1 Biopharmaceutics & pharmacokinetics - LADMER & biopharmaceutics

Biopharmaceutics

study of the relationship between drugs physico-chemical properties and the pharmacology or clinical response observed after its administration

LADMER System

• Liberation

• Absorption

• Distribution

• Metabolism

• Excretion

• Response

There are several steps a dosage form/delivery system has to undergo before it produces a therapeutic response. This can be explained by the ____ system

Liberation

• First step process

• Drug release from the drug product

Aqueous

in the Liberation process, the drug must be in ____ solution before absorption

TRUE

TRUE OR FALSE

Drugs are mostly weak electrolytes/unionized

• Drug factors

• Excipient Factors

• Dosage form factors

What are the three factors affecting the oral absorption?

• pH rules

• Dissolution

• Crystal Forms

• Drug Stability

• Adsorption

6 Drug Factors that affect the oral absorption

ALL

Strong acids or bases = ionized at ____ pHs

CERTAIN

Weak acids or bases = only ionized at ______ pHs

Polar (Excretable)

An ionized drug means what?

pKa

Solubility depends on ____

Dependent

% ionization is pH ___

High

Weak acids are highly ionized at _____ pH

Low

Weak bases are highly ionized at _____ pH

Henderson-Hasselbach Equation for Weak Acids

Henderson-Hasselbach Equation for Weak Base

Ionizable

if the pH > pka, the weak acid is __

Unionizable

if the pH < pka, the weak acid is __

50% ionized & 50% unionized

if the pH = pka, the weak acid is __

pH-Partition Theory

“states that ionizable compounds penetrate biological membranes primarily in the unionized forms”

Low

Acidic drugs are best absorbed at _________ pH

High

Basic drugs are best absorbed at _________ pH

• ↑ contact time of drugs in the small intestine

• ↑ Surface Area

Despite their high degree of ionization (pH < pKa), weak acids are highly absorbed in small intestine. Why?

Dissolution

process by which a solid drug substance is dissolved in a solvent over time

Noyes-Whitney

dissolution rate is governed by ___________________ equation

Noyes-Whitney Formula:

↑rate of dissolution

↑Cs-Cb - __ rate of dissolution

Sink Condition

• Cb«««Cs

• C~0

↑rate of dissolution

↑Surface Area = ____ rate of dissolution

↓Particle Size

↑Surface Area = ____ Particle Size

↑rate of dissolution

↓Particle Size = _____ rate of dissolution

↓rate of dissolution

↑Thickness = ____ rate of dissolution

Amorphous

• Non-crystalline solids

• Irregular

Crystalline

Crystal forms that have regular shape

Less stable & Faster Dissolution rate

Irregular shapes tend to be __ stable, thus, they have _ dissolution rate

More stable & Slow Dissolution rate

Regular shapes tend to be __ stable, thus, they have _ dissolution rate

Polymorphism

• arrangement of a drug substance in various molecular packing (crystal forms)

• affects the stability, solubility, dissolution rate etc

Pseudopolymorphs

Hydrates or solvates of a drug substance

FALSE

Ampicillin (Anhydrous) has a faster dissolution rate

TRUE or FALSE

Ampicillin (trihydrate) has a FASTER dissolution rate compared to Ampicillin (Anhydrous)

Delays the dissolution

erythromycin (Acid unstable) + enteric coat = _____ dissolutions

pH

basis for optimum stability & solubility of the final product

↑solubility

acidic drug + basic solvent = __ solubility

↑solubility

basic drug + acidic solvent = __ solubility

poorly absorbed

streptomycin + mucin = ___ absorbed

well absorbed

Tetracycline + Calcium ions = ___ absorbed

well absorbed

Lipophilic drug + water soluble complexing agent = __ absorbed

decrease in absorbent of drug

Drug + Adsorbent (activated charcoal) = ____ absorbent of drug

Excipient factors

They are also known as the inactive ingredients that enhance the property of dosage forms

• Lubricant

• Disintegrants

• Coatings

Three Excipient factors

↓rate of dissolution

↑lubricant = ___ rate of dissolution rate

↓rate of dissolution

↓disintegrant = ___ rate of dissolution rate

↓rate of dissolution

↑coating = ___ rate of dissolution rate

TRUE

TRUE OR FALSE

Liquid Dosage Forms have a FASTER dissolution rate compared to Solid Dosage Forms

TRUE

TRUE OR FALSE

Liquid Dosage Forms does NOT go through Liberation, they right away go through the systemic circulation

TRUE

TRUE OR FALSE

Aspirin is more absorbable in Small Intestine

• Novobiocin

• Chloramphenicol palmitate

examples of Amorphous drugs

FALSE

Their amorphous form is active and have a better absorption compared to their crystalline form, which is inactive & have a less absorption

TRUE OR FALSE

The crystalline nature of Novobiocin & Chloramphenicol palmitate have a BETTER absorption compared to its amorphous form.

Intermediate acting; Lente

• Semi Lente is an amorphous short acting agent

• Ultra Lente is a crystalline long acting agent

The combination of Semi Lente + Ultra Lente have a ____ acting

Beta Chloramphenicol

• Alpha Chloramphenicol - stable

• Gamma Chloramphenicol - unstable

Which drug has a high rate of dissolution and is meta stable?

1. Alpha Chloramphenicol

2. Beta Chloramphenicol

3. Gamma Chloramphenicol

A. Liberation

Which of the following is purely a biopharmaceutics parameter?

A. Liberation

B. Response

C. Absorption

D. Metabolism

B. Stomach

An acidic drug is mostly unionized in the

A. Duodenum

B. Stomach

C. Small Intestine

D. Blood

Hydrate

A drug that is united to water molecule forming a crystal is called:

B. The surface area of drug particle

The rate of drug dissolution from a tablet dosage form will increase with:

A. The particle size of the drug

B. The surface area of drug particle

C. The disintegration time

D. The amount of excipients to dilute the drug

Pharmacokinetics

it answers the question “what the body does to the drug?”

Handerson-Hasselbach Equation

This describes the relationship between pH and pKa