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Drug absorption from GIT

The document discusses the structure and function of the human gastrointestinal tract (GIT) and the mechanisms and factors affecting drug absorption through the GIT. It covers the parts and functions of the GIT, as well as the accessory organs of the liver, pancreas, and gallbladder. It then discusses the three main mechanisms of drug absorption - passive diffusion, carrier-mediated transport, and pinocytosis. Finally, it outlines various pharmaceutical and patient-related factors that can influence drug dissolution and absorption in the GIT.

Health & Medicine◦
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Presented by: Mahewash A. Pathan
 Structure and function of human GIT  Absorption of drugs  Mechanisms of Absorption  Factors affecting drug Absorption  Dissolution of drugs  Factors affecting dissolution  Noyes- Whitney equation  pH Partition theory
(Digestive tract, digestional tract, gut, alimentary Canal) “An organ system within humans and other animals which takes in food, digests it to extract and absorb energy & nutrients, & expels the remaining waste as feces”  Parts of human GIT:- 1. Mouth 2. Oesophagus 3. Stomach 4. Small intestine 5. Large intestine 6. Rectum 7. Anus.
 The accessory organs of GIT 1. Liver 2. Pancreas 3. Gall bladder.  Functions of GIT 1. Transportation 2. Digestion 3. Absorption of food
 Mucosal layer is composed of stratified squamous epithelial cells.  Main structures: 1. Tongue 2. Salivary glands 3. Teeth 4. Pharynx  Fun- breakdown of food into smaller parts.
 “Food tube.”  Produces mucus which acts to- 1. Facilitates the passage of food. 2. Lubricate & protect the oesophagus.  At the lower end there is a GASTROEOSOPHAGEAL SPHINCTER ( cardiac SPHINCTER ) which prevents the reflux of gastric contents into the oesophagus.
 Parts- 1. Cardiac region 2. Fundus 3. Body of stomach 4. Antrum 5. Pylorus  PYLORIC SPHINCTER allow passage of chyme into the small intestine.  Fun- store, churn & puree food into chyme. Digestion of fats, proteins, alcohol, water & glucose. Production of gastric acid.
No. Gastric cells Secretion 1 Goblet cells Mucus 2 Parietal cells HCl 3 Chief cells Pepsinogen 4 G cells Gastrin
 Parts- 1. Duodenum 2. Jejunum 3. Ileum  Fun- Absorption of vitamins & nutrients including electrolytes, iron, carbohydrates, proteins& fats.  Absorbs approx. 8000 ml water per day.
 The digestive enzymes secreted in small intestine: 1. Lipase 2. Amylase 3. Maltase 4. Lactase 5. Sucrase 6. Dextrinase Intestinal hormones: 1. Enterogastrone 2. Gastric inhibitory polypeptide 3. Secretin 4. Cholecystokinin 5. Vasoactive intestinal peptide 6. Somatostatin.
 Parts- 1. Ascending Colon 2. Transverse Colon 3. Descending Colon 4. Sigmoid colon.  Fun- Water Absorption, Absorption of sodium, potassium & chloride.
Liver:-  Largest organ, located in the upper abdomen.  3 lobes- right, left & caudate, subdevided into further 8 segments.  Functional unit is Acinus.  Play imp role in metabolism. Gall bladder:-  Pear shaped, sac like organ attached to liver.  Store bile salts, which absorb & emulsify fats & fat soluble vitamins.
Pancreas:-  Both an endocrine & exocrine gland.  Digestive enzymes secreted by pancreas are- 1. Trypsin 2. Lipase 3. Amylase
No. Parts of GIT ph 1 Salivary glands 7.5 2 Upper stomach 4 -6.5 3 Lower stomach 1.5 - 4 4 Duodenum 7 – 8.5 5 Small intestine 4-7 6 Large intestine 4- 7
“The movement of unchanged drug from the site of administration to systemic circulation”. Or The process of movement of unchanged drug from the site of administration to the site of measurement. i.e., plasma.
Main Mechanisms Of Drug Absorption /Transport:- 1. Passive diffusion 2. Carrier mediated transport 3. Pinocytosis
 E.g. Absorption of urea, water, sugar.  Entry of drugs into liver  Removal of drugs from CSF.
 E.g. Entry of glucose into RBCs.  Intestinal absorption of vit B.
 E.g. Absorption of 5- FU through pyrimidine transport system.  Absorption of methyl - dopa & leavodopa through L- amino acid transport system.
E.g. Polio vaccine & large protein molecules
(A)Pharmaceutical factors (1)Physicochemical factors a) Ph partition hypothesis b) Polymorphism & amorphism c) Salt form of a drug d) Particle size & effective surface area (2)Formulation factors a) Disintegration time b) Manufacturing variables c) Pharmaceutical ingredients (Excipients, Adjuvants) d) Nature & type of dosage form e) Product age & storage conditions
(B)Patient related factors (1)Physiological conditions a) Membrane physiology i. Membrane Structure ii. Transport Process b) GI physiology c) Characteristics of GI Physiology d) GI Motility and emptying e) Blood flow through GIT f) Influence of food g) Intestinal transit time h) Pre-systemic metabolism by various enzymes. i) Age (2)Clinical factors a) diseases b) surgery c) infections d) interactions
 Dissolution is referred as a process in which solid phase goes into liquid phase  Dissolution rate is defined as ‘amount drug subs that goes in the solution per unit time under standard conditions of temperature & solvent composition.’
1. Physicochemical Properties of Drug a) Drug solubility b) Salt formation c) Particle size d) Solid state characteristics e) Co-precipitation 2. Drug Product Formulation Factors a) Diluents b) Disintegrants c) Binders & granulating agent d) Lubricants e) Surfactants f) Water soluble dyes g) Coating polymers
3. Processing Factors a) Method of granulation b) Compression force c) Drug excipient interaction d) Storage conditions 4. Factors Relating Dissolution Apparatus a) Agitation b) temperature c) Disso media.
 Based on Fick’s second law of diffusion, . dc/dt = k ( Cs – Cb ) Where, dC/ dt : rate of dissolution k : rate constant ( per sec) Cs : solution conc at solid surface Cb : conc in the bulk.
 Dissolution from a single spherical particle.  Based on Fick’s first law of diffusion, . dm/ dt= D A kw/o ( Cs – Cb ) / V h Where, dm / dt : rate of mass transfer D : diffusion coefficient A : surface area kw/o : Partition coefficient ( Cs – Cb ) : conc gradient V : volume of dissolution media h : thickness of boundary layer.
. “For drug compounds of molecular wt greater than 100, their transport across the biomembrane by passive diffusion, is governed by : 1. The dissociation constant of drug 2. Lipid solubility 3. pH at the Absorption site.”  Brodie proposed this theory.  Hsnderson – hasselbach equation, . For an acid, pH = pka + log 10 ( [A-] / [HA] ) For a base, pH = pka + log10 ( [B] /[ BH+ ])  pka = - log10 k.
Drug absorption from GIT