Pharmaceutical solutions Flashcards
What is the definition of solutions?
Liquid preparations containing chemical substances dissolved in a solvent or mixture of miscible solvents
What is the definition of solubility?
Maximal concentration of a solute that can dissolve in a solvent at a given temperature
How to read the solubility table?
The more parts (can be g or ml) I need, to dissolve a solute, the weaker the solubility
If I don’t need much solvent to dissolve a solute, the solubility is strong
What are the components of a solution?
- API
- Vehicle
- Co-solvent
- Preservatives
- Stabilizers
- Color and Flavor
Which properties should an active pharmaceutical ingredient (API) have?
-soluble and stable in a solvent (hydrolyzes if not stable)
-in case of low solubility -> co solvent is added
-to be absorbed it need to be unionized -> so there are mostly weak acid or bases
-flavors may be added in case of bitterness
Why are Solvents needed?
-to enhance the solubility of semi-polar drugs that mix water only to a degree -> so we add a solvent that mixes with water and the drug
Water, Ethanol, Propylene glycol, Isopropyl glycol, Glycerin, Acetone, Non-polar solvents
What is the difference between Bulk and packaged water?
-Bulk water: produced and used on the same site, don’t need to package
-Packaged water: produced somewhere and need to be packed and sterilized to prevent microbial growth
What are the types of Bulk water?
-Purified water: used as a diluent in the production of non-sterile products -> not pyrogen-free
-Pure steam: used for sterilizing porous (steam gets easier into pores) equipment, pretreated water is vaporized and distributed under pressure (e.g. autoclaving)
-Hemodialysis: used for dilution of hemodialysis concentrate (dialyzer: artificial kidney to clean the blood) -> not for injection
-Water for injection (WFI): sterilized and pyrogen free for sterile products
What are the types of packaged water?
all STERILE
-Sterile purified water: for preparation of sterile products and analytical applications
-Sterile water for injection (WFI): sterile products used for IV packaged for a single dose
-Bacteriostatic WFI: preparation for sterile products (IV) for multiple doses -> PRESERVATIVES and ANTIMICROBIALS added
-Sterile water for inhalation: used in inhalators, but not as strict as with water for IV
-Sterile water for irrigation: used to clean body cavities, not as strict as with water for IV
What are other solvents/vehicles?
other solvents may be added to water for semi-polar drugs
-Ethanol -> ETHYL ALCOHOL: preservative, mixes easily with water, for internal and external use
-Isopropyl alcohol: similar to ethyl alcohol but can’t be used internally, it is used as a disinfectant when more than 91%
-Glycerin (diol) and Propylene glycol (Triol) have multiple OH groups making them easy to mix with water,
Glycerin can be used as a preservative at high concentrations and tastes sweet, both for internal and external use
-Acetone: doesn’t have OH group, hence no H-bonding, but dipole-dipole interactions - CANNOT BE USED INTERNALLY
When are non-polar solvents used?
If the drug doesn’t interact with water at all (not often), the form of interaction is dipole moments
-f.e. fixed oils -> often used external preparations, internally in form of emulsions
Other excipients:
Preservatives, Flavor, Color, Sweetener, Buffers, Viscosity enhancer, anti oxidants
When are preservatives added?
-if alcohol with more than 10% or Glycerin in high concentration is added we don’t need preservatives
-examples: Benzoic acid, Sodium benzoate, Methylparaben and other parabens
What might be an issue when adding flavors and colors?
They are not very soluble, alcohol might be added as a cosolvent
-synthetic or natural oils
Which sweeteners cant be used for certain patients?
-Sucrose: not for diabetic patients
-Sorbitol: not for patients with irritable bowel syndrome (IBS), bc it causes GI distress
-Aspartame: phenylketonuria patients cant metabolize it
What is the purpose of buffers and antioxidants?
-Buffer: to control the pH
-Viscosity: for syrups you want a certain viscosity so that it suits a bit in the throat and GI to act there (cellulose)
-anti-oxidant: for substances that oxidize easily (not stable), e.g. Vitamin C
What are the advantages and disadvantages of oral solutions?
Advantages:
-Taste
-Easier for patients with difficulties swallowing
-faster absorption (no disintegration step)
-simple preparation
Disadvantages: hard to produce if it is not stable in water or is not soluble in water (here you could add a non-polar solvent), bulky and inconvenient to transport
Types for oral solution:
Dry Mixture for solution
-The powder needs to be reconstituted with a diluent -> afterward not stable for a long period of time
e.g. antibiotics must be kept in the fridge (expires after 14 days)
Types for oral solution:
Oral solutions
-Oral colonic lavage solution: solution of electrolytes with Polyethylene glycol -> colonoscopy or surgery -> LAXATIVE
-Oral rehydration solution: for rehydration after diarrhea
-Magnesium citrate solution: saline laxative
-Sodium citrate/citric acid solution: for systemic alkalinization for patients with uric acid or to dissolve kidney stones
Types for oral solution:
Syrups
-high concentration of sucrose, often used as a solvent/vehicle
-simple syrup, NF has 85% w/v or 65% w/w (at this concentration it acts as a preservative, if diluted you need one)
Why does syrup need to be heated carefully?
-when heated add heat-stable ingredients -> then volatile ingredients -> let cool down
-has to apply heat gradually to prevent inverted syrup -> the breakdown in fructose and glucose (sweeter, darker) -> more heat leads to caramel
What is the role of Disodium calcium EDTA?
-Act as a chelating agent; e.g. metal ions can cause oxidation
-> so it is a stabilizer for oxidation
Types for oral solution:
ELIXIERS
-comparable to Syrup, but they have an alcohol content of 15-50% (not for kids and diabetics -> because it can cause hypoglycemia)
-it is not as sweet (less sucrose), less viscous as Syrups
-careful with closing bc alcohol is volatile and it need be me stored away from heat and light
Types for oral solution:
Tinctures
-derived from vegetable materials or chemical substances
-might be more content of alcohol than in Elixier 15-80% (not for kids)
-mixing with water or another solvent can lead to the precipitation of the drug
-store away from heat and light
Types for oral solution:
Aromatic water, fluid extract, Spirit
-Aromatic water: saturated aqueous solution of oil used for aromatic therapy
-Fluid extract: similar to a tincture but more concentrated
-Spirit: volatile drug put in alcohol or mixture of alcohol and water (for disinfecting) -> topically and orally
What should be considered when dispensing solutions?
-use the calibrated device (tsp, tbsp - not from the kitchen)
-take a glassful of water
-alcohol containing (like elixirs and tinctures) are not for diabetics and it should not be taken with coated tablets + interaction with other drugs like antibiotics
-expiration days for compounded solutions (BUD)
What are the properties of topical solutions?
-similar to oral ones but often alcohol vehicles bc we want them to sitck at the skin
-has an applicator to tip it to the skin
-are self-preservative or have preservatives
-has a die to mark the site
What are Liniments?
-Alcoholic or oleaginous solution or emulsions
containing the medication -> made of oily substances
-is counterirritant -> countering the initial irritation to trick the brain
-may have menthol for a cooling sensation
What are Collodions?
-Liquid preparations composed of pyroxylin (a form of nitrocellulose) dissolved in alcohol and ether
-leaves a thin layer on the skin
What are topical oral solutions?
-Aqueous solutions often in concentrated form
containing an active ingredient and excipient
-therapeutic or cosmetic
-topical oral: because used in the oral cavity but not swallowed
Topical tinctures:
-vegetable sources
-higher alcohol content 15-80% -> careful with storing
-used to desinfect
