Ceutics Flashcards
What is the relationship between particle size and dissolution rate?
The smaller the particle size, the greater the effective surface area of the drug particle, thus the higher the dissolution rate.
Methods of particle size reduction include mortar and pestle, mechanical grinders, and solid dispersions in readily soluble materials.
What is the effect of a wetting agent like Tween 80 on drug absorption?
It can have a beneficial effect on the overall absorption by preventing very small particles from clumping together.
What factors affect the diffusion coefficient (D)?
The size of the molecule and the viscosity of the dissolution medium.
How does intrinsic solubility in the diffusion layer (Cs) affect dissolution rate?
The dissolution rate of a drug is directly proportional to its intrinsic solubility in the diffusion layer surrounding each dissolving drug particle.
How do salts of weak acids and weak bases compare to their free forms in terms of solubility?
Salts generally have much higher aqueous solubility than the free acid or base.
What happens to the dissolution rate of a weakly acidic drug in gastric fluid (pH 1–3.5)?
The dissolution rate will be relatively low.
What effect does increasing the pH in the diffusion layer have on a weakly acidic drug?
It increases the solubility (Cs) of the acidic drug, enhancing its dissolution rate in gastric fluids.
What is the difference in pH between the diffusion layer and bulk gastric fluid when a weakly acidic drug is converted to a basic salt?
The pH of the diffusion layer would be higher (5-6) than the low bulk pH (1-3.5) of gastric fluids.
What form does the drug precipitate into when the free acid is in solution in gastric fluid?
Very fine, non-ionized, wetted particles that have a large surface area in contact with gastric fluids.
What is an example of a drug whose dissolution and bioavailability profiles vary with salt forms?
Penicillin V.
What is polymorphism in the context of drugs?
Some drugs exist in multiple crystal forms or polymorphs, which may have different solubility properties.
Which polymorphic form of chloramphenicol is stable?
Form A.
What is the characteristic of the metastable polymorph (Form B) of chloramphenicol?
It is more soluble.
How does the absorption of chloramphenicol change with the proportion of polymorphic form B?
The extent of absorption increases as the proportion of polymorphic form B is increased.
What is the dissolution characteristic of the amorphous form of a drug?
It dissolves more rapidly than the corresponding crystalline form.
What happens to the amorphous form of novobiocin over time?
It slowly converts to the more stable crystalline form, resulting in a loss of therapeutic effectiveness.
What are solvates in the context of drug formulation?
Crystalline forms produced when a drug associates with solvent molecules.
What is the difference between an anhydrous form and a trihydrate form of a drug?
The anhydrous form dissolves faster and is better absorbed than the slower dissolving trihydrate form.
What strategies can protect drugs from degradation in the gastric fluid?
- Enteric coated tablets
- Chemical derivatives (prodrugs)
Example: Erythromycin can be protected by these methods.
What is complexation in pharmacology?
The interaction of a drug with other substances that may be beneficial or detrimental to absorption.
Give an example of a poorly absorbed complex involving a drug.
- Intestinal mucosa (mucin) + Streptomycin
- Calcium + Tetracycline
- CMC + Amphetamine
These interactions can lead to reduced drug absorption.
What is biopharmaceutics?
The study of physiological, dosage form, and drug factors that affect the rate and extent of systemic drug absorption.
What does the acronym ADME stand for?
Absorption, Distribution, Metabolism, and Excretion.
What is bioavailability?
The rate and extent of drug absorption.
Define minimum effective concentration (MEC).
The minimum concentration of drug needed at the receptors to produce the desired pharmacologic effect.
What is the relationship between peak plasma level and drug absorption?
The peak plasma level is proportional to the rate of drug absorption.
What is vesicular transport?
The process of engulfing particles or dissolved materials by the cell.
Differentiate between pinocytosis and phagocytosis.
Pinocytosis refers to the engulfment of small molecules or fluid, while phagocytosis refers to the engulfment of larger particles or macromolecules.
What is the role of transport proteins in pore (convective) transport?
They form an open channel across the lipid membrane of the cell, allowing small molecules to cross.
What is ion pair formation?
The process where strong electrolyte drugs form neutral complexes with oppositely charged ions, facilitating membrane penetration.
What are the two main classifications of drug administration routes?
- Enteral
- Parenteral
What are the main factors affecting oral absorption?
- Physiological factors
- Physical-chemical factors
- Formulation factors
What is the significance of gastrointestinal pH in drug absorption?
It may affect chemical stability, dissolution, and absorption of drugs.
What enzymes are found in gastric juice?
Pepsin, lipases, amylases, and proteases.
What effect does partial or total gastrectomy have on drug absorption?
It may result in an increased overall rate of absorption of drugs that are absorbed in the small intestine.
What is the active drug produced from sulphasalazine?
5-aminosalycylicacid
Sulphasalazine is a prodrug used to treat inflammatory bowel disease.
What can local diseases alter that affects drug absorption?
Gastric pH
Alterations in gastric pH can affect the stability, dissolution, and absorption of drugs.
What is the effect of partial or total gastrectomy on drug absorption?
Increased overall rate of absorption of drugs absorbed in the small intestine
Drugs reach the duodenum more rapidly, which may enhance absorption.
What is the unstirred water layer?
A stagnant layer of water and mucous adjacent to the intestinal wall
It can provide a diffusion barrier to drugs.
What is the term for the time a dosage form takes to traverse the stomach?
Gastric residence time
Other terms include gastric emptying time or gastric emptying rate.
How does gastric emptying affect drug absorption?
Drugs are better absorbed in the small intestine than in the stomach
Quicker stomach emptying increases drug absorption.
True or False: Slower stomach emptying can cause increased degradation of drugs.
True
This is due to prolonged exposure to a slower pH.
What factors affect gastric emptying?
- Volume of ingested materials
- Type of meal
- Temperature of food
- Body position
- Viscosity
- Drugs
- Emotional states
- Exercise
- Disease states
Each factor has specific effects on gastric emptying rates.
What is the effect of food on drug absorption?
Food can influence the rate and extent of absorption
Mechanisms include complexation, alteration of pH, and stimulation of gastrointestinal secretions.
Fill in the blank: Tetracycline forms non-absorbable complexes with _______.
calcium and iron
It is advised not to take calcium or iron products at the same time as tetracycline.
What is presystemic metabolism?
Metabolism of orally administered drugs by gastrointestinal and hepatic enzymes
This process reduces the amount of unmetabolized drug reaching systemic circulation.
What is the primary pathway for most drugs to reach circulation from the villi?
Capillary network
The villi and microvilli present a large surface area for drug absorption.
What happens to drugs in the duodenum?
They are subjected to a drastic change of pH and encounter additional enzymes
The duodenum is one of the most efficient areas for drug absorption.
What is the role of bile salts in drug absorption?
They are efficient emulsifiers that increase the surface area for fat absorption
Bile salts can also form insoluble complexes with some drugs.
True or False: Drugs administered via the oral mucosa bypass the liver.
True
This route allows drugs direct access to the systemic circulation.
What is the order of bioavailability for different oral dosage forms?
Solution > Suspension > Capsule > Tablet > Coated Tablet
A drug must be in solution to be absorbed efficiently from the gastrointestinal tract.
What is the effect of emotional states on gastric emptying?
Stressful emotional states increase gastric contraction and emptying rate
Depression reduces both gastric contraction and emptying rate.
What is the significance of the small intestine in drug absorption?
It is the main site of absorption with a large surface area
The small intestine has a calculated active surface area of approximately 100 m2.
What is the effect of food-induced changes in blood flow on drug bioavailability?
Increased blood flow to the GIT and liver can enhance drug bioavailability
This is especially true for drugs susceptible to first-pass metabolism.
What is the role of mucosal adhesive systems in drug administration?
They are used for administration of drugs through the gingiva
This method allows for rapid absorption into systemic circulation.
What is a key feature of the large intestine regarding drug absorption?
Absorption primarily occurs through tight junctions and carrier-mediated uptake mechanisms
Villi are absent in the large intestine.
Fill in the blank: Drugs that are ideal for gastric absorption are only _______% absorbed from the stomach.
10–30
This is due to the short residence time in the stomach.
What is the effect of temperature on gastric emptying?
Increase in temperature increases gastric emptying
This can enhance the absorption rate of drugs.
What is the role of a surface active agent in drug absorption?
It will improve the absorption of very fine particle size suspensions.
What should happen to the hard gelatin shell of a capsule dosage form?
It should disrupt rapidly and allow the contents to be mixed with the GIT contents.
What should be added to a capsule formulation if a drug is hydrophobic?
A dispersing agent.
What are the potential consequences of tightly packed capsules?
They may have reduced dissolution and bioavailability.
What is the most commonly used oral dosage form?
Tablet.
List the ingredients that may be included in tablet dosage forms.
- Drug
- Lubricant
- Granulating agent
- Filler
- Wetting agent
- Disintegration agent
What is the purpose of coated tablets?
To mask an unpleasant taste, protect tablet ingredients during storage, or improve appearance.
What are enteric coated tablets designed to do?
Dissolve in the intestine but remain intact in the stomach.
Name some routes of absorption by other delivery methods.
- Intramuscular and subcutaneous injection
- Transdermal delivery
- Eye delivery
- Ear delivery
- Vaginal delivery
- Nasal and inhalation delivery
- Rectum delivery
- Intrathecal delivery
What factors affect drug release from intramuscular and subcutaneous injections?
Not all drugs are efficiently or uniformly released from i.m. or s.c. sites.
What does the pH of tissue affect in drug absorption?
It will determine whether drugs will dissolve in the tissue fluids or precipitate.
What are the three main types of formulations used for injections?
- Aqueous solutions
- Aqueous suspensions
- Oily solutions
How does blood flow affect intramuscular injection absorption?
Different rates of blood flow in different muscles can be crucial.
What is the primary function of biological membranes?
To separate the inside of the cell from the outside.
What are the main components of the cell membrane?
- Phospholipids
- Proteins
- Other macromolecules
What is the role of cholesterol in biological membranes?
It helps maintain membrane structural integrity and reduces permeability.
What is P-glycoprotein and its role in drug absorption?
It is an ATP-dependent efflux transporter that generally inhibits absorption.
What is the difference between active transport and facilitated diffusion?
Active transport requires energy and can move substances against a concentration gradient; facilitated diffusion does not require energy and only moves substances down a concentration gradient.
What is passive diffusion?
The process where most drugs cross biological membranes when the concentration on one side is higher than on the other.
What is the pH-partition theory?
It states that the gastrointestinal epithelia acts as a lipid barrier towards drugs, and lipid-soluble drugs will pass across the barrier.
What effect does ion trapping have on drug absorption?
It prevents the drug from passing back across the membrane once ionized.
What is the Henderson-Hasselbalch equation used for?
To calculate the extent to which a weakly acidic or basic drug ionizes in solution.
Fill in the blank: The extent to which a weak acidic drug ionizes is determined by the _______.
Henderson-Hasselbalch equation.
True or False: Most drug absorption occurs in the stomach.
False.
What does the pH-partition hypothesis suggest about drug absorption?
It suggests that drug absorption is influenced by the pH of the environment and the drug’s ionization state.
This hypothesis states that non-ionized drugs are more readily absorbed.
What is a significant limitation of the pH-partition hypothesis?
Most absorption occurs in the small intestine, where pH is close to 7, leading to poor correlation of pH-partition predictions with actual absorption.
The hypothesis fails to account for dynamic processes involved in absorption.
What is the partition coefficient (p)?
It is defined as the ratio of the concentration of a drug in lipid phase to its concentration in aqueous phase.
Higher values indicate better absorption.
What is the Noyes-Whitney equation used for?
It describes the dissolution rate of drugs in a stagnant layer surrounding solid particles.
Key variables include diffusion coefficient, surface area, solubility, concentration in bulk solution, and thickness of the stagnant layer.
Fill in the blank: Drug dissolution is considered to be a _______ controlled process.
diffusion
What physiological factors affect the dissolution rate of drugs?
Factors include:
* Diffusion coefficient
* Drug surface area
* Thickness of the diffusion layer
* Concentration of drug in solution
These factors can significantly influence the rate of drug absorption.
What does drug distribution refer to?
The reversible transfer of drug from one location to another within the body.
This process depends on lipophilicity and protein binding.
What is the apparent volume of distribution (V)?
It is a parameter that describes the distribution of a drug in the body, with no upper limit but a theoretical minimum of 7L in a 70-kg person.
V can indicate the pattern of drug distribution.
List the four types of drug distribution patterns.
- Largely within the vascular system
- Uniformly distributed throughout body water
- Concentrated in specific tissues
- Non-uniform distribution across the body
Each pattern reflects how drugs interact with body compartments.
How does membrane permeability affect drug distribution?
Lipid soluble drugs pass through capillary walls rapidly, while water soluble compounds penetrate more slowly based on size.
Drugs with a molecular diameter above 100 Å have slower transfer rates.
What is the blood-brain barrier?
A barrier that restricts the transfer of polar substances from blood to brain tissue, allowing only lipid-soluble compounds to pass readily.
This barrier plays a crucial role in protecting the brain from potentially harmful substances.
What is the primary organ for drug excretion?
The kidney.
The kidney’s functional unit, the nephron, is responsible for filtration, secretion, and reabsorption.
What is the difference between excretion and elimination?
Excretion refers to the irreversible loss of the drug from the body, while elimination involves metabolism and/or excretion of the parent drug.
Elimination can include both processes.
What factors affect the extent of drug distribution?
- Lipid solubility
- pH - pKa
- Plasma protein binding
- Tissue drug binding
These factors determine how widely a drug is distributed throughout the body.
What role does plasma protein binding play in drug action?
Extensive plasma protein binding decreases the amount of free drug available, potentially delaying elimination and affecting therapeutic effects.
Changes in plasma protein levels can significantly influence drug efficacy.
What is renal clearance?
A quantitative measure of the renal excretion of drugs, indicating how efficiently a drug is removed from the body.
It can help investigate the mechanisms of drug excretion.
Fill in the blank: A low plasma protein level may occur due to _______.
malnutrition
What is passive glomerular filtration?
The process by which substances are filtered from blood into the renal tubule without requiring energy.
What is active tubular secretion?
The process that involves the active transport of substances from the blood into the renal tubule.
What is passive tubular re-absorption?
The process by which substances are reabsorbed from the renal tubule back into the blood without energy.
What does renal clearance indicate?
It quantitatively describes the renal excretion of drugs.
What is a normal renal clearance value?
About 120 ml/min in normal subjects.
If renal clearance is less than 120 ml/min, what can be assumed?
At least two processes are in operation: glomerular filtration and tubular re-absorption.
If renal clearance is greater than 120 ml/min, what does this indicate?
Tubular secretion is contributing to the elimination process.
Name factors that lower renal drug clearance.
- Elderly and Newborn
- Women (20%) than men
- Kidney and Heart Disease
- Patients taking drugs that block secretion (e.g., aspirin, probenecid)
What is hemodialysis?
A therapy used in renal failure to remove toxic waste material by diverting blood externally across a semi-permeable membrane.
What are the characteristics of drugs effectively removed by hemodialysis?
- Good water solubility
- Not tightly bound to plasma protein
- Smaller molecular weight
- Small apparent volume of distribution
What is fecal excretion?
Elimination of toxicants in the feces through processes such as excretion in bile and direct intestinal excretion.
What are the substances likely to be excreted via bile?
- Heavy metals (e.g., arsenic, lead, mercury)
- Large molecular weight conjugates (e.g., morphine glucuronide)
What is enterohepatic circulation?
The process where substances excreted in bile are either eliminated in feces or reabsorbed, prolonging drug life in the body.
What enhances intestinal excretion of lipophilic substances?
Increasing the lipid content of the intestinal tract.
What is pulmonary excretion?
The elimination of gaseous and volatile substances primarily through expiration.
What factors influence salivary excretion?
pH partition and protein binding.
What substances are excreted in sweat?
- Iodine
- Bromine
- Benzoic acid
- Salicylic acid
- Lead
- Arsenic
- Mercury
- Alcohol
What types of substances can be excreted into breast milk?
- Basic substances
- Lipid-soluble compounds
- Substances chemically similar to calcium
- Ethanol and tetracycline
What is drug metabolism?
The irreversible biotransformation of drugs in the body, typically making them more polar for renal excretion.
What are the main outcomes of drug metabolism?
- More hydrophilic
- Decreased or increased action
- Less or more toxic metabolites
- Different effects or toxicity
Where does drug metabolism primarily occur?
Mainly in the liver, but also in the kidney, lung, intestine, and placenta.
What are Phase I metabolic reactions?
Reactions that change drugs to more hydrophilic metabolites, often involving oxidation, reduction, or hydrolysis.
What is oxidation in drug metabolism?
The addition of oxygen or removal of hydrogen, typically involving cytochrome P450.
What is reduction in drug metabolism?
Adding hydrogen or removing oxygen from the molecule.
What is hydrolysis in drug metabolism?
The addition of water leading to the breakdown of the molecule.
What are Phase II metabolic reactions?
Reactions that involve conjugation, adding large polar molecules to drugs or metabolites to make them inactive and excretable.
What is glucuronidation?
The main conjugation reaction occurring in the liver, where lipophilic alcohols and phenols are conjugated.
What is enzyme induction?
The process that increases metabolic activity of enzymes, leading to decreased drug concentration.
What is enzyme inhibition?
The process that decreases metabolic activity of enzymes, leading to increased drug concentration.
How does age influence drug metabolism?
Drug metabolism is slower in fetal, neonatal, and elderly humans compared to adults.
How does sex influence drug metabolism?
Women metabolize alcohol more slowly than men.
What is the effect of grapefruit juice on drug metabolism?
It inhibits drug metabolism by interfering with hepatic cytochrome P450.
What is genetic variation in drug metabolism?
Differences in metabolic rates among individuals due to genetic polymorphisms, such as slow vs. fast acetylators.
How can liver disease affect drug metabolism?
It can impair hepatic drug-metabolizing enzymes, affecting drug elimination.
How does cardiac disease affect drug metabolism?
It may impair drug disposition due to limited blood flow to the liver.
