UNIT 2 (DRUG PRODUCT STABILITYㅡPACKAGING & LABELLING)

Question 1

• 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

Answer 1

STABILITY

Question 2

• drug molecules interact with water molecule to yield breakdown product.
• susceptible to the hydrolytic process: esters, substituted amides, lactones, and lactams

Answer 2

Hydrolysis

Question 3

• this drug undergo hydrolysis. It combines with water molecules and hydrolysis into one molecule of salicylic acid and one molecule of acetic acid.

Answer 3

ASPIRIN

Question 4

• 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.

Answer 4

OXIDATION

Question 5

• 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.

Answer 5

Autoxidation

Question 6

Five types of Stability

Answer 6

Chemical
Physical
Microbiologic
Therapeutic
Toxicologic

Question 7

• 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.

Answer 7

Reaction kinetics

Question 8

● description of the drug concentration with respect to time.

Answer 8

Reaction rate

Question 9

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).

Answer 9

Reaction order

Question 10

• 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.

Answer 10

Q10 METHOD

Question 11

waterproof protective coating applied in the tablet or keeping in tightly closed container

Answer 11

water-labile drug

Question 12

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

Answer 12

Reconstitute

Question 13

● For unstable preps: storage under refrigeration optimum stability:

Answer 13

pH 5 ㅡ 6

Question 14

● Oxygen sensitive drugs add antioxidants:

Answer 14

o in aqueous preparations:

▪ Na2SO3 | NaHSO3 | Na2S2O5 | H3PO2 | ascorbic acid

o in oleaginous/ unctuous preparations:

▪ alphatocopherol, butylhydroxyanisole & ascorbyl palmitate find application

Question 15

• Constant source of difficulty in preparing stable solutions of oxidizable drugs

Answer 15

● Trace metals form drug, solvent, container or stopper

Question 16

● Trace metals form drug, solvent, container or stopper is eliminated by:

Answer 16

○ 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)

Question 17

• catalyst to oxidation reactions transferring its energy (photons) to drug molecules, making the latter more reactive through increased energy capability

Answer 17

Light

Question 18

IN SUMMARY, EASILY OXIDIZABLE DRUGS MAY BE STABILIZED IN FORMULATION BY:

Answer 18

● 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

Question 19

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

Answer 19

Polymerization

Question 20

● Studies designed to increase the rate of chemical degradation or physical change of a drug substance or drug product by using exaggerated storage conditions as part of long-term, intermediate, and accelerated studies.

Answer 20

Accelerated testing

Question 21

The dosage form in the final immediate packaging intended for marketing.

Answer 21

Drug product

Question 22

● The unformulated drug substance that may subsequently be formulated with excipients to produce the dosage form.

Answer 22

Drug substance

Question 23

● Anything other than the drug substance in the dosage form.

Answer 23

Excipient

Question 24

● The date placed on the container label of a drug product designating the time prior to which a batch of the product is expected to remain within the approved shelf life specification, if stored under defined conditions, and after which it must not be used.

Answer 24

Expiration date

Question 25

● The time period during which a drug product is expected to remain within the approved shelf life specification, provided that it is stored under the conditions defined on the container label.

Answer 25

Shelf life (also referred to as expiration dating period)

Question 26

● Studies undertaken to elucidate the intrinsic stability of a drug substance. Such testing is part of the drug development process and is normally carried out under more severe conditions than those used for accelerated testing.

Answer 26

Stress testing (drug substance)

Question 27

● Studies undertaken to assess the effect of severe conditions on the drug product. Such studies include photo stability testing as well as the specific testing of certain product types (e.g., metered dose inhalers, creams, emulsions).

Answer 27

Stress testing (drug product)

Question 28

● Four climatic zones can be distinguished for the purpose of worldwide stability testing, as follows:

Answer 28

✔ Zone I: temperate

✔ Zone II: subtropical with possible high humidity

✔ Zone III: hot/dry

✔ Zone IV: hot/humid

Question 29

another term for drug product

Answer 29

ARTICLE

Question 30

• protects the contents from extraneous solids and from loss of the article under ordinary conditions of handling, shipment, storage & distribution

Answer 30

➔ WELL-CLOSED CONTAINER

Question 31

• protects the contents from contamination by extraneous liquids solids, or vapors, from loss of the articles, and from efflorescence, deliquescence, or evaporation under the ordinary or customary conditions of handling, shipment, storage and distribution and is capable of tight re-closure

Answer 31

➔ TIGHT CONTAINER

Question 32

• Impervious/resistant to air or any other gas under the ordinary or customary conditions of handling, shipment, storage, and distribution
• Ex. Teflon - polytetrafluoroethylene, a material used in seal out hermetic container.

Answer 32

➔ HERMETIC CONTAINER

Question 32

• one that holds a quantity of drug intended as a single dose and, when opened, cannot be resealed with assurance that sterility has been maintained
• Ex.
• Ampule - you open this container by tearing the cap. So once it was teared, it could no longer be sealed back
• single dose syringes like clexane - an anticoagulant drug use to treat a type of blood cloth, the deep vein thrombosis.
• solo Medrol vial - its container known as ACT -O vial. This is a dual components vial system that allows reconstitution of sterile injectable medication by pressing on the cap. Interestingly, the container is divided by rubber stopper where the upper part contains water and the lower part contains the powder.

Answer 32

➔ SINGLE-DOSE CONTAINER

Question 33

• hermetic container that permits withdrawal of successive portions of the contents without changing the strength or endangering the quality or purity of the remaining portion.
• referred as vials
• contain more than a single unit or dose of the medication
• Ex. Amber glass, diazepam vial, ( for anxiety) insulin pens ( for diabetes).

Answer 33

➔ MULTIPLE-DOSE CONTAINER

Question 34

• designed to hold a quantity of drug intended for administration as a single dose promptly after the container is opened
• Advantages

o positive identification of each dosage unit and reduction of medication errors

o reduced contamination of the drug due to its protective wrapping

o reduced dispensing time

Answer 34

➔ SINGLE UNIT PACKAGES

Question 35

• required by many pharmaceutical products to protect them from photochem. deterioration

▪ Meaning to say these products are sensitive to light or will degrade if they will be directly exposed to light.

• amber glass or light resistant opaque plastic will reduce light transmission sufficiently to protect a light-sensitive pharmaceutical
• UV absorbers may be added to plastic to decrease the transmission of short UV rays

Answer 35

➔ LIGHT RESISTANT CONTAINERS

Question 36

CLASSIFICATION OF GLASS USED IN PACKAGING PHARMACEUTICALS: depending upon the chemical constitution of the glass and its ability to resist deterioration:

Answer 36

I

Highly resistant borosilicate glass

II

Treated soda lime glass

III

Soda lime glass

NP

General purpose soda lime glass

Question 37

• Low Density PE: squeezable

▪ eye drops, medicine dropper, spray bottles

• High Density PE: hard-thermoset

▪ Solid dosage forms

Answer 37

Polyethylene

Question 38

• For beverages

Answer 38

Polyethylene Terephthalate

Question 39

• Made by addition of chlorine atom to every other carbon atom in the polymer chains of polyethylene.
• Characteristics: resistant to permeation, it is rigid, it has good clarity however it is not suitable for gamma sterilization.
• Blister Packaging of tablets and capsules.

Answer 39

Polyvinyl Chloride

Question 40

PROBLEMS ENCOUNTERED IN THE USE OF PLASTICS IN PACKAGING

Answer 40

➔ Permeability of the containers to atmospheric oxygen and to moisture vapor

➔ Leaching of the constituents of the container to the internal contents

➔ Absorption of drugs from the contents to the container

➔ Transmission of light through the container alteration of the container upon storage

Question 41

● considered a process of solution and diffusion, with the penetrant dissolving in the plastic on one side and diffusing through to the other side.

Answer 41

PERMEABILITY

Question 42

● movement of components of a container into the contents

● Compounds leached from the plastic containers are polymer additives as the plasticizers, stabilizers or antioxidants

Answer 42

LEACHING

Question 43

• binding of molecules to polymer materials

• absorption and adsorption are considered as a single process

Answer 43

Sorption

Question 44

o this is a process in which a fluid is dissolved by a liquid or a solid.

Answer 44

Absorption

Question 45

this is a process in which atoms or molecules from a substance adhere to the surface of adsorbents

Answer 45

Adsorption

Question 46

defined as:

o significantly difficult for children under 5 years of age to open or to obtain a harmful amount of its contents within a reasonable time

o not difficult for “normal adults” to use properly.

Answer 46

• Child-resistant container

Question 47

TERMS EMPLOYED FOR THE DESIRED CONDITIONS AS DEFINED BY THE USP:

Answer 47

• Cold

• any temp not exceeding 8°C (46˚F)
• a refrigerator is a cold place where the temp. is maintained bet. 2 °C and 8°C (36° and 46°F)

• Cool

• any temp bet. 8 ° and 15 ° C (46˚ and 59˚F)

• Room Temp.

• temp prevailing in a working area
• 20˚ to 25˚C (68˚F to 77˚F) but also allows for temp variations bet 15˚ and 30˚C (59˚ and 86˚F) experienced in pharmacies, hospitals, and drug warehouses

• Warm

• any temp bet 30˚ and 40˚C (86˚F)

• Excessive Heat λ

• any temp above 40˚C (104˚F)

Question 48

SIGNS OF DEGRADATION OF THE SPECIFIC DOSAGE FORMS MUST BE OBSERVED AND REPORTED:

Answer 48

• Tablets: Appearance (cracking, chipping, mottling), friability, hardness, color.

• Capsules: Moisture tackiness, color appearance, shape, brittleness and dissolution

o Moisture tackiness - when hard capsule gel turns to soft gel.

• Oral Solutions and Suspensions: Appearance, precipitation, pH, color, odor, dispersibility (suspension) and clarity (solutions)

• Oral Powders: Appearance, color, odor, moisture

• Metered–dose inhalation aerosols delivered dose per activation, number of metered doses, color, particle size distribution, loss of propellant, pressure, valve corrosion, spray pattern, absence of pathogenic microorganism

• Topical creams: ointments, lotions, solutions, and gels. Appearance, color, homogeneity, odor, pH, resuspendability (lotions), consistency, particle size, distribution strength, weight loss.

• Ophthalmic and Nasal and Oral inhalation preparations: Appearance, color consistency, pH, clarity (solutions), particle size, and resuspendability (suspensions, ointments), strength and sterility.

• Small Volume Parenterals: Appearance, color, clarity, particulate matter, pH volumes and extractable (when plastic containers are used), sterility, pyrogenicity and closure integrity.

• Suppositories: Softening range; appearance and melting.

• Emulsions: Appearance (such as phase separation) color, odor, pH, and viscosity.

• Controlled release membrane drug delivery systems: seal strength of the drug reservoir, decomposition products, membrane integrity, drug strength and drug release rate.