Solutions Flashcards
1
Q
Define Solutions
A
A chemically and physically homogenous liquid preparation of two or more substances
2
Q
List some characteristics of solutions
A
Homogenous one phase system
Uniform distribution of drug throughout the preparation
3
Q
What is the most common solvent?
A
Water
4
Q
What is possible other ingredients that may exist within a pharmaceutical solution?
A
Excipients
Colouring
Flavour
Presertevt
5
Q
What are advantages of solutions?
A
Can be intended for multiple routes of administration
Oral solutions – drug available for absorption
Flexible dosing
No shaking of solutions needed (complete dissolution)
6
Q
What are some disadvantages of solutions?
A
Drug stability may be compromised
Technical accuracy or delivery devices needed for dose accuracy
Solubility properties of drug must be matched with excipients
Bulky storage and transportation
7
Q
What dosage forms utilizing solutions?
A
Injectable
Paediatric formulation
Ophthalmic preparation
8
Q
What are some other solvent vehicles?
A
Alcohol
Isopropyl alcohol
Glycerin
Propylene glycol
PEG
9
Q
Define Solubility
A
The quality of solute that will dissolve in a specified quantity of solvent to form a saturated solution
10
Q
Define dissolution
A
The transfer of molecules and ions from a solid phase into a solution
11
Q
What is the difference betweeen solubility and dissolution?
A
Solubility is a property while dissolution is a phenomenon/process
12
Q
What are some thing that happen in dissolution?
A
The removal of a molecule of a drug from the solid state
The formation of cavity within the solvent
The accommodation of the drug molecule into the formed
The process involves the breakage of solute-solute and solvent-solvent bonds and the formation of a bond between the solute and solvent
13
Q
What is the general rule with dissolution?
A
The more soluble the drug
The faster the dissolution into the solvent
14
Q
List some ways to enhance dissolution
A
Some solids require triturating to reduce the particle size and decrease the solution time
Sometimes heat is required to enhance the dissolution
Some vigorous shaking or stirring is required
15
Q
Describe dissolution
A
The process by which a drug particle dissolves
A process by which a solid of specific solubility characteristics enter into the solution
16
Q
The smaller the particles the increase in
A
Dissolution
And
Absorption
17
Q
List factors that affect solubility
A
Molecular weight
Volume
Presence of functional groups and their position
Acids or bases
18
Q
What is difference in characteristics between aqueous solution and pure water?
A
Aq has higher boiling point and a lower freezing point
19
Q
An increase in temp _____ solubility of solids
A
Increases
20
Q
List the types of solutions
A
Gases in liquids
Liquids in liquids
Solids in liquids
21
Q
Define miscibility
A
Expresses the mutual solubility of components in a liquid-liquid system
22
Q
List the Types of liquid pairs
A
Soluble in all proportions
Soluble in definite proportions
23
Q
List examples of soluble in all proportions (liquid pairs)
A
Alcohol and water
Glycerin and water
24
Q
List examples of soluble in definite proportions (liquid pairs)
A
Phenol and water (influenced by temp)
25
What is an example of immiscible?
Oil and water
26
In Gases in liquids how does an increase in pressure affect
Increase solubility of gas in liquids
27
In Gases in liquids how does an increase temperature affect
Decrease solubility of gas in liquid
28
What are the two factors that determine the amount of gas that will dissolve in a liquid?
Temperature
Gas
29
List the factors affecting solubility
temperature
pharmaceutical solvents
mixed solvents
complexation
30
Explain how temperature affects solubility in an exothermic reaction
decrease solubility with the increase in temperature
31
Explain how temperature affects solubility in an endothermic reaction
increase solubility with the increase in temperature
32
Define endothermic
positive heat of solution
the solution process requires the input of energy or heat is absorbed when the solute is dissolving
33
Define exothermic
negative heat of solution
in the solution process heat is given off when the solution is dissolving
34
Define Normothermic
heat is neither absorbed nor given off during the solution process
35
Give an example of exothermic reaction
NaOH dissolving in water
36
Give an example of when endothermic reaction is used
creating syrups
37
Give an example of normothermic
KCl
38
What are the types of pharmaceutical solvents?
non-polar and polar
39
Define polarity
a separation of electric charge leading to a molecule or its chemical groups having an electric dipole moment, with a negatively charged end and a positively charged end
40
List the small or no dipolar characteristics
fixed oils - non volatile
hydrocarbons
41
List the uses of non polar solvents
vehicle for injections
external preparations
42
Explain of polar solvent
potable water
43
What is the natural salts in potable water?
Ca, Mg, Fe, K & Na
organic matter
atmospheric gases
suspended materials
44
Rendering water potable requires?
removal of insoluble matter by settling and filtration
destruction of pathogenic organisms by chlorination
45
List primarily semi polar solvents
alcohol
isopropyl alcohol
glycerin
propylene glycol
polyethylene glycol 400
46
What is the most common solvent?
alcohol
47
explain why alcohol is used
by mixing with water it creates a hydro alcoholic solution both alcohol and water soluble compounds
48
Advantages of Semi Polar solvents
better solubility for many compounds
can be used as co solvent
better stability
49
How can semi polar solvents have better drug stability
decreases hydrolysis
bacterial growth
50
Limits for Alcohol in OTC products
Children < 6 = < 0.5%
Children 6-12 = <5%
Adults = <10%
51
List miscible with a wide range of solvents
caster oil
water
alcohol
52
List the types of alcohols
denatured alcohol
absolute alcohol
diluted alcohol NF
rubbing alcohol
53
Define denatured alcohol
has additives to render it more poisonous and unfit for internal uses
54
Define absolute alcohol (100%)
dehydrated alcohol UPS
water free ethanol
55
Define diluted alcohol NF
prepared by diluting Alcohol USP with an equal volume of purified water
useful as hydro alcoholic solvent in pharm preps
56
Define rubbing alcohol
around 70% by volume
effective antiseptic -disinfectant
for external use only
57
Define Miscible solvents
a solute may be more soluble in a mixture of solvents than in one solvents
58
Explain the cosolvent effect
the solubility is improved if some alcohol is added to an aqueous formulation
59
Explain mixed solvents
if there are two or more solvents and two or more solutes in formation
each soluble should be dissolved in the solvent in which it is most soluble before mixing with other liquids
60
Explain Complex formulation
complexes are loose molecular association that can either increase or decrease solubility
61
What points should be shared in counseling when using a complex formulation?
tell pt to avoid taking milk or dairy products containing calcium within 2 hours of taking tetracycline
62
What should you avoid with calcium and iron?
certain antibiotics
certain medications used to treat osteoporosis
thyroid medication
63
when preparing a solution, solubility is improved by
stirring
elevated temp
reduction of particle size
salt form rather than base form
sometimes: mixed solvent system
64
List ways that drug concentrations of a drug can be expressed
mol/L
mol/kg
g/l
w/v, w/w, v/v
ppm
65
Why are additives added to oral adminstration?
storage stability, enhance solubility, taste
66
Requirements in the preparation of oral solutions
physical stability
chemical stability
microbiological stability
67
Describe Physical stability and list examples
stability that can be seen or felt
no discoloration/cloudness
no precipitation
no loss of elegance
no loss of taste
68
Define chemical stability
there must not be changes to the molecular structure of the drug
69
What are some factors of chemical stability?
pH
hydrolysis and oxidation
70
How can you reduce these chemical instabilities?
Hydrolysis can be controlled by using non-aqueous solvents e.g. alcohol
Oxidation can be controlled by adding antioxidants e.g. ascorbic acid, sodium bisulfate
71
Explain microbiological stability
Enhanced by the use of solvents with “preservative” action e.g. >20% glycerin, alcohol
72
Explain why it need to be palatability
The product must taste good
Sweeteners e.g. sucrose, sorbitol, etc.
Flavours
73
Explain the need for a pleasing appearance
The product must look good “pharmaceutical elegance”.
in order to be used and sold
74
How could we have pleasing appearance?
often add colors or viscosity inducing agents to solutions
75
List characteristics of the Ideal additive
1. pharmacologically inactive and non-toxic
2. potent, therefore can be used in low concentrations
3. no unpleasant odour or flavour
4. compatible with drug and other excipients
5. stable to changes in pH or exposure to light and heat etc.
6. soluble in the vehicle/solvent
76
What are the types of flavors?
salty
bitter
sour
sweet
77
What is the mechanism of taste?
*A substance dissolves in the water layer on the tongue
*The solution is in contact with the taste cells and initiates a nerve impulse
*The impulse is transmitted via the cranial nerve to the brain; the perception of taste results
78
What must happen for the substance to be tasted?
they must be dissolved
79
Explain sweet
low molecular weight poly-hydroxyl compounds (e.g. sucrose, sorbitol, mannitol)
(number of OH groups ∝ sweetness)
80
Explain Sour
a result of H+ ions, therefore proportional to [H+]/acidity
81
Explain bitter
high molecular weight salts, free
bases and nitrogen containing compounds like amides (e.g. caffeine, codeine)
82
Which flavour is the most objectionable and most common?
Bitter
83
Explain Salty
low molecular weight salts and ionic compounds (anion + cation)
(e.g. NaCl, ammonium chloride, Na salicylate)
84
What is one major thing to keep in account when selecting flavoring agents?
look at str of empds in your formula and can estimate what it'll taste like
85
List flavoring techniques
1. Physiological
2. Physical
3. Masking or overshadowing 4. Blending
5. Chemical
86
Explain how physiological flavoring techniques work
anaesthetizethetastebuds/receptors
87
How does physical work for flavoring
prevent dissolution of drug
88
Examples of physiological flavoring techniques
carbonated beverages
stores produce in fridge
apply ice cubes on tongue before taking the medication
89
Examples of physical flavoring techniques
use of a viscous fluids
formulate an emulsion instead of a solution
coating tablet
90
Explain how overshadowing flavoring techniques work
Addition of a flavour whose intensity is longer and stronger than the taste of the drug
91
Explain how blending flavoring techniques work
add flavours which compliment the taste and modify the flavour perception
92
List examples of blending flavoring technique
sour taste - blended with fruit flavours
bitter taste - adding salty, sweet and sour flavour
93
Explain how chemical flavoring tech works
drug can be complexed or a prodrug can be made
used in drug product manufacturing
Should not affect the overall therapeutic profile of the drug Microencapsulation or nanoencapsulation also done
94
Give an example of chemical flavoring technique
tetracycline dispensed as HCl salt
95
What are 2 categories of sweeteners?
natural sweeteners
artificial sweeteners
96
List of desired properties of sweeteners
Colourless
Odourless
Solubility in water at the concentration needed for sweetening
Pleasant tasting
No aftertaste
Stable over a wide pH range
97
Examples of Sweeteners - Sugars
Sucrose
Lactose
Dextrose
98
Define Sucrose
disaccharide (glucose,fructose)
standard for sweetness
99
What are some possible concerns with sucrose?
high water solubility but may reduce the water solubility of other solutes/drug
may pose a problem for diabetic pt
has a tendency to crystallize on the threads of bottle caps
inversion & caramelization
100
Define Lactose
milk sugar
disaccharide --> galactose-glucose
less sweet than sucrose
101
Define dextrose
glucose, corn sugar
monosaccharide
less sweet than sucrose
generally not used in oral products but sometimes as IV solutions
102
List types of sweeteners - artificial polyols
glycerine
propylene glycol
103
List types of sweeteners - natural polyols
sorbitol
mannitol
xylitol
sucralose
stevia
104
Define Sorbitol
approximately 2.6 cal/g (4 for sucrose), more slowly absorbed
less sweet than sucrose (0.6 x sucrose)
Can cause gas/flatulence
105
Define Mannitol
approx, half the caloric value of sucrose
less sweet than sucrose
high intake has laxative effects
106
Define Xylitol
approx. equal sweetness to sucrose but absorbed more slowly, negligible affect on blood sugar metabolized irrespective of insulin
more expensive than sucrose
107
Define Saccharin
tends to have a bitter metallic after taste
108
define cyclamate
approx. 30 times sweeter than sucrose
109
define aspartame
non-carb nutritive sweetener
ADR - seizures, headache
110
Problems with Aspartame
intolerance in pt with PKU
- this is a deficiency in the enzyme phenylalanine hydroxylase
111
Define Sucralose
600 x sweeter than sucrose
not metabolized (non-caloric)
not bitter after taste
112
Define Stevia
200 x sweeter than sucrose --> some after taste
113
Why is flavoring needed?
most flavors are bitter and require sweetening to make them more pleasant to taste
114
Why use colors?
to enhance the esthetic quality of the preparation
to act as a sensory adjunct to flavor
115
Why do pt usually reject dark colors?
because they are often associated with poisons
116
Two possible instances this speculation will not work?
Not practical for a child because they have not yet developed color/aroma/taste correlation.
It is deterrent if the patient must take multiple doses, so it is best to avoid this method when possible
117
As a compounding pharmacist do you think it is safe to use liquid stock colorants available in grocery store as they are also FD&C approved?
No
need material safety data sheet
- impurities
- stability
-interaction
118
Types of Natural Coloring Agents
mineral pigments
plant pigments
animal pigments
119
Define mineral pigments
primarily used for lotions, cosmetics and other external preparation
120
define pigments
insoluble materials that give colors when dispersed in some liquid
121
List some examples of mineral pigments
yellow ferric oxide
white titanium dioxide
red (red ferric oxide and carbon black)
122
List some examples of plant pigments
green chlorophyll
orange B carotene
yellow saffron
123
List synthetic color certifications
FD&C
D&C
external D&C
124
Explain what FD&C
food, drug and cosmetic
125
Explain what D&C
drug and cosmetic
126
Explain D&C
not allowed in products for lips
127
Problems with Synthetic Color Agents
carcinogenicity probability
hypersensitivity
hyperactivity
128
When are preservatives CI?
neonates
ophthalics
parenteral greater than 30 ml
129
Alternative strategies when preservatives are needed but contraindicated:
Prepare single doses
Prepare a limited quantity that will be used within a short time period
store under refrigeration and label with a short beyond use date
130
Requirements for preservations
activity needs to be broad spectrum
must reduce a microbial population significantly and prevent subsequent re-growth
synergistic combinations like benzalkonium pathogens like P aeruginosa
131
Define Antioxidants
divert the oxidative process
132
How do antioxidants work?
by reacting with one or more compound in the formulation to prevent free radical medicated chain reaction
133
Antioxidants for aqueous systems
for ascorbic acid
Na sulfite
bisulfite
134
Antioxidants for oil systems
BHA
alpha-tocopherol
135
Define buffers
control the ph of solution and therefore the staiblity of the product
buffer solution contains a weak acid and its conjugate base so that the pH of the solution changes little when acid is added
136
What are viscosity Inducing agents?
used to change the consistency of a preparation to render it more resistant to flow
makes the product easier to pour for the pt
may improve appearance and palatability
137
For topical solutions, viscosity is essential:
for achieving desired smoothness and consistency
ease in applying
will remain in contact with affected area like in ophthalmic formulations to increase residence time
138
List some examples of viscosity inducing agents
methylcellulose
carboxymethylcellulose
hydroxypropyl methylcellulose
acacia
tragacanth
bentonite
139
What is the challenge with viscosity?
creates difficulty when trying to dissolve drugs in the vehicle
140
What is the solution to viscosity affecting dissolution?
do not try dissolving drug in a viscous medium
add viscosity inducer after dissolving the drug
141
Explain surface active agents
chemicals that contain both hydrophilic & hydrophobic regions
also called wetting agents
modulate solubility of ingredients to improve stability and sometimes bioavailability
142
Classifications of aqueous solutions
syrups
aromatic waters
143
Classifications of non-aqueous solutions
elixirs
spirits
tinctures
144
Define aqueous solutions
the most prevalent of the oral solution
dissolving a drug in water along with excipients makes an aqueous solution
145
What is always used in preparing compounded aqueous solutions?
distilled or purified water
146
why we should know about the compatibilities of medicinal ingredients in solvents used in commercial products?
we need to know if something looks wrong so we don't endanger the pt
147
Define syrups
are concentrated, viscous, sweetened, aqueous solutions that may contain less than 10% alcohol
148
List some non medicinal ingredients
Citric acid, flavor, glycerin, polyethylene glycol, propylene glycol, sodium benzoate, sodium citrate, sorbitol, sucralose, water and xanthan gum.
149
the most common oral solutions dispensed to patients are ___ and ___?
syrup and elixir
150
Compared to syrups, elixirs are generally:
______ sweet
less
151
Compared to syrups, elixirs are generally:
______ viscous
less
152
Compared to syrups, elixirs are generally:
______ effective in masking bitterness
less
153
Compared to syrups, elixirs are generally
Always contain ______ in ranges between _____%
alcohol
3-44%
154
Compared to syrups, elixirs are generally:
______ stable physically
more
155
Compared to syrups, elixirs are generally:
______ stable chemically
more
156
Simple syrup contains ____ w/v or ____ w/w sucrose in water
85%
65%
157
Common form of tincture seen in pharmacy is _____ which is used as an _____
iodine tincture
antiseptic
158
0.5 grams dissolved in 100 ml of solution --> best way to represent its concentration is ______
percentage
159
What level of sugar does the syrup have to be in order to need antimicrobial preservative?
<80%
160
Purpose of colorant
may be added to a syrup to enhance the appeal of the syrup
mostly it is correlated with the flavor
161
Define cherry syrup
a sucrose based syrup containing 47% by volume cherry juice
162
What is the case when the coloring does not match the flavor?
raspberry flavor but colorless solution
163
What is cocoa syrup flavored with?
vanilla to help with the bitter taste
164
What need to be determined before using a flavoured syrup?
if acidic, neutral or slightly basic and whether this will cause a problem with stability of the added medicinal agent
165
Why should we be aware of flavoring agents stability or ph?
solubility is dependent on pH
chemical stability of acid or base liable drugs
166
Define Simple Syrup
Saturated solution of sucrose in water.
85% w/v or 65% w/w
Sucrose 850g + purified water qs ad 1000ml.
Syrup is fully saturated and self-preservative
If diluted, it will support mold and other microbial growth.
167
What is the compounding methods for a drug within syrup-based formulations?
In formulas containing both drug and sucrose, each ingredient is usually dissolved separately and then mixed together in such a way to avoid precipitation
168
Define aromatic waters
are clear, saturated aqueous solutions of volatile oils or other aromatic substances
used as flavoring or perfuming solutions
169
What might be used to make aromatic waters?
use of talc
170
What are the steps for compounding aromatic water?
volatile oil + talc + purified water
thorough agitation for 30 minutes
filtration is performed
171
What is the role of talc?
acts as a distribution agent
act as a filter aid
172
Explain how talc acts as a distribution agent
increase the surface area of the volatile substance that is exposed to water and to facilitate the saturation of the solution with oil
173
Explain how talc acts as filter aid
remove excess volatile substance
174
What are some limiting factors on non aqueous solutions?
their irritation or toxicity profiles
175
List some examples of non aqueous solutions for internal use
glycerin
alcohol
propylene glycol
176
List some examples of non aqueous solutions for topical solutions
aliphatic hydrocarbons
ether
glyceryl esters of aliphatic acids
177
Common non aqueous solutions are
elixirs
spiritis
tinctures
178
Define elixirs
clear, sweetened hydro alcoholic solution intended for oral use
179
What is the range for elixirs
3 to 44%
most 5 to 10 %
180
What level for elixirs does it require antimicrobial preservative?
10-12%
181
Compared to syrups, elixirs are
______ able to maintain water and alcohol soluble components in solution
more
182
Compared to syrups, elixirs are
______ long term stability
more
183
Compared to syrups, elixirs are
______ strict storage conditions due to alcohol
more
184
Define compounding elixirs
Alcohol soluble constituents are dissolved in the alcohol portion and water-soluble constituents are dissolved in the water portion simple solution by agitation
185
Why is aqueous solution added to alcohol solution with constant stirring?
Order is important to maintain the highest possible alcoholic strength* at all time so that minimal separation of the alcohol soluble components occur
186
What to do if elixir shows precipitation?
Glycerin, sorbitol or propylene glycol aids in dissolution
Permit to stand for few hours provide time to ensure saturation and then remove the insoluble material by filtration.
187
Define spirits
alcoholic or hydro alcoholic solutions of volatile substances
188
What alcohol range is need for spirits?
62-85%
189
what are most spirits used for
flavouring agents in small quantities
stock solution as a convenient means of obtaining a proper amount of flavoring oil
190
Define tinctures
Are alcoholic or hydro alcoholic solutions of non-volatile substances prepared from vegetable or chemical substances.
191
What is the alcohol concentration for tinctures?
15-80%
192
Why should it be stopped and not exposed to high temperatures?
high alcohol content - explosive or evaporation
193
What is tinctures of potent drugs have?
10 g of drug per 100 ml
194
What is non potent tinctures?
20 g of drug per 100 ml
195
Why do we not use many tinctures?
not prescribed anymore usually due to high alcoholic
196
Do tincture need preservatives?
no because Alcoholic content of these preparations protects against microbial growth and keeps the alcohol-soluble material in solution
197
What cannot be mixed with tinctures?
successfully with liquids too diverse in solvent character without inducing precipitation of the solute.
198
what is one storage requirement for tinctures?
Must be stored in light resistant containers and protected from sunlight. Most contents of vegetable oils are light sensitive
199
List some examples of tinctures
Oral – may have unpleasant or burning taste due to alcohol content
Oral – example: opium tincture (17-21% ethanol)
Topical – examples: iodine (first aid antiseptic), thimerosol (antiseptic) – these are about 50% ethanol
Flavouring agents – vanilla tincture, sweet orange peel tincture
Glycerin may be included to increase solubility and stability of the active agents in the tincture
200
List some other pharmaceutical liquids
Gargles, mouthwashes
Otic solutions
Ophtalmic solutions
Nasal solutions – nasal wash or medicated
Lotions
Liniments
Enemas
Parenteral injectables (SQ, IV, IM)
201
Why are dryg mixtures for reconsitiuted solutions?
to extend the shelf life
this drug mixture may then be reconstituted as a solution
have 7 - 14 days
