Jan 26 - Solution Dose Forms Flashcards
What is a solution?
A solution is a thermodynamically stable, one-phase system composed of two or more components, one of which is completely dissolved in the other. It is homogenous because the solute is dispersed throughout the solvent in molecular or ionic sized particles
What are common solutes?
Active drug components, flavouring, colouring agents, preservatives, and stabilizers or buffering salts
What is the most common solvent? What are other options?
Water is the most common solvent for pharmaceutical solutions, but ethanol, propylene glycol, isopropyl alcohol or other liquids may be used, depending on the product requirements
What is an appropriate solvent?
Must completely dissolve the drug and other solid ingredients at the desired concentration.
Must be nontoxic and safe for ingestion or topical application
Must be aesthetically acceptable to the patient
What are advantages to solution dose forms?
Solutions are completely homogenous
Immediately available for absorption into the body (whereas a solid dose form has to dissolve before it can be absorbed)
Flexible in terms of dose adjustment
May be used by any route of administration
Can be administered to patients who cannot swallow tablets or capsules
What are disadvantages to solution dose forms?
Drugs are less stable when in solution
Some drugs are not soluble in solvents that are acceptable for pharmaceutical use
Drugs with objectionable taste require taste making
Heavier and bulkier than solids so they are difficult to handle, package, transport, and store
Require measurement by the patient or caregiver. Often less accurate than individual solid dosage forms, such as tablets and capsules
What considerations should be taken into account with solution dose forms?
The solubility of each ingredient must be considered
To keep all the ingredients in solution, dissolve solids in the solvent in which they are most soluble
Other solvents in which the solid is less soluble should be added with stirring to prevent precipitation of the solute (ex. syrup preserved with alcohol)
Rate of dissolution may be increased by heating but solvent must be non-volatile and the solute stable to heat
Reduction of particle size and stirring will also increase the rate of dissolution
Final products must show pharmaceutical elegance. Explain
Solutions should be very clear
Small particulates can be removed by filtration
Particulates may be from packaging materials or very small amounts of degradation products
Solution must never be filtered to remove undissolved solute
Elegance reinforces patient confidence
What is solubility?
Solubility of an agent indicates the maximum concentration to which a solution can be prepared using that agent, solvent and temperature
What is the dissolution?
The process of dissolution involves breaking of the solvent-solvent and solute-solute forces and establishment of solvent-solute forces
What are factors in solubility and dissolution?
Temperature is a factor in solubility
Particle size and agitation affect the rate of dissolution but not solubility
pH may be a very significant factor if the drug is ionizable
What happens to the state of a solute when it dissolves?
When a solute dissolves, a change of state analogous to melting occurs. Heat is required to break the bonds holding the solute together (and solvent). Heat is released when the solute-solvent bonds form
What is the relationship between temperature and solubility?
Typically, when the temperature rises, solubility increases (however there are exceptions, e.g., calcium phosphate). If the heat given off in the hydration process is less than the heat required to break the solute-solute and solvent-solvent bonds, the process is endothermic (energy is required); the application of heat facilitates breaking of bonds and increases solubility. If the heat given off in the hydration process is more than the heat required to break the solute-solute and solvant-solvant bonds, the process is exothermic (energy generated); the application of the heat inhibits hydration and reduces solubility
When 70.0 ml of water is mixed with 30.0 ml of ethanol at 25 C, the final total volume of the solution is not 100.0 ml, but rather 97.0 ml. Why is this?
Two reasons: the intermolecular forces between two water molecules or between two ethanol molecules are different from the intermolecular forces between a water molecule and an ethanol molecule. Secondly, water and ethanol molecules have different sizes and shapes so the molecules will fit together differently in a solution compared to either pure ethanol or water
When 70.0 ml of water is mixed with 30.0 ml of ethanol at 25 C, the final total volume of the solution is not 100.0 ml, but rather 97.0 ml. What is the solution if we want a solution of exactly 100 ml?
We ‘qs ad’ the solution. We add the 30 ml of ethanol and approximately 60 ml of water. We allow the solution to cool then we add enough water to bring the solution up to 100 ml.
What is displacement volume? Why is this important?
A ‘displacement volume’ is the volume occupied by the powder when a suitable diluent is added during reconstitution. This is particularly important to take into account when the dose needed is only a proportion of the vial content. Displacement volume is different for each drug, for each strength of drug and for different brands/manufacturers formula
What are alkaloids?
It’s a generic term. They are weak bases that come from a natural source. They contain nitrogen atoms. They have huge pharmacology (big activity)
Free bases has poor solubility
How does pH affect solubility?
Many drugs are either weak bases or acids and solubility will be affected by pH of the solvent as they are able to form salts. Alkaloids like morphine, cocaine and atropine are insoluble but are weak bases and can form water-soluble salts with acids
What happens of the pH of a solution of morphine sulfate is raised?
If the pH of a solution of morphine sulfate is raised by the addition of an alkali, the morphine as a free base may come out of the solution
What are free bases typically soluble in?
Free bases may be soluble in organic solvents like alcohol so hydro-alcoholic vehicles may maintain solubility of a product even if pH adjustment results in some free base
What are some solubility generalizations?
Like dissolves like (a solvent having a chemical structure similar to the solute will likely dissolve it)
Organic molecules with polar functional groups can hydrogen bond with water to effect solution
The more polar functional groups present the more likely the molecule will be water soluble
Introduction of a halogen atom into a molecule will reduce solubility; increase in molecular weight without increase in polarity
What is the importance of the Noyes-Whitney equation?
The Noyes-Whitney equation defines the rate of solution of solids when the process is diffusion-controlled and involves no chemical reaction
What happens to the dissolution rate if the diffusion coefficient of a drug is decreased (e.g., in the presence of substances which increase viscosity of the medium)?
The rate of dissolution will decrease
What happens to the dissolution rate if the area exposed to the solvent is increased (e.g., by micronization of amorphous form used)?
The rate of dissolution will increase
What happens to the dissolution rate if the thickness of the diffusion layer is decreased (e.g., by agitation)?
The rate of dissolution will increase
What happens to the dissolution rate if the solubility in diffusion layer changes (e.g., a change in temperature and for ionisable drugs, a change in pH by the use of a buffer)?
The dissolution rate will increase or decrease, accordingly
What happens to the dissolution rate if the concentration in bulk solution is decreased (e.g., by addition of a fluid or removal of a drug by adsorption or absorption)?
The rate of dissolution will increase
Name four different pharmaceutical solvents
Purified water USP
Alcohol USP
Propylene glycol USP
Glycerin USP
Describe purified water USP as a solvent
Can be obtained using distillation, ion-exchange and reverse-osmosis
Contains no added substances
Cannot contain more than 0.001% of solids
Describe alcohol USP as a solvent
In pharmaceutical usage “alcohol” refers to ethanol or ethyl alcohol (95% ethanol)
Very useful solvent with preservative properties
For oral use in children under 6 years, content should not exceed 0.5%; for 6-12 years 5% and for children older than 12 years, the recommended maximum is 10%
Water miscible and useful in preparing solutions of drugs with limited solubility
When is methanol used?
Methanol is never used pharmaceutically due to toxicity
When is isopropanol used?
Isopropanol may be used in some topical preparations
Describe propylene glycol USP as a solvent
Miscible with alcohol and water and may be used in combination with them or as a substitute for alcohol
Some preservative activity
Other polymeric glycols such as polyethylene glycol (PEG) may be used but ethylene glycol is never used due to toxicity
Describe glycerin USP as a solvent
Glycerin (glycerol) can be used as a solvent
Very viscous
Some preservative activity
Name three different solution types?
Oral
Ophthalmic, otic and parenteral (for use in eye, ear or injection)
Topical (for application to the skin; requires a “for external use” auxiliary label
Describe oral solution types
May contain excipients like sweeteners and preservatives
Volumes per dose may include drop, teaspoonful (5 ml) or tablespoonful (15 ml)
Name six different categories of solutions
Elixirs Tinctures Aromatic waters Spirits Collodions Syrups
Describe elixirs
Clear hydro-alcoholic oral solutions
Alcohol content varies up to about 30%
Propylene glycol may be used to replace some of the alcohol
Usually flavoured and sweetened with sugars or artificial sweeteners but less sugar than syrups
Effective for water and alcohol soluble components
Because of alcohol and volatile oil (flavourings) store in tight light-resistant containers away from excessive heat
Describe tinctures
Hydro-alcoholic solutions containing between 15% and 80% alcohol
Dilution with water usually results in the precipitation of the ingredients
May be used for topical or oral use
Use has been declining over the past 50 years
Describe aromatic waters
Clear aqueous solutions saturated with volatile oils
Used for flavour or odour (dill, peppermint, orange, rose water)
Describe spirits
Like aromatic waters but contain varying amounts of alcohol
Higher content of volatile oil
Describe collodions
Liquid preparations containing pyroxylin
Solvent usually alcohol and diethyl ether
Has been used for delivery of keratolytic medications
Describe syrups
Concentrated aqueous preparations of sugar or sugar-substitute
May contain flavouring but not medication
Used as vehicles into which medications may be added
Examples: cherry, orange, cocoa syrups
May be sugar-free; may include propylene glycol, glycerin, sorbitol
May be polymeric hydrogel like hydroxypropyl methylcellulose with saccharine os aspartame
May contain preservatives, colour and flavour
Used for extemporaneous compounding
Why is preservation of syrups important? How is are syrups preserved?
It is needed to prevent microbial growth. The quantity need depends on amount of free water (water available for microbial utilization). The concentration of preservative in free water must be effective but low enough to avoid toxicity
What are commonly used preservatives for syrups?
Alcohol
Benzoic acid or sodium benzoate 0.1-0.2%
Potassium sorbate 0.1%
Parabens (mix of methyl and propyl esters) 0.1%
When is a preservative for a syrup required?
Simple syrup (sucrose 85%) contains no free water and is therefore self-preserving. If diluted to a concentration of <85%, it requires a preservative
If a drug tastes salty, what are masking flavours?
Butterscotch, apricot, peach, vanilla, wintergreen mint
If a drug tastes bitter, what are masking flavours?
Cherry, mint, anise
If a drug tastes sweet, what are masking flavours (or in this case, flavours to add on to the sweetness)?
Chocolate, vanilla, fruit and berry
If a drug tastes sour, what are masking flavours?
Citrus flavours, raspberry
Describe how syrups are prepared
Syrups may be prepared using heat if no volatile or heat-liable components are used
May also use stirring without heat or percolation
Must be careful with heat not to caramelize sucrose
Simple syrup is 85% sucrose but 1 g of sucrose can dissolve in 0.5 ml so not saturated and syrup can be stored at cool temperatures without crystallization
Syrup has lower solvent power than water
What is the function of benzethonium chloride?
Antimicrobial, antiseptic
What is the function of alcohol?
Solvent, preservative
What is the function of methyl salicylate?
Scent
What is the function of purified water?
Solvent
What is the function of antipyrine?
Antipyretic, analgesic
What it the function of hydrocortisone?
Anti-inflammatory, steroid
What is the function of neomycin sulfate?
Antibiotic
What is the function of sodium metabisulfite?
Antioxidant
What is the function of glycerin?
Humectant, solvent
What is the function of propylene glycol?
Preservative, solvent
What is the function of purified water?
Solvent vehicle
Explain the apothecaries’ fluid measurements
60 minims = 1 fluidram 8 fluidrams = 1 fluidounce 16 fluidounces = 1 pt 2 pt = 1 qt 4 qt = 1 gal
Explain the apothecaries’ measures of weight
20 grains = 1 scruple
3 scruples = 1 dram
8 drams = 1 ounce
12 ounces = 1 pound
How many minims are in a millilitre?
16.23 minims
How many grains are in a gram?
15.432 grains
Explain the avoirdupois measure of weight
437.5 grains = 1 ounce
16 ounces = 1 pound
How many avoirdupois pounds are in a kilogram?
2.2 pounds
