterase and peptidase enzymes which enhance stability
• Drug related factors affecting rectum absorption


  • Solubility in water and vehicle
  • Particle size (50-100μm)
  • pKa
• Uses of Rectal Drug Delivery

  • Local action: Treatment of haemorrhoids, constipation
  • Systemic action: Analgesics, anti-asthmatics, anti-inflammatories, anti-epileptics
• Advantages of Rectal Drug Delivery

  • Suitable for drugs liable to degradation in GIT
  • Partially avoid hepatic first pass elimination
  • Can accommodate small and large doses
  • Suitable for children, vomiting and nauseous patients
• Disadvantages of Rectal Drug Delivery


  • Poor patient compliance, especially for long term treatment
  • Upward movement of the dose increases first pass metabolism
  • Slower drug absorption compared to oral or IV
  • Suppositories can leak
• Rectal Dosage Forms


  • Suppositories
  • Rectal capsules
  • Rectal tablets
  • Rectal solutions, emulsions and suspensions
  • Rectal foams and tampons
• Suppositories

  Most commonly used rectal dosage form, a single dose preparation with a shape, volume and consistency appropriate for rectal administration
• Requirements of an Ideal Suppository Base

  • Melt or disperse at body temperature (below 37°C)
  • Non-irritating
  • Physically and chemically stable
  • Pharmacologically inert
  • Compatible with range of drugs
  • Convenient to handle during manufacturing and storage
  • Good viscosity
• Types of Suppository Vehicles

  • Fatty vehicles (e.g. Witepsol, Fattibase, Cotmar)
  • Water-soluble vehicles (e.g. Glycerinated gelatin, Polyethylene glycol)
• Hydroxyl Number


  A number that reflects the amount of glycerides in the fatty base, higher number means more hydrophilic and better decomposition
• Properties of Fatty Suppository Bases

  • Mixture of triglycerides, waxes and fatty alcohols
  • Combination of components can alter melting points
  • Poor water-absorptive power
• Properties of Water-soluble Suppository Bases


  • Hydrophilic, less frequently used due to small amount of mucus in rectum
  • Glycerinated gelatin (mixture of gelatin, glycerol and water)
  • Polyethylene glycol (versatile polymers of different molecular weights)
• Properties of PEG Suppository Bases


  • PEG 1000 (95%) + PEG 4000 (5%): low melting, fast drug release
  • PEG 1000 (75%) + PEG 4000 (25%): higher melting, sustained release
• Disadvantages of PEG Suppository Bases

  • Can develop peroxides on storage
  • Hygroscopic, adsorb water from rectum
• Other Rectal Dosage Forms


  • Enemas (liquid preparations for systemic, local actions and diagnostic purposes)
  • Microenemas (small volume solutions/dispersions)
  • Rectal capsules (shell suppositories)
  • Rectal tablets (not ideal due to lack of disintegrating fluid)
• Vaginal Drug Delivery


  Less common than rectal, mainly for local effects rather than systemic
• Local Actions of Vaginal Drug Delivery

  • Anti-infectives
  • Spermicides
  • Microbicides
• Systemic Actions of Vaginal Drug Delivery

  Higher bioavailability compared to oral (avoid first pass and high blood supply)
• Vagina

  Fibro-muscular tube connecting uterus to external environment, covered in cervico-vaginal fluid for protection and lubrication
• Vaginal Fluid


  • Contains microflora that converts glycogen to lactic acid, making it slightly acidic (pH 3.5-4.5)
  • Acidic environment provides protection from infections
• Drug Absorption in Vagina

  • Well suited for systemic absorption due to vast network of blood vessels
  • Drugs drained by vaginal vein into inferior vena cava, avoiding first pass effect
• Advantages of Vaginal Drug Delivery

  • Suitable when oral intake is restricted
  • Avoid interaction with gastric content
  • Avoid first pass metabolism
  • High vascularization
  • Relatively large surface area
  • Relatively low enzymatic activity
  • Uterine pass effect
• Disadvantages of Vaginal Drug Delivery

  • Gender specific
  • Drug absorption affected by menstrual cycle and hormonal variations
  • Leakage of dosage form
  • Microbial infections affecting pH, drug stability and release
  • Potential for systemic absorption of locally administered drugs
• Vaginal Dosage Forms


  • Liquids (solutions, emulsions, suspensions)
  • Semisolids (creams, gels, ointments)
  • Solids (pessaries, rings, films, tablets, capsules)
  • Gaseous (foams, sprays)
• Ideal Vaginal Dosage Forms


  • Long acting
  • Stable in vaginal fluid
  • Non-irritating
  • No leakage
  • Easy to insert
  • No effect on sexual activity
• Vaginal Dosage Forms


  • Pessaries (vaginal suppositories)
  • Vaginal rings
  • In-situ gels
  • Microbicides
• Pessaries


  Solid, single dose, usually ovoid shaped vaginal suppositories containing API, diluents, lubricants, preservatives, surfactants
• Vaginal Rings


  Circular systems that entrap the drug inside a polymer
• In-situ Gels


  Mucoadhesive formulations prepared using temperature-sensitive and mucoadhesive polymers
• Microbicides


  Creams, gels, films, or foams inserted into vagina or rectum to protect against STIs, containing anti-retroviral drugs