Solutions (Part 1) Flashcards
Define pharmaceutical solutions
liquid preparations that contain one or more chemical substances dissolved in a suitable solvent OR mixture of mutually miscible solvents
Name FIVE factors that affect solubility
-attractive forces
-repulsive forces
-van der waals forces (dipole-dipole) - dipolar molecules
-ion-dipole force
-hydrogen bond
dipole-dipole forces are also known as…
ven der waal forces
hydrogen bonding occurs between….
polar and non polar molecules and ions
hydrogen bond is a hydrogen molecule attached to….
oxygen, nitrogen, or fluorine
in a solution, what are the solutes?
medicinal agents OR additional agents (excipients) such as color, flavor, sweetness, or stability)
to achieve the solute-solvent attraction, what has to happen?
the solute-solute forces and the solvent-solvent forces must be broken to achieve the solute-solvent attraction
the SOLUBILITY of an agent in a particular solvent indicates what?
the maximum concentration of the drug in solution
when is a solution said to be saturated?
when a solvent at a given temp has dissolved all of the solute possible
what is unique about Calcium Hydroxide Topical Solution, USP?
calcium has negative heat effect. the solubility of calcium hydroxide DECREASES with rising temperature
name the solute(s) and solvent(s) of Calcium Hydroxide Topical Solution, USP
1 solute: Calcium hydroxide (excess amount)
1 solvent: purified water
what is the % w/v of Calcium Hydroxide Topical Solution USP?
explain
0.14% w/v
0.14 g solute in 100mL solution
this is the solubility of calcium hydroxide at room temperature
VERY LOW SOLUBILITY
Name the solute and solvent of Potassium Iodide Oral Solution USP
1 solute: potassium iodide
1 solvent: purified water
give the solubility of Potassium Iodide Oral Solution USP at room temp.
100% w/v
100 g of solute in 100 mL solution
What can be changed in regards to the SOLUTE to increase solubility?
-solubilizing agent (excipient)
-using a chemical salt of the API (medicinal agent)
Is it preferred to alter the solubility by changing the API or changing the solvent(s)?
preferred to change the solvents.
How can the solvent be altered to adjust the solubility of a drug?
substitution (in part or whole)
ie: use of a cosolvent is done most of the time
Explain how the SOLUTION ITSELF can be altered to adjust the solubility of the API
changing the pH or the temperature of the final solution.
pH of the solution is adjusted based on what equation?
hendersen hasselbach equation
why is changing the temperature of the final solution NOT really used to increase solubility?
because the solution is stored at room temperature usually and the solubility will change once the heat is removed in the laboratory setting
Explain how altering the solution of iodine granules + purified water can increase solubility.
iodine granules by itself is not very soluble in purified water. 1 g of solute in 3000mL solution (0.033%w/v)
however, Iodine Topical Solution USP has the iodine granules (2%) and 2.4% of sodium iodide (SERVES AS A SOLUBILIZING AGENT) as the solutes and purified water as the solvent.
this makes the solution much more soluble
SOLUTES: iodine and sodium iodide (solubilizing agent; excipient)
SOLVENT: the same – purified water
Name the USP relative terms of solubility and the meaning behind them
very soluble
freely soluble
soluble
sparingly soluble
slightly soluble
very slightly soluble
Practically insoluble/insoluble
“parts of solvent required to dissolve 1 part of the solute”
very soluble: <1
freely soluble: 1-10
soluble: 10-30
sparingly soluble: 30-100
slightly soluble: 100-1,000
very slightly soluble: 1,000-10,000
practically insoluble/insoluble: >10,000
“parts of solvent required to dissolve 1 part of the solute”
be specific…
mL of solvent required to dissolve 1 g of solute
Explain what happens when you convert a drug to its salt form
when a drug is converted to its salt form, the drug’s solubility in water is increased due to the “like dissolves like” principle (both are polar)
however, converting to salt form means that if alcohol is the solvent, much more of it is required to dissolve this salt form of the drug.
what is the salt form of codeine? explain the process in getting to this point
the acceptable salt form of codeine is codeine PHOSPHATE.
Codeine sulfate was originally made, but this salt form turned out to be only soluble in water, and very slightly soluble in alcohol (1,280)
so, codeine phosphate was created to combat this issue of insolubility in alcohol. Codeine phosphate is freely soluble in water, and slightly soluble (325) in alcohol, which is much more acceptable than the 1,280 of codeine sulfate.
which are more soluble in alcohol – organic bases or their corresponding salt forms?
organic bases
name the 10 POLAR GROUPS from the slides
OH
CO
CHO
COH
CH2OH
COOH
CHOH
NO2
NH2
SO3H
Are most drugs organic or inorganic? What does organic/inorganic mean?
must drugs are organic, meaning that they contain carbon
what can you say about the solubility of monovalent molecules?
they are easily broken and have good water solubility.
rank the following according to solubility (most soluble –> least soluble)
-one of the 2 ions in an ionic compound is monovalent
-both the cation and anion are multivalent
-both the cation and anion are monovalent
most soluble: both the cation and anion are monovalent
middle: one of the 2 ions is monovalent
least soluble: both the cation and anion are multivalent (double bond)
name 2 ways that we can alter solubility by altering the medicinal agent (API) itself
-change it to its salt form
-change functional groups
name the 4 general rules of solubility for organic molecules
- Molecules with 1 polar functional group are usually soluble to a TOTAL CHAIN LENGTH OF 5 CARBONS
- Molecules having branched chains are more soluble than corresponding straight chain compound
- Water solubility DECREASES with an increase in MW
- Increased structural similarity between solute and solvent gives increased solubility
true or false
molecules having 1 polar functional group are usually soluble to a total chain length of 6 carbons
FALSE — 5 carbons
True or false:
molecules having branched chains are more soluble than the corresponding straight chain compound
TRUE
true or false:
water solubility increases with increasing molecular weight
FALSE – water solubility DECREASES with an increase in molecular weight
true or false:
compounds with similar dielectric constants will have better solubility than compounds with differing dielectric constants
TRUE
remember: like dissolves like
name the alcohols in order of number of carbons, from 1 carbon - 10 carbons
methanol
ethanol
propanol
butanol
pentanol
hexanol
heptanol
octanol
(idk 9?)
decanol
Name 7 solvents for liquid preparations
Alcohol, USP
Diluted alcohol, NF
Rubbing alcohol
Glycerin, USP
Isopropyl rubbing alcohol
Propylene Glycol, USP
Purified water, USP
Is
Alcohol, USP
a product or an ingredient (API)
PRODUCT – you can tell by the capital A and the USP after it
Alcohol, USP contains what compound?
Ethyl alcohol, also known as ethanol
what is the PRIMARY SOLVENT for organic compounds?
alcohol
Describe the % V/V of Alcohol, USP
94.9-96% v/v of ethanol
it is a HYDROALCOHOLIC MIXTURE. the remaining ~5% is made up of water
WHY is Alcohol, USP not 100% v/v of ethanol?
because it is more stable at 95%. In a sealed container of 100% alcohol, it will become 95% when opened and exposed to the air
name the alcohol-content limits that exist in OTC oral products
in children <6 years old — 0.5% limit
in children 6-12 years old — 5% limit
in people >12 years old —- 10% limit
Explain what Diluted Alcohol, NF is
Diluted Alcohol, NF is a mixture of EQUAL VOLUMES of Alcohol, USP (the PRODUCT)
and Purified Water, USP (PRODUCT)
Diluted Alcohol, NF is a useful ____ solvent
HYDROALCOHOLIC
true or false:
In Diluted Alcohol, NF, the final volume of the mixture is the sum of the individual volumes of the 2 components
FALSE
Diluted Alcohol, NF has the contraction effect. the final volume is reduced ~3% from the sum
Is Rubbing Alcohol used topically or orally?
topically
Explain the contents of Rubbing Alcohol (the PRODUCT)
70% by volume of dehydrated ethyl alcohol (100% alcohol. NOT the product Alcohol USP which is 95%)
the remaining 30% consists of water and denaturants
WHY are there denaturants in rubbing alcohol?
the denaturants make the separation of alcohol from the denaturants impossible with ordinary distillation apparatus.
-discourages illegal removal and usage as an alcoholic beverage
What is Rubbing Alcohol used as?
(he said in class that this is very important to know)
Used as a rubefacient and germicide to prevent the growth of bacteria on the skin
Name the components of Glycerin, USP
glycerol
Which has the HIGHEST viscosity – alcohol, water, or glycerol?
glycerol
What does auxiliary solvent mean?
what is often used as an auxiliary solvent with water or alcohol?
co-solvent; Glycerol, USP
Explain the physical characteristics of Glycerin, USP
higher viscosity than alcohol and water
it is a clear, syrupy liquid – therefore, it is good to use when we use simple syrup
does Glycerin, USP have preservative activity?
it technically does, but it’s only a 1:1 ratio
true or false
glycerin is often used as a stabilizer
true
Explain the contents of Isopropyl Rubbing Alcohol
70% by volume of isopropyl alcohol, the remainder is water.
Contrast Rubbing Alcohol and Isopropyl Rubbing Alcohol
Rubbing Alcohol is 70% ethanol while Isopropyl Rubbing Alcohol is 70% isopropyl alcohol
Isopropyl Rubbing Alcohol is less dehydrating and preferred for diabetics. It is also better than ethyl alcohol in germicidal activity
which is used in preparing needles and syringes for hypodermic injections of insulin and for disinfecting the skin:
-Rubbing Alcohol or
-Isopropyl Rubbing Alcohol
Isopropyl Rubbing Alcohol
Name the uses for Isopropyl Rubbing Alcohol
rubefacient, germicidal activity, soothing rub, vehicle for topical products, AND in preparing needles and syringes for hypodermic injections of insulin and for disinfecting the skin
what is the substitute for Glycerin, USP?
Propylene Glycol, USP
Propylene Glycol, USP can be nicknamed..
PPG
Name 4 ways in which Propylene Glycol, USP is similar to Glycerin, USP
-higher viscosity than alcohol and water
-preservative activity
-stabilizer
-auxiliary solvent with alcohol or water
which is used 1st – Glycerin or PPG?
Glycerin. PPG is only used if there is a problem
true or false
both Glycerin, USP and Propylene Glycol, USP are miscible in both water and alcohol
TRUE – remember – they are often used as auxiliary (co) solvents with them
Purified Water, USP is more free of solid impurities than drinking water.
Give the altering percentages
0.001% impurity vs 0.1% impurity
how many preparation methods of purified water are there? name them
3 methods of preparing purified water:
-distillation
-ion-exchange
-reverse osmosis
can Purified Water, USP be used for parenteral administration?
NO – use Water for Injection, Bacteriostatic Water, or Sterile Water
PURIFIED WATER CANNOT BE USED
