Pharmaceutics I - Exam 3, Antioxidants

Each active ingredient in the formalation should retain its _______________ and _______________, with specified limits. Certain drugs may exhibit instability due to their propensity to become oxidized.

Chemical integrity

Labeled potency

____________ is the combination of a substance with oxygen to form an oxide, resulting in the loss of electrons.

Oxidation

In this reaction, which substance is oxidized and which is reduced?

2H2 + O2 -> 2H2O

H is oxidized

O is reduced

_______________ is a common degradation process for many organic molecules.

Spontaneous oxidation during exposure to air

Oxidation may manifest as changes in product _________, _________, _________, and/or slight loss of ____________.

Odor

Taste

Appearance

Activity

______________ occurs due to hydrogen ion/electron loss.

Oxidation

______________ occurs due to hydrogen ion/electron gain.

Reduction

_________________ is the spontaneous oxidation under normal conditions of preparation, packaging, and storage.

Auto-oxidation

Auto-oxidation involves. series of free chain radical reactions, including _____________, ____________, and ______________.

Initiation

Propagation

Termination

_______________ is a chemical species with one or more unshared electrons in its outer shell.

Free radical

_____________ are substances that prevent or inhibit oxidation and are added to dosage forms to protect susceptible components from oxidative chemical degradation.

Antioxidants

________________ are organic compounds that can form complexes with metal ions, thereby inactivating those ions in the oxidation process.

Chelating agents

The presence of ___________, ____________, ____________, and ___________ affect the rate of oxidation.

Oxygen

Light

pH

Temperature

The process of oxidation begins with the formation of a free radical due to the loss of a __________. The free radical then interacts with molecular oxygen to form a ___________________. A chain reaction is propagated by the interaction with another organic molecule and continues until ______ is consumed.

Hydrogen atom

Peroxy free radical

Organic molecule

The alteration of oxidation with light is called _____________, ____________, or ________________.

Photolysis

Photodegradation

Light-catalyzed oxidation

What does this equation describe?

RH + hv -> H + R

Photodegradation

As the wavelength of light (decreases/increases), the energy produced when light is absorbed is (decreased/increased), resulting in more rapid photochemical reaction.

Decreases

Increased

As pH is increased, the oxidation potential of a system (decreases/increases).

Increases

T/F: Reductions in pH diminish loss of a proton from the organic compound.

True

Many oxygen-sensitive compounds are formulated at (lower/higher) pH values.

Lower

(Lower/higher) temperature lessens the probability of catalyzing a free radical formation.

Lower

There are many measures that can be taken during compounding to prevent or minimize oxidation: use _________ water, add ______________ to the preparation as early as possible, _____________ mixing method, replacement of air with _______ prior to mixing, adding a buffer to maintain _________, use ingredients with __________ content, and decrease ______________ during preparation.

De-aerated

Antioxidants

Air-free

N2

Low pH

Low heavy-metal content

Temperature

To prevent/inhibit oxidation, an antioxidant must...

Prevent or interfere with initiation or propagation

Cause termination

Metal ions act as oxidation _____ as unshared electrons occur in their outer shell.

Initiators

0.0002 M copper has been shown to (decrease/increase) the rate of absorbic acid oxidation by a factor of 10,000 compared to the absence of copper.

Increase

____________ inhibit oxidation by complexing metal ions that catalyze oxidation reactions

Chelating agents

Chelating agents such as ________, _________, and __________ act by binding metal ions through complexation.

Edetic acid

Citric acid

Tartaric acid

Antioxidants are added to ____________ pharmaceutical products and ____________-compounded preparations when the product/preparation contains an ingredient, either active or excipient, that is subject to chemical ____________ by oxidation

Manufactured

Extemporaneously

Degradation

Addition of antioxidants to compounded preparations should take into account:

Ingredients subject to degradation

Dosage form

Route of delivery

Packaging

Anticipated storage conditions

Use and BUD desired

What is the most common approach for handling non-sterile preparations subject to oxidation? What is this approach not commonly used for?

Non-sterile preparations

IV admixtures

When handing drugs subject to oxidation, antioxidants that prevent or inhibit oxidation by acting as _____________ or ____________ should be added.

Oxygen scavengers

Reducing agents

In general, antioxidants are used in relatively (low/high) concentrations. The (lowest/highest) concentration should be used.

Low

Lowest

What is the usual concentration range of antioxidants added?

0.001% to 0.2%

Selection of an appropriate antioxidant depends on...

Solubility

Location of the agent in the formulation

Toxicity

Irritation

Efficacy at low concentrations

T/F: The ideal antioxidant is only effective at high concentrations.

False

T/F: The ideal antioxidant is stable under normal use conditions.

True

T/F: The ideal antioxidant is insoluble at the required concentration.

False

T/F: The ideal antioxidant is only compatible with particular drugs and excipients.

False

T/F: The ideal antioxidant is available in different colors and flavors.

False

What are the antioxidants used for aqueous systems, or the water-soluble antiboxidants?

Absorbic acid

Sodium bisulfate

Sodium metabisulfate

Sodium thiosulfate

What are the antioxidants used for oil systems, or the water-insoluble antioxidants?

Ascorbyl palmitate

Butylated hydroxanisole

Butylated hydroxyoluene

Propyl gallate

Tocopherol

How can preparations by protected from light?

Use of light resistant containers

Enclosure of drug containers with light-resistant wrapping

What are the strategies for handing drugs subject to oxidation?

Addition of antioxidants

Protection from light

Addition of metal chelating agent

Use of acidic solutions

Avoid high temperatures

Chelating agents are not usually used for _________________.

IV admixtures

The (lower/higher) the pH of a solution, the less the oxidation-reduction potential, and the greater resistance of the drug to oxidation.

Lower

Some pharmaceutical preparations are formulated at a pH less than ___________ to take advantage of oxidative stability.

3.5

(Higher/lower) temperatures can cause an acceleration of degradation of antioxidants present in the formulation.

Higher