3.2) Physicochemical properties

Question 1

What are physicochemical properties of an active pharmaceutical substance?

Answer 1

They are the physical and chemical reactions involved in the formation of ore changes in the structure of atoms and molecules

Question 2

Interactions of physicochemical properties affect

Answer 2

the active ingredient kinetics

Question 3

Why are physicochemical properties of an API important

According to study guide?

Answer 3

Because each type of dosage form requires careful study of the API substance’s physical and chemical(physicochemical) properties

Question 4

Why are physicochemical properties of an API important

According to tut

Answer 4

Important to pre-formulation as they will not only affect the choice and design of formulation but also influence the performance of dosage forms

Question 5

Why is this study of physicochemical properties necessary

Answer 5

to achieve a stable and efficacious product

Question 6

Name the physicochemical properties

Answer 6

-Particle size and SA
-Solubility
-Dissolution
-Partition coefficient and PKa
-Crystal properties: polymorphism
-Stability
-Organoleptic properties
-Other properties

Question 7

Physicochemical properties and API-additive interaction can

Answer 7

profoundly affect the APIs physiological availability and physical and chemical stability

Question 8

How can the most suitable API form and additives be selected to formulate a chosen dosage form

Answer 8

By considering the physicochemical properties with info and knowledge of pharmacological and biochemical properties

Question 9

Relationship btwn particle size and SA

Answer 9

by reducing the size of a particle, it increases the SA of the active ingredient

Question 10

What is dependent on particle szie of an active ingredient

Answer 10

-dissolution rate
-absorption rate
-dosage form content uniformity
-stability

Question 11

Define dosage form content unity

Answer 11

How evenly the active ingredient will be distributed through the dosage forms

Question 12

Define stability according to particle size and SA

Answer 12

time in years before the active ingredient begins to lose its effectiveness in the dosage form

Question 13

Why is it necessary to reduce particle size for both active ingredients and additives

Answer 13

to achieve the desired physicochemical characteristics

Question 14

Define solubility

Answer 14

maximum amount of API that can dissolve in a solvent

Question 15

Why is it of importance that an active ingredient regardless of its admin route needs to have some solubility in water

Answer 15

to ensure a therapeutic effect as majority of the human body is H2O

Question 16

How is an AI chemically formulated

Answer 16

in a soluble salt derivative to achieve solubility in water

Question 17

Techniques that AIs undergo to increase solubility

Answer 17

-Micronizing
-Complexation
-Solid dispersion

Question 18

Define Micronizing

Answer 18

process of reducing the average diameter of a solid material’s particles

Question 19

Define Complexation

Answer 19

Combining individual atom grups, ions or molecules to create one large atom or molecule.

Question 20

What is the focal point of a complex

Answer 20

One atom or ion

Question 21

What does this central atom contain

Answer 21

empty electron orbitals that enable bonding with other atoms

Question 22

Define Solid Dispersion

Answer 22

the dispersion of one or more AIs in an inactive carrier or matrix at a solid-state prepared by the melting (fusion), solvent or melting-solvent method

Question 23

Solubility is depedent to an extent on what

Answer 23

on pH and pKa

Question 24

How is solubility dependent on pH and pKa

Answer 24

The solubility of a strong acid salt is less affected by a change in pH that the solubility of a weak acid salt
*When pH is lower, the WA salt hydrolysis resulting in decreased solubility

Question 25

What is dissolution

Answer 25

the process by which the AI particles dissolve.

Question 26

What needs to occur before an AI can be absorbed

Answer 26

it must first dissolve in the fluid at the absorption site

Question 27

1st step in dissolution process

Answer 27

-The AI molecules on the surface layer of the particle dissolve -they form a saturated solution around the molecule -the saturated solution is called the Diffusion Layer

Question 28

2nd step in dissolution process

Answer 28

the dissolved AI molecules move through the diffusion layer through the dissolving fluid -they make contact with the mucosa where its absorbed

Question 29

3rd step in dissolution process

Answer 29

once the dissolve AIs have left diffusion layer, new molecules dissolve in it and the absorption process continues

Question 30

What happens if the dissolution process is fast or the AI is already in a solution form

Answer 30

the absorption rate is dependent on the Ais ability to cross the absorbing membrane

Question 31

What happens if the dissolution process is slow due to physicochemical properties or formulation factors

Answer 31

dissolution is the speed-limiting step in absorption and influences AI bioavailability

Question 32

What is the rate-limiting step in absorption process for insoluble compounds

Answer 32

the rate of dissolution

Question 33

What is the rate-determining step for soluble compounds

Answer 33

rate of permeability (absorbency) across the biological membranes

Question 34

The permeation rate is dependent on

Answer 34

-size of AI molecule -relative aqueous (water) and lipid (fat) solubility of the AI molecule -ionic charge of the AI molecule

Question 35

What is the partition coefficient

Answer 35

a measure of lipophilic character

Question 36

The biological absorbing membrane acts as

Answer 36

a lipophilic barrier (allows fat-soluble ingredients thru) for the crossing of AIs

Question 37

Most smaller molecular AIs are

Answer 37

weak acids or bases

Question 38

Biological adsorbing membranes are more permeable to

Answer 38

unioised forms of AIs that ionised due to greater lipid solubility of the unionised form

Question 39

What happens to the ionised forms

Answer 39

The highly charged nature of the biological membrane either binds to it or wards it off thus decreasing the penetration of AI

Question 40

Most AIs are in what form

Answer 40

powder at some stage or another

Question 41

Powder form of AIs can be

Answer 41

-amorphous: without regular molecular framework arrangement -crystalline -anhydrous (contains no H2O) -at various degrees of hydration -solvate with other entrapped solvent molecules

Question 42

Can AI substances exist in more that one form

Answer 42

yes they can with different molecular arrangements *Known as Polymorphism

Question 43

How can Polymorphism be made

Answer 43

by manipulating the conditions which particles form during crystallisation e.g temperature and rate of cooling

Question 44

Physical properties that polymorphs vary in

Answer 44

-dissolution rate -solid state solubility -processing behaviour during manufacturing

Question 45

Principle of dosage form design is

Answer 45

ensuring that chemical integrity of AI remains the same throughout the life of the medicine

Question 46

Most important aspect when formulating medicie dosage forms

Answer 46

chemical stability of an AI AIs compatibility with other formulation ingredients

Question 47

Another thing that plays a role in stability of an AI

Answer 47

the packaging of dosage form

Question 48

AIs decompose as result of

Answer 48

-Heat -Oxygen -moisture

Question 49

Ais can be classified according to

Answer 49

their sensitivity to breakdown Egs: kaolin: stable in all conditions aspirin: stable if only handled correctly vitamins: moderately stable even with special handling certain antibiotics in solution: very unstable

Question 50

Requirements of medicine today

Answer 50

it must be acceptable to the patient

Question 51

Do AIs require flavoring and colouring

Answer 51

yes as they ae not good tasting nor good locking

Question 52

Flavouring is mostly necessary for

Answer 52

oral liquid formuations

Question 53

Colouring is used to

Answer 53

-improve existing AI colour -mask the AI colour -compliment a flavour (pink with strawberry flavour)

Question 54

Other than ensuring that a dosage form is chemically and physically stable and efficacious, what else is needed

Answer 54

that it needs to be maufactured on a large scale

Question 55

Hygroscopic AIs require

Answer 55

low moisture manufacturing environments and need to avoid water during prep

Question 56

Poorly flowing formulations need

Answer 56

addition of flow agents

Question 57

Tablet machines are used because

Answer 57

they are used in formulation labs to foresee any potential problems with compacting

Question 58

Therefore physicochemical properties of Ais alone and when combined with additives its important they

Answer 58

-dosage form design and processing -product performance