pharm. final review part 2 Flashcards
What are the three main suppository dosage forms discussed as part of this lecture?
What are preferred bases used during preparation, and what routes of administration are recommended for use?
1 - Rectal, into the rectum, cocoa butter
2 - vaginal (also called pessaries), into the vagina, PEG
3 - urethral (also called bougies), into male or female urethra, PEG
bases
- PEG for vaginal & urethral
- Cocoa butter - rectal
2) How much does each suppository type weigh, and how is each type shaped?
- rectal for adults weigh 2g, for children weighs 1 g (or half), shaped like a bullet, a torpedo, or the little finger
- vaginal weighs 5g (when cocoa butter is the base) and has a globular, oviform, or cone shape. PEG is preferred. Ideal MW: 1000! Melts at 37 to 40*C
- The urethral for males weighs 4g, for women weighs 2g (or 1/2 of the male urethra), and has a slender or pencil shape. PEG is preferred based
Discuss the fundamental difference(s) between the properties associated with use of cocoa butter and poly-ethylene-glycol when used as a suppository base.
cocoa butter: Cocoa butter melts between 30 and 36 °C. This is ideal. It’s a solid at room temperature and melts just below body temperature, which will be a faster release of the drug
- The addition of phenol and chloral hydrate can lower melting temp. (ex: cetyl esters wax & beeswax)
- melts
poly-ethylene-glycol: PEG suppositories will NOT melt at room temperature, but will dissolve slowly in body fluids. This lowers the release rate of drug substances.
- dissolves
neither one will be liquid at room temp.
4) What is MUSE? Briefly mention what it is used to treat (i), route of administration (ii) and any potential side effects (iii) associated with patient use.
it is a urethral suppository! also called alprostadil
treatment: MUSE is indicated for the treatment of erectile dysfunction. Erectile dysfunction (or impotence) is the inability to attain or maintain an erection sufficient for sexual intercourse.
ROA: the urethra
side effects:
* Aching in the penis, testicles, legs, and the perineum (area between the penis and rectum)
* Warmth or burning sensation in the urethra
* Redness of the penis due to increased blood flow
* Minor urethral bleeding or spotting due to improper administration.
* Prolonged erection
* Swelling of leg veins
* Light-headedness/Dizziness
* Fainting
* Rapid pulse
What are the advantages of using rectal suppositories for systemic action over the oral route of drug administration?
Drugs destroyed or inactivated by the pH, or enzymatic activity of the stomach, are ideal candidates
Drugs irritating to the stomach may be given without irritation
Drugs destroyed by the portal circulation may bypass the liver after rectal absorption
Convenient route for administration of drugs to adult or pediatric patients who prefer not to swallow medication
A convenient, and effective way to administer drugs to patients experiencing vomiting episodes and is used as a tranquilizer
- Prochlorperazine and chlorpromazine
What’s the functional role of hemorrhoidal veins and lymphatic circulation during the drug absorption process?
Hemorrhoidal veins surrounding the colon receive the absorbed drug and initiate its circulation throughout the body bypassing the liver - part of systemic action?
Lymphatic circulation assists with rectal drug absorption
Abundant vascularization of the submucosal region of the rectum wall with blood and lymphatic vessels
most of the time,
List physiologic and physicochemical factors influencing drug absorption.
Physicochemical factors,
- Relative solubility in lipid and in water
- Particle size of dispersed drug
- Ability to melt, soften, or dissolve at body temperature
- Ability to release the drug substance
Physiologic factors
- Diarrhea, circulation route, colonic obstruction due to tumors, and tissue dehydration can all slow down the rate of drug absorption
- Abundant vascularization of the submucosal region of the rectum wall with blood and lymphatic vessels
- Hemorrhoidal veins and lymphatic circulation (assist hem. vein) are responsible for drug absorption
- human rectum
- pH and lack of buffering capacity of the rectal fluids]- Rectal fluids are neutral in pH [no effective buffering capacity] and so drugs will not be changed chemically
- Greater absorption is expected from a rectum that is without fecal matter than with it. Why? without fecal matter, there is increased interaction of drug products with the intended absorbing surface
what do you know about the local action of suppositories?
How is local action different from systemic action?
What factors should you consider?
Local action of suppositories
Rectal suppositories:
- Frequently used to relieve constipation or the pain, irritation, itching, and inflammation associated with hemorrhoids
- Antihemmorhoidal suppositories typically contain a multitude of different agents (i.e., local anesthetics, vasoconstrictors soothing emollients, astringents, protective agents, etc…)
- When inserted the suppositories must melt or dissolve and distribute drug substances
- Transport from rectal epithelium primarily involves two transport processes: Paracellular route and transcellular route
Systemic Action
The mucous membranes of the rectum and vagina permit the absorption of many drug agents.
(The vagina is NOT used as frequently as the rectum for delivering drug substances; the vagina permits local drug effects only).
The anal canal is lined by a mucous membrane that covers the internal sphincter.
A suppository is inserted with the rounded end first so that it can be pushed in with the flat end.
The smooth muscles of the rectum quickly grip the inserted suppository and push it in further.
Once inserted, the cold, solid suppository picks heat from the body and then slowly melts to release the active ingredients inside it.
Local effects occur in the area of the body that has been in contact with the chemical.
Systemic effects occur after the chemical has been absorbed and distributed from the entry point to other parts of the body.
factors: physiological and physicochemical
Briefly discuss attractive and repulsive forces in a solution.
What is the relationship between hydrogen atoms and electronegative atoms?
attractive forces in solution allow the molecules in the solution to have attraction for one another due to their opposite charges and this will allow the molecules to dissolve and have interactions with each other
repulsive forces in solution repel the solutions from each other and this prevents the molecules from interacting with each other this is usually the case when there is an undissolved particles in the solution
Hydrogen bonding-
– Hydrogen atoms move in close to electronegative atoms (i.e., F, O, N)
in a homogenous mixture, there are more attractive forces then repulsive forces. In a mixture where there is precipitation, there are more repulsive forces that attractive forces
want the solutes and solvent to have a balance of attractive and repulsive forces but more attractives forces so that the solute can dissolve and not remain as a clump in solution :)
9) What can a pharmacist do to increase apparent drug solubility?
increase the amount of attractive forces
Different solubilizing agents
Different chemical salt forms of medicinal agent
Alteration of the pH of a solution - can change the charge of the molecule so that it can be more soluble. Charged molecules are usually more soluble :)
Partial or whole substitution of a solvent
factors influencing solubility
Temperature:
– “Positive heat of solution”
pH of the solution:
- Weak acids or weak bases
Physical agitation:
- The extent to which solvent passes over solute
Particle size:
- Finer the powder, the greater the surface area, and the more rapid dissolving process
True or False. If false, what would make the statement true? See pg 335; Edition 10 textbook
Molecules having branched chains are less soluble than straight chains. ____________________________
_______________________________________________________________________________________
What influence (if any) does an increase in the molecular weight of a drug have on solubility? _______________
Molecules having branched chains are less soluble than straight chains - false
actually:
molecules having branched chains are MORE soluble than straight-chain compounds
What influence (if any) does an increase in the molecular weight of a drug have on solubility?- the bigger the MW, the less soluble the drug; they are inverse;
What exactly is meant by “positive heat of solution” and “negative heat of solution”? See pg. 333.
“positive heat of solution”- adding heat will make the compound dissolve better
“negative heat of solution”- adding heat will not make the compound dissolve better but may make it precipitate more
Review your two different Pharmaceutics class worksheets on Liquid Solutions, and the one on Special Solutions. I will assume that you have done so when preparing your final exam questions.
11)
Syrups:
- alcohol: 0%
very little if any
- components: purified water, sucrose
flavoring agents, coloring agents, therapeutic agents
- purpose: pleasant tasting vehicle for extemporaneous preparations, added to standard formula for medicated syrups
elixirs
- alcohol: 10-12%
- components: water, alcohol (hydroalcoholic), additives, glycerin, propylene glycol, colorants, flavorants
- purpose: Nonmedicated elixirs used as vehicles
Medicated elixirs used to exert drug effect orally used
sprays
- alcohol: 0%
- components: can have antihistamines, and antibiotics
- purpose: applied in nose to be relieve nasal congestion apply drugs systemically and quickly, one-way pump sprays prevent drawback of particles into bottle, nothing can go inside product to contaminate it
tinctures
- alcohol: 15-80%
- components: vegetables materials, alcohol & water
- purpose: to dissolve inorganic compounds due to high amount of alchol
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
What is a tincture? What importance does the alcohol content serve (be specific)?
Alcoholic or hydroalcoholic solution; high [ ] of plant extract
high alcohol is help to dissolve inorganic compounds and help preserve
What are major components of Opthalmic solutions?
- for eye drops have to be sterile
- some have preservatives and some do not
- buffer
What are reasons for buffering an ophthalmic solution?
To achieve greater comfort to the eye
To render the formulation more stable
To enhance aqueous solubility
To enhance drug’s bioavailability
To maximize preservative efficacy
Why is the viscosity of the (ophthalmic) solution important?
- Increasing the viscosity of the solution will improve duration that the eye is exposed to drug, compared to when less viscous substance is employed.
- more viscous stays on 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 for a longer time
- 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
alcohol
(Ethyl alcohol, ethanol, C2H5OH
- USP
- 94.9% to 96.9% ethanol
- external or internal
- primary solvent for organic compounds
- used for drugs not soluble in water (for its miscibility in water)
- help dissolve organic compounds to be mixed in water
diluted alcohol
- NF
- 50% alcohol, 50% purified water
- external
or internal
- useful hydroalcoholic solvent
- help to dissolve organic compounds
rubbing alcohol
- USP
- 70% ethyl alcohol by volume
30% water, stabilizers, perfume oils, color additives, denaturants
- external (discourage oral by adding sucrose octa-acetate)
- disinfectant
glycerin
- USP
- Clear syrupy
miscible in water and alcohol
- Internal but can be for external too
- preservative
-stabilizer
isopropyl alcohol
- ~70% isopropyl alcohol
remaining amount is water, stabilizers, perfumes
- Externally
but 91% can be internal
To prepare diabetic needles and syringes for hypodermic injections of insulin, a commercially available ~91% isopropyl rubbing alcohol is used also.
- as *rubefacient and soothing rub vehicle for topical purposes.
propylene glycol
- USP
- propylene glycol
- internal or external
- Used as a solvent for flavors, extracts, drugs, food antioxidants as well as a heat transfer medium
- Can substitute for glycerin in pharmaceutical formulations - for diabetic patient who cannot have lots of sweet things
purified water
- USP
- PURE WATER
- Internal or external
- Used in the preparation of aqueous dosage forms (except for IV administered drug substances)
To be clear, know the differences between Alcohol (Ethyl Alcohol), Diluted Alcohol, Glycerin, Isopropyl Alcohol, Propylene Glycol and Purified Water.
Alcohol (ethyl Alcohol)
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.
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
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
Glycerin
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 Alcohol
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.
Propylene Glycol
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.
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
How is Purified Water, USP obtained?
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)
propylene glycol and glycerin are both miscible in water and alcohol
Rank the following aqueous preparations in terms of their alcohol content.
Which of the following is correct?
A) Syrups > Tinctures > Elixirs
B) Tinctures > Syrups > Elixirs
C) Syrups > Tinctures = Elixirs
D) Tinctures > Elixirs > Syrups
Tinctures > Elixirs > Syrups
b) What is the purpose of buffering a pharmaceutical preparation?
1) To achieve greater comfort to the eye
2) To render the formulation more stable
3) To enhance aqueous solubility
4) To enhance the drug’s bioavailability
5) To maximize preservative efficacy
The pH of tears is _______________ which can neutralize ____________________ and _____________________ ions introduced with the solution.
pH of normal tears is 7.4
Tears can neutralize any excess hydrogen and hydroxyl ions introduced with the medicated solution
d) Why is increasing the viscosity of a solution important?
What therapeutic benefit might increasing the viscosity of the solution provide?
increases the duration that the drug is on the eye
This helps to retain the drug in contact with the tissues to enhance therapeutic effectiveness.
Describe 4 physical changes that occur when a solute is added to pure solvent in preparation of a solution. These are also known as colligative properties.
Vapor pressure lowering
Boiling point elevation
Freezing point depression
Osmotic pressure
What is a Liniment dosage form?
B) Describe the difference between an oleaginous and alcohol-based liniment in terms of application and use.
Liniments are nonaqueous solutions that can be alcoholic, oleaginous solutions, or emulsions, intended to be rubbed on skin.
Alcoholic based liniments
- Counter irritant or if penetrating action is needed
Oleaginous liniments
* When massage is desired; less irritating to the skin compared to alcoholic liniments
Which liniment variety is Wintergreen used to prepare?
B) Can emulsions be used to prepare liniments? Yes, or No.
Oleaginous liniments use wintergreen
- 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
yes emulsion can be used to prepare liniments
- Emulsions are prepared first, and added to desired solvent
What are the FOUR parenteral routes of administration discussed as a part of this lecture?
Next to each provide needle gauge sizes and information regarding the injection site.
intravenous
- 23 gauge size (for bolus injections)
- 18 gauge size (for continuous IV infusions)
- flow rates: 42-150 mL/hour and lower flow rates
- rapid action due to direct injection into blood
intramuscular
- needle gauge: 20-22
- less rapid
intradermal
- needle gauge: 23 to 26
The injection is made when the bevel just disappears into the corium
The volume injected: approximately 0.1 ml is the limit
subcutaneous
- needle gauge: 24-26
The maximum volume injected comfortably is approximately 1.3 ml and slightly above.
2 ml is enough to cause painful pressure
f) Discuss the difference between water for injection and sterile water for injection? Be specific.
sterile water
- Water is intended to be used as a solvent, vehicle, or diluent for already sterilized and packaged injectable medications
- Water that is sterilized and packaged in single-dose containers of not more than 1-liter size.
- Must be pyrogen-free and may not contain antimicrobial agents or any other added substances
- Water is intended to be used as a solvent, vehicle or diluent for already sterilized and packaged injectable medications
- One-liter bottles cannot be administered intravenously because they lack tonicity. These are used to reconstitute antibiotics.
- Suitable injection: water is added directly to the medicinal substance such as with dry powders or granular substances
*******************
Tonicity: For our purposes, it is the osmotic pressure or tension of a solution, usually relative to that of blood
water for injection
- Water for injection is water of extra high quality without significant contamination.
- Most frequently used solvent in the large scale manufacturer of injections
- Water used for injection is usually purified by distillation or reverse osmosis, and should be used within 24 hrs after collection
- Not required to be sterile (free from all live bacteria and microorganisms)
- Must be pyrogen-free (whatever organisms are present should not result in an infection or fever) at time of use.
Once product is prepared is must be sterilized.
Water should be collected in sterile and pyrogen– free containers, and the containers are usually glass or
g) What is the difference between an aqueous solution and a non aqueous solution (or vehicle)?
aqueous solutions (syrups, elixirs, sprays) are water-based
nonaqueous are more oleaginous or alcohol-based
complete the information below-
3 Methods of sterilization (discussed as part of lecture topic)
Sterilization Type
Advantages
Advantages/ limitation
3 methods:
Steam
- May be used to sterilize bulk solutions, glassware, surgical dressings and instruments.
- Not useful for oils, fats and oleaginous preparations
Dry Heat
- Used for sterilizing glassware, surgical instruments, oils, glycerin, mineral oil and heat-stable powders
- Higher temperatures and longer sterilization times
Filtration
- Advantage of filter units: Speed in filtration, relatively inexpensive and complete removal of living and dead microorganisms
- Disadvantage of filter units: Proper inspection of filter unit is necessary to avoid using systems that are ruptured or faulty in some other way.
- Systems can be flawed during assembly
i) Define the term Biologics
Any substance produced by a living source.
Biologics include antibiotics, hormones, vitamins etc… Also know as immunobiologics
j) What are the 3 different types of Natural Immunity (discussed as part of lecture topic)?
Species Immunity
Some diseases naturally occur in humans, some in animals
Racial Immunity
Human races differ in general susceptibility to common infections
Individual Immunity
Differences in capacity to resist familiar diseases (i.e., common cold, skin disorders)
Review Lecture notes on Production, Packaging and Storage of Biologics
production
All biologics must meet standards as set by Center for Biologics Evaluation and Research of the FDA.
Tests must be performed to establish product,
Potency
General safety
Sterility
Purity
Water (residual moisture)
Pyrogens
Indentity
Constituent materials
Packaging and labeling requirements are similar to all other injectables
Other packaging requirements include,
Title or proper name (name under which the product is licensed under Public Health Service Act)
Name, address, license number of manufacturer
Lot number and expiration date
Recommended individual dose for multiple-dose containers
Preservative type and amount
Amount of product in the container
Recommended storage conditions
Statement that freezing is to be avoided (if necessary)
Biologics are sensitive to extreme temperatures
Heating or freezing can decrease potency & effectiveness
Real Potential Dangers
Patient gets little or no intended benefit.
Patient does not build up an immunity and is now exposed
Pharmacists should maintain the “cold chain”
If you receive it from manufacturer cold, keep it cold
Refrigerators should not be overstocked with products; cool air must have room to circulate
Separate refrigerator for biologics is advisable, this will cut down on number of times refrigerator is opened and closed
Pharmacists should educate and train every person who will handle biologics in good storage and handling procedures
Always store bottles containing the same vaccine material together. This will reduce chances of selecting the wrong product.
“Look-alike packaging and sound-alike names can confuse even most conscientious practitioner”
Center for Disease control issues on line publication describing storage and handling requirements for vaccines
