Exam 2 Flashcards
What is a mole?
The molecular weight of a substance in grams (6.02x10^23 particles)
What is molarity?
The number of moles of a solute in one liter of solution
What is molality?
The number of moles of solute in 1000g of solvent
Why is molarity temperature dependent?
The density will change with temperature and molarity is measured in a volume of solution (D=m/v)
What are electrolytes?
Minerals which carry an electric charge when dissolved in water
What are miliequivalents
Measure of the chemical activity of an electrolyte
What are millequivalents dependent upon?
Valence of electrons
What are milliequivalents used to express?
The concentration of solutions of electrolytes
What is an equivalent weight?
The amount of substance that will combine with or displace a given weight of another substance
How would you get one-gram equivalent?
Atomic Weight over valence (the charge it carries)
Why are molecules hydrated?
To improve crystalline stability
What is osmolarity?
The concentration of solution expressed as the number of particles per liter
(combines molar concentration and osmotic pressure)
What is osmotic pressure
When solvent levels are different across the membrane so pressure is created
What happens to osmotic pressure when the solute is a nonelectrolyte?
The solution contains only molecules so the pressure varies with the concentration of the solute
What happens to osmotic pressure when the solute is an electrolyte?
The solution contains ions so the osmotic pressure varies with concentration of solute and its degree of dissociation
Do undissociated molecules exert more pressure than dissociated?
No since solutions that dissociate present a greater amount of particles, they exert a greater osmotic pressure
What is the osmolarity when the solute is a non electrolyte?
The same as the molar concentration because there is only one particle
What happens to osmolarity when the solute is an electrolyte?
It increases because of the increase in the number of particles due to dissociation of the solute
What is the difference between osmolarity and osmolality
Osmolality is temperature independent
What is a bioassay?
A biological testing procedure to estimate the concentration of a drug by measuring the biological response it produces
What are some drugs that use units for its strength?
Antibiotics
Vitamins
Endocrine products
What does potency compare?
The relative strength of a drug to produce the reference standard
How is potency expressed?
In terms of the amount of a drug required to produce an effect of given intensity
What are biologics?
Preparations produced from a living source (vaccines)
What is a solution?
Chemically and physically homogenous mixture of 2 or more substances
What does homogenous mean?
Term used to imply that a mixture is uniform (all parts are identical)
(physically and chemically stable)
What is a binary solution?
Mixture of only 2 components (solute and solvent)
What is usually the solvent for oral solutions?
Water
What are examples of oral solutions?
elixirs
syrup
How does one take parenteral solutions?
By injection (sterile)
What are the advantages of solutions?
Faster onset
Good for elderly and children
Homogeneous
Flexibility with dosing
What are the disadvantages to solutions?
Bulkiness (weigh alot)
Leakage from container
Less stable (can evaporate)
More pronounced taste
What is normality based on?
Chemical activity
What are ideal solutions?
Solutions for which there is no change in the physical properties of the components other than dilution when they are mixed
What are the three main points to an ideal solution?
No heat is given off or taken in
Volume does not shrink or expand
Final volume is the sum of the component volumes
What does raoult’s law state?
The vapor pressure of each volatile constituent is equal to the vapor pressure of the pure constituent multiplied by its mole fraction in the solution
What are real solutions?
Solutions for which changes in the physical properties of the solution occur when the components are mixed
What kind of relationship is shown for ideal solutions?
linear
What kind of line is shown for Raoult’s law for real solutions?
A curve up or down (depending if there are stronger adhesive or cohesive attractions )
How do most solutions in the pharmacy behave?
Nearly like ideal solutions when they are mixed
What is the difference between positive deviation and negative deviation?
Positive = cohesive forces predominate (wants to stay together - alcohol and water) Negative = adhesive forces predominate (wants to bind to other things -HCL/water)
What does positive deviation between alcohol and water result in?
Volume reduction
want to stay together since they share H-bonds so they are more compact
Why do solutions with non electrolytes not conduct currents?
They do not contain ions
How do strong electrolytes dissociate in solutions?
Completely and are 100% ionized
What kind of electrolytes are in most drug solutions?
Partially ionized/ weak electrolytes that have induced dipoles
How do the physical properties of solutions vary?
Based on the concentration of dissolved solute
What are the 4 colligative properties?
Osmotic pressure
Vapor Pressure Lowering
Freezing point depression
Boiling Point Elevation
What do each of the 4 colligative properties depend on?
Number of particles dissolved in the solution
What is osmosis?
When the concentrations of solute on two sides of a membrane are equalized
What does osmotic pressure depend on if the solute is an electrolyte?
Concentration of the solute and the degree of dissociation
What maintains compartmental balance of body fluid distribution?
Blood pressure and osmosis
What flows freely between compartments that house body fluid?
water
What molecules are the main ions outside of the cell?
Na+ and Cl-
What are the main ions inside the cell?
K+ and( PO4)^2-
What does blood pressure due to liquids in compartments?
Forces liquid into the extracellular compartment
What is colloidal oncotic pressure?
Osmotic pressure including colloidal proteins
What are colloids?
Proteins in the plasm that create a protein based pressure
Where does the systolic reading come from?
It is the higher reading of blood pressure form the arterial side (pumped in so higher pressure)
Where does the diastolic reading from blood pressure come from?
The venous side (blood pumped out so pressure is lower)
What is the normal figure for body osmolality?
300 mOsmol
What can happen if an IV infusion is not isotonic?
Substantial osmotic differences that can be severe (cell swelling or shrinking)
What happens if the IV infusion is hypertonic?
Crenation of cell shrinkage
What happens if the IV infusion is hypotonic?
The cell swells and can lyse
What is directly affected by tonicity of IV solutions?
Red blood cells
can later cause tissue damage and necrosis or dying of tissues
What is the name for two solutions that have the same osmotic pressure?
Isosmotic
What is isotonic?
When a solution has the same osmotic pressure as a specific body fluid
What is the most commonly used colligative property for preparing isotonic solutions?
Freezing point
What is the accepted freezing point of blood serum and lacrimal fluid?
-0.52 C
What is the freezing point of a solution when one gram molecular weight (mole) of any non electrolyte is dissolved in 1000g of water?
1.86 C below the freezing point of water
What is osmotic pressure dependent on with electrolytes? Why?
The number of particles
Substances that dissociate have a tonic effect that increases with the degree of dissociation
(the greater the dissociation, the smaller quantity required to produce any osmotic pressure)
What is the i factor for Na+Cl- in a weak solution that is 80% dissociated?
1.8
80 particles of Na+ dissociated
80 particles of Cl- dissociated
20 particles not dissociated
=180 particles in 100 particles so 180/100 = 1.8
Why do we use freezing point for isotonicity?
Easier to measure than other properties
Why are we using molecular weights for isotonicity?
Because we are comparing unlike things so we need to use moles
What effect does dissociation have on particle numbers?
The higher the dissociation the more particles which means the less amount is needed to make osmotic pressure increase
What is the most convenient and commonly employed route of drug delivery?
Oral injestion
What is the major challenge to design oral dosage forms?
Poor bioavailability (amount of drug present in the body)
What does oral bioavailability depend on?
Aqueous solubility, drug permeability, dissolution rate
What plays a major role for many dosage forms?
Solubility
How would a drug be able to be absorbed into the body?
The drug must be present in the form of an aqueous solution at the site of absorption (fluids in the intestines are aqueous based)
What is the solvent of choice for liquid pharmaceutical formulations?
Water
What is a major problem encountered in formulation development?
Low aqueous solubility
What are most of drugs with poor solubility (low bioavailability)?
Weakly acidic or weakly basic
What is solubility?
The amount of a solid solute that can dissolve in a given solvent at equilibrium
(max amount of solute that can be dissolved in a given amount of solvent)
What is kinetic solubility?
The amount of solute in solution prior to reaching equilibrium solubility (max)
What are the steps of solubility process?
Solute-solute intermolecular bonds breakup
Solvent-solvent intermolecular bonds breakup
Solute-Solvent intermolecular bond formation
(solids is broken and then solvent and solute and solvent form bonds)
How does solvent allow binding of a solute?
The solvent creates a cavity and then brings in the solute into the cavity of solvent
When does the max amount of solute exist in solution?
At equilibrium solubility (saturation level)
What are the three forces that must be balanced to reach equilibrium of solubility?
Solvent-solvent
Solute-solute
Solvent-solute
What happens if solvent solvent attraction is greater than solvent solute attraction?
The solvent molecules will be attracted to each other and the solute will be excluded
What happens if the solute-solute attraction is greater than solvent solvent attraction?
The solvent will not be able to break the binding forces between solute molecules
What does miscibility refer to?
To a homogenous solution of a liquid (all parts of solution are identical) solute in another liquid solvent at any concentration
T/F Alcohols are miscible
True
T/F Glycerin is immiscible
False
TF Acetic acid is miscible
True
TF light mineral OIL is immiscible
True (remember oil does not dissolve easily in solvent so it would not be homogenous in a solvent)
What dielectric constant would be preferred to dissolve a nonpolar compound?
You would need a nonpolar (like intermolecular forces) solvent that has a low dielectric constant (nonpolar molecules do not carry charges)
What is dielectric property?
The ability of a molecule to store or carry a charge
What functional groups can form hydrogen bonds?
OH, NH, and SH
They are attracted to water which favors solubility
What are more soluble, Amorphous or crystalline drugs?
Amorphous solids are more soluble
What is more soluble in water? Anhydrous or hydrous?
Anhydrous (why would hydrous give up an H to make a new H bond)
TF: A drug with the lowest melting point usually has the lowest solubility?
FALSE
If it has a low melting point that means it is less stable so solubility would increase
Why are larger molecules harder to dissolve?
The solvent has a harder time making larger cavities to encircle the molecule
TF: Branching of the number of carbons will increase solubility
True
Since branching reduces the size of the molecule, it will make it easier to solvate the molecules
What happens to surface area to volume ratio when a particle becomes smaller?
The surface area to volume ratio increases
(more surface area increases which means more interactions with the solvent without having to make a large cavity to encircle it)
What must be overcome in order for a solute to be dissolved?
The intermolecular forces between the solute molecules must be overcome
What happens to solubility when the heat of a solution is high?
The solubility increases because heat was risen during the solubilization process
What can adjusting the pH of a solution with ionizable solutes do?
Improve solubility (changing pH will ionize the weak acids and bases)
What increases solubility for non-ionizable solutes?
Lowering the dielectric constant of the solvent with a co-solvent
When does solubility increase for solutions of weakly acidic drugs in terms of pH and pKa?
When pH is above the pKa (remember when pH is above pKa the weak acid will predominate meaning positive charges will be exposed)
How can water solubility of a solute be enhanced in terms of bonds?
by forming H-bonding (OH, NH, COOH, etc)
When will water solubility decrease in terms of carbon atoms in solute?
With an increase in the number of carbon (nonpolar) atoms in the solute
What happens to solubility when the melting point of a solute increases?
Solubility decreases since the higher the melting point the more stable interactions their are so it cannot dissolve
How can you reduce particle size to increase solubility?
Micronization and nanonazation
What modifications are made to crystalline forms to increase solubility?
Create polymorphs, amorphous forms, and cocrystallization
What are the three physical modifications that can be made to a drug to increase the solubility?
Particle size reduction
Modification of crystalline structure
Dispersion systems
What chemical modifications can be made to increase solubility?
Change pH, Use of buffer, Derivation, Complexation, and salt formation
What is a solid dispersion?
Mixture of a solid drug with diluents (carrier)
What does a solid dispersion consist of?
A hydrophilic carrier and a hydrophobic drug
How are inclusion complexations formed?
Insertion of a nonpolar molecule into a cavity (cavity is hydrophobic and outer layer is hydrophillic) of another molecule or group of molecules
What are cosolvents?
water-miscible organic solvents
What do cosolvents do for solubility?
They are lipophilic in nature and enhance aqueous solubility of poorly water soluble drugs (increase solvent capacity of water)
What are liposomes?
Vesicles obtained either from natural phospholipids or synthetic ones
What are salts?
Poorly water soluble weakly acid or basic drugs with their counter ion
Does pKa change of a solute change when it is made into a salt?
No the salt will change the pH of solution to be on ionized side of pKa
What is a prodrug?
A drug with a covalently bound, inactive moiety, where the inactive moiety will be cleaved upon admin to regenerate the parent drug in the body
What is dissolution?
The process by which a solid substance enters the solvent phase to yield a solution
What is often the rate limiting process that affects bioavailibility?
Dissolution rate
What kind of reactions are involved in Dissolution?
Heterogeneous reactions
What are the processes in dissolution?
Removal of the solute from the solid phase
Accommodation of the solute in the liquid phase
Diffusion of the solute away from the solid/liquid interface into the bulk phase
What is the drug dissolution rate directly proportional to?
The drug solubility
Surface area of drug particles
The concentration gradient of the drug between the diffusion layer and bulk solution
What is the drug dissolution rate inversely proportional to?
The thickness of the diffusion layer surrounding the dissolving solid drug particles
The volume of the solution
What are the dissolution rate factors?
Physiochemical properties of the drug (size, solid phase, solubility) Drug product formulations and dosage forms (powder vs granules vs tablets, immediate vs delayed release) Manufacturing processes (tablet compression and compaction
Does an acid lose a proton or gain a proton?
Lose a proton (Proton donor)
Does a base lose or gain a proton?
Gain a proton (acceptor)
What does Ka and pKa do?
They are ionization/dissociation constants
They measure the strength of acids
How do you calculate the pH of a weak acid solution?
pH=1/2(pKa)-1/2(log concentration)
How do you get pH from H+ concentration?
pH= -(log(concentration of H+)
What is a buffer?
Aqueous solution that has the ability to resist change in pH containing a weak acid and conjugate base or weak base with its conjugate acid
What is the henderson hasselbalch equation?
pH = pKa + log (concentration of base/concentration of salt)
What is buffer capacity?
The ability of a buffer solution to resist change in pH upon addition of acid or base
(expression ofr evaluating the strength of a buffer solution)
What is the buffer capacity equation?
Beta= (change in acid or base in equivalent weight)/(change in pH)
What is the van slyke buffer capacity equation?
Beta= 2.303 C(Ka *concentration of H+)/(Ka+ concentration of H+)^2
C is the total buffer concentration (sum of the molar concentrations of weak acid/base and its salt
When does buffer capacity reach maximum?
When pH=pKa
What is the equation for buffer capacity?
Beta max= 0.575*C
What factors does buffer capacity depend on?
The value of the ratio of concentration of salt/ concentration of acid
The magnitude of the individual concentrations of buffer components
What are buffers used for in pharmaceuticals?
To control the pH of the formulated products
To optimize the physicochemical performance of the product
How does a buffer optimize physiochemical performance of the product?
Enhances solubility and stability
What buffer is only used nonsystemically due to the toxicity?
Borate
What are the factors to consider when selecting buffer system?
Toxicity for route of admin
Irritation
Odor/taste for oral
Usually the buffer capacity is less than 0.5 for pH range of 4-8
What are the steps for preparing a buffer system?
Determine optimal pH for product
Select weak acid with a pKa near the desired pH
Calculate the concentration ratio of salt to acid
Specify the desired buffer capacity of product
Calculate the total buffer concentration required to produce the buffer capacity
Determine the pH and the buffer capacity of the completed buffer solution by using a reliable pH meter or pH paper
What is an excipient?
Any substance other than the active drug or pro-drug that is included in the manufacturing process or is contained in finished dosage form
(inactive ingredients)
What are the purposes of excipients?
Protect, support or enhance stability Add bulk (increase size of form) Improve patient acceptance (flavoring) Help improve bioavailability of drug Enhance safety and effectiveness
How are excipients classified?
Origin (animal source, synthetic etc)
Pharmaceutical formulation type (solid, liquid)
Function (sweetener, etc)
What are the three types of reactions with excipients?
Drug-Excipient interactions
Excipient-excipient interactions (desirable or undesirable)
Package-excipient interactions
What do disintegrates do as excipients?
Reduce cohesive forces and speed time for tablet to break apart
What do binders do as excipients?
Impart cohesive qualities to powdered material (holds it together)
What do coating materials do as excipients?
Ease swallowing
Protection
Taste masking
Aesthetics
What do lubricants do as excipients?
They are hydrophobic and can slow dissolution (extended release)
What do glidants do as excipients?
Improve flow of powder blends in manufacturing
What do wetting agents and surfactants do as excipients?
If drug is hydrophobic, then these improve wettability and facilitate dissolution
What do salts of drugs do?
Increase solubility Increase stability Reduce toxicity Improve absorption Improve manufacturing process
What is pKa rule?
For basic drugs the pKa of the chosen counter ion should be at least 2 pH units LOWER than the pKa of the drug
For acidic pKa of counterion should be at least 2 pH units HIGHER than the pKa of the drug
What is hygroscopicity?
The ability of a material to absorb and retain moisture at various temperatures and humidity
for drugs we want low hygroscopicity
What is flowability?
The ability of a powder blend to easily flow with consistency into the manufacturing equipment
Prefer crystalline structures for flowability
What are the most common anions for injectable drugs?
Maleate, chloride, sulfate and acetate
What are the most common cations for injectable drugs?
Sodium, potassium, calcium
What are the most common anions for oral drugs?
Chloride, sulfate and maleate
What are the most common cations for oral drugs?
Sodium, potassium, calcium
What are some physical interactions for drug-excipient interactions?
Rate of dissolution
Dosage uniformity
What is a chemical interaction for drug-excipient interactions?
Formation of unstable compounds
What are some biopharm interactions for drug-excipient interactions?
Effects are observed AFTER admin
Cause alterations of rate of absorption
