Exam 1 Definitions and Concepts 1-4 Flashcards
pharmaceutics
- discipline of pharmacy that deals with the science of dosage form design and the process of turning a new chemical entity into a medication that can be safely and effectively used
- art and applied science
- interface between drug and body
pharmacodynamics
drug action and mechanism on the body
pharmacokinetics
body acting on the drug
absorption, distribution, metabolism, excretion
absorption
variety when people have health issues, oral vs. IV injection
distribution
benign cancer local vs malignant cancer being in many sites
metabolism
all food and drugs undergo it
*liver
*prodrugs
excretion
removal from body, may want to extend time
*kidney
chemical
a substance composed of chemical elements
drug
- substance recognzied by an official pharmacopoeia or formulary
- substance intended for the use in diagnosis, cure, mitigation, treatment, or prevention of disease
- intended to affect the structure or any function of the body
drug product
finished dosage form that contains a drug substance, generally, but not necessarily in association with other active or inactive ingredients
dosage form
physical form in which a drug is produced and dispensed
active ingredient
- component intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease
- affects the structure or any function of the body
- causes medication’s desired effect
inactive/inert ingredient
any component of a drug product other than active ingredient
*dyes, preservatives, and flavoring agents
brand drug
when the FDA approves a drug for the first time, there is only one manufacturer that makes and sells a drug
generic drug
produced after the brand name drug’s patent has expired, also must be approved by the FDA
over the counter drugs
can be dispensed without a prescription
prescription/legend drug
can only be dispensed with prescription from a licensed HCP
ex. estrogen
for: hormone replacement therapy for treatment of symptoms of menopause
molecules administered: conjugated estrogens, estradiol, estrone
dosage forms: tablets, transdermal patch, transdermal gel, vaginal ring
tablet
- compressed contains micronized estradiol
- micronization to improve dissolution
- may have high first pass effect
transdermal patch
- bypasses first-pass metabolism
vaginal ring
- topical application for local symptoms
dosage forms for safe and convenient delivery of accurate dosage
tablet, capsule syrup
dosage forms that protect a drug from chemical degradation, usually due to atmospheric oxygen or humidity (increase shelf life)
coated tablets, sealed ampoules
dosage forms that provide protection of drug form influence of gastric acid and saliva after oral administration
enteric coated tablets
dosage forms that mask taste of expensive drugs
capsules, coated tablets, flavored syrups
dosage forms that provide liquid preparation, even for drugs that are either insoluble or unstable
syrups, suspensions
dosage forms that provide injectable dosage forms with the correct composition (tonicity and pH) for compatibility with surrounding tissue
injections
*sterility and stability
dosage forms that provide slow or targeted release of drug
implants
dosage forms that provide optimal topical administration
creams, ointments, ophthalmic, ear, nasal
dosage forms that provide the optimal characteristics for the insertion of a drug into one of the body’s orifices
rectal and vaginal suppositories
dosage forms that provide the requirements for inhalation of drugs to the lung
inhalants
classes of pharmaceutical dosage forms, according to the overall physical properties of dosage froms
gaseous
liquid
semisolid
solid
gaseous dosage froms
medicinal gases
aerodispersions
medicinal gases
inhalation/volatile anesthetics (vaporized before admin by inhalation)
aerodispersions
solid particles or liquid particles
liquid dosage forms
solutions
emulsions
suspensions
solutions
prepared by dissolving one or more solutes in a solvent
*very small particle size
emulsions
a dispersion system consisting of 2 immiscible liquids
*oil in water or water in oil
suspensions
dispersion system where solid particles are dispersed in liquid phase
*larger particle size
*not intended for systemic admin of drugs with high potency
semi solids
gels
creams
ointments
pastes
*unshaped
gels
semisolid system in which a liquid phase is contained within a 3D cross-linked matrix
creams
semisolid emulsion systems (O/W, W/O), >10% of water
- O/W creams are more comfortable and cosmetically acceptable as they are less greasy and more water washable
- W/O creams accommodate and release better lipophilic API, moisturizing, cold creams
ointments
semisolid dosage forms with the oleaginous (hydrocarbon), water-soluble or emulsifying base
*oleaginous base- petrolatum (Vaseline)
*water soluble base- PEG
pastes
semisolid dispersion system, where solid particles are dispersed in ointments
*mostly oleaginous
shaped semi solids
suppositories (rectal)
*diff shapes
*melt/dissolve at body temp
*oleaginous (cacao butter, adeps neutralis) or aqueous (PEGs, glycerinated gelatine)
pessaries (vaginal)
*similar as above
*PEGs or glycerinated gelatine are often used as base
solid dosage forms
unshaped- powders
shaped- tablets, capsules, implants, transdermal patches
systemic admin
PO
sublingual and buccal
rectal
parenteral
transdermal
inhallation
local admin
topical on skin or mucosa (eye, nose, ear, mouth, vagina, rectum, bronchi, skin)
local pareneral
generations of dosage forms
1st gen- immediate release of API
2nd gen- controlled release of API (CR)
3rd gen- targeted distribution of drug delivery systems
1st gen dosage forms
- disintegration of dosage form and dissolution of API is spontaneous
- absorption and distribution is based only on physiochemical properties of API
2nd gen dosage forms
- release of API is under control of drug delivery system (temporal control)
- advantages: avoids fluctuations of plasma drug conc for safety and efficacy, decreased frequency of drug admin for better compliance, may overcome some problems with BAV, can be more economical
-SR- release of initial API and futher prolonged release
-CR- properly controlled release of API - pulsatile release- think diabetes devices
targeted drug delivery
drug delivery system provides altered PK profile, targeting drug to particular organ/tissue
*improved selectivity of action
*can overcome unfavorable PK properties
*improved efficacy
*improved tolerability/decreased toxicity
passive targeting
passive accumulation of drug at site of pathology due to the leaky vasculature and poor venous/lymphatic drainage, solid tumors draw more blood and may have larger pores
active targeting
drug delivery system with specific ligand with high affinity to receptor exposed selectively on the target cells
possible inert ingredients
anti-adherents
binders
coatings (change dissolution rates)
disintegrants
fillers/diluents
flavors and colors
glidants and lubricants (prevent aggregation)
preservatives
sorbents (so can be ok with some moisture)
sweeteners
cost to get one new medicine onto the market
$500-800 million
how many years to make a drug
12-15
how many out of 5,000 that enter preclinical testing make it to human testing
5
preclinical phase
research and development
clinical phase
also research and development, includes phases 1-3
postmarketing
surveillance, adverse reaction reporting, survey sampling, inspections
thermodynamics
describes the changes in the form of energy when a reaction occurs
*ex. converting chemical energy to heat
*will the reaction occur or not? feasible with stable product
*Ea (activation energy)
kinetics
describes the speed at which a reaction occurs
*rate and mechanism of action
*state functions (delta G, H, S,E)
first law of thermodynamics
energy is conserved, it can be neither created nor destroyed
second law
in an isolated system, natural processes are spontaneous when they lead to an increase in disorder, or entropy
third law of thermodynamics
the entropy of a perfect crystal is zero when the temperature of the crystal is equal to absolute zero
steady state
state in which the concentration, pH, etc. do not change with time
equilibrium
describes a state in which the concentrations of reactants and products do not change with time
*reactions occurring at same rate in forward and reverse
pharmaceutical equilibrium
solubility, pH, complexation, protein binding, partition equilibria
state of the system
can be completely described by specifying four thermodynamic variables
*composition, temperature, pressure, and volume
BUT if system is homogenous only need 3 (no composition)
equation of state
relationship between P,V, and T
open system
a system in which both energy and matter can leave
closed system
a system in which matter is not exchanged with the surroundings
isolated system
a system in which neither matter nor energy is exchanged with the surroundings
isothermal process
a process that occurs with no exchange of heat
adiabatic process
a process that occurs with no exchange of heat
intensive property
a property of a system that does not depend on the size of the system, for example, temperature and density
*temperature, color, hardness, melting/boiling point, pressure, concentration
extensive property
a property of a system that does depend on the size of the system, volume for example
*mass, volume, length
internal energy (E)
the sum of the kinetic and potential energies
kinetic molecular theory
temperature of an ideal gas is directly proportional to the average kinetic energy of its molecules
internal energy of an ideal gas is directly proportional to
the temperature of the gas
enthalpy
heat
at constant pressure, change in Esys=
change in H
the heat given off or absorbed when a reaction is run at constant volume is equal to
the change in the internal energy of the system
*change in Esys=qv (constant volume)
the heat given off or absorbed when a reaction is run at constant pressure is equal to
the change in the enthalpy of the system
*change in Hsys=qp (constant pressure)
the difference between delta E and delta H is _ for reactions in condensed phases (liquids and solids)
negligible
*because there is little if any change in the volume of the system during the reaction
to change the internal energy of a system must be accompanied by
transferring either heat or work to its surroundings
exothermic _ heat
gives off
are their spontaneous reactions that absorb energy?
yes- water boils spontaneously even though rxn is endothermic
change in Ssys > 0 implies that the system becomes _ disordered during the reaction
less
volume changes, temperature changes, phase transitions, and mixing components all lead to
a change in disorder
number of microstates
our ability to know exactly where each molecule is
at a phase change _ changes abruptly
entropy
standard state conditions
standard pressure = 1 bar
standard temperature = 25 degrees C
solutions 1 molar
1 mole of a gas
liquids and solids in pure state
standard-state entropy of reaction
when change in entropy is measured under standard-state conditions
enthalpy
H, heat gained by the system
entropy
S, change in the disorder of a system
spontaneous reactions must _ or _
give off energy in the form of heat, lead to an increase in disorder
Gibbs’s free energy
combines contributions of enthalpy and entropy to define the spontaneity of a process
*state function (in terms of thermodynamic properties that are state functions)
magnitude of delta G standard tells us
how far standard state is from equilibrium
equilibrium constants change with
temperature
&Van’t Hoff
solubility
amount of solute that can be completely dissolved in solvent at a well defined temperature
driving forces of solubility
Van der Waals
ionic bonds
covalent bonds
H bonds
dipole dipole interactions
2 types of H bonds
intramolecular- H bonds within itself
intermolecular- H bonds between separate molecules
to increase solubility
increase temperature
increase surface area (crush)
increase pressure
change pH
add cosolvent
agitation of solution
alcohols
always ethyl alcohol
alcohol content allowed
peds (<6 years)- 0.5% w/v
6-12- 5% w/v
12+- 10% w/v
alcohol content allowed
<6 years- 0.5% w/v
6-12 years- 5% w/v
12+- 10% w/v
diluted alcohols
alcohol with 50% water and 50% ethanol
*100mL combines becomes 97mL because of H bonding
rubbing alcohols
70% of ethyl alcohol w/v
pharmaceutical waters
purified by distillation, ion exchange
*removing ions for higher purity
but if for injectables and ophthalmic formulations must be purified and sterile (no ions or bacteria)
cosolvents
solvent systems besides water
semi-aqueous solvents
syrups
tinctures
elixirs
syrups
Syrup NF 85% (w/v) sucrose
tinctures
higher alcoholic content than elixirs
used to extract natural products
elixirs
slightly lower alcoholic content than tinctures
for making medicated syrups
weight concentration
weight of solute in weight of solution
molarity
moles / liter of solution
*can be used for non-ionic compounds that don’t dissociate
normality
equivalents / liter of solution
*can be used for ionic compounds defined by dissociated ions used a lot for acids
molality
moles / kg solvent
mole fraction
moles of solute / total # moles
solution properties are _ than the pure solvent or the solute
different
colligative properties
properties of a liquid that may be altered by the presence of a solute
*depend only on the amount of solute in solution
*does not depend on the identify of the solute
*vapor pressure lowering, boiling point elevation, freezing point depression, osmotic pressure
non-colligative properties
depends on the identity of the dissolved solute and the solvent
*taste, color, viscosity, surface tension, solubility
osmotic pressure determines
the physiological acceptability of parenteral, ophthalmic, and nasal solutions
vapor pressor of solution _ pure solvent
<
effect on solute on vapor pressure
when a nonvolatile solute is dissolved in solvent, the vapor pressure of the resulting solution is lower than that of the pure solvent
*amount of vapor pressure lowering is proportional to the amount of solute and not its identity
boiling point elevation
colligative property related to vapor pressure lowering, solution requires higher temp to reach its boiling point
freezing point depression
disruption in the freezing process results in a depression of the freezing point for the solution relative to the pure solvent
*solute molecules disrupt the formation of crystals of the solvent
*colligative
osmotic pressure
pressure caused by solutes
isotonic
equal osmotic pressure
crenation
shrinkage of RBCs in hypertonic solution
hemolysis
burst of RBCs in hypotonic solutions
Raoult’s law
vapor pressure of a solution equals the mole fraction of the solvent multiplied by the vapor pressure of the pure solvent
P1 = P0 x X1
ideal solution
a solution that obeys Raoult’s law
* Ptotal = XaPa0 + XbPb0
calculating mole fraction
A = nA / (nA + nB)
Avogadro’s number
6.023 x 10^23
non-ideal / real solutions
solutions that show a deviation from Raoult’s law
*may be positive or negative
*negative if solute is strongly held by solvent
*positive if solute and solvent are not tightly bound
change in boiling point
boiling point of a solution made of a liquid solvent with a nonvolatile solute is greater than the boiling point of the pure solvent
*higher temp required
van’t Hoff factor
i
number of dissociated moles of particles per mole of solute
*i=1 for non electrolytes, i= number of ions released for electrolytes
*as solution concentration increases the multiplier effect diminishes
*ion pairs begin to form, 2 oppositely charged ions stick together and act as a single particle
change in freezing point
if there are impurities in a liquid, it is inherently less ordered
*a solution is more difficult to freeze than the pure solvent
osmotic tablets
have a semipermeable membrane with laser-drilled hole, osmotically active core containing drug
extensive effects on chemical potential
volume, enthalpy, free energy, entropy
intensive effects on chemical potential
temperature, density, refractive index
partial molar quantity
quantity denoting the rate of increase in the magnitude of an extensive property with an increase in the number of moles of a substance added to the system at constant temp and pressure
chemical potential of a component
contribution of each mole of that component to the free energy of the system containing it (at constant T and P)
when solid and liquid water exists in equilibrium, temperature is
0 degrees C
the chemical potential of water in the liquid _ the chemical potential of ice
equals
*same with ointment on skin, solid in aqueous solution
chemical potential relation to mole fraction
difference between chemical potential of a drug in solution and chemical potential of drug at standard state is a function of mole fraction
*u2 = u2o + RT lnx2 or lna2
activity of a solute
a2
effective concentration that reflects not only the concentration, but also any interactions that cause deviations from ideality
*ratio of asolution/areference
reference state
activity is 1
*for solvent it is pure liquid, if solid it is pure substance
for saturated solutions, the chemical potential of drug in solution equals
the chemical potential of drug in the solid
*activities are equal
Debye-Huckel theory
-logy = |z+||z-| x A sqrt(I)
*higher ionic strength reduces activity of electrolytes
*I = ionic strength
*activity coefficient of higher valence ions is affected more by addition ions
solubility
the maximum amount of solute dissolved in a solvent at equilibrium
supersaturated
a solution that contains more solute than the solvent can dissolve
* solid particles of solute may be present and solution phase will be in equilibrium with the solid
dissolution rate
rate at which drug dissolves from its solid state
*higher solubility = more rapid rate of dissolution
hydration
binding of water to solvent molecules
*solvation refers to solvent in general
increasing chain length _ solubility, branching _ solubility
decreases, increases
factors affecting solubility
nature of drug molecule
hydrophobicity
shape
surface area
state of ionization
influence of pH
pKa
intrinsic solubility
concentration of unionized drug in equilibrium with solid drug
measured/total solubility
total concentration of drug in all forms in equilibrium with solid drugs
solubility depends on
-the lattice energy of the drug crystal (higher lattice energy, lower solubility)
-hydrophobicity of the drug molecule (higher log P = more hydrophobic)
and more
miscibility
analogous to solubility for liquids in liquids
*may be complete or partial
