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Drug Absorption from the Gastrointestinal Tract

Drug absorption from the gastrointestinal tract can be influenced by many factors. The drug must first disintegrate, dissolve, and permeate the gastrointestinal membranes before being absorbed into systemic circulation. The rate of absorption is determined by the slowest of these steps. Factors that can affect absorption include the drug's physicochemical properties, dosage form characteristics, and patient factors like gastrointestinal pH, transit time, and presence of food or enzymes. Understanding these biopharmaceutical factors is important for optimizing drug product design and therapeutic efficacy.

Health & Medicineā—¦
DRUG ABSORTION FROM THE GASTROINTESTINAL TRACT By, Feba Elsa Mathew 2nd semester M.Pharm Submitted to, Mrs. Juna Brigit Chacko Asst. professor Dept. of Pharmaceutics
CONTENTS DRUG ABSORTION FROM THE GASTROINTESTINAL TRACT: GASTROINTESTINAL TRACT MECHANISM OF DRUG ABSORTION FACTORS AFFECTING DRUG ABSORTION
Definition of some terms ļ± Biopharmaceutics: It is defined as the study of factors influencing the rate and amount of drugs reaches the systemic circulation and the use of this information in optimise the therapeutic efficacy of drug products. ļ± Bioavailability: is defined as the rate and extent of drug absorption ļ± Pharmacokinetics: is defined as the study of time course of drug ADME and their relationship with its therapeutics and toxic effects of the drug. Pharmacokinetics is the kinetics of ADME OR KADME
Drugadministrationandtherapycannowbeconvenientlydividedinto fourorprocess The pharmaceutical phase: It concern with a) Physicochemical properties of the drug and b) Design and manufacture of an effective drug product for administration by suitable route. The pharmacokinetic phase: It concern with the ADME of the drug as elicited by the plasma drug concentration-time profile and its relationship with the dose, dosage forms and dosing frequency and route of administration. The Pharmacodynamic phase: It is concerned with the biochemical and physiological effects of drug and its mechanism of action. The Therapeutic Phase: It concern with the translation of pharmacological effect into clinical benefit
Absorption of Drugs Absorption is the process of movement of drug from its site of administration to the systemic circulation. DRUG ABSORTION: is defined as the process of movement of unwanted drug from the site of administration to systemic circulation.
Gastrointestinal tract Basic structure The gastrointestinal tract is a muscular tube lined by a special layer of cells, called epithelium. Although each section of the tract has specialized functions, the entire tract has a similar basic structure with regional variations.
The wall is divided into four layers as follows: 1. Mucosa The innermost layer of the digestive tract has specialized epithelial cells supported by an underlying connective tissue layer called the lamina propria. The lamina propria contains blood vessels, nerves, lymphoid tissue and glands that support the mucosa. Depending on its function, the epithelium may be simple (a single layer) or stratified (multiple layers). 2. Submucosa The submucosa surrounds the muscularis mucosa and consists of fat, fibrous connective tissue and larger vessels and nerves. At its outer margin there is a specialized nerve plexus called the submucosal plexus or Meissner plexus. This supplies the mucosa and submucosa.
3. Muscularis externa This smooth muscle layer has inner circular and outer longitudinal layers of muscle fibers separated by the myenteric plexus or Auerbach plexus. Neural innervations control the contraction of these muscles and hence the mechanical breakdown and peristalsis of the food within the lumen. 4. Serosa/mesentery The outer layer of the GIT is formed by fat and another layer of epithelial cells called mesothelium.
Cell membrane structure and physiology For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport.
The cellular membrane consist of a double layer of amphiphilic phospholipid molecules arranged in such a fashion that their hydrocarbon chains are oriented inwards to form the hydrophobic or lipophilic phase and their polar heads oriented to form the hydrophobic or lipophilic phase and their polar heads oriented to form the outer and inner hydrophilic boundaries of the cellular membrane that face the surrounding aqueous environment. The bio membrane acts like semipermeable barrier permitting rapid and limited passage of some compounds while restricting that of others
Mechanisms of drug absorption The three board categories of drug transport mechanisms involved in absorption are:- A. Transcellular/ intracellular transport B. Paracellular/ intercellular transport C. Vesicular transport
Transcellular/intracellular transport It is defined as the passage of drugs across the GI epithelium. It is the most common pathway for drug transport . 3 steps involved in transcellular trans[ort of drugs are ā€“ i. Permeation of GI epithelial cell membrane ii. Movement across the intracellular space iii. Permeation of the lateral or basolateral membrane Two types of transcellular transport are: 1. Passive transport processes 2. Active transport processes
Passive Transport Processes: These transport processes do not require energy other than that of molecular motion(Brownian motion) to pass through the lipid bilayer. They are classified into: a) Passive diffusion b) Pore transport c) Ion-pair transport d) Facilitated- or mediated-diffusion Active Transport Processes: These transport processes require energy from ATP to move drug molecule from extracellular to intracellular milieu. They are of two types: a. Primary active transport b. Secondary active transport ā€“ they are i. Symport (Co-transport) ii. Antiport (counter-transport)
Paracellular/ Intercellular Transport It is defined as the transport of drugs through the junction between the GI epithelial cells. This pathway is of minor importance in drug absorption. The two mechanisms involved in drug absorption are- 1. Permeation through tight junctions of epithelial cell 2. Persorption
Vesicular or Corpuscular Transport (Endocytosis) Like active transport, these are also energy dependent processes but involve transport pf substances within vesicles into a cell. Since the mechanism involves transport across the cell membrane. They re classified into two categories 1. Pinocytosis 2. Phagocytosis
Summary of important transport processes and drugs absorbed through them ABSORPTION MECHANISM DRUGS ABSORBED Passive Diffusion Most drug having high lipophilicity and MW in the 100-400 Pore Transport Water- soluble drugs of MW less than 100 Ion-pair Transport Drugs that ionise at all pH conditions absorbed after complexing with oppositely changed ions Carrier- mediated Transport Structure-specific drugs with affinity for carriers transported from specific sites Endocytosis Macromolecular nutrients and drugs as solid particles or oily droplets
Factors affecting Drug Absorption The chain of events that occur following administration of a solid dosage form such as a tablet or a capsule until its absorption into systemic circulation. The process consist of four steps: 1. Disintegration of the drug product. 2. Deaggregation and subsequent release of the drug. 3. Dissolution of the drug in the fluids at the absorption site. 4. Absorption i.e. movement of dissolved drug through the GI membrane into the systemic circulation and away from the absorption
In a series of kinetic or rate processes, the rate at which the drug reaches the systemic circulation is determined by the slowest of the various steps involved in the sequence. Such step is called as the rate determining or rate-limiting step(RDS). The rate and extent of drug absorption from its dosage form can be influenced by a number of factors in all these steps. The various factors that influence drug absorption called as biopharmaceutic factors in dosage for design.
Biopharmaceutic factors of dosage form design PHARMACEUTICAL FACTORS: include factors relating to the physiochemical properties of the drug and dosage form characteristics and pharmaceutical ingredients. Physicochemical properties of drug substances 1. Drug solubility and dissolution rate 2. Particle size and effective surface area 3. Polymorphism and amorphism 4. Pseudo polymorphism (hydrates/solvates) 5. Salt form of the drug 6. Lipophilicity of the drug 7. pKa of the drug and gastrointestinal pH 8. Drug stability 9. stereochemical nature of the drug
Dosage form characteristics and a Pharmaceutical Ingredients (Pharmaco-technical factors): 1. Disintegration time(tablets/capsules) 2. Dissolution time 3. Manufacturing variables 4. Pharmaceutical Ingredients (excipients/ adjuvants) 5. Nature and type of dosage form 6. Product age and storage conditions
PATIENT-RELATED FACTORS: include factors relating to the anatomical, physiological and pathological characteristics of the patient. 1. Age 2. Gastric emptying time 3. Intestinal transit time 4. Gastrointestinal pH 5. Disease state 6. Blood flow through the GIT 7. Gastrointestinal contents a) Other drugs b) Food c) Fluids d) Other normal GI contents
8. Contact time with gastrointestinal mucosa 9. Presystemic metabolism by 1.Luminal enzymes 2.Gut wall enzymes 3.Bacterial enzymes 4.Hepatic enzymes
Reference ļ‚§https://healthengine.com.au/info/gastrointestinal- system ļ‚§Biopharmaceutics and pharmacokinetics ā€“A treatise D M Brahmankar, Sunil B. Jaiswal Page no: 1- 26