Solubility Flashcards
explain the energy in bond breaking
requires energy and will absorb heat
describe the energy of bond making
releases energy and heat
what is the general dissolution net effects
absorb heat
positive heat of solution
increase in temperature
is solubility of substance at stated temp constant?
yes
what does solubility of ionizable functional groups depend on
pH
explain solubility of weak acid barbiturates
water soluble salts in alkaline
acidic ph causes free form to come out of solution, much less soluble
both cation and anion monovalent
soluble
one ion in a salt is monovalent
soluble
both cation and anion multivalent
limited water solubility
salts of alkali metals and ammonia
water soluble
nitrates, sulfates, halides
water soluble
hydroxides and oxides salts
not water soluble except for alkali metals and ammonium
phospahtes, carbonates, silicates, borates
insoluble excpet for salts of alkali metals and ammonium
molecules with polar functional group soluble up to how many carbons
5
branched or straight chained molecules more soluble?
branched
increased molecular weight effect on solubility
decreases solubility
why is water solubility desirable in liquid dose from
dose of drug is in reasonable volume
which dose forms do you want reduced solubility
suspensions
organoleptic reasons- mask taste
sustained release
when is a drug considered highly soluble
highest dose strength soluble in <250ml water over a pH range of 1-7.5
when is a drug considered highly permeable
when extent of absorption is >90% of administered dose
class 1 drug
soluble and permeable
class two drug
rate limiting step is solubililty
class 3 drug
rate limiting step is permeability
class 4 drug
no solubility or permeability
how do you determine what dose:solubility ratio must be
less thn the fluid volume of where it is being administered
eyedrop d:s
less than 0.02ml
nasal d:s
less than 0.3ml
how is solubility related to ionization
ionized- water soluble
unionized- insoluble
what is the target ph for a formulation
+/- 1 ph unit from ph of max solubility
what is a salt
ionizable drug with ionizable counter ion of opposite charge
whats the most common reason for using a salt form
enhanced solubility leadin to improved bioavailability
what should you consider for counter ion selection
pka of conjugate base should be greater than the conjugate acid
common ion effects
hygroscopicity
what is hygroscopicity
ability to absorb moisture from the air
what is the common ion effect
adding ions common to the solid will shift the equilibrium back towards the solid and reduce it solubility
why is dissolution of salt faster than the parent drug
salt can act as its own buffer in the diffusion layer
what cosolvents can be used to increase solubility of parenteral drugs and reduce water content to prevent hydrolysis
glycerin, alcohol, propylene glycol, polyethylene glycol
define dielectric constant
ability of solvent to keep twp charges separate
in a mixed solvent how do you determine the dielectric constant
multiply volume fraction of each solvent bys its dielectric constant and add them all
what do most cosolvent cause
local irritation
hemolysis
tissue damage
what cosolvents do opthalmic products contain
glycerin
polyethylene glycol
propylene glycol
what is the cause of phlebitis
dilution of product prepared with cosolvents given as iv and drug comes out of solution
how do cosolvents affect reaction rates
shifr equilibrium between reactants and transition state
if the transistion state created by cosolvent is more ionized than reactants how does the cosolvent affect the reaction rate
increasing the polarity of the solvent will increase reaction rate, decreasing the polarity of the solvent will decrease the reaction rate
what are surfactants
molecules with polar and non polar regions
what is the critical micelle concentration
concentration of surfactant when soluble micelles form
what surfactants are used in parenterals
tween and cremophor
what do complexing agents do
incorporate with drug so outer hydrophilic groups of the agent interact with water and make the whole complex soluble
what are cyclodextrans
molcules with 6,7,8 glucopyranoside units joined through 1-4 bonds
what is cyclodextrin used for
complexes with lipid soluble drug molecule on the inside to make the whole complex soluble
