IPS1 - [Introduction] - Physical and Chemical Properties of Drug Substances

Proverbs 16:3

Drug

This refers to any article or agent that is used for diagnosis, mitigation, treatment, prevention and cure of diseases in man and in animals.

Diagnosis

The process of DETERMINING the disease by examining and identifying its signs, symptoms, and cause.

Mitigation

The process of ALLEVIATING, LESSENING, or EASING the severity or effects of a disease or condition.

Treatment

The process of MAKING SOMEONE HEALTHY AGAIN through proper medical care or interventions.

Prevention

The process of STOPPING a disease or condition from occurring or spreading.

Cure

The process of RELIEVING symptoms and completely removing the disease or condition.

Dosage Forms

These are PREPARATIONS designed to contain a specified quantity of medication for ease and accuracy of dosage administration.

Dosage Forms

These are drug products containing:

● Active Pharmaceutical Ingredients (API)/Drug - the one that exerts therapeutic effects

● Non-Active Ingredients/Excipients/Additives/Adjuncts - non-drug substances which are usually inert

● Active Pharmaceutical Ingredients (API)/Drug - the one that exerts therapeutic effects

● Non-Active Ingredients/Excipients/Additives/Adjuncts - non-drug substances which are usually inert

Dosage Forms are drug products containing: [2]

● Excipients

● Additives

● Adjuncts

Non-Active Ingredients are also known as [3]

Active Pharmaceutical Ingredients (API)/Drug

The one that exerts therapeutic effects.

Non-Active Ingredients/Excipients/Additives/Adjuncts

These are non-drug substances which are usually inert.

● Physical Description

● Particle Size

● Partition Coefficient & Dissociation Constant

● Polymorphism

● Solubility

Physical and Chemical Properties of Drug Substances [5]

Physical Description

[PHYSICAL AND CHEMICAL PROPERTIES OF DRUG SUBSTANCES]

Substances may exist in different states of matter such as SOLID, LIQUIS, or GAS.

Physical Description

[PHYSICAL AND CHEMICAL PROPERTIES OF DRUG SUBSTANCES]

The PURITY of the chemical substance is essential for its identification and for evaluation of its chemical, physical and biological properties.

Physical Description

[PHYSICAL AND CHEMICAL PROPERTIES OF DRUG SUBSTANCES]

This includes CHEMICAL, PHYSICAL, and BIOLOGICAL properties of drug substances.

Chemical Property

[PHYSICAL DESCRIPTION]

This property refers to the STRUCTURE, FORM, and REACTIVITY of the compound.

● Structure

● Form

● Reactivity

[PHYSICAL DESCRIPTION]

Chemical properties include [3]

Physical Property

[PHYSICAL DESCRIPTION]

This property encompasses PHYSICAL DESCRIPTION, PARTICLE SIZE, CRYSTALLINE STRUCTURE, MELTING POINT, and SOLUBILITY of the compound.

● Physical description

● Particle size

● Crystalline structure

● Melting point

● Solubility

[PHYSICAL DESCRIPTION]

Physical properties include: [5]

Biological Property

[PHYSICAL DESCRIPTION]

This property refers to the ability of the compound to get to the SITE OF ACTIONS and ELICIT RESPONSE.

Particle Size

[PHYSICAL AND CHEMICAL PROPERTIES OF DRUG SUBSTANCES]

This property influences the:

● Dissolution rate

● Bioavailability

● Content uniformity

● Taste

● Texture

● Color

● Stability

● Flow properties

● Sedimentation rates

● Dissolution rate

● Bioavailability

● Content uniformity

● Taste

● Texture

● Color

● Stability

● Flow properties

● Sedimentation rates

[PHYSICAL AND CHEMICAL PROPERTIES OF DRUG SUBSTANCES]

Particle Size influences the following properties:

Dissolution

[PARTICLE SIZE]

• The RATE LIMITING STEP in the absorption process

• Affects onset, intensity and duration of response and control the overall bioavailability of the drug from the dosage form.

Bioavailability

[PARTICLE SIZE]

The PROPORTION of a drug or other substance which enters the circulation when introduced into the body and so is able to have an active effect.

Content Uniformity

[PARTICLE SIZE]

The EQUIVALENT amount of active pharmaceutical ingredient (API) or drug substance present in each dosage unit, as confirmed through qualitative assessment or quantitative testing.

Flow Properties

[PARTICLE SIZE]

These properties may be free-flowing (move easily) or cohesive (stick together).

● Free-flowing

● Cohesive (sticky)

[PARTICLE SIZE]

Flow Properties may be:

Sedimentation Rate

[PARTICLE SIZE]

The TIME it takes for POWDERS in a suspension to SEPARATE and settle at the bottom of the container.

Polymerization

[PARTICLE SIZE]

This refers to the structural state of the material, whether CRYSTALLLINE (ordered) or AMORPHOUS (disordered).

● Crystalline

● Amorphous

[PARTICLE SIZE]

Polymerization of substances can be [2]

Solubility

[PARTICLE SIZE]

The ability of a drug to DISSOLVE in a solvent, often measured in water for therapeutic purposes.

Partition Coefficient

[PHYSICAL AND CHEMICAL PROPERTIES OF DRUG SUBSTANCES]

• A measure of a drug's LIPOPHILIC property

• Describe how the drug distributes itself between two immiscible phases (commonly oil/lipid and water).

Dissociation Constant (pKa)

[PHYSICAL AND CHEMICAL PROPERTIES OF DRUG SUBSTANCES]

The EXTENT of IONIZATION of a drug, which has a strong effect on its absorption, distribution, and elimination.

Polymorphism

[PHYSICAL AND CHEMICAL PROPERTIES OF DRUG SUBSTANCES]

This property is affected by MELTING POINT and SOLUBILITY.

● Melting point

● Solubility

[PHYSICAL AND CHEMICAL PROPERTIES OF DRUG SUBSTANCES]

Polymorphism is affected by [2]

Solubility

[PHYSICAL AND CHEMICAL PROPERTIES OF DRUG SUBSTANCES]

This property is affected by PARTICLE SIZE and pH.

● Particle size

● pH

[PHYSICAL AND CHEMICAL PROPERTIES OF DRUG SUBSTANCES]

Solubility is affected by [2]

Stability

This is defined as the EXTENT to which a product RETAINS, within specified limits, and throughout its period of storage and use, the SAME PROPERTIES and characteristics that it possessed at the time of its manufacture.

● Chemical

● Physical

● Microbiological

● Therapeutic

● Toxicological

Five types of Stability

Chemical

[TYPES OF STABILITY]

Each active ingredient retain its chemical integrity and labeled potency, within specified limits.

● Select proper storage conditions

● Select proper container

● Anticipate drug interaction when mixing

[TYPES OF STABILITY]

Key considerations in chemical stability [3]

Physical

[TYPES OF STABILITY]

The original physical properties, including appearance, palatability, uniformity, dissolution and suspendability are retained.

● Appearance

● Palatability

● Uniformity

● Dissolution

● Suspendability

[TYPES OF STABILITY]

Physical properties that should be retained include [5]

Microbiological

[TYPES OF STABILITY]

Sterility or resistance to microbial growth is retained. Antimicrobial agents that are present and effective within specified limits.

Therapeutic

[TYPES OF STABILITY]

The therapeutic effect remain unchanged.

Toxicological

[TYPES OF STABILITY]

No significant increase in toxicity occur.

● Hydrolysis

● Oxidation

● Polymerization

● Decarboxylation

● Deamination

Mechanisms of Degradation [4]

Hydrolysis

[MECHANISMS OF DEGRADATION]

A solvolysis process in which drug interact with water to yield breakdown products of different chemical constitution.

● Replace water with solvents

● Use buffering agent

● Refrigeration

● Reconstitution

[MECHANISMS OF DEGRADATION]

Prevention strategies for HYDROLYSIS [4]

● Glycerin

● Propylene glycol

● Alcohol

[MECHANISMS OF DEGRADATION]

HYDROLYSIS

Substances used to replace water in LIQUID preparations [3]

Vegetable oils

[MECHANISMS OF DEGRADATION]

HYDROLYSIS

Substances used to replace water in PARENTERAL preparations [1]

● 1 week at room temperature

● 2 weeks if refrigerated

[MECHANISMS OF DEGRADATION]

HYDROLYSIS

For reconstitutable products (e.g., antibiotics in dry powder form), expiry date changes to:

Oxidation

[MECHANISMS OF DEGRADATION]

This involves the LOSS OF ELECTRONS from an atom or a molecule (antioxidant).

● Aldehydes

● Alcohols

● Phenols

● Sugars

● Alkaloids

● Unsaturated fats

● Oils

[MECHANISMS OF DEGRADATION]

Example of compounds susceptible to OXIDATION. [7]

● Sodium sulfite

● Sodium bisulfite

● Sodium metabisulfite

● Hypophosphorous acid

● Ascorbic acid

[MECHANISMS OF DEGRADATION]

OXIDATION

Antioxidants for AQUEOUS systems [5]

● α-Tocopherol (Vitamin E)

● Butylated hydroxyanisole (BHA)

● Ascorbyl palmitate

[MECHANISMS OF DEGRADATION]

OXIDATION

Antioxidants for OILY/OLEAGENOUS systems [3]

Polymerization

[MECHANISMS OF DEGRADATION]

This involves a reaction between two or more identical molecules with a resultant formation of a NEW and generally LARGER molecule.

Decarboxylation

[MECHANISMS OF DEGRADATION]

The decomposition of an ORGANIC ACID with the consequent RELEASE of CARBON DIOXIDE (CO₂).

Deamination

[MECHANISMS OF DEGRADATION]

A chemical reaction involving the removal of the NITROGEN-containing group from an ORGANIC AMINE.