pharmaceutics exam 3 Flashcards
what are solutions
what may solutions be
“Liquid preparations that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents”.
Solutions may be,
- Oral
- Otic
- Opthalmic
- Topical
What is the maximum concentration to which a solution can be prepared with that agent and solvent?
Attractive forces- what do they cause molecules to do
Repulsive forces- what does it cause molecules to do
Dipolar molecules-
Hydrogen bonding-
in solution, are there are attractive or repulsive forces
what do you want a balance of
what atoms of hydrogens move close to
what molecules also form hydrogen bonds
Solute must dissolve – attractive forces cause molecules to cohere and adhere to each other based on their attractiveness
Repulsive: prevents the molecules from interpenetrating each other
In a solution, there are both but if they are equal then the potential energy is minimal – do not have too many attractive or repellent forces and that’s when the solution is most stable and dissolved
Want a balance of both attractive and repulsive forces
Dipolar molecules align to each other based on negative and + end
Hydrogen atoms move in close to electronegative atoms (i.e., F, O, N)
Hydrogen bonds exist also with
Esters, Carboxylic acids, Aldehydes, Polypeptides
How to improve solubility conditions
What options are available to pharmacists?
what consists of 0.03% iodine
can use:
Different solubilizing agents
Different chemical salt form of medicinal agent
Alteration of the pH of a solution
Partial or whole substitution of a solvent
Example; 1g of iodine granules in 3,000 mL (0.03% iodine)
Alternative: dissolve in Potassium Iodide, Sodium Iodide
Iodine Topical Solution, USP (contains 2% iodine, 2.4% sodium iodide)
How do you make sure that solute gets into solution:
what do undissolved solutes need to do
in dissolved solution, what does the solvent have a higgher affinity for
How do you make sure that solute gets into solution: excipients – additives to improve solubility.
Example: pure water, can add some alcohol
Undissolved solute: water/solvent needs to overcome the balance of attractions between the solute molecules (so the affinity for one molecule for another); solvent needs to be able to overcome the solute-solute attraction to make a solute-solvent attraction
- (easier to do for monovalent molecules or molecules where at least ine atom is monovalent than a molecule that is multivalent).
- Need to overcome the attraction of the solute
In dissolved, the solvent has a higher affinity for the solute and was able to overcome the solute-solute attraction
Want a solute-solvent interaction.
The potential energy is a mimimum and you have a more stable solvent
When the exact solubility is not known (or has yet to be
determined), general expressions of relative solubility may be used.
what are they and how many are there
what is the unit
what do you need to do if you have more and more insoluble particles
Very Soluble <1
Freely Soluble 1-10
Soluble 10-30
Sparingly Soluble 30-100
Slightly Soluble 100-1000
Very Slightly Soluble 1,000-10,000
Practically Insoluble >10,000
or Insoluble
all in parts per whole
More and more insoluble: need more and more solvent
what Factors influence solubility
what is a positive heat of solution
what is a negative heat of solution
Temperature:
- “Positive heat of solution”
pH of the solution:
Weak acids or weak bases
Physical agitation:
Extent to which solvent passes over solute
Particle size:
Finer the powder, greater the surface area, the more rapid dissolving process
Most drugs have a positive heat of solution so they dissolve with heat. Some might have a negative heat of solution, and do not dissolve and this makes things worse
Solubility: Beneficial considerations
are salts more or less soluble in water
what are organic bases most soluble in
is alcohol more or less lipophlic
Salts of organic compounds are more soluble in water compared to their organic base counterparts.
Organic bases are more soluble in organic solvents
Like prefers like
For atropine 455.0 mL of water for 1 g of drug
For atropine sulfate 0.5 mL of water for 1 g of drug
Alcohol is more of a lipophilic environment so molecules might dissolve better.
- this is why for drugs that are not as soluble in water, alcohol is used as an alternative
“like dissolves like”
wha do solvents need in order to dissolve
what are organic molecules most soluble in and what is the exception
what are examples of polar groups
do halogens increase or decrease solubility and why
what happens in Cl or F is added
Solvents having chemical structures most similar to the solute will most likely dissolve it.
For i.e., organic compounds are more soluble in organic solvents compared to in water.
One exception is if organic compound has polar functional group.
Polar groups are:
OH, CHO, COH, CHOL, CH2OH, COOH,
NO2 and SO3H – dissolve well in water
In general, halogen atoms decrease solubility
–Because of an increase in MW without proportionate increase in polarity
If Cl or F is added, then there is more MW without the proportional increase in polarity which is why the single addition of a Cl or F does not improve solubility but actually decreases it
Inorganic MOLECULES
what does monovalent mean
If cation and anion of an ionic compound are monovalent, what is easily overcome
what is you have two ions
what happens in the catiion and anion are multivalent
how much solubility is there for this
are ammonium and quaternary ammonium salts water or lipid soluble
what kind of molecules are water insoluble
If cation and anion of an ionic compound are monovalent, solute-solute attractive forces are easily overcome by the solvent. Not very strong
(i.e., NaCl, LiBr, KI).
Same is true if one of the two ions in an ionic compound is monovalent (i.e., BaCl2, MgI2)
If both the cation and anion are multivalent, the solute-solute interaction may be too great to overcome (i.e., CaSO4, BaSO4) by the solvent
This results in POOR WATER SOLUBILITY
Ammonium and quaternary ammonium salts are water soluble
Phosphates, Carbonates, Silicates, Borates, and Hypochlorites are water insoluble (except for their alkali metal salts and ammonium salts).
organic MOLECULES
molecules what number of polar functional groups is sufficient to solubilize chain lengths with how many carbons
what is more soluble: branched or straight chains
how does MW affect water solubility
what is can increase in structural similarity between solutes result in
Molecules having one polar functional group is sufficient to solubilize chain lengths consisting of 5 carbons
Molecules having branched chains are more soluble than corresponding straight-chain compounds
Water solubility decreases with increase in molecular weight (like with adding F, increase in MW without proportional increase in solubility)
Increased structural similarity between solute and solvent = increased solubility (remember: “like dissolves like”)
Solvents for liquid preparations
Alcohol, USP: Ethyl alcohol, ethanol, C2H5OH
A primary solvent for many organic compounds
When mixed with water = hydroalcoholic mixture
Alcohol USP is 94.9% to 96.0% C2H5OH by volume, when determined at 15.56 °C
15.56 °C (U.S. government standard temp. for alcohol determinations).
Dehydrated Alcohol, USP contains not less than 99.5% C2H5OH.
Want to promote solute, solvent interactions
add ethyl alcohol to be a part of solution
Dehydrated: less water
for drugs not soluble in water, what is a suitable alternative and why
what are examples of insoluble agent
when alcohol is too much, what can be used
are the limits of alcohol content for For children < 6 years, 6-12 and 12+
For drugs not soluble in water, alcohol is preferred as a suitable alternative due to its miscibility in water and ability to dissolve many water insoluble agents.
For e.g., Drug agents, flavorants, antimicrobial preservatives.
When alcohol content is too much, glycerin and glycols can be used to reduce total amount of alcohol needed.
FDA proposed for manufacturers of OTC oral drug products
For children < 6 years of age alcohol limit is 0.5%
For children 6 to 12 years of age, limit is 5%
For children over 12 years of age & adults limit is 10%
Diluted Alcohol, NF
how is it prepared
since liquids tend to contract, what is the final volume
what is diluted alcohol useful for
Prepared by mixing equal parts of alcohol USP with purified water
Since liquids tend to contract during mixing the final volume is generally 3% less than what otherwise should be expected.
For example, if 50 mL of each component is combined the result is 97 mL.
Dilute alcohol is a useful hydroalcoholic solvent in various pharmaceutical processes and preparations
Rubbing Alcohol
how much ethyl alcohol does it have
To discourage oral ingestion each, how much of a certain solution is added to each ____mL of solution – how does it taste
what is the denaturant that is employed called
what is it made of
Rubbing alcohol contains about 70% ethyl alcohol by volume, remaining is water, denaturants (with or without color additives and perfume oils and stabilizers).
To discourage oral ingestion each 100 mL must contain not less than 355mg of sucrose octa-acetate (or 1.4 mg of denatonium benzoate) which has a bitter taste and discourages internal use.
Internal Revenue Service- U.S. Treasury Department, the denaturant employed is called Formula 23-H
8 Parts (by volume) of acetone
1.5 Parts (by volume) of methyl isobutyl ketone
100 parts (by volume) of ethyl alcohol
Glycerin, USP (Glycerol)
A clear syrupy liquid with a sweet taste
Miscible in water and in alcohol
Glycerin is naturally viscous, but can be made less viscous by heating
Can be used as a preservative or stabilizer
Can also be used for internal applications in addition to external use
Isopropyl rubbing alcohol
how much isopropyl alcohol does it have
where is it used
how much of it is used to prepare diabetc needles and syringes
what is a rubefacient and what is its mechanism
Isopropyl rubbing alcohol, ~70% isopropyl alcohol.
Remaining components are water (with or without colorants), stabilizers and perfumes.
Used externally as *rubefacient and soothing rub vehicle for topical purposes.
To prepare diabetic needles and syringes for hypodermic injections of insulin, a commercially available ~91% isopropyl rubbing alcohol is used also.
- “A rubefacient is a substance for topical application that produces redness of the skin e.g. by causing dilation of the capillaries and an increase in blood circulation”
Propylene glycol, USP
Viscous liquid, miscible in alcohol and water
Relatively nontoxic liquid that is practically colorless, odorless, and tasteless.
Used as a solvent for flavors, extracts, drugs, food antioxidants as well as a heat transfer medium
Can substitute for glycerin in pharmaceutical formulations
Purified Water, USP, H20
Must meet U.S. Public Health Service regulations with respect to bacteriologic purity.
Drinking water should be,
Clear, colorless, odorless, neutral or slightly acidic or alkaline.
Tap water not acceptable for manufacturing or extemporaneous compounding
Contains 0.1% of solids per 100 mL of evaporated H2O
Possible chemical incompatibilities between solids and drug agent could result.
Signs that chemical incompatibilities have occurred
Precipitation, discoloration, effervescence
Preparation of solutions
usually, which is greater amount of solute or solvent
how are pharmaceutical preparations expressed
what are
W/V
V/V
W/W
what are the unfavorable interactions
usually, the amount of solute is far less than the amount of solvent
pharmaceutical preparations are expressed in percent strength
W/V:
percent weight in volume
- solids in liquids
V/V:
percent volume in volume
liquids in liquids
W/W: percent weight in weight
- solids in semisolids
unfavorable interactions to know:
- Liquid pharmaceuticals for oral administration to patient usual dose = 5 (one teaspoonful), 10, 15 mL (one tablespoon).
Purified Water, USP, H20
how is it obtained/what kinds are there
how many impurities does it have in comparison to drinking water
when evaporated how much is in solid form
what is it used for
Distillation, Ion exchange treatment, reverse osmosis
As a result, fewer impurities than drinking water
When evaporated no more than 0.001% total solid (1 mg of solids per 100 mL of water)
Used in the preparation of aqueous dosage forms (except for IV administered drug substances)
Considerations for pharmacists
some chemical agents do what
what can you do
Some chemical agents take longer to dissolve.
what you can do to help with this
- Apply heat
- Reduce particle size of the solute
- Use a solubilizing agent
- Apply vigorous agitation
Which of the following would suggest that your newly prepared solution contains chemical incompatibilities?
A) Effervescence
B) Discoloration
C) Precipitation
D) A and B only
E) A, B and C
All of them!
Signs that chemical incompatibilities have occurred
Precipitation, discoloration, effervescence
From slide 21 :)
Dry Mixtures for Solution
it contains everything for formulation except what
after reconstitution, where should it be placed, and for how long
with any remaining amounts, what should the pharmacist tell the patient?
what are examples of this
what needs to be done for oral powders
Dry mixtures for solution contain all of the required components of the formulation (i.e, colorants) EXCEPT the solvent.
Following reconstitution using required volume of liquid solution, it should be stored in the refrigerator for a period not to exceed what’s written on label.
Typically 7 to 14 days
Pharmacist to instruct patient to discard remaining
Examples are,
Cloxacillin Sodium for Oral Solution, USP- an anti-infective antibiotic
Penicillin V Potassium for Oral Solution, USP- an anti-infective antibiotics
Potassium Chloride for Oral Solution, USP- a potassium supplement
For oral: powder that needs to be reconstituted
Oral Solutions
When will a pharmacist be required to dispense a commercially prepared oral solution?
- commercial
- pediatric
- bulk
When will a pharmacist be required to dispense a commercially prepared oral solution?
When necessary to dilute a commercial preparation
When necessary to prepare a pediatric solution by reconstitution of a dry powder
When necessary to extemporaneously compound an oral solution from bulk components
Ex: 1 Oral Rehydration Solutions
what can lead to dehydration and/or death
what can rapid fluid loss lead to
depeltion of what ions results from this as well
what kind of solutions are effective for this problem
Bodily fluid loss (such as with diarrhea) can lead to dehydration and/ or death.
5 million children < 4 years old die from diarrhea annually worldwide.
The rapid fluid loss can lead to loose, watery stools and dehydration.
Depletion of sodium, potassium, and bicarbonate ions results as well.
Oral rehydration solutions are effective with volume depletion of 5 to10%
of body weight.
Ex: 2 Oral Colonic Lavage Solution
what is it used for
how long must you be on a _____ diet
what must you take the night before
what is an alternative drink for this procedure
Preparation of the bowel for colonoscopy
Clear liquid diet for 24-48 hrs prior to procedure
Oral laxative (i.e., magnesium citrate or bisacodyl) night before; cleansing enema 2 to 4 hours prior.
Poor compliance can be a problem, but often not.
Hospital stays are sometimes recommended to monitor the period prior to procedure
Alternative to this procedure:
PEG-3350-Electrolyte Solution
Oral administration of balanced solution of electrolytes with polyethylene-glycol.
Ex: 2 Oral Colonic Lavage Solution
adult dose of soln
how much soln before GI procedure
how fast should the patient consume the solution
when will the first BM be
what is the drinking regimen
Adult dose: 4 L of solution before GI procedure.
Patient should rapidly consume 240 mL of solution every 10 minutes until all is consumed.
First bowel movement will occur within 1 hr.
Different regimens
3 hrs drinking, 1 hr waiting to complete waste removal
Ideally, NO food intake 3 to 4 hrs prior to procedure
Definitely, NO food intake 2 hrs prior to procedure.
Product is to be stored in refrigerator after reconstitution
Formulation:
PEG-3350 236.00g
Sodium sulfate 22.74g
Sodium bicarbonate 6.74g
Sodium chloride 5.86g
Potassium chloride 2.97g
Ex.3: Sodium Citrate and Citric Acid Solution
what are the components
useful for patients requiring what?
Official Solution:
Sodium citrate 100 mg/mL
Citric acid 67 mg /mL
Dose 10 to 30 mL, up to 4 times daily
Useful for patients requiring alkaline urine
For example, uric acid with urinary tract
Or, gout therapy- to reduce crystallization of urates
Syrups
how much alcohol
what are the standard components
what is the purpose of this dosage form
Alcohol content
- very little if any
Standard components
- purified water
- sucrose
- flavoring agents
- coloring agents
- therapeutic agents
Purpose of dosage form
- pleasant tasting vehicle for extemporaneous preparations
- added to the standard formula for medicated syrups
- To be added to the preparation of standard formula for medicated syrups (syrups containing medicinal agents).
- Medicated syrups are commercially prepared from individual components (i.e., purified water, sucrose, flavoring agents, coloring agents, therapeutic agents, etc…).
elixirs
how much alcohol
what are the standard components
what is the purpose of thiis dosage form
Alcohol content
- 10-12%
Standard components
- alcohol and water, additives: glycerin, propylene glycol, colorants, flavorants
Purpose of dosage form
- Nonmedicated elixirs used as vehicles
- Medicated elixirs used to exert drug effect
orally used
sprays
how much alcohol does it have
what is the purpose of the dosage form
- how is it ofetn administered and why
- what are one-way pumps used for
- what is the dosage form for
Alcohol content
- very little if any
Standard components
- can have antibiotics and antihistamines
Purpose of dosage form
- Often administered intranasally to relieve nasal congestion and inflammation
applied in the nose to relieve nasal congestion
- apply drugs systemically and quickly
- one-way pump sprays prevent the drawback of particles in the bottle, nothing can go inside the product to contaminate it
- One-way pump sprays, developed to deliver drugs to the nose. Used for prescription and non-prescription medications.
- dosage form for the nasopharyngeal tract or to the skin
tinctures
how much alcohol
what are the standard components
what is the purpose of this dosage form
Alcohol content
- 15% - 80%
Standard components
- vegetable materials
- alcohol and water
Purpose of dosage form
- - to dissolve inorganic compounds due to high amount of alcohol
What is another name for Syrup NF? Discuss the composition. When are preservatives used?
simple syrup is another name
- made of purified water and sucrose, medicate syrup add on flavoring agents, coloring agents, therapeutic agent
- preservatives are used to prevent microbial growth and to ensure their stability during their period of use and storage.
What is a tincture? What importance does the alcohol content serve (be specific)?
Alcoholic or hydroalcoholic solution; high [ ] of plant extract
- high alcohol helps to dissolve inorganic compounds and help preserve
What are the major components of Ophthalmic solutions?
- for eye drops have to be sterile
- some have preservatives and some do not
- buffer
What are the reasons for buffering an ophthalmic solution?
To achieve greater comfort to the eye (because if too acidic, would be irritating for people that cannot produce tears)
To render the formulation more stable
To enhance aqueous solubility
To enhance the drug’s bioavailability
To maximize preservative efficacy
Why is the viscosity of the (ophthalmic) solution important?
Increasing the viscosity of the solution will improve the duration that the eye is exposed to the drug, compared to when a less viscous substance is employed.
- more viscous stays on the eye longer
A patient has dry eye (no tear production), how may this affect ophthalmic drug therapy?
want eye drop content to stay on eye as much as possible, so make eye drops more viscous because we want it to stay on the eye
- Tears can neutralize any excess hydrogen and hydroxyl ions introduced with the medicated solution. So the eye drop cannot be acidic.
- Tears can prevent any discomfort associated with use of medicines; most agents are weakly acidic (and have a weak buffering capacity). So patient is not able to prevent discomfort because they do not have tears and so eye drop cannot be overstimulating or acidic because they cannot prevent discomfort
Syrups
what is it
for non-medicated use, what is it used for
this vehicle (syrup) is meant to be added to what
how are medicated syrups prepared?
What are the two forms that it can come in
“Concentrated aqueous preparations of sugar (or a sugar substitute) with or without a flavoring agent and medicinal substances”
Non-medicated (flavored vehicles)
Intended Purpose:
Pleasant-tasting vehicles to be added to extemporaneously compounded preparations
To be added to the preparation of standard formula for medicated syrups (syrups containing medicinal agents).
Medicated syrups are commercially prepared from individual components (i.e., purified water, sucrose (the active substance in syrup), flavoring agents, coloring agents, therapeutic agents etc…).
can have medicated and non-medicated
syrups
how much alcohol does it have
what can be added to syrup and what must you be mindful of
what pH can the syrup medium be
what meds are usually used in syrup
Syrups contain very little (if any) alcohol so preferred by parents over other alternatives for their kids
If the drug is stable in solution it can be added to flavored syrup.
—Be mindful of unfavorable drug interactions
—what versatile drug substance
The syrup medium may be basic, acidic, or neutral, and should be selected with knowledge of drug stability in each. So can use syrup for any drug
The most frequently used medications in syrup form are,
Antitussive agents and Antihistamines
Opioid Analgesic
what is the active ingredient
what is the active ingredient’s concentration
what is it used for
Antihistamine, CHLOR-TRIMETON SYRUP OTC
what is the active ingredient
what is the active ingredient’ [ ]
what is it used for
Antiviral, NORVIR® (ritonavir)
what is the active ingredient
what is the active ingredient [ ]
what is it for
Antidepressant, Celexa (Forest)
what is the active ingredient
what is the active ingredient [ ]
what is it for
Opioid Analgesic, Demerol® Hydrochloride Syrup
Active agent: Meperidine HCL,
Concentration of active agent, 50 mg/5ml
For the treatment or relief of moderate to severe pain
Antihistamine, CHLOR-TRIMETON SYRUP OTC
Active agent: Chlorpheniramine maleate,
Concentration of active agent, 2 mg/5ml
For the prevention, treatment of allergic reactions
Antiviral, NORVIR® (ritonavir)
Active agent: Ritonavir
Concentration of active agent, 80 mg/ml
For the treatment of HIV
Antidepressant, Celexa (Forest)
Active agent: Citalopram hydrobromide
Concentration of active agent, 10 mg/5ml
For the treatment of depression (alternative to antipsycotic agents)
soothing, yummy taste, very stable over long period of time
Components of Syrups
what do syrups contain
what is not common to find in syrup
what can you add in low amounts and what thickness will it result compared to it in high amounts
what are the components of simple syrup and what is it considered to be
if you need to add antimicrobial preservatives or flavorants depends on what
for diabetic patients, what do you replace the sugar with
Most syrups contain:
- Purified water
- Sugar (usually sucrose)- typically 60 to 80%
—-Sorbitol, glycerin, and propylene glycol are all alternatives - Antimicrobial preservative?
- Flavorants?
- Colorants?
- Not uncommon to find the following in commercially prepared syrups,
—–Solubilizing agents, thickeners, stabilizers
add the low amount of sugar, will not be as thick compared to the high amount of sugar
simple syrup: 85 grams of sucrose to 100 mL of water, so much sucrose that it is a self-preservative
do I need antimicrobial preservatives or flavorants, depends on the amount of sucrose
For diabetic patients:
- replace sucrose with methyl cellulose to get the same viscosity but is tasteless then add artificial sweetener, this is equivalent to 60 to 80% sucrose
Preparation of Syrups
what are the 4 methods
- heat
- shake
- add
- percolation
One of 4 methods are generally employed,
- Solution of ingredients with aid of heat
- Solution of ingredients with agitation (no heat)
- Addition of sucrose to a prepared medicated (or to a flavored) liquid
1, 2 & 3 are preferred
- Percolation of either the source of the medicating substance or the sucrose. Ex. Ipecac syrup
Elixirs
what are they and are they usually flavored
if yes for what reason
what are non-medicated and medicated elixirs used for
are they easier to manufacture compared to syrups
are they as sweet as syrups
do they have a lot of sugar and what does it allow
what two componets in solution can it solubilize
what drug do you use when using an elixir
“Clear, sweetened hydroalcoholic (has water and alcohol) solutions intended for oral use, and are usually flavored to enhance their palatability.”
–Nonmedicated elixirs used as vehicles
–Medicated elixirs used to exert drug effect
Are easier to manufacture compared to syrups
Are not as sweet or viscous (thick) as syrups.
Contain less sugar, and so are less able to mask the unpleasant tastes of medicinal agents
Are capable of solubilizing both water-soluble and alcohol-soluble, components in solution.
use drug that is water soluble and low aqueous solubility– uh okay
what does the Amount of alcohol required to prepare an elixir depend on
The addition of several different drug agents will require what
what are common additives
what are used as substitutes to prepare elixirs containing a high alcohol content
what are elixirs that contain a high amount of alcohol considered
Due to high oil and alcohol content, where should elixirs be stored
what will happen if elixirs are not stored correctly
Amount of alcohol required to prepare an elixir will depend on water solubility of the medicinal agent
The addition of several different drug agents will require specific blending of alcohol and water to achieve the desired solution.
Glycerin, propylene glycol, colorants and flavorants are all commonly used additives
Artificial sweeteners (i.e., saccharin) are used as substitutes to prepare elixirs containing a high alcohol content. This is because sucrose is only partially soluble in alcohol and requires a lot more to achieve the same effect.
Elixirs containing high amounts of alcohol (10% – 12%) are “self-preserving” (not requiring the addition of antimicrobial agents).
Due to high oil and alcohol content, elixirs should be stored in tight, light-resistant containers and protected from excessive heat
–USP monographs provide standards for preparing Elixirs, but NOT formulas. The individual manufacturer can decide on the formula
if not stored correctly, like leaving the cap loose, then the alcohol can evaporate
Preparation of Elixirs
what are alcohol and water soluble drugs dissolved in
which is added to what, the water drug solution or the alcohol solution
why is it done that way
once the two mixtures are mixed, what happens
what often results from the separation
what is done if that happens
The agitation of components in solution (~ simple solution) and/ or admixture of two or more liquid ingredients
Alcohol-soluble drugs are dissolved in alcohol, and then
Water-soluble drugs are dissolved in purified water
The water drug solution is added to the alcohol solution (not the other way around). Why?
—When added In this order the highest alcohol content is maintained
Once the two mixtures have been mixed the desired solvent is added until the desired volume is achieved.
–Cloudy final mixture often results from the separation of flavorant oils in the reduced alcoholic solution.
If this occurs, the mixture sits (typically for a couple of hours) for the globules to coalesce. The formation of large globules makes for easier removal by filtration.
Elixirs
what is used to absorb an excess amount of oils
presence of what can assist with disolution of the solute and enhance ____
what is the downside of adding components
Talc is a frequently used filter which can absorb the excess amount of oils from the solution.
Presence of glycerin, syrup, sorbitol and propylene glycol in elixirs can assist with dissolution of the solute, and enhance stability.
The downside is the additionally added components will slow down rate of filtration due to the increased viscosity resulting from the addition of the 4 different components.
Tinctures
what does the high alcohol content allow for
because of all the alcohol, what must they be kept from
is it preferred by physicians and parents of kids
why is it usually stored in dark bottles
what does it sometimes have for disinfection
Alcoholic or hydroalcoholic solution preparations prepared from vegetable materials or chemical substances”
—Vary in terms of method of preparation, strength of active ingredient, alcoholic content, and intended use in pharmacy
Alcohol content: ranges from 15% to 80%
- The alcohol content protects against microbial growth and keeps alcohol-soluble agents in the solution
Due to high alcohol content, tinctures must be kept away from heat and tightly stopped.
Not preferred by physicians (or by parents of children) for the same reason.
Many of the components are light-sensitive so should be stored in light-resistant containers (protected from light). So usually in dark bottles
Examples, Opium Tincture, USP
highest alcohol content. compared to syrups (0%) and elixirs (10-12%)
sometimes has dye used for disinfection
Example of Tinctures
Vanilla Tincture, USP
*Vanilla, cut into small pieces
100g
*Purified Water
200mL
*Alcohol
207mL
*Sucrose, in coarse granules
200g
*Diluted Alcohol, a sufficient quantity
to make
1000mL
procedure:
Add Purified Water to the comminuted Vanilla in a suitable covered container, and macerate for 12 hours, preferably in a warm place.
Add Alcohol to the mixture, mix, and macerate for about 3 days.
Transfer the mixture to a percolator containing Sucrose, and drain.
Pack the drug firmly, and percolate slowly, using Diluted Alcohol as the menstruum.
Example of Tinctures
what can it be used for
how much iodine does it have
how much alcohol does it have
Iodine Tincture, USP
A tincture of iodine can be used to disinfect the area around an epidural catheter. Marks the area really well
Usually, between 2 and 7% Iodine is used
47% alcohol!
from tutor:
iodine is an inorganic molecule
adding it to a tincture will help it to dissolve because tinctures have a lot of alcohol
Sprays
what kind of solutions are they
what size are the droplets
where is it administered
what can it contain
why were one-way pump sprays developed
Why are one-way pump sprays are important?-
what must meds. for external use read
where must you not put a label
“Aqueous or oleaginous solutions (no alcohol, similar to syrups in regards to alcohol content) in the form of coarse droplets or as finely divided solids to be applied topically, most usually to the nasopharyngeal tract or to the skin.”
Often administered intranasally to relieve nasal congestion and inflammation
Often contain antibiotics, antihistamines
Can administer drugs systemically and quickly
—For example, Insulin, glucagon
One-way pump sprays were developed to deliver drugs to the nose. Used for prescription and non-prescription medications.
Why one-way pump sprays are important?-
Prevents drawback contamination of nasal fluids into the bottle after administration such as viral particles with the common cold.
Medications for external use to read: FOR EXTERNAL USE ONLY and keep out of reach of children make sure to put on be careful in lab
do not put a label on top of a label
Which agent will increase the hardness of a suppository when the incorporated drug lowers the melting temperature of the suppository base?
A
Ascorbic acid
B
Cetyl esters wax
C
Poly-ethylene glycol
D
Suspending agent
E
Emulsifying agent
B
Cetyl esters wax
stiffening agent!
Which of the following could the pharmacist do while filling the following prescription? *Salicylic acid 3g Sulfur 7g Lanolin 10g White petrolatum 10g Note: *Salicyclic acid = drug
A
Reduce the particle size to achieve non-grittiness
B
Place the ingredients on an ointment pill tile and mix with a spatula
C
Use an absorption base to incorporate liquid drug in an oleaginous base
D
All of the above
E
None of the above
- drug agent
** used in derm. prep
D
All of the above
topical application
for B: in the video: use an ointment slab
in oleaginous, there is no water
which of the following solvents is the most viscous
A
ethyl alcohol
B
propylene glycol
C
rubbing alcohol
D
dehydrated alcohol
E
purified water
B
Propylene glycol
CORRECT- GREAT JOB MICHELLE
it is the only one here that is viscous
can be glycerol but it is sweet and do not want for diabetic patients
viscosity
thickness etc
dosage form vs effectiveness
when should you not change the product
Note: If a drug has bioavailability Issues, or if patient has had success with a particular product in the past, product should not be changed without an understanding of behavior of the new product
on graph looks like solutions works a little better
Nonaqueous solutions
liniments
3 types
used for
solvents used
Liniments are nonaqueous solutions that can be alcoholic, oleaginous solutions, or emulsions, intended to be rubbed on skin.
there are two types:
- oleaginous with alcohol
- emulsions
1) Alcoholic-based liniments
—Counter irritant or if penetrating action is needed
2) Oleaginous liniments
- When massage desired; less irritating to the skin compared to alcoholic liniments
- The solvent may be almond oil, peanut oil, sesame oil cottonseed oil, or some volatile substance (i.e., wintergreen) or a combination of oil & volatile substance
3) Emulsion liniments
Emulsions are prepared first, and added to desired solvent
Linaments that are emulsions or contain insoluble matter must bear suitable labels such as
- SHAKE WELL (to distribute disperse phase)
Linaments should bear a label indicating
- for EXTERNAL USE ONLY
Vaginal Solutions
what is used to prepare solutions for vaginal douches - what are these used for
how can the thing used to prepare be packaged
- how are they used by the teaspoonful or tablespoonful
how is it prepared:
A measured amount of ____ is added to ___ _____, stirred, and _____
what is the purpose of vaginal douche’s
Powders are used to prepare solutions for vaginal douche, i.e., for irrigation cleansing of the vagina.
Powders can be prepared and packaged in bulk or as unit packages
—Bulk powders are used by the teaspoonful or tablespoonful to prepare solution
A measured amount of powder is added to warm water, stirred, and dissolved
The purpose is for their hygienic effects.
What do special solutions have?
do you understand why it would be a separate dosage form?
what are the specific sites of application
These solutions possess additional features making them better suited for ophthalmic, nasal, or otic use.
Based on Chapt. 13 (Solutions) and 14 (Suspension) lectures.
The specific sites of application are,
Ophthalmic Drugs
Nasal Preparations
Otic Preparations
Ophthalmic Drug Delivery
The normal volume of tear fluid in the cul-de-sac of the human eye is ~7 to 8 μl.
When an eye does not blink, it accommodates a maximum of 30 μl of fluid. When blinking it can retain ~10 μl.
Whether externally added or naturally produced, excessive liquids rapidly drain from the eye. Can only have so much there, issue: hard to deliver a good amount of drug to the eye
A single drop of an ophthalmic solution or suspension measures about 50 μl, so the majority of it gets drained.
The optimal volume to add is 5 to 10 μl.
—Unfortunately, the average dropper delivers ~25 to 50 μl/ drop, and other microliter dosing droppers do not exist
cannot be too small otherwise will poke eye
retention of solution
is the retention time for ophthalmic solutions long or short
how much of the dose administered is absorbed into the eye
example: how much of pilocarpine is flushed out of the eye
because of this, what needs to be done
what will improve the duration that the drug is exposed to the eye
what solution can be used and why
The retention time of ophthalmic solution on the eye surface is short.
The amount of ophthalmic solution absorbed is thus a small fraction of the dose administered.
For example,
- When pilocarpine ophthalmic solution is flushed from the eye within 1 to 2 minutes, the amount absorbed is <1%.
Due to the small fraction of absorbed drugs, repeated administration of solutions is required to achieve the maximum benefit of the therapy.
Increasing the viscosity of the solution will improve the duration that the eye is exposed to the drug, compared to when a less viscous substance is employed.
because methyl cellulose is tasteless and can be used in opth. solutions too
anatomy of eye
To minimize systemic absorption of active agents,what must you do
lacrimal gland
lacrimal sac
To minimize systemic absorption of active agents apply pressure to the lacrimal sac for 3 to 5 minutes following administration.
A recommendation to pharmacists: May be useful to inform patients using eye drops
Categories of Ophthalmic drugs
1) Anesthetics
2) Antibiotic and Antimicrobial agents
3) Antifungal agents
4) Anti-inflammatory agents
5) Antiviral agents
6) Astringents
7) Beta-adrenergic blocking agents
8) Miotics and other glaucoma agents
9) Mydriatics
10) Protectants and artificial tears
11) Vasoconstrictors
Sterility and preservation
which prep. must be sure to be sterilized
how is the sterilization don e
what is the benefit of filtration
what needs to be done if antimicrobial preservatives are to be added
how are they packaged if antimicrobial preservatives are not added
Ophthalmic preparations must be sterilized
Sterilization by bacterial filtration or by autoclave has been used.
The benefit of filtration is the removal of all particulate matter (microbial, dust, fibers) from preparation.
If antimicrobial preservatives are to be added, formulation stability, chemical and physical compatibility with other formulation components, and effectiveness must be determined.
–This is generally done at the preformulation stage
If antimicrobial preservatives are not added they are generally packaged in single-use containers.
Antimicrobial preservatives used,
are they always used or are there some limitations
can you autoclave chlorobutanol why or why not
Benzalkonium chloride, 0.004% to 0.01%
Benzethonium chloride, 0.01%
Chlorobutanol, 0.5%*
Phenylmercuric acetate, 0.004%
Phenyl mercuric nitrite, 0.004%
Thimerosal, 0.005% to 0.01%
There are limitations to their use,
For example,
It is not possible to autoclave chlorobutanol* due to instability when exposed to even moderate heat because the heat decomposes it to HCL
Review of Colligative Properties
what are they
what do the properties depend on
what do the properties not depend on
what happens when you increase solute
Physical changes that result when adding solute to solvent ( the properties will always change when solute is added to solvent)
- The properties depend on how many solute particles are present, and the solvent amount
- The properties do not depend on the type of solute, but rather the solvent type employed
increase solute: more and more changes
Colligative properties are,
Vapor pressure lowering
Boiling point elevation to a certain point
Freezing point depression, usually much greater
Osmotic pressure
Colligative properties continued: osmotic pressure
where does water flow
this happens until what
“Water flows through the semipermeable membrane to dilute the alcohol solution
until the force of gravity pulling down on the column of this solution balances the osmotic pressure, pushing the water through the membrane. “
Isotonicity Value
what is osmosis
what is osmotic pressure
the [ solution ] with respect to osmotic pressure is concerned with what
what is the concentration if the solute is not an electrolyte
what is critical for electrolytes
what do highly ionized substances do to particles
how does the number of particles effect pressure
Osmosis: The movement of water across a selectively permeable membrane from an area of high water potential (low solute concentration) to an area of low water potential (high solute concentration).
Osmotic pressure: the minimal pressure applied by a solution to prevent the inward flow of water across a semi-permeable membrane.
—The concentration of a solution with respect to osmotic pressure is concerned with the # of particles of solute in a solution.
If the solute is not an electrolyte, the concentration of the solution depends on the number of particles.
- For electrolytes, such as sodium chloride, the number of particles and degree of ionization are both critical.
- Highly ionized substances contribute a greater number of particles to the solution, compared to the same amount of poorly ionized particles- if more ionized then there will be higher pressure
So What?? The greater the number of ionized particles the greater the pressure
isotonicity and RBCs
body fluids like ___, have how much osmotic pressure corresonding to ___ of NaCl
what can the solution be considered because of this
what are hypotonic solutions defined as, what is the result
what are pertonic solutions defined as, what is the result
what is the range of isotonicity for ophthalmic solutions adn. without doing what
Body Fluids (blood and tears) have an osmotic pressure corresponding to that of 0.9% solution of sodium chloride.
–Therefore, the solution is ‘isosmotic’ (or having an osmotic pressure equal to physiologic fluids).
Solutions with lower osmotic pressure than body fluids (or 0.9% sodium chloride) are called hypotonic solutions. so less than 0.9%
–Hypotonic solutions may cause hemolysis of red cells
Solutions with higher osmotic pressure than body fluids are hypertonic.
–Hypertonic solution added to the body can draw water from cells toward the site of topical application, causing blood cells to shrink (crenate- crenation).
Isotonicity limits of an ophthalmic solution (in terms of sodium chloride) may range from 0.6% to 2.0%, that is without causing any discomfort.
Buffering
Why does a solution have to be buffered?
To achieve greater comfort to the eye
To render the formulation more stable
To enhance aqueous solubility
To enhance the drug’s bioavailability
To maximize preservative efficacy
do not want too acidic
pH and ophthalmic
what is the pH of normal tears
what can tears neutralize
what can tear prevent
when a drug is too acidic, what may happen
pH of normal tears is 7.4. Tears have a buffering capacity.
Tears can neutralize any excess hydrogen and hydroxyl ions introduced with the medicated solution.
Tears can prevent any discomfort associated with the use of medicines; most agents are weakly acidic (and have a weak buffering capacity).
When a drug is very acidic (i.e., pilocarpine hydrochloride, epinephrine bitartrate) it can overwhelm the natural buffering capacity of tears.
Viscosity and Thickening Agents
Viscosity: The force required to move one plane surface past another when the space between the surfaces is a liquid.
– Viscosity of water is given as 1 centipoise (1.0087cP).
A liquid material that is 10 times as viscous as water (at the same temperature) has a viscosity of 10 cP.
– The optimal range for ophthalmic use is between 15 to 25 cP.
Viscosity generally decreases with increasing temperature, so important to note temperature.
Methylcellulose
what does it do and for what kind of solution
what are hydroxypropyl methylcellulose and polyvinyl alcohol used for
Why is increasing viscosity important?
Methylcellulose is added to increase viscosity during the preparation of ophthalmic solutions.
–Hydroxypropyl methylcellulose and polyvinyl alcohol are often used as thickeners in ophthalmic solutions as well.
Why is increasing viscosity important?
- This helps to retain the drug in contact with the tissues to enhance therapeutic effectiveness.
- enhance duration of drug exposure
Packaging of ophthalmic solns
how are most packaged
what are the volumes of the containers that they usually are packaged with
what should patients protect ophthalmic solutions from and how will they do that
what are ophthalmic solutions that are packaged as eyewashes also packaged with
Most are packaged in small plastic containers with a fixed built-in dropper.
Ophthalmic solutions are commonly packaged in containers holding 2, 2.5,5,10, 15, and 30 mL of product.
Patients should protect ophthalmic solutions or suspensions from external contamination.
—Avoid the tip of the dropper from touching eyes or eyelids
Ophthalmic solutions used as eyewashes are packaged with eye cup, it must be washed and dried before use, and following each use.
what is a parenteral used for
what must the finished product be
what are pyrogens
To minimize systemic absorption of active agents as opposed to oral system which uses the systemic system to treat the illness - so parenteral will cause more localized absorption
A finished product must be
- Sterile,
- Non-pyrogenic*
- Free from insoluble materials
Pyrogens: “fever-producing organic substances from microbial
contamination”
Sterile conditions
what is used to administer sterile preparations via intravenous push or infusion systems and in what environment
where is this done
The syringe is used to administer sterile preparations via intravenous push or infusion systems
Positive
Flow hood
Intravenous route
what did Sir Christopher Wren do
Intravenous injection (I.V.) of drugs had its scientific origin in 1656 of Sir Christopher Wren who was an amateur scientist.
Injected wine, opium and other substances into dog veins and studied their effects
Drugs were administered to humans in 1662 but for some time were not used due to the occurrence of thrombosis and embolism in treated patients
Potential Problems
what do thrombus and embolus mean and what do they have to do with intravenous administration
when was the hypodermic needle introduced
Thrombus (blood clot)
embolus (traveling blood clot)
thrombus and embolus formation may be induced by intravenous administration.
These clots can lodge in a blood vessel and obstruct flow, and this happens when the needle comes in direct contact with the vessel wall
The Hypodermic needle was later introduced for injection of sodium chloride and glucose
