drug stability

what is stability?

extent to which a product retains, within specified limits, and throughout its period of storage and use (i.e. its shelf life), the same properties and characteristics that are possessed at the time of its manufacture

what is the responsibility of the pharmacist?

• monitor for and comply with expiration dates, rotate stock, and use older products first

• observe products for instability

• properly handle drugs and drug products that require extemporaneous preparation

• package products using recommended containers and closure

• educate patients about correct storage and use of products

what are the solubilities of chlorpromazine?

• HCl: 1g/2.5mL water
• base: insoluble in water

what happens if you raise the pH of an aqueous solution of chlorpromazine HCl?

• some of the salt form of the drug would be converted into the unionized free form
• if the concentration of the chlorpromazine base exceeds its water solubility, it will precipitate

what are the effects of temperature on solubility?

decreases as the temperature of the solution decreases

why is refrigeration recommended for drug solutions?

• to increase their chemical stability and retard microbial growth
• may cause problems with precipitation
• e.g. fluorouracil, cisplatin, metronidazole, brands of aminophylline

what are efflorescent powders?

• powders contain water of hydration that may be released when powders are triturated/stored in low relative humidity
• e.g. atropine sulfate, caffeine, cocaine, codeine, sodium acetate, terpin hydrate, morphine acetate, scopolamine, hydrobromide, etc.

what are hygroscopic and deliquescent powders?

• hygroscopic drugs absorb moisture from the air
• deliquescent refers to hygroscopic powders that absorb enough moisture to dissolve and form a solution
• e.g. ammonium bromid, ephedrine sulfate, phenobarbital Na, potassium acetate, lithium bromide, CaCl, Ca bromide, epsin, etc.

what are eutectic mixtures?

• 2 or more substances that liquify when mixed at room temperature
• e.g. acetaminophen, aspirin, benzocaine, camphor, chloral hydrate, lidocaine, menthol, phenacetin, prilocaine, salicylic acid, thymol, resorcinol, phenylsacylate (salol), aminopyrine, etc.

what are solvent effects?

• 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 precipitate
• e.g. digoxin

what are polymorphic conversions?

• drugs which exist in different crystalline stucture in the solid state, although they are identical chemically in liquid and gas states

• e.g. cocoa butter

what is chemical kinetics?

• involved kinetics of stability and decomposition
• all human clinical pharmacokinetics also involved same fundamental principles and equations
• [ ], temperature, light, and catalysts play an important role

what is dc/dt?

• the rate velocity, or speed of a reaction
• dc: increase/decrease of [ ] over an infinitesimal time interval, dt

what is the law of mass action?

rate of reaction is proportional to the product of molar [ ] of reactants raised to the power usually equal to the # of molecules a and b of substances A and B undergoing reaction

what is pseudo first order reaction?

rate depends only on first power of [ ]

what are zero order reactions?

• e.g. loss of color of a drug
• change of absorbance A with time is constant
• reaction rate is independent of concentration
• in a C vs t plot, you get a straight line with slope -k, and rate is independent of C

what is half life?

• time for half of the original [ ] to disappear
• aka shelf life

how are suspensions apparent zero order reactions?

• case where [ ] in solution depends on drug's solubility
• as drug decomposes in solution, more drug is released from suspended particles, keeping the overall [ ] in solution relatively constant

why is the reservoir of solid drugs in suspension important?

for maintaining the drug's equilibrium solubility

what is apparent zero-order reaction?

when A is contant: k[A] = k_0

what is first order reaction?

• rate dependent on [ ] c
  -dc/dt = kc

what is the plot of a first order reaction?

• logC vs time

• slope = -k/2.303

what are second order reactions?

involved bimolecular reactions: occur when 2 molecules come together

what is the substitution method?

try date in equations and see which fit best

what is the graphic method/linear regression?

c vs time:

• straight line: zero order
• logc vs time: first order
• 1/c vs time: second order

what is the half life method?

each order has different equations so see which fits best

what are the effects of temperature on rate of reaction?

the speed of reactions increased by temperature, catalyts, solvents, and light

what is the decomposition of medicinal agents?

affects stability in liquid, solid, and semisolid products

what are the classifications of pharmaceutical decompositions?

hydrolysis, oxidation, isomerization, epimerization, photolysis

what drug classes are susceptible to oxidation?

• catacholamines (epinephrine)
• phenolics (morphine, phenyephrine)
• phenothiazines (chlorpromazine)
• steroids and tricyclic antidepressants
• thiols (captopril)
• amphotericin B, tetracycline, furosemide, etc.

what is the concentration dependence of each order?

zero order: -dc/dt = k0

first order: -dc/dt = kc
second order: dc/dt = k(a-c)^2

how do you determine order?

• based on half life
  zero order: c vs time
  first order: logc vs time
  second order: 1/c vs time