UNIT 2 (DRUG PRODUCT STABILITYㅡPACKAGING & LABELLING) Flashcards
- extent a product retains, within specified limits, and through its period of storage and use the same properties and characteristics that it possessed at the time of its manufacture
STABILITY
- drug molecules interact with water molecule to yield breakdown product.
- susceptible to the hydrolytic process: esters, substituted amides, lactones, and lactams
Hydrolysis
- this drug undergo hydrolysis. It combines with water molecules and hydrolysis into one molecule of salicylic acid and one molecule of acetic acid.
ASPIRIN
- loss of electrons from an atom or molecule;
- In organic chemistry, oxidation is defined as the loss of hydrogen in molecule. Meanwhile, in inorganic chemistry, oxidation is defined as the increase in the positive valence of an element.
- Involves free radicals (molecules or atoms containing one or more unpaired electrons). These radicals tend to take electrons from other chemicals, thereby oxidizing the donor.
OXIDATION
- Many oxidative changes in pharmaceutical preparation have the character of autoxidation.
- occur spontaneously under the initial influence of atmospheric oxygen and proceed slowly at first and then more rapidly
- As pharmacist in the industry like manufacturing and formulation, keeping an eye on these processes is important.
- The process has been described as a type of chain reaction commencing with the union of oxygen with the drug molecule and continuing with a free radical of this oxidized molecule participating in the destruction of other drug molecules and so forth.
Autoxidation
Five types of Stability
Chemical
Physical
Microbiologic
Therapeutic
Toxicologic
- the study of the rate of chemical change and the way this rate is influenced by concentration of reactants, products, and other chemical species and by factors such as solvent, pressure, and temperature.
Reaction kinetics
● description of the drug concentration with respect to time.
Reaction rate
be the overall order (the sum of the exponents of the concentration terms of the rate expression) or the order with respect to each reactant (the exponent of the individual concentration term in the rate expression).
Reaction order
- estimate the shelf life of a product that has been stored or to be stored under a different set of conditions.
- In other words, it is useful for estimating the shelf life at room temperature of product recommended for cold storing. So it is one way to determine the stability of the drug product.
Q10 METHOD
waterproof protective coating applied in the tablet or keeping in tightly closed container
water-labile drug
o is adding a specified volume of purified water before we dispense.
The reason of this since the drug degrade easily on water. So the moment we reconstitute, the drug’s shelf life also lessen. Therefore, it is imperative as pharmacist to inform the patients to store suspensions on refrigerator
Reconstitute
● For unstable preps: storage under refrigeration optimum stability:
pH 5 ㅡ 6
● Oxygen sensitive drugs add antioxidants:
o in aqueous preparations:
▪ Na2SO3 | NaHSO3 | Na2S2O5 | H3PO2 | ascorbic acid
o in oleaginous/ unctuous preparations:
▪ alphatocopherol, butylhydroxyanisole & ascorbyl palmitate find application
- Constant source of difficulty in preparing stable solutions of oxidizable drugs
● Trace metals form drug, solvent, container or stopper
● Trace metals form drug, solvent, container or stopper is eliminated by:
○ purification of source of contaminant
○ chemically complexing or binding metal by using specialized agents make it chemically unavailable for participation in the oxidative process. (chelating agents- Ca Disodium edetate & EDTA)
- catalyst to oxidation reactions transferring its energy (photons) to drug molecules, making the latter more reactive through increased energy capability
Light
IN SUMMARY, EASILY OXIDIZABLE DRUGS MAY BE STABILIZED IN FORMULATION BY:
● Selective exclusion from the system of:
o Oxygen, oxidizing agents, trace metals, light, heat, other chemical catalysts to oxidation.
● Add to create and maintain a favorable pH:
o Antioxidants, chelating agents, buffering agents
reaction between two or more identical molecules with resultant formation of new & generally larger molecule (formaldehyde)
● Process where one or more active chemical groups removed:
o Chemical decarboxylation: decomposition of RCOOH & release of CO2
o Deamination: removal of nitrogen containing group from organic amine (ex. Insulin)
▪ These processes occur less frequently and is only peculiar or particular to only small groups of substances
Polymerization