What is Drug absorption

ABSORPTION

Introduction The desired therapeutic objective can be achieved if the drug product delivers the active drug at an optimal rate and extent.  If a proper biopharmaceutical design is maintained, the rate and extent of drug absorption (or bioavailability) or the systemic delivery of drug into the body can be altered from rapid and complete absorption to slow and sustained absorption;  however, this depends on the desired therapeutic action.  The events that occur after a solid dosage form tablet or a capsule) is administered until systemic circulation are shown in the figure 1.1

These events comprise of the following four steps: 

1 ) Disintegration of the drug product

 2 ) De - aggregation and release of the drug .  

3) Dissolution of the drug in aqueous fluids at the absorption site, and 

4) Movement of the dissolved drug through the gastrointestinal membrane into the systemic circulation and away from the absorption site.

  

A drug molecule gets absorbed from the GIT and enters the systemic circulation only if it effectively penetrates all the intestinal regions.  Once the drug enters the solution , its absorption is governed by the following three important factors :

 1 ) The physicochemical properties of the drug molecule , 

2)properties and components of the GI fluids , and 

 3 ) The nature of the absorbing membrane .  

Mechanisms of Drug Absorption Through GIT

 The drug after entering the GI fluids exists in the form of a solution and can get absorbed .  The drug's physicochemical properties (its inherent absorbability) and the environmental properties around it (such as pH, presence of interfering materials, and local properties of the absorbing membrane) decide whether or not the drug is in absorbable form.  If there are no interfering materials ( that affect

drug absorption ), the drug molecule diffuses from the Gl fluids to enter the absorbing membrane surface.  A drug molecule gets absorbed from the GIT and enters the systemic circulation only if it effectively penetrates all the intestinal regions. 

The pathways of drug transport show that drug absorption from the GI lumen into the systemic circulation involves the passage of drug molecules across several cellular membranes and fluid regions in the mucosa, i.e.  , the gastrointestinal - The GIT epithelium lining is the major cellular barrier to the absorption of drugs from the GIT.  The drug molecules in GI fluids should cross the unstirred aqueous layer, mucus layer, and glycocalyx to reach the apical cell membrane. 

The following mechanisms are involved in the transport of drug molecules across the cell membrane :

1)  Passive diffusion , 

2 ) Carrier - mediated transport :

 i ) Facilitated diffusion , and

ii ) Active transport , 

3 ) Pore transport ,

4) Ionic or electrochemical diffusion ,

5  ) Ion - pair transport , and

6) Endocytosis .  

Passive diffusion

Passive diffusion ( or non - ionic diffusion ) is the major process for absorption of more than 90 % of drugs .  It is defined as the difference in the drug concentration on either side of the membrane.  Concentration or electrochemical gradient the driving force for this process.

The kinetic energy of drug molecules is responsible for the movement of drugs.  Since no energy source is required , the process is called passive diffusion , during which the drug in the aqueous solution at the absorption site , partitions and dissolves in the lipid material of the membrane and leaves it by dissolving in an aqueous medium at the inside of  the membrane.

Passive diffusion can be expressed by Fick's first law of diffusion, according to which the drug molecules diffuse from a region of higher concentration to lower concentration until equilibrium is achieved, and the rate of diffusion is directly proportional to the concentration gradient across the membrane.  Fick's first law diffusion is mathematically expressed as:

Carrier - Mediated Transport 

Some polar drugs pass through the membrane more rapidly than can be predicted from their concentration gradient and partition coefficient values ​​.  This is due to a specialized transport mechanism , without which the presence of monosaccharides , amino acids , and vitamins (essential water - soluble nutrients ) will undergo poor absorption .  The mechanism involves a membrane component, called the carrier that reversibly or non-covalently binds to the solute molecules to be transported.  after which , the carrier returns to its original site and accepts a fresh solute molecule thereby completing the cycle.

Carrier - mediated transport system is of two types : 

1 ) Facilitated diffusion , and 

2 ) Active transport .  

1)Facilitated diffusion

Facilitated diffusion is a carrier - mediated transport system that works at a much faster rate than the passive diffusion .  Concentration gradient is the driving force for this process that operates down the hill and thus is a passive process.

Since the process involves and the system is not inhibited by metabolic poisons.  Some applications of facilitated diffusion system in drug absorption are: 

1 ) Its major application involves entry of glucose into RBCs .  

2 ) Another application involves intestinal absorption of vitamins B₁ and B₂ .  

3 ) The most significant application involves gastrointestinal absorption of vitamin B₁2 (figure 1.4 ) , which forms a complex with glycoprotein [ an intrinsic factor ( IF ) , gastric parietal cells ] : and then this complex is transported across the intestinal membrane through a carrier system. 

 

2)Active transport

Active transport involves movement of a substance from a region of low concentration to high concentration, i.e.  , against its concentration gradient.  In all the cells, this is concerned with accumulating high concentrations of ions.  glucose , and amino acids that the cell requires ( figure 1.5 ) .  

Active transport uses energy, unlike passive transport that does not use any type of energy.  If it uses chemical energy from ATP, it is termed as primary active transport.  If it uses an electrochemical gradient, it is termed as secondary active transport.  

The significance of active transport process in the absorption of nutrients and drugs is more than the facilitated diffusion , and both the processes differ in the following aspects : 

1 ) In active transport drug is transported from a region of lower concentration to a region of higher concentration  ie  , against the concentration gradient or uphill transport.  

2) Active transport is an uphill process, thus energy is required in the work done by the carrier. 

3 ) Active transport process requires energy, thus it can be inhibited by metabolic poisons (like fluorides, cyanides, di-nitrophenol, lack of oxygen, etc.) that interfere with energy production.

Sodium , potassium , calcium , iron , glucose , certain amino acids and vitamins like niacin , pyridoxine and ascorbic acid are the endogenous substances that are actively transported .  Drugs that are structurally similar to such agents ( mainly the agents used in cancer chemotherapy ) are actively absorbed.  For example, absorption of 5 fluorouracil and 5-bromouracil through pyrimidine transport system;  absorption of methyldopa and levodopa through L-amino acid transport system;  and absorption of enalapril (ACE inhibitor) through small peptide carrier system.  

An example of competitive inhibition of drug absorption through active transport is the impaired absorption of levodopa when taken with protein - rich meals.  Active transport is also important in renal and biliary excretion of many drugs and their metabolites and secretion of certain acids out of the CNS.  

 

Pore ​​Transport 

Pore transport ( or connective transport , bulk flow or filtration ) involves the absorption of low molecular weight , low molecular size , and water-soluble drugs (eg, urea, water, and sugar) through narrow, aqueous filled channels or pores in  the membrane structure.  This facilitates mechanisms the transport of molecules into the cell through protein channels present in the cell membrane.  Chain-like or linear compounds of 400 Daltons molecular weight can be observed by filtration Hydrostatic pressure or the osmotic differences across the membrane is the driving force for this process.  Due to this , bulk flow of water along with small solid molecules occurs through such aqueous channels .  Water flux is promoting such a transport is called as solvent drag.  Drug permeation through water - filled channels is significant in renal excretion , removal of drug from the cerebrospinal fluid , and entry of drugs into the liver . 

Ionic or Electrochemical Diffusion

 Ionic or electrochemical diffusion involves the diffusion of ionic molecules across the membrane as a function of potential difference or electrical gradient while non-ionic diffusion involves the diffusion of uncharged molecules.  No matter TECNO molecules diffuse through the membrane at a slower rate than Opicharged molecules, still they undergo significant absorption The our Sullide of membrane is positively charged, while its intracellular surface carries negative charge.  Cationic drugs , due to the repulsion between similarly charged molecules , show electrostatic repulsion on the outer surface of the membrane .  Thus , the molecules with a high kinetic energy can only cross the membrane barrier .  On the other hand, cationic drugs inside the membrane undergo significant interaction with the negatively charged intracellular membrane, and create the electrical gradient, causing electrical diffusion.  Electrochemical diffusion is the function of electrical field as well as the concentration difference across the membrane, and this process lasts till equilibrium is achieved.  

 Ion - Pair Transport

Drugs with a Zwitter ion undergo ionisation over the entire pH range of the GIT , e.g.  , ampicillin, amoxicillin, and tetracycline.  Smaller ionic drugs travel through the water - filled pores ;  but , the Zwitter ionic drugs are large enough to pass.  through the water - filled pores and are also highly lipid insoluble to partition through lipoidal membrane .  Thus , these drugs use their charge to pair with the endogenous ions of the GIT and cross the membrane .  The resulting paired molecule partitions into the lipoidal membrane ( figure 1.6 ).  These drugs are ionic , but show passive absorption and maximum partition coefficient when the net charge on the molecule is minimum .

 

Endocytosis 

Endocytosis is a minor transport mechanism in which the extracellular materials are engulfed within a segment of the cell membrane to form a saccule or a vesicle, which is then pinched-off intracellularly (figure 1.7).  Thus, this process is also called as corpuscular or vesicular transport.  

The process of TECnosis helps in the cellular uptake of macromolecular Ok fats and starch , oil-soluble vitamins (like A , D , E , and K ), and drugs tuke sul SPARK ocess is also significant because since the drug is absorbed into the  Lymphatic circulation, it bypasses first - pass hepatic metabolism.

Types of Endocytosis

 The process of endocytosis is of the following two types. 

 1 ) adsorptive uptake of solid particulates .  

2 ) Pinocytosis ( Cell Drinking ) : This process involves uptake of fluid solute ;  for example , orally administered Sabin polio vaccine and large protein molecules are absorbed by pinocytosis .  

At times, transcytosis occurs in which an endocytic vesicle is transferred from one extracellular compartment to another.

 FAQ:- 

Q.1 What are the steps of drug absorption?

And.1)  Passive diffusion 

2 ) Carrier - mediated transport

 i ) Facilitated diffusion

ii ) Active transport

3 ) Pore transport

4) Ionic or electrochemical diffusion

5  ) Ion - pair transport and

6) Endocytosis .  

Q.2 What is drug absorption in pharmacy?

Ans. Introduction The desired therapeutic objective can be achieved if the drug product delivers the active drug at an optimal rate and extent.  If a proper biopharmaceutical design is maintained, the rate and extent of drug absorption (or bioavailability) or the systemic delivery of drug into the body can be altered from rapid and complete absorption to slow and sustained absorption;  however, this depends on the desired therapeutic action.  The events that occur after a solid dosage form tablet or a capsule) is administered until systemic circulation.

Q.3 What are the two mechanisms of absorption?

Ans. The drug after entering the GI fluids exists in the form of a solution and can get absorbed . The drug's physicochemical properties (its inherent absorbability) and the environmental properties around it (such as pH, presence of interfering materials, and local properties of the absorbing membrane) decide whether or not the drug is in absorbable form. If there are no interfering materials ( that affect

drug absorption ), the drug molecule diffuses from the Gl fluids to enter the absorbing membrane surface. A drug molecule gets absorbed from the GIT and enters the systemic circulation only if it effectively penetrates all the intestinal regions. 

The pathways of drug transport show that drug absorption from the GI lumen into the systemic circulation involves the passage of drug molecules across several cellular membranes and fluid regions in the mucosa, i.e. , the gastrointestinal - The GIT epithelium lining is the major cellular barrier to the absorption of drugs from the GIT. The drug molecules in GI fluids should cross the unstirred aqueous layer, mucus layer, and glycocalyx to reach the apical cell membrane.