The effectiveness of any medicine depends upon its bioavailability. It indicates the ability of drug by which it can enter the blood stream and provide a therapeutic effect. Even the most active chemical must be bioavailable to effectively treat the condition for that it was given.
Through knowing the various factors impacting the bioavailability of medications, scientists can design the proper dosage forms, allowing patients maximum benefit from their therapeutic treatment.
The article will explain why bioavailability is important and provide an overview of many of the factors that affect medication bioavailability.
Examples of bioavailability include 100% of an intravenous (IV) dose of medication since it goes directly into the liver and into the bloodstream, whereas an orally taken tablet will typically have a lower bioavailability because the tablet does not enter the bloodstream completely and has to go through "first-pass" metabolism before reaching the target organs.
1. Therapeutic efficacy of drugs - determines whether the drug reaches its effective plasma concentration
2. Dosing regimen - determining how much and how often the medication needs to be taken
3. Formulation design - helps determine what excipients, what type of particle sizes and what delivery systems should be used in creating the formulation
4. Regulatory approval - is an important part of bioequivalency studies for generic medications.
When bioavailability is low or variable, the treatment may be ineffective and when bioavailability is too high, this could potentially lead to toxicity.
A. Solubility – A drug to be absorbed by the patient it must dissolve in liquid. Drugs that are not soluble (like griseofulvin and digoxin) have relatively low bioavailability in comparison with soluble drugs. Different techniques are there to enhance solubility including salt formation, preparation of a solid dispersion of a drug and the micronization of a drug to improve bioavailability.
B. Particle size – The size of the particles of any drug must be considered. Smaller particles have greater surface area available for absorption, thus creating a more rapid dissolution and absorption of the material. For example, micronized steroids would exhibit higher bioavailability than non-micronized steroids.
C. Polymorph – Different crystalline forms of a drug can have different solubility and dissolution rates. Crystalline forms of a drug that are more soluble in liquid usually have higher bioavailability compared to those that are less soluble.
D. Lipophilicity – For drugs to enter the body’s systemic circulation, they must cross lipid membranes. Therefore, a drug must possess an ideal balance of both lipid solubility (for crossing lipid membranes) and aqueous solubility (for dissolving in liquid) in order to enter the body.
- Using sustained release formulations the absorption of a drug will be slowed down to achieve a stable plasma concentration.
- Surfactants used in formulation improve drug solubility.
- Binders or lubricants can impede drug dissolution.
- Disintegrants encourage faster drug release.
The selection of excipients and their compatibility with one another are essential for producing consistent bioavailability
- Intravenous administration = 100% bioavailability
- Intramuscular and Subcutaneous = High level but relatively slower rate of absorption.
- Oral administration = Variable due to the presence of digestive enzymes and first-pass metabolism.
- Transdermal, Inhalation and Rectal Routes = Mostly avoid partial First-Pass metabolism, thereby increasing some drugs’ overall bioavailability.
- Weak base medications like Diazepam are more readily absorbed when an alkaline medium like in empty stomach.
- Slower gastric emptying due to eating a large high fat meal or due to any disease slower down the rate of absorption of a medication.
- Increase in absorption with certain lipophilic medicines like Griseofulvin results in stimulation of bile production.
- Decrease in absorption with medicines that are chelated to food components like Doxycycline with Calcium.
Propranolol, morphine and nitroglycerin are some examples of drugs that are extensively metabolized after the first pass through the liver.
Sublingual dosage forms, transdermal dosage forms and parenteral dosage forms are the formulations that bypass the first-pass metabolism.
- Antacids alter the acidity level of the stomach (an effect on the stomach), which in turn alters how much of an acid drug is absorbed through your intestines and how fast.
- Grapefruit juice acts upon the liver to prevent a chemical action (the cytochrome P450 enzymes) that promotes how drug molecules are transported through your bloodstream. If this is prevented, blood levels of many drug molecules may be higher than expected.
- High-fat meals delay how long it takes a person to process the food they ingest, i.e. how long until their food leaves the stomach (another stomach effect), which affects drug dissolution.
1) Liver disease: Decreases metabolism which increases bioavailability.
2) Malabsorption syndromes: Decrease the amount of drug that is absorbed.
3) Gastrointestinal disorders: Cause changes in pH and motility that may affect dissolution and transit time.
- Newborns have immature enzyme systems and therefore poor metabolic functions.
- Hormones may also affect drug absorption and metabolism differently between men and women.
1. Particles can be made smaller by micronization or using nanocrystals.
2. Formulating drugs with salts or in complexes.
3. Using surfactants or cosolvents to assist in the absorption of drugs.
4. Developing prodrugs to increase the amount of the drug that is absorbed and metabolized.
5. Using new delivery systems such as liposomes, nanoparticles and solid dispersions.
Bioavailability is the determining factor for the effectiveness of all dosage forms - from the quickness of an analgesic tablet to the precision of chemotherapy agents.
Bioavailability involves a number of different factors, including physicochemical properties of the drug and body, physiological conditions in the patient and how the dosage form has been formulated. Pharmaceutical scientists use these factors to maximize the bioavailability of a drug to have their control on drug release in any medicine.
Through knowing the various factors impacting the bioavailability of medications, scientists can design the proper dosage forms, allowing patients maximum benefit from their therapeutic treatment.
What is Bioavailability
Bioavailability is the measure of a drug that how much and how quickly it enters the bloodstream after administration. Bioavailability is expressed as a percent of the total amount of drug that was administered.Examples of bioavailability include 100% of an intravenous (IV) dose of medication since it goes directly into the liver and into the bloodstream, whereas an orally taken tablet will typically have a lower bioavailability because the tablet does not enter the bloodstream completely and has to go through "first-pass" metabolism before reaching the target organs.
The Importance of Bioavailability
Bioavailability affects:1. Therapeutic efficacy of drugs - determines whether the drug reaches its effective plasma concentration
2. Dosing regimen - determining how much and how often the medication needs to be taken
3. Formulation design - helps determine what excipients, what type of particle sizes and what delivery systems should be used in creating the formulation
4. Regulatory approval - is an important part of bioequivalency studies for generic medications.
When bioavailability is low or variable, the treatment may be ineffective and when bioavailability is too high, this could potentially lead to toxicity.
Factors Affecting Bioavailability
Bioavailability is influenced by various factors that relate to the drug itself, the formulation, the physiology of the individual taking the drug and how a drug has been administered to the patient or person.1. Physicochemical Properties of the Drug
Unique properties of a drug molecule itself are the most direct factors affecting bioavailability.A. Solubility – A drug to be absorbed by the patient it must dissolve in liquid. Drugs that are not soluble (like griseofulvin and digoxin) have relatively low bioavailability in comparison with soluble drugs. Different techniques are there to enhance solubility including salt formation, preparation of a solid dispersion of a drug and the micronization of a drug to improve bioavailability.
B. Particle size – The size of the particles of any drug must be considered. Smaller particles have greater surface area available for absorption, thus creating a more rapid dissolution and absorption of the material. For example, micronized steroids would exhibit higher bioavailability than non-micronized steroids.
C. Polymorph – Different crystalline forms of a drug can have different solubility and dissolution rates. Crystalline forms of a drug that are more soluble in liquid usually have higher bioavailability compared to those that are less soluble.
D. Lipophilicity – For drugs to enter the body’s systemic circulation, they must cross lipid membranes. Therefore, a drug must possess an ideal balance of both lipid solubility (for crossing lipid membranes) and aqueous solubility (for dissolving in liquid) in order to enter the body.
2. Excipients and Formulations
The design of the formulation is one of the most critical aspects of how the drug will be released and absorbed.A. Type of Dosage Formulation
- When comparing syrups and suspensions with tablets and capsules the liquid formulations are absorbed more rapidly than the solids.- Using sustained release formulations the absorption of a drug will be slowed down to achieve a stable plasma concentration.
B. Excipients
The types of excipients used in formulation also affect the dissolution and finally absorption of the drug.:- Surfactants used in formulation improve drug solubility.
- Binders or lubricants can impede drug dissolution.
- Disintegrants encourage faster drug release.
The selection of excipients and their compatibility with one another are essential for producing consistent bioavailability
C. Manufacturing Process
Compression forces, granulation methods, and coating conditions have an effect on how porous the tablets will be, how they will disintegrate and ultimately how much of the drug will be absorbed.3. Route of Administration
The method of delivery will directly influence how much of the drug is absorbed into circulation after it goes through its first time in the liver (the so-called "first pass") before reaching the systemic circulation.- Intravenous administration = 100% bioavailability
- Intramuscular and Subcutaneous = High level but relatively slower rate of absorption.
- Oral administration = Variable due to the presence of digestive enzymes and first-pass metabolism.
- Transdermal, Inhalation and Rectal Routes = Mostly avoid partial First-Pass metabolism, thereby increasing some drugs’ overall bioavailability.
4. Physiological Factors
A. Gastrointestinal pH
- The acidity and alkalinity of the GI tract affect the solubility of the drugs. Weak acid drugs like Aspirin are absorbed better when taken with an acidic medium like in full stomach.- Weak base medications like Diazepam are more readily absorbed when an alkaline medium like in empty stomach.
B. Gastric Emptying and Intestinal Transit Time
- Faster gastric emptying rate will deliver faster the drug to the intestine and therefore, have an increased chance of absorption.- Slower gastric emptying due to eating a large high fat meal or due to any disease slower down the rate of absorption of a medication.
C. Presence of Food
Food can increase or decrease the bioavailability of medications. For example,- Increase in absorption with certain lipophilic medicines like Griseofulvin results in stimulation of bile production.
- Decrease in absorption with medicines that are chelated to food components like Doxycycline with Calcium.
D. Blood Flow to Absorption Site
Increased blood flow results in increased absorption rates like in the case of sublingual (under-the-tongue) absorption due to the high blood flow in that area.E. Intestinal Transporters and Enzymes
Transporters that can actively transport a drug back into the GI tract such as P-Glycoprotein (P-gp) will decrease absorption while the presence of drug metabolizing enzymes like CYP3A4 will metabolize a drug before it can reach the systemic circulation resulting in increased absorption of drug.5. First-Pass Metabolism
First-pass metabolism involves the metabolic breakdown of drug molecules before it reaches to systemic circulation. It is also called presystemic metabolism. Drugs that enter the body via the GI tract must first travel to the liver. Here metabolic enzymes create a wide variety of chemical reactions which can greatly reduce the amount of active drug in the blood.Propranolol, morphine and nitroglycerin are some examples of drugs that are extensively metabolized after the first pass through the liver.
Sublingual dosage forms, transdermal dosage forms and parenteral dosage forms are the formulations that bypass the first-pass metabolism.
6. Drug-Drug and Drug-Food Interactions
Some drugs absorb better when taken with food and some foods and medicines combined create a stronger chemical interaction.- Antacids alter the acidity level of the stomach (an effect on the stomach), which in turn alters how much of an acid drug is absorbed through your intestines and how fast.
- Grapefruit juice acts upon the liver to prevent a chemical action (the cytochrome P450 enzymes) that promotes how drug molecules are transported through your bloodstream. If this is prevented, blood levels of many drug molecules may be higher than expected.
- High-fat meals delay how long it takes a person to process the food they ingest, i.e. how long until their food leaves the stomach (another stomach effect), which affects drug dissolution.
7. Disease States
The following physiologic variables may influence absorption and metabolism:1) Liver disease: Decreases metabolism which increases bioavailability.
2) Malabsorption syndromes: Decrease the amount of drug that is absorbed.
3) Gastrointestinal disorders: Cause changes in pH and motility that may affect dissolution and transit time.
8. Age and Gender
- Elderly patients could display decreased bioavailability due to slower gastric emptying rates and decreased activity of metabolic enzymes, therefore, they should avoid medications requiring rapid absorption.- Newborns have immature enzyme systems and therefore poor metabolic functions.
- Hormones may also affect drug absorption and metabolism differently between men and women.
9. Physical Activity and Body Position
Blood flow increases during physical exercise and can lead to an increased absorption rate of some medications. Conversely, lying down right after taking an oral dose can slow down gastric emptying.Ways to Improve Drug Bioavailability
The pharmaceutical scientist has options for improving drug bioavailability:1. Particles can be made smaller by micronization or using nanocrystals.
2. Formulating drugs with salts or in complexes.
3. Using surfactants or cosolvents to assist in the absorption of drugs.
4. Developing prodrugs to increase the amount of the drug that is absorbed and metabolized.
5. Using new delivery systems such as liposomes, nanoparticles and solid dispersions.
Bioavailability is the determining factor for the effectiveness of all dosage forms - from the quickness of an analgesic tablet to the precision of chemotherapy agents.
Bioavailability involves a number of different factors, including physicochemical properties of the drug and body, physiological conditions in the patient and how the dosage form has been formulated. Pharmaceutical scientists use these factors to maximize the bioavailability of a drug to have their control on drug release in any medicine.
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