Drug Stability - intro to pharm

the extent to which a product retains, within specified limits, and throughout its period of storage and use (shelf life), the same properties that is processed at the time of its manufacture

definition by USP

drug stability

a pharmacist must watch out and comply to USP recommendations by

1. expiration dates

2. rotate stick

3. use older products first

what should you be cautious of when dealing with CHLORPROMAZINE?

pH

• chlorpromazine HCl is more soluble in water than chlorpromazine base

KEEP pH LOW SO STAYS AS ACID

what happens to solubility of a drug as the temperature decreases?

temp increase = solubility increase

temp decrease = solubility decrease

what effect does refrigeration have on drug stability?

increase

does refrigeration cause or block microbial growth?

block

what problem arises with refrigeration?

precipitation

why can’t parenteral drugs be refrigerated?

precipitation

what is special about efflorescent powder?

contain waters of hydration that are released when powders are triturated (ground) or stored in low relative humidity

hygroscopic powders that can absorb enough moisture to dissolve and form a solution

deliquescent powder

_____________ drugs absorb moisture from the air

hygroscopic

two or more liquids that liquefy when mixed at room temperature

eutectic

when a drug is dissolved in a solvent and a second solvent, one in which the drug is poorly soluble is added, the drug may ____________________

• list an example

precipitate

shouldn’t be diluted

digoxin

Polymorphic conversion:

drugs that exist in different __________ structures in the _____ state, although they are identical chemically in liquid and gas states

crystalline solid

What can impact chemical kinetics?

1. concentration

2. temperature

3. light

4. catalysts

what does dC / dt represent?

change in concentration / change in time

rate of reaction

According to the law of mass action the rate of the reaction is proportional to…

the product of molar concentration of reactants raised to the power usually equal to the number of molecules of a and b substances A and B undergoing reaction

basically

reaction rate = [A]^ax [B]^b

aA + bB +cC = products

the rate of reaction is

-1/a x d(A)/dt

-1/b x d(B) /dt

= K [A]^a [B]^b

rate constant

k

overall ORDER of the reaction

(a+b)

if

a=1

b= 1

what is the order of the reaction?

SECOND ORDER bc/ order = (a+b) = 1+1 = 2

what is meant by PSUEDO first order

if technically both reagents effect the products BUT one reagent is MUCH more prevalent than the other and another CHANGES throughout the reaction

PSUEDO first order

k [more prevalent reagent that DOESNT change]

loss of color is experienced in which order reaction?

zero

A_t =A₀ - K₀t

C= C_o - kt

zero order reaction

what is the slope of zero order reactions

-k

the rate is independent of C in which order reaction?

zero

which order reaction?

Zero

Which order reaction?

First

what is the half life equation for first order reactions?

what is half life / period?

the amount of time it takes for half the original concentration to disappear

how do you find the rate (k) for zero-order reactions if given the initial concentration and concentration after time t?

A_t-A_{0 ⁼} -k_o t

k= - (A_t - A₀) /t

half life equation for zero order equations (HOURS)

t_0.5= 0.5A₀ / k₀

which order are suspensions?

APPARENT zero order

Suspensions:

• ________ order reactions

• the concentration of solution depends on the drug’s ______________

• as the drug decomposes in solution, more drug is released from suspended particles, keeping the overall concentration in solution relatively ___________________

• the ________________ of solid drug in suspension is important to maintaining the drug’s equilibrium solubility

• APPARENT zero

• solubility

• constant

• resovoir

what plays a key role in maintaining a drug’s equilibrium solubility?

solid reservoir

as it dissolves it keeps levels fairly constant

what is the reaction rate of suspensions?

k₀ = k [A]

what is the reaction rate of aspirin?

solubility = 0.33 g/100mL

first-order rate constant for degradation =

4.5 × 10^-6

concentration in suspension = 6.5 g / 100mL

k₀ = k [A]

k₀ = (4.5 × 10^-6 sec-1) (6.5 g/ 100 ml) =

1.5 × 10^-6 g / 100 ml sec_^-1

what equation do you use to find how long it would take for a drug to get to a certain percentage?

C_t = C₀ - kt

t= (C₀ -C) / k

t= (percentage of degradation as decimal) (initial concentration) / k

given:

k₀ = 1.5 × 10^-6

concentration = 6.5 g / 100mL

find: shelf life = time it takes for 90% to have disappeared

t= (Co - C ) / ko

t = 0.10 (6.5) / 1.5× 10^-6

t= 5 days

use 0.10 because that’s HOW MUCH CONCENTRATION YOU HAVE LEFT IT 0.90 IS USED UP

in which order reaction is the rate dependent on Concentration C?

first order

ONLY ONE FACTOR DETERMINES RATE

are solutions or suspensions first order?

solutions

how fast the DRUG dissolves (rate depends on drug)

what is the rate for first order reactions? (both equations)

k= (2.303 / t ) (log ( Co / C ))

OR

C = C₀ e^-kt

how to find the concentration of a drug in a SOLUTION after t time ?

C = C₀ e^-kt

half life equation for first order reactions?

t1/2 = 0.693 / k

ln2 / k

A linear plot of _________ vs _______ for first order reaction

logC vs time

what is the slope of a linear first order reaction with logC (Y) vs time (X)

-k /2.303

find half life of first order if

C0 = 500

C = 300

t= 40 days

k= (2.303 / 40) (log 500/300)

k = 0.013

half life = ln2 / k

ln2 / 0.013 = 54.3 days

what order reaction involves biomolecular reactions which occur when 2 molecules come together

2nd order

rate of reaction of second order reactions

k= k[A][B]

if a = initial concentration of A

and b = initial concentration of B

and a=b

and x= concentration in time t

then k=

k= k (a-x)²

what is the equation for k for second order reactions?

2.303 / t(a-x) x log b(a-x) / a(b-x)

what is the half life of second order reactions?

1/ak

what are three ways you can figure out what order a reaction is in?

1. substitution method

2. graphic method

3. half life method

how can you use the substitution method to find out which order reaction you have?

substitute the numbers of your experiment into the different equations and see which one fits

Zero order: C=Co-kt

First order: C= Coe^-kt or 2.303/t x log (C0/C)

Second order = k= 2.303/t(a-x) (log b(a-x) / a (b-x ))

how can you use the graphic method to find out which order reaction you have?

check if the following give you a linear relationship (straight line)

• zero order: concentration vs time

• first order: log concentration vs time

• second order: 1/c vs time

a linear relationship between 1/c vs time is what order reaction?

second order

how can you use the half life method to find out which order reaction you have?

each order has different equations for half-life

• zero order: t= 0.5 C₀ / k_{0 ^{(in hours)}}

• first order: ln2/k

• second-order: 1/ak

  (a=initial concentration of A and B)

what can increase the speed of a reaction?

1. temperature

2. catalysts

3. solvents

4. light

the ______________- equation describes the effect of temperature

arrhenius

K = Ae^-Ea/RT

or logK = logA- Ea/2.203 × 1/RT [Ae^-Ea/RT]

are both the _____________ equation which explain the effect of __________ on the rate of a reaction

Arrhenius

effect of temperature on rate of reaction

pharmaceutical decomposition can be classified as:

all aid in stability

• hydrolysis

• oxidation

• isomerization

• epimerization

• photolysis

• zero order: -dc/dt =

• first order: -dc/dt =

• second order: dc/dt =

• ko

• kc

• k(a-c) _²

if you have a large undissolved reservoir in a suspension with ALOT of solvent which order is the reaction? why?

zero

there will be equilibrium as the reservoir will slowly continue to change in a large body of solvent

will hardly notice the change

if a reservoir of a suspension is exhausted, what order is the reaction? why?

first

concentration of drug will change reaction as mostly all of it dissolves since reservoir is small

if you have a small amount of solvent in a suspension what order is your reaction? why?

second order

both the solvent and drug will make a difference unlike if the solvent was large