Liquid Dosage Forms Flashcards
What are the two physical states of liquid dosage forms?
True solutions and dispersions
What dosage forms are considered dispersions?
Suspensions and emulsions
What is the definition of a solution?
Liquid preparation that contains one or more chemical substances dissolved in a suitable solvent or mixture of miscible solvents (drug is individual molecules surrounded by solvent molecules)
What are the two delivery modes of liquid dosages and how are they given?
Systemic (oral, injection, sometimes to other membranes like nasal or rectal) and local (direct application to skin, eye)
Are drugs in solution absorbed into the body quickly or slowly?
Quickly, because the drug is already in solution and ready to pass through a biological membrane
What are some advantages of liquids?
They are easy to swallow and easy to spread, easy to administer (except injection), easy to make dose adjustments, and they are rapidly absorbed
How do you adjust the dose of a solution?
Changing the volume of a solution adjusts the dose
What is a co-solvent’s role in a solution and how does it work?
Co-solvents are necessary to help dissolve poorly soluble drugs, and they work by modifying the dielectric constant so the solution dissolves the drug easier
Liquids that contain ethanol as a co-solvent are called…
elixirs
What are some common ingredients found in liquid dosage forms?
Water and co-solvents (if needed), sweeteners (oral doses), preservatives (multi-dose containers), buffers, flavors and colors
What are the two kinds of preservatives and what are their roles?
Antimicrobial (inhibits bacteria and mold) and chemical (prevents degradation of the product, especially because of oxygen)
What is the role of buffers in liquid doses?
Controls pH
What are the three solvent vehicles that are suitable for oral administration?
Simple, Syrup, Elixir
What is contained in a simple solvent?
Water and minimum ingredients (may contain buffers, preservatives)
What is contained in a syrup solvent?
Large amounts of sucrose, flavors, and sweeteners
What is contained in an elixir solvent?
Water and ethanol, as well as sweetener if oral
What are some disadvantages of solutions?
The shelf life of a solution is not as long as solid state products (drug degrades faster), they are not very portable (inconvenient to carry large volumes around), poor taste can lower compliance, most drugs not very soluble
What is the ideal volume for adults that a drug should be soluble enough to be administered in?
5-15 milliters
Which drugs, polar or nonpolar, tend to be poorly water soluble?
Non-polar
What are the three common co-solvents?
Ethanol, propylene glycol, glycerin
What is a disadvantage of using co-solvents?
They have pharmacologic activity and so can’t be used in very high concentrations
At high concentrations, what effects does glycerin have?
Strong GI discomfort (diarrhea), and also supports microbial growth
At high doses, what effect does propylene glycol have?
Can be cardiotoxic
What kind of water is never used in pharmacy products?
Drinking water
What is required of sterile water for injection?
That it be both sterile and pyrogen-free
What are pyrogens?
Organism by-products like cell membrane fragments and lipo-proteins
Which are the three sterile waters might contain preservatives?
Sterile water for inhalation, purified water (distilled water), sterile water for irrigation
What is the purpose of preservatives in sterile water for inhalation?
Large batches could be made at one time, or the pt could be inhaling the solution over a long period of time
What is the most common sterilization method?
Steam sterilization
What symptom do pyrogens cause?
Fever
Which solution, opthalmic or otic, must be sterile?
Opthalmic
Are ear, eye, and nasal solutions made to be absorbed into the bloodstream?
No, they are made to act locally
What are the three types of sterile solutions applied directly to the eye and what are they for?
Washes (get rid of debris), therapeutic effect on surfaces (cornea and conjunctiva), therapeutic effect on deeper structures (must pass through cornea)
Why is it important for therapeutic eye treatments not to irritate the eye?
Eye irritation promotes tearing and crying, which would wash the drug out of the eye
What is an aerosol solution?
A drug solution broken up into very small droplets
What size droplet is required for an aerosol solution to fully penetrate the lungs?
droplets 5 microns in diameter
When trying to deliver drug to the nasal cavity, where is the drug deposit goal area?
Turbinate regions (systemic seems to work best specifically at Superior Turbinate)
What size droplets are key for nasal delivery?
20 microns in diameter or larger (b/c deposit into turbinate regions best)
What nasal delivery device was developed at the UK college of pharmacy in the late 1980s?
The metered pump
What are the advantages of the metered pump for delivering nasal solutions?
Can be designed for systemic absorption, can deliver a well-defined, precise dose
What is meant by the term parenteral?
A needle is needed to inject the drug (into various depths of the body)
What are the different parenteral routes?
Intramuscular (IM), intravenous (IV), subcutaneous, intradermal
Does a larger or smaller gauge number indicate a larger needle diameter?
A smaller gauge number means a larger needle diameter
What form of parenteral route do insulin patients commonly use?
Subcutaneous
Why do parenteral drugs need to be sterile and pyrogen-free?
Because they are piercing the major mechanical barrier of the body, the skin
What is an ampoule?
An all glass, single use container used for up to 50 ml of liquid; the top must be broken off to access solution
What are some problems with ampoules?
Possibility of glass shards in the solution (use needles with a built-in filter), and possibility of injury from opening
What is a vial?
Glass, multi-dose container with rubber membrane on the top (septum)
What are three types of small volume parenterals?
Ampoules, vials, prefilled syringes
Why do you need to use needles with filters when getting drug from a vial?
To make sure there are no rubber pieces in the solution
What is lyophilization?
Freeze drying, when sterile aqueous solutions of drug frozen and then subjected to a high vacuum, so the water sublimes and only the drug and other ingredients remain solid and ready to be reconstituted
What are large volume parenterals commonly used for?
A vehicle for intravenous drug delivery, fluid replacement, or delivery of nutrients
What volume usually constitutes a large volume parenteral?
100 mls or more
What is an administration set?
Device to transfer large volume parenterals (LVP) from container to patient
What is the most rapid method to supply drug to blood?
Intravenous delivery (bypasses all barriers)
Why is IV delivery the most dangerous technique?
High chance of blood-borne infections and clot (thrombus) formation because of vein irritation or particles
Are larger or smaller veins ideal for IV use?
Larger veins, which aren’t irritated as easily
What are the three types of IV administration?
IV push, Intermittent IV infusion, Constant IV infusion
With IV push, what volume of drug is given and over what period of time?
Only a few mls given, over 1-2 minutes (short and fast)
With Intermittent IV infusions, what volume of drug is given and over what period of time?
Several doses of 50-100 mls, given over 10-60 minutes, with 4-6 hours between doses
With Constant IV infusion, what volume of drug is given and over what period of time?
Large volume, given over several hours
Of the three IV infusions, which administers the highest drug concentration? The lowest?
IV push is highest, Constant IV infusion lowest
Of the three IV infusions, which gives you the most control over how high the concentration in the blood gets?
Constant IV infusion, because you control the rate
What does the concentration vs. time graph start to level out for Constant IV infusions?
Because the rate of infusion starts to equal the rate of elimination
Which of the three IV administrations is used for antibiotics most commonly?
Intermittent IV infusion
Why are Intermittent IV infusions used for antibiotics rather than Constant IV infusions?
Intermittent infusions are cheaper, easier on nurses, sometimes drugs not stable enough in solution for constant IV
Which parenteral delivery route uses the largest needles (smallest gauge)?
Intramuscular delivery
What volume of solution is usually delivered intramuscularly?
5ml for gluteus and 2ml for deltoids
What are some examples of large muscle masses good for IM administration?
Deltoids, midlateral of the thigh, gluteus
Even though IM administration takes longer to reach peak blood levels, what are some advantages of this method?
Less invasive than IV treatment (no direct blood access), concentration levels can be maintained longer with a single injection
On the concentration vs. time graph, IM administration tends to longer ____ and lower ____
Tmax, Cmax
Where are three good places for subcutaneous injection?
upper arm, anterior thigh, lower abdomen
What is the maximum volume that should be injected subcutaneously? Why?
The max volume is 1 ml, because any larger and the solution would overflow the hole created by the needle
Does it take longer for IM or subcutaneous dosages to reach the blood?
Subcutaneous dosages, because they have farther to diffuse
Which parenteral route is used for TB tests?
Intradermal
What is a dispersion?
Usually liquid dosage form where drug molecules aggregated together in large groups
What is the difference between dispersions and solutions?
In dispersions, drug molecules clump together, whereas in solutions drug molecules exist singly surrounded by solvent
What is the difference between suspensions and emulsions?
In suspensions, there are insoluble solid particles (usually drug) in the liquid; in emulsions, there are two liquid phases that don’t mix combined
What is the “dispersed phase” of the dispersion?
The drug particles or oily droplets
Even in a dispersion of poorly soluble drugs, does some of the drug exist in solution?
Yes, a small part of the drug solubizes
Can dispersions, suspensions, or emulsions be given via IV?
Dispersions and suspensions cannot, but emulsions can (rarely)
Are dispersions designed for both systemic and local administration?
Yes
Since dispersions and suspensions cannot be given via IV, what parenteral routes are acceptable?
Intramuscular and subcutaneous
Are dispersions immediately ready to be absorbed after being injected?
No, in suspensions the drug particles must still dissolve and in emulsions the oily droplets must separate from the solution before they can be absorbed
For which class of drugs is reconstitution common?
Antibiotics
What are some advantages of dispersed systems?
Allows reasonable drug volume to be administered (when large volume of drug in solution impractical), easy to adjust dosage, slightly easier to mask drug taste (less interaction with taste buds because drug not fully in solution), can be used to modify rate of release of active agent
What are some requirements of dispersions?
Small, uniform dispersed phased that doesn’t sediment rapidly, easily redisperses once sedimented, easy to pore/inject, acceptable color/taste/odor
What are the excipients of a suspension?
Wetting agent, suspending agent, protective colloid, flocculating agent, buffers, preservatives, sweeteners, flavors, colors
What is a flocculating agent suspension excipient?
Helps particle aggregates in suspensions easily break up with shaking
What is the purpose of a protective colloid excipient in suspensions?
It inhibits particles from forming large aggregates
What does a suspending agent excipient in suspensions do?
Increases the viscosity of the suspension (not too high)
Emulsions, based on the dispersed phase, are classified as either _____ dispersed in ___ (w/o) or ____ dispersed in _____ (o/w)
water, oil, oil, water
What is an example of an opthalmic emulsion?
Restasis
