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Drug release / Dissolution
Terms in this set (67)
What is a solvent?
This is your dissolving medium
What is a solute?
This is the substance that dissolves in the solvent to form a solution. Solute becomes a solution after being placed in the solvent. Example adding a crystal (solute) water (solvent) and the crystal + water (solution)
The process in which a substance goes from a solid state to a solution in a solvent (water with a buffer)
The amount of solute (drug) that dissolves in a given volume of solvent at a given temperature and pressure
How are solubility and dissolution related?
Solubility is the amount of dissolution that occurs per given sets of conditions (temp, time, pressure, volume)
What do S and So stand for? Also if we increase the temperature what effect does that have on solubility?
S= Drug solubility at current conditions (mg/ml) (ionized)
So= Saturation solubility of a given drug (unionized)
If we increase the temp we will increase the solubility
How do we calculate pH, pKa using S, and So
pka = pH-10g[So/S-So]
According to USP a solution that dissolves ______ or more of solute is considered soluble
What is the rate limiting step in drug absorption?
What are the two steps of dissolution?
1) Interfacial Rxn
2) Development of a [___] gradient
Explain both the interfacial Rxn and development of a  gradient
Interfacial rxn: Drug begins to dissolve at the surface of the solid particle, forming a thin layer
a [ ] gradient develops with a high drug concentration in the diffusion layer and a low drug [ ] in the bulk of the solvent
Show an example of the two steps
Show the different forms of how a drug can go from tablet to granules to fine particles, also identify when dissolution will occur
How do we calculate dissolution rate?
List some factors that influence dissolution
1) Particle size (as particle size get bigger, there is more surface area, so there will be more dissolution)
2) Viscosity of diffusion layer (food increases viscosity, decrease dissolution rate)
3) Use of a highly water soluble salt of the parent substance (increase dissolution rate)
5) Agitation/gastrointestinal motility
6) pH of medium, PKA of drug
7) MW of drug (smaller MW more dissolution)
How many different classes are there in the Biopharmaceutical Classification System?
Explain Class I, give an example
High solubility / high permeability
Rapidly transverse the gut wall
Explain Class II, give and example
Low solubility / high permeability
rapidly transverse the gut wall
Explain Class III, give an example
High solubility / low permeability
slowly transverse the gut wall
Explain Class IV, give an example
Low solubility / low permeability
slowly transverse the gut wall
Example of this is Amphotericin B
What are the three types of pharmaceutical dispersion's?
Explain True solutions
Mixture of two or more components that form a homogeneous molecular dispersion
Solutes here are less than 1nm so they will not disperse light (transparent)
Explain Colloidal dispersions, what are the 3 categories of them?
A dispersion containing particles between 1-500nm
These may scatter light, have turbidity
-Lyophillic: (have affinity for dispersion medium)
-Lyophobic: (no affinity for dispersion medium)
-Association colloids: self association of amphillic solutes forming colloids (micelles) above a specific 
Explain Coarse dispersion
A dispersion containing particles greater than 500nm
Particles here will scatter light, and appear cloudy
Solid in liquid coarse dispersion (suspension)
liquid in liquid coarse dispersion (emulsion)
What are the advantages of a solution?
- Easy to administer
- Drug dissolved in formulation making it easier to absorb
- Taste masking is achieved
What are the disadvantages of a solution?
- Unsuitable for therapeutic agents that are unstable in water
- Some drugs have poor solubility so they will not dissolve in solution
- Expensive to ship
- Inconvenient for patient to carry and use
What are some components of a pharmaceutical solution?
-Solvent or vehicle
-Taste masking agent (sweeteners, flavoring agent etc...)
-Antioxidants / chelators
What is the most common vehicle (solvent) used for suspensions?
How can we improve aqueous solubility?
-Optimize the pH by using a buffering system that keeps the API in an ionized form
-API's with ionizable groups at pH 2-8 can have their solubility optimized using a buffering system
What are the common buffering systems?
What are 2 other ways that we can improve aqueous solubility?
Make a salt, add a co-solvent
Addition of a water miscible organic solvent to reduce polarity of an aqueous system,
Helps to solublize non-polar/non-ionized drugs and the unionizable portion of ionizable drugs
What are some examples of Co-solvents?
-Low molecular weight (200-400g/mol) poly ethylene glycol (PEG)
What is the 1 other way we can improve aqueous solubility?
What are the three general classes of CD's? What if the drug is too big?
If an aqueous solution cannot be formulated what can we use?
-Peanut oil, corn, soybean
Most drugs are bitter so what must we do? What does aversive mean?
We must mask the taste, aversive means bitter
Can we dilute the taste of an API by mixing it with food? If yes why isn't this always ideal?
Yes we can, not always ideal b/c the entire dose is not consumed in one quantity and we need to test the drug with the foods it can be given with
What are the two types of sweeteners that we can give to mask the bitter taste of API's? Explain them.
Bulk sweeteners: Provide body and texture to the solution (high viscosity sucrose syrup)
Intense sweeteners: Provide sweet taste at very low [ ] example of this would be aspartame
What is an example of a natural sweetener, what is an example of an atrifical sweetener?
How do we choose a sweetener?
Sweeteners are chosen based on processability (ability to be stable at a certain pH and temperature)
What are flavoring agents?
These are used to compliment the taste of an API
How many bitter taste receptors do we have? Explain how taste receptor blockers function with regards to receptor antagonist and stopping signal transduction
We have greater than 25 different types of taste receptor blockers.
Taste receptor blockers function by: (antagonist)
-Completely block the binding site or block the release of G-protein
Blocking signal transduction:
Can we use complexation to improve the bitter taste of API's?
Yes we can, Cyclodextrins will complex with API's impeding their contact with taste receptors
Are higher viscosity solutions better at masking the taste of API's?
How is viscosity increased?
By the addition of non-ionic and ionic polymers
What are some examples of Ionic and non-ionic polymers?
-Sodium carboxymethylcellulose (anionic)
-Sodium alginate (anionic)
What are some properties of an ideal preservative?
-Broad spectrum antimicrobial activity
-Adequate aqueous activity
-Chemical and physical stability on shelf
-Low toxicity to patient
What are some common preservatives? Explain the mechanism of action for a preservative?
Benzoic acid, Sorbic acid
-Unionized acidic preservative will partition across the membrane of a microorganism
-Within the cytoplasm the pH is neutral so these preservatives will ionize, leading to the denaturation of protein and thus stoppage in cell growth
Explain what form of a preservative posses preservative capability
Only the unionized form possess preservative
capability as the ionized form cannot
penetrate into the microorganisms. The
concentration of unionized preservative must
be > the minimum inhibitory concentration
(MIC) of the preservative.
What are three important factors to consider when using an acidic preservative?
1) Formulation pH (optimal < 4.5)
2) Presence of Micelles (preservative can partition into the micelles), reduces preservative  in microbe
3)Presence of hydrophilic polymers (Methycellulose):
Preservative can interact chemically or electrostacially which will reduce preservative [ ] in microbe
What are some other types of preservatives?
-Parabens (denature proteins)
-Quaternary ammonium salts (benzalkonium chloride): lysis of cell membrane
-Mercurials (thiomersal): disrupt function of enzymes by interacting with thiol group
-Alcohols >12% (lysis of cell membrane)
What do antioxidants do?
Enhance stability of API that are prone to oxidation
What are antioxidants?
These are molecules that have a higher oxidative potential than the API, so they will protect the API
Give examples of Water soluble antioxidants and Water insoluble antioxidants. Also what do you need in solution with water in-soluble antioxidants to make them good antioxidants?
Water soluble antioxidants:
-Sodium sulphite, sodium metabisulphite,
sodium formaldehyde sulphoxylate,
Water insoluble antioxidants:
-Butylated hydroxytoluene, propyl gallate
Need ethanol in solution to make these good antioxidants
What do heavy metal chelators do?
What are two common chelators?
Heavy metals like Pb can increase the oxidative degradation of an API, Heavy metal chelators will form complexes on the heavy metal to slow down the oxidative degradation
EDTA (make 6 connections with heavy metal)
Citrate (make 4 connections with heavy metal)
Explain solution by chemical rxn and solution by extraction
Solution by chemical rxn: React two or more substances together in a solvent to increase solubility
Solution by extraction: Use isolate pharmaceutical products from vegetable or animal product (many herbal meds extracted this way)
What is a syrup? What do we normally use
What are syrups common for?
Concentrated aqueous preparation of a sugar or sugar substitute, with or without flavoring agents and API's.
Usually use sucrose b/c it is viscous and sugar
Common for pediatric patients b/c they contain little to no sugar.
What is a common alternative to sucrose in syrups?
What are Elixirs? Compared to syrups how do elixirs relate in terms of viscosity and taste?
Sweetened hydroalcoholic solutions that are better at maintaining water soluble or alcohol soluble API's
Generally greater than 10% etoh
Less viscous and taste worse (do not mask taste fo API that well)
What is a tincture?
Hydroalcoholic solution prepared via extraction from vegetable or animal source, contain 15-90% alcohol.
What are spirits?
Alcoholic or hydroalcoholic solutions , with greater than 60% EtOH, can contain greater concentrations of aromatic compounds b/c they are more soluble here, can be used as flavoring agents and medically for aromatic compounds
What were the three ways to improve solubility again?
Optimization of pH, Addition of a co-solvent, Complexation with a cyclodextrin
What is one last way to improve solubility?
Add a surfactant
What are surfactants, What occurs above critical micelle concentration (CMC)? give examples of types used
Surface active agents, that contain both a hydrophobic and hydrophillic area, these will help mask non-polar areas of an API, Above CMC surfactants will form Micelles, that partition the non polar regions together and the polar regions together, non-polar will be inside of micelle and polar will be outside.
sodium dodecyl sulfate
(anionic), trialkylammonium (cationic) or
What are some benefits of using cyclodextrin?
a)Enhance the solubility of the API (i.e.,
b)Enhance the bioavailability of the API
c)Improve the chemical, physical and
thermal stability of the API
d)Reduce irritation in the GIT
e)Help to prevent compatibility issues with
other APIs/ excipients
f)Help to mask API odor/ taste
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