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
