PHA 338 - Chemical Kinetics and Solution dosage Form L3

Chemical kinetics

The study of the mechanism and rate of a chemical reaction from initial state to final state

What does “kinetics” mean?

Movement and rate

Why is chemical kinetics important in pharmaceutics?

It helps predict drug stability, shelf life, and storage conditions

Why is chemical kinetics important in pharmacokinetics?

It helps explain half-life, clearance, and volume of distribution

Collision theory

A reaction occurs when atoms or molecules collide and transfer energy

What happens during a molecular collision?

Energy is transferred, increasing kinetic energy or breaking bonds

How does concentration affect collisions?

Higher concentration increases collisions because molecules are more crowded

How does heat affect reaction rate?

Heat increases energy and collisions, increasing reaction rate

Reaction rate

The speed at which reactants are converted into products

How is reaction rate measured?

By following concentration changes over time

According to the law of mass action, reaction rate depends on what?

The concentration of reactants

Order of reaction

The sum of the exponents of concentration terms in the rate equation

Overall order of reaction

In Rate = k[A]^a[B]^b, the overall order is a + b

Zero-order reaction

A reaction whose rate is constant and independent of reactant concentration

Zero-order reaction equation

C = C0 − k0t

What is the graph shape of a zero-order reaction?

A straight line

Slope of a zero-order reaction graph

-k

Does a zero-order reaction depend on concentration?

No

First-order reaction

A reaction whose rate is directly proportional to reactant concentration

First-order reaction equation

lnC = lnC0 − kt

Alternative first-order equation

C = C0e^-kt

Slope of a first-order reaction graph

-k

Half-life equation for first-order kinetics

t1/2 = 0.693/k

What does k represent in kinetics?

Rate constant

What happens to concentration in first-order kinetics?

It decreases exponentially over time

Second-order reaction

A reaction where the overall reaction order equals 2

Example of a second-order reaction

A reaction first-order in two reactants where a+b=2

Half-life

The time required for a drug concentration to decrease to 50% of its initial value

Shelf-life (t90)

The time required for a drug to decrease to 90% of its original concentration

What percentage of drug remains at shelf-life?

90%

Expiration date

The date before which a drug is expected to remain within approved specifications

About how many half-lives remove almost all drug from the body?

About 7.5 half-lives

If 100 mg of drug is given, how much remains after 1 half-life?

50 mg

If 100 mg of drug is given, how much remains after 2 half-lives?

25 mg

If 100 mg of drug is given, how much remains after 3 half-lives?

12.5 mg

Factors affecting reaction rate

Temperature, catalysis, solvent, ionic strength, and dielectric constant

Specific acid-base catalysis

Catalysis caused by pH

General acid-base catalysis

Catalysis involving acids or bases other than H+ or OH-

Enzymatic catalysis

Catalysis caused by enzymes

Metal catalyst example

Nickel used in H2O production from H2 and O2

Single-phase solution

A homogeneous mixture with one phase

Suspension

A two-phase dosage form that must be shaken before use

Emulsion

A two-phase liquid system of immiscible liquids

Pharmaceutical solution

A liquid preparation containing dissolved drug or excipient in a suitable solvent

Common classifications of pharmaceutical solutions

Oral, otic, ophthalmic, topical, and parenteral

Vehicle

A liquid used to carry dissolved medicinal substances

Oral solution

A solution taken by mouth for systemic effect

Topical solution

A solution applied to skin or mucous membranes

Oral-dental solution

A solution used topically in the mouth

Otic solution

A solution used in the ear

Ophthalmic solution

A sterile isotonic solution used in the eye

Parenteral solution

A sterile injectable solution

Characteristics of ophthalmic solutions

Sterile, isotonic, and particulate-free

Characteristics of parenteral solutions

Sterile, isotonic, pyrogen-free, and particulate-free

Pyrogen

A substance that can cause fever

Characteristics of otic solutions

Usually viscous

Examples of solvents used in otic solutions

PEG, glycerin, and propylene glycol

Syrup

A concentrated aqueous sugar solution with or without medication

Why are syrups commonly used?

They improve taste and are easier for children and elderly patients to swallow

Elixir

A sweetened hydroalcoholic oral solution containing dissolved drugs

Alcohol content of elixirs

Usually 5–40%

Tincture

An alcoholic or hydroalcoholic solution prepared from vegetable materials or chemicals

Alcohol content of tinctures

Usually 15–80%

Fluidextract

A concentrated alcoholic liquid preparation of vegetable drugs

Spirit or essence

An alcoholic solution of volatile aromatic substances

Aromatic water

A saturated aqueous solution of volatile oils or aromatic substances

Oral rehydration solution

A solution used to treat dehydration caused by diarrhea

Optimal glucose concentration in ORS

110 mM or about 2%

Optimal sodium concentration in ORS

60 mEq/L

What helps sodium absorption in ORS?

Glucose transport

Oral colonic lavage solution

A bowel-cleansing solution used before colonoscopy

PEG in colonic lavage solution

Acts as an osmotic agent

Magnesium citrate oral solution

A saline laxative used for constipation

Sodium citrate and citric acid solution

Used to alkalinize urine

Systemic alkalinizer

A substance that makes urine less acidic

Solubility

The amount of solute that dissolves in a solvent

Factors affecting solubility

Particle size, viscosity, temperature, concentration, pH, and co-solvents

What can increase solubility?

Adding co-solvents or modifying chemical structure

Examples of co-solvents

Alcohol, PEG, and propylene glycol

Alcohol USP

Ethanol 94.9–96% by volume (180 proof)

Dehydrated alcohol USP

Alcohol containing at least 99.5% ethanol (200 proof)

Diluted alcohol NF

A 50% mixture of USP alcohol and purified water

Rubbing alcohol

70% ethyl alcohol with denaturants

What proof is rubbing alcohol?

140 proof

What proof is dehydrated alcohol?

200 proof

What proof is USP alcohol?

180 proof

What proof is diluted alcohol?

100 proof

Why is rubbing alcohol denatured?

To prevent its use as a beverage alcohol

Which alcohol is monitored by the IRS?

Rubbing alcohol

Glycerin USP

A sweet viscous liquid miscible with water and alcohol

Uses of glycerin

Moisturizer, stabilizer, preservative, and solvent

Why do solutes dissolve slowly in glycerin?

Because glycerin is very viscous

Isopropyl rubbing alcohol

70% isopropyl alcohol used as an antiseptic

Rubefacient

A substance that causes redness by dilating blood vessels

Uses of isopropyl rubbing alcohol

Antiseptic, topical rub, and skin disinfectant

Propylene glycol USP

A viscous solvent miscible with water and alcohol

Uses of propylene glycol

Solvent, moisture-retaining agent, and substitute for glycerin

What type of preparations commonly use propylene glycol?

Otic preparations

Purified water USP

Water purified for pharmaceutical use

Why is tap water unsuitable for pharmaceuticals?

It contains dissolved solids and microorganisms