Solutions Review questions

Question 1

Define solution, solute, and solvent.

Answer 1

a) Solution – a chemically and physically homogeneous mixture of two or more substances
b) Solute – the compound which is dispersed or dissolved
c) Solvent – the compound which is the dispersing medium; defines the phase of the

resulting solution (solid, liquid, or gas); usually the major component

Question 2

Describe the classification of solutions.

Answer 2

classified according to:

route of administration (eg. oral, injectable, topical etc.)

type of solvent: (aqueous, non-aqueous)

Question 3

Define saturated and unsaturated solution.

Answer 3

Saturated = solution in which molecules leaving the surface of solute are in equilibrium with molecules in solvent @ given temperature

* Any further addition can lead to visible particles and remain in undissolved state.

Unsatuurated = ore solute can be added at a given temperature and pressure

* inc in temp can inc solubility of some solutes

Question 4

Advantages of solution dosage form

Answer 4

a) Provide completely homogeneous doses
b) Doses are easily adjusted
c) Immediately available for absorption and distribution (faster therapeutic response)
d) Can be used by any route of administration
e) Can easily be administered to patients unable to swallow capsules or tablets

Question 5

disadvantages of the solution dosage form?

Answer 5

Lower stability of compounds

Drug may be insoluble in required solvent

Microorganism growth – requires preservatives

Problems with handling, transport, and storage

Requirement of additives for organoleptic properties (ORAL)

Less accurate dosing by patient/caregiver

Question 6

Explain the principle concept of solubility of gases in liquids

Answer 6

Henrys law

@ constant temperature, the solubility of a gas in a liquid is directly proportional to the pressure of the gas above the liquid.

C = kP

(k = henrys law const, P = partial pressure)

Question 7

Explain the principle concept of solubility of liquids in liquids

*define miscible, partially miscible and immiscible

Answer 7

Miscible – soluble in all proportions (alcohol or glycerin in Water
Partially miscible – soluble in definite proportions (phenol and water)
Immiscible – insoluble or nearly insoluble in any proportion (mineral oil and water)

Question 8

Explain the principle concept of solubility of solids in liquids

Answer 8

soubility = amount of solute which can be dissolved in a given amount of solvent to form a saturated solution

*Like dissolves like principle

Polar solutes dissolve in polar solvents, Non-polar dissolve in non-polar solvents

The solubility of solids in liquids is dependent on several factors:Temperature, Structure, Solvents and co-solvents, Other solutes, Solubilizing agents, Complex formation, pH

Question 9

Define Dissolution and Dissolution Rate

Answer 9

transfer of molecules (or ions) from the solid state to solution

• the rate of dissolution describes how fast this process occurs

* NOT equal to solubility, but mathematically related though Noyes -Whitney equation

Question 10

What are the two stages of the dissolution process? Which is the rate-limiting step

Answer 10

1. Transfer of solute from solid to liquid state; i.e. melting
2. Migration of solute from surface of solute through the stagnant layer into the bulk
   solution. *This is usually the rate limiting step.

Question 11

Identify the stagnant layer in the following diagram indicate the points at which:

1) the concentration is equal to the solubility (i.e. saturated concentration)
2) the concentration is equal to the bulk concentration.

Answer 11

Question 12

Describe how each term of the Noyes-Whitney equation impacts dissolution rate.

Answer 12

* K= K₁/h = D/h ie k₁=D

i) D = diffusion coefficient, given by the Stokes-Einstein equation D = kT/6πrη smaller particles (r) and lower viscosity have higher diffusion
ii) A= SA of solute particle, inversly proportional to size smaller particles have a greater surface area and will dissolve more rapidly
iii) C_S is the solubility; greater solubility will dissolve more rapidly; often increase w/ temperature to increase dissolution rate
iv) h is the thickness of the stagnant layer, this can be decreased by stirring, increasing dissolution rate.

Question 14

define sink conditions

Answer 14

• molecules diffuse in the direction of lower concentration
• high concentration gradient can be maintained if the diffused molecules can be removed or the volume of the compartment into which the molecules diffuse are large enough that the concentration can be considered negligible, i.e. sink conditions can be maintained

Question 15

How to utilize Noyes Whitney equation to enhance solubility:

Answer 15

dm/dt =(D/h)A (Cs-Ct)

i. Increase surface area by decreasing particle size.
Effective surface area is area in direct contact with water, inc SA leads to inc solubility.

ii. Mechanical stirring leads to reduced diffusion layer thickness (reduced drug concentration in diffusion layer) leading to increased solubility.

Question 16

Define solubility

Answer 16

maximum amount of solute that can be dissolved in a fixed volume of solvent to form a saturated solution

Question 17

What is a supersaturated solution? How can we prepare a supersaturated solution? Are they stable?

Answer 17

supersaturated solutioncontains an amount of solute in excess of its solubility.

• prepared by making a saturated solution at a higher temperature and then cooling to a lower temperature (where the solute has a lower solubility)

not stable and will eventually exhibit precipitation

Question 18

What is the USP convention for the expression of solubility?

Answer 18

uses the volume of solvent needed to dissolve 1g of solute

i.e. solubility of sucrose is 1.0 g in 0.5 mL of Water

Question 19

What is the purpose of in vitro dissolution testing

Answer 19

measure the rate at which the drug substance is released from the dosage form and dissolves in a particular dissolution medium

Two main uses:

1. to assess the quality of solid drug products (i.e. a quality control tool)
2. prognostic tool for the performance of solid drug products in the gastrointestinal tract (predictive dissolution; IVIVC = in vitro in vivo correlations)

Question 20

Define partition coefficient. Explain how log P is derived.

Answer 20

Partition coefficent = K_o/w and log P – a measure of lipophilicity:

P_o/w = C_{organic phase} / C_{aq phase}

LogP is used to compare lipophlicity

log P > 0 drug is lipid soluble

log P < 0 drug is water soluble

*optimal p vlaue is 3 (100x more soluble in octanol) , if too high or too low will have absoption issues

Question 21

List the six factors affecting solubility.

Answer 21

Temperature, structure of drug, solvent and co-solvents, other solutes, complex formation, pH, solubilizing agents

Question 22

Can potable water (i.e. tap water) be used in any pharmaceutical preparation?

Answer 22

No, the minimum acceptable grade of water used for pharmaceutical preparations is Purified Water; water that has been purified by distillation, ion-exchange, or reverse osmosis.

Question 23

List the different types of pharmaceutical water types

Answer 23

Purified water (BP or USP) – used in non-parenteral solutions

Question 24

What is Water for Injection (WfI, USP) used for?

Answer 24

Water for Injection (WfI) - a pyrogen-free water for parenteral solutions (the finished product can be terminally sterilized)

Question 25

Can Sterilized Water for Injection contain any preservative compounds?

Answer 25

Sterilized Water for Injection USP cannot contain any additional substances or preservatives.

It is prepared from Water for Injection USP by heat sterilization and suitably packaged

Question 26

Define pyrogen-free water

Answer 26

free from pyrogenic materials

* pyrogen = material which when injected into a patient will cause a rise in body temperature (pyrexia).

The lipopolysaccharides that comprise a major part of the cell wall of Gram-negative bacteria, called endotoxins, are the most commonly encountered pyrogens.

Question 27

What are the four common types of alcohol USP? What are the differences between each type?

Answer 27

• Alcohol USP is 95% Ethanol (94.9 – 96% Ethanol at 15.56 C).
• Denatured Alcohol is alcohol that has been rendered unfit for internal use by addition of additives such as ketones or kerosene.
• *Dehydrated Alcohol USP (99.5%)** is the same as Absolute (100%) ethanol and is water free,

Diluted Alcohol NF or USP is prepared from equal volumes of Water and Alcohol USP and contains approximately 49% ethanol by volume.

Question 28

List three other common pharmaceutical solvents and indicate their miscibility with water.

Answer 28

1. Alcohol or glycerin in water: miscible
2. Phenol in water: patially miscible
3. mineral oil in water: insoluble or nearly insoluble in any portion

Question 29

Define salting-in and salting-out

Answer 29

Salting-in: an added salt increasing the solubility of a nonelectrolyte in solution

Salting-out: an added salt decreasing the solubility of a nonelectrolyte in solution

Question 30

what is common ion effect

Answer 30

decrease in the solubility of an electrolyte as a result of an added salt that contains an ion in common with the electrolyte.

Question 31

How does complex formation increase the solubility of a compound?

Answer 31

The addition of an electrolyte that reacts with a solute to form an inorganic complex ion can increase or decrease the solubility of a compound depending upon the solubility of the complex ion that is formed.

Question 32

What is the purpose of a solubilizing agent?

Define and describe the two main classes of solubilizing agents.

Answer 32

purpose: increase the solubility of poorly soluble drugs.

Classes: surfactants and complexing agents

surfactants: amphiphilic compounds that aggregate into micelles which shield the hydrophobic groups from water, provide a hydrophobic phase that hydrophobic drugs can be solubilized in.

complexing agents: orm a complex (either through stacking interactions or as an inclusion complex) with the drug thereby increasing its solubility.

Question 33

What is the effect of an increase in pH on the solubility of a weak acid and a weak base?

Answer 33

• WA: Increase in pH causes increate in total solubility (will deprotonate)
• WB: inc pH will cause decrease in total solubilty (will be protonated)

Question 34

pKa of naprozen is 4.2. If two solutions of naproxen are made, one at pH3 and the other at pH 6 which will havve creater conc>

Answer 34

* taling about solubility, the more soluble one has creater concentration

• so pH 6 has creater conc

Question 35

List the factors affecting the solubility of solids in liquids.

Answer 35

– Temperature, Structure, solvents and co-solvents, Other solutes, Solubilizing agents, Complex formation, pH

Question 36

What is the difference between endothermic and exothermic dissolution processes?

Answer 36

* dissolution is usually endothermic - abs heat

1. if process is enothermic the inc in temp causes inc in solubility
2. if exothermic, inc in temp causes decrease in solubility

Question 37

which solvents listed below, would be suitable to dissolve resorcinol, a hydrophilic drug substance?

Water
Propylene glycol

Peanut oil

Chloroform

Ethanol

Answer 37

Water : Y

Propylene glycol: Y

Peanut oil: N

Chloroform: N

Ethanol: Y

Question 38

Which is not a common non-aqueous oral solution:

A) Elixir, B) Syrup, C) Tincture, D) Spirit?

Answer 38

* SYRUP: it is a common AQUEOUS solution

Question 39

What is the MAIN difference between an Elixir and a Syrup? Is the distinction between a syrup and an elixir always well defined?

Answer 39

Elixir = hydroalcholic MUST contain alcohol, usually between 5-510%

• syrup may contain alc, but not required (for this reason distinction not always well defined)

Question 40

What are aromatic waters and spirits generally used for?

Answer 40

Aromatic waters and spirits are aqueous and alcoholic (hydroalcoholic) solutions (respectively) of volatile compounds generally used as flavoring or aromatizing agents.

Question 41

Why should the use of heat not for the preparation of a syrup be carried out with caution

Answer 41

Excessive heating of sugars can cause hydrolysis of sucrose into monosaccharides (invert sugar) a process known as inversion.

Heat should also be avoided if heat labile ingredients are being used.

Question 42

Describe 3 key differences between syrups and elixirs.

Answer 42

Compared to syrups, elixirs are less viscous, less sweet, less effective at masking taste, and always contain alcohol

(any 3 of these 4 would be correct)

Question 43

List 3 primary uses for topical preparations

Answer 43

antiseptic, astringent, moisturizing

Question 44

What is a collodion? What is added to basic collodion to increase its flexibility?

Answer 44

collodion = solution designed to be painted on the skin, upon drying leaves a film on the skin containing the drug.

• contain partially nitrated cellulose or pyroxylin in ether/alcohol, which forms a tough flexible film on drying
• Vegetable oils are added to collodions to increase the flexibility of the resulting films

Question 45

List 5 types of solution dosage forms

Answer 45

any of these:

i) Syrup, elixir, tincture (Oral)
ii) Liniment, collodion (topical)
iii) Douches, enemas, mouthwashes, gargles (specific body cavities)

iv) Nasal solutions
v) Inhalations
vi) Otic solutions
vii) Ophthalmic solutions

Viii) parenteral solutions

Question 46

What are the properties of an ideal pharmaceutical excipient?

Answer 46

a) Should be pharmacologically inactive and non-toxic
b) Should be effective at low concentrations
c) Should be compatible with drug and other excipients

d) Should be stable in solution and with respect to heat and light

e) Should be soluble in the solvent or vehicle of choice
f) Should not impart any unpleasant taste or odor

Question 47

What are the primary tastes and chemical types associated with them?

Answer 47

a) Sweet – low molecular weight polyhydroxyl compounds (e.g. sucrose, sorbitol,

mannitol)

b) Sour – a result of H+ ions, therefore proportional to [H+] (acidity)
c) Bitter – occurs when one ion in a salt is a high molecular weight compound or

compound is a free base or amide (caffine, codine); most frequent taste of drugs

d) Salty – ionic compound (e.g. NaCl, ammonium chloride, Na salicylate)

Question 48

List and describe 3 techniques that can be used to mask objectionable tastes.

Answer 48

1. Blending – add flavors that either complement a taste (i.e. add citrus flavor for sour tastes) or are associated with a particular type of drug product
2. Physical – formulate an insoluble compound or emulsify the drug in an oil phase
3. Chemical - complex the drug with an ingredient that eliminates the taste (i.e. form an insoluble complex)
4. Overshadowing – use strong and intense flavors to cover up unpleasant taste
5. Physiological methods – anaesthetize or desensitize taste buds or cool the preparation

Question 49

artificial vs natural sweeteners

Answer 49

Natural sweeteners are nutritive (i.e have caloric content)

, artificial sweeteners are generally non-nutritive.

Artificial sweeteners generally much sweeter than natural sweeteners -> used at much lower concentrations.

Question 50

What level of certification should an artificial color being used in an oral dosage form possess? What concentrations of dyes are generally used for coloring?

Answer 50

• color having the FD&C or food, drug, cosmetic classification is the safest type of artificial color and should be used for oral dosage forms.
• dye concentration of between 0.0005% and 0.001% is generally sufficient

Question 51

Distinguish between an antioxidant and a chelating agent and give an example of each.

Answer 51

Chelating agent: complex trace metal ion contaminants in soltion, sto from catalyzing free rad rxns

*ex: EDTA

antioxidant: distrupts free radical chain by more favourably reacting with free radicals
ex: ascorbic acid and sulfur containing salts like sodium thiosulfate or sodium bisulfite (sq system)
ex: BHA , BHT or vit E for oil systems

Question 52

What are the main classes of preservatives?

Answer 52

Alcohols, acids, and esters (in particular the parabens or esters of p-hydroxybenzoic acid)

Question 53

What is the purpose of using a buffered solution? What are some examples of pharmaceutically acceptable buffer systems?

Answer 53

purpose: control the pH of a solution to increase the stability of the drug, obtain a specific ratio of ionized to unionized drug, or to adjust the pH to levels comparable to a specific physiological pH.
examples: carbonates, citrates, gluconates, lactates, phosphates, or tartrates

*Boric acid/borate buffer = EXTERNAL ONLY buffers

Question 54

What are the most common tonicity modifiers? When should the tonicity of a preparation be adjusted?

Answer 54

Sodium chloride and dextrose = common tonicity modifiers.

The tonicity of a preparation should be adjusted after the effect of all other ingredients is accounted for.

Question 55

What are viscosity modifiers used for? What types of compounds are usually used as viscosity modifiers?

Answer 55

Viscosity modifiers are used to increase the viscosity of a preparation.

Most viscosity modifiers are polymeric compounds.