Routes Of Administration: Oral

• What is absorption?

  Movement of drug from site of administration to thebloodstream
• What types of lipids are in biological membranes?

  SphingomyelinPhosphatidylcholinePhosphatidylserinePhosphatidylinositolPhosphatidylethanolamine

  Glycolipid – lipid with a carbohydrate attachedCholesterol – a type of lipid
• What are the two types of cellular transport across membranes?

  *transcellular*paracellular
• What are the types of transcellular transport?

  • Passive diffusion
  • Carrier mediated transport
  • Facilitated diffusion
  • Active transport
  • Vesicular transport (endocytosis)
• What is the type of paracellular transport?

  • Tight junctions
• What structures are involved in the GI tract?

  *small intestine*vilus*epithelial cells with microvilli
• Describe pressure changes during gastric emptying of food

  • Stomach pressure remains constant until ~1 L of food ingested
  • Relative unchanging pressure results from intrinsic ability ofsmooth muscle to exhibit “plasticity”
• Describe what happens to chyme (stomach acid) during gastric emptying

  Chyme is either:* Delivered in small amounts (about3 mL) to the duodenum* Forced backward into the stomachfor further mixing
• What is gastric emptying regulated by?

  *neural reflex* hormonal mechanisms
• What is gastric emptying affected by?

  *meal volume*meal composition *pH content
• How does meal composition affect gastric emptying?

  • Stomach empties liquids faster than solids
  • Carbohydrate-rich chyme quickly moves through duodenum
  • Fat-laden chyme is digested more slowly causing food to remain in the stomachlonger
• How does pH content affect gastric emptying?

  • Acids delays gastric emptying
  • pH of chyme in the small intestine of (< 3.5– 4) will activate reflexes to inhibit stomachemptying until duodenal chyme can beneutralised by pancreatic and othersecretions
  • Careful of antacids (e.g. aluminiumhydroxide gel) that raise the pH of stomachcontents
• What is GER?

  • Gastric emptying rate (GER) = Speed with which substances leave thestomach after ingestion
• How do the structures of the GI tract do drug gastric emptying?

  • The duodenum has the greatest capacity for the absorption of drugs from the GI tract
  • Anatomically, a swallowed drug rapidly reaches the stomach
  • Eventually, the stomach empties its contents into the small intestine
  • Delay in the gastric emptying time will slow the rate and possibly the extent of drug absorption
• What type of advice can be given for oral drugs and the disadvantages?

  • Take with food
  • May irritate the gastric mucosaduring prolonged
  • Take before food
  • Improve absorption as food canaffect absorption
• What is the rate limiting step?

  Slowest step in the series, which controls the overallrate and extent of appearance of the intact drug in the systemiccirculation
• What are the various rate limiting steps for different drugs?

  Rate-limiting step differs from drug to drug:* Drug release from dosage form – disintegrate* Gastric emptying* Dissolution – high log P hardly dissolves* Permeability – low log P is hardly absorbed* Metabolism – including metabolism in the liver (first pass effect)
• what is the SA of the small intestine epithelium?

  • Epithelium brush border
  • 3000 microvilli per cell
  • 200,000,000 per mm2
• How will the epithelium brush SA help?

  • With this surface areaeven ionised weak acidswill be absorbed insufficient quantities
• What are the different types of tablets? 6 types + example

  *disintegrating tablet (Zantac)*lozeneges (strepsils)*chewable tablets (gaviscon)*effervescent tablets (beroca)*sublingual tablets (nicorette)*buccal tablets (buccastem m)
• What are the advantages of tablets?

  • Ease of administration and patient acceptance
  • Swallowing
  • Chewable formulations
  • Elegance
  • Convenient handling/compactness
  • Accurate dosage
  • Chemical and physical stability
  • Different to tamper with
  • Low cost of manufacturing, packaging, shipping
• What are the types of capsules?

  *hard capsules *soft capsules
• What are hard capsules composed of?

  • Gelatin(bovine, porcine, fish)
  • Alternative polymers(HPMChydroxypropylmethylcellulose,pullulan)
• What are soft capsules composed of?

  • Gelatin
  • Vegetarian option (Vegecaps)
• What are the advantages to capsules? in terms of patient compliance

  Patient compliance* Easier to swallow* Smooth & slippery* Tasteless and odourless* Eliminate all contact between drugand mouth)* Can be opened up* Contents sprinkled on food* Clear, high-gloss coloured film* Can be printed on
• What are the advantages capsules? in terms of drug delivery

  • Fast acting
  • Breakdown of capsule shell occursreadily ≈ disintegration of tablet
  • Beads/pellets/granules inaddition to dry powder fills
  • A mixture of beads with differentrelease rates
  • Other dosage forms in a capsule
  • Mini tablets and liquids
• Describe dissolution of capsules containing both hydrophobic and hydrophilic drug particles

  *Hard gelatin capsules containinghydrophobic drug particles andhydrophilic diluent particles * the capsules will dissolve in GI liquid leaving a porous mass of drug*GI fluids can penetrate porous mass*Effective surface area ofdrug and hence dissolutionrate is increased
• Describe dissolution of capsules containing only hydrophobic drug particles

  *hard capsule containing only hydrophobic drug particles *the capsule shell will dissolve in GI fluid exposing contents *Contents remain as capsule-shaped plug.Hydrophobic nature of contents impedes penetration of GI fluids*Dissolution of drug occurs only from surface of plug-shaped mass. Relatively low rate of dissolution
• Why are oral solutions give+ absorption?

  • Drugs are commonly given in solution
  • in cough/cold remedies
  • for the young and elderly
  • Absorption from an oral solution is often rapid and complete, greaterbioavailability compared to other oral dosage forms
• What is the absorption of oral suspensions like?

  • Second to a solution in terms of superior bioavailability
  • Absorption may well be dissolution-limited
  • Suspension of a finely divided powder will maximize the potential for rapiddissolution
• What are sublingual tablets for?

  • Sublingual – application to themembranes of either the floor ofthe mouth or the underside of thetongue and entry into systemiccirculation following absorption
• What are buccal tablets for?

  • Buccal – application to the liningof the cheek – entry into thesystemic circulation followingabsorption
• What makes up the Floor of the mouth, the soft palate, the lips and the cheek?

  Non-keratinised mucosa
• What makes up Hard palate, gingiva and tongue?

  Keratinised mucosa
• What is the epithelium thickness of the sublingual route?

  100 – 200 µm on the undersideof the tongue and on the floor ofthe mouth
• What is the epithelium thickness of the buccal route?

  500 – 800 µm in the buccalcavity
• What are some properties of the sublingual route?

  • Relatively permeable
  • Rapid absorption
  • Unsuitable for retentive system
  • Ideal for rapid onset of action
  • Sprays or fast-dissolving tablets
• What are some properties of the buccal route?

  • Relatively less permeable
  • Not rapid absorption
  • Suitable for retentive system
  • Ideal for sustained release
  • Adhesive tablets or patches
• What are the three sublingual oral types?

  *chewable tablets*sprays *tablet
• What are each sublingual oral route made of?

  • Sublingual tablets
  • Consist of lactose mannitol sucrose for fast dissolution
  • Solutions and sprays
  • Administration of nitroglycerin (angina prevention)
  • Chewing gum
  • A gum base of a cellulosic or acrylic polymer