Solutions Flashcards
Physicochemical Terms
Solution can be prepared from combination of solid, liquid and gas
Pharmaceutical Terms
Solutions are liquid preparation containing drug or chemical substances dissolved in solvent of mixture of mutually miscible solvents
Pharmaceutical Solutions
Generally, solutions as liquid dosage forms contains solid drug dissolved in liquid medium
Monophasic system
Advantages of solution
Homogenous and monophasic mixtures
- Typically, no need to shake well before use
Easy to measure accurately
- Volumetric devices can be very precise and accurate if YOU take care
Easy to swallow (children, elderly, and disabled person)
Amenable to administration by any route
- For example:
- suspension cannot be given IV
No lag time due to dissolution
- Rapid onset of action
Disadvantages of solutions
Not a unit dosage form
- Bulky and typically not convenient to carry around
Solution chemistry poses many stability issues
- Physicochemical degradation (shelf-life, storage requirement)
- Reactivity (containers, tubing, etc.)
- Shorter expiry than other dosage forms
Additional sterility concerns
Solubility may be limiting
Need to mask taste (oral)
- Example:
- suspension is “harder” to taste
Solutions
Homogenous mixtures of solutes dissolved in solvents
Syrups
Aqueous solutions containing a high concentration of sugar or sugar-substitute with or without medicinal substances
Elixirs
Flavored, sweetened hydro-alcoholic solutions for use
Spirits
Solutions of aromatic materials in alcohol
Aromatic Waters
Solutions of aromatic material in water
Tinctures
Alcoholic solutions prepared by extracting active constituents from crude drugs
Tinctures / Spirit / Elixirs
May be useful for delivering lipophilic constituents at a required concentration
Sprays
Aqueous or oleaginous solutions in the form of coarse-droplets or as finely divided solids to be applied topically (nasal / skin)
Collodions
Liquid preparations composed of nitrocellulose in a solvent mixture (alcohol + ether)
Liniment
Alcoholic solutions or emulsions of various medicinal substances to be rubbed on the skin
Typical composition of pharmaceutical solutions
Calling a homogenous mixture a solution does NOT imply that it is composed of one solute solvent
- Active component
- Flavorants
- Sweeteners
- Colorants
- Stabilizers
- Viscosity modifiers
- Preservatives
- Co-solvents
When preparing a solution, the pharmacist must consider the solubility and compatibility of each ingredient that will be present in the solution
Solvent Selection Considerations
Solubility
Low Toxicity
Compatibility with other ingredients
Chemical Inertness
Clarity
Palatability (for oral preps)
Odor
Color
Cost
Solvents used for liquid preparations
Alcohol, USP: Ethyl Alcohol, Ethanol
Diluted Alcohol, NF
Alcohol, Rubbing
Glycerin, USP (Glycerol)
Isopropyl Rubbing Alcohol
Propylene Glycol, USP
Purified Water, USP
Fixed Oils
Alcohol, US: Ethyl Alcohol, Ethanol (C2H5OH)
Alcohol is the most useful solvent in pharmacy next to water
Alcohol, USP = 94.9 to 96% C2H5OH by volume (v/v) at 15.56 degrees Celsius
Dehydrated Alcohol, USP = absolute alcohol contains not less than 99.5% v/v C2H5OH
- Used when water-free alcohol is desired
Together with water, it forms a hydroalcoholic mixture that dissolves both alcohol-soluble and water-soluble substances, a feature especially useful in the extraction of active constituents from crude drugs
It is also used in liquid products as an antimicrobial preservative alone or with parabens, benzoates, sorbates, and other agents
Alcohol is frequently used with other solvents, such as glycols and glycerin, to reduce the amount of alcohol required
However, concern has been expressed over the undesired pharmacologic and potential toxic effects of alcohol
Alcohol, USP: Ethyl Alcohol, Ethanol (C2H5OH) Limits
Children < 6 years of age = alcohol (OTC) limit 0.5%
6-12 years of age = 5%
Over 12 years of age and adults = 10%
Rubbing Alcohol
It is employed as a rubefacient externally and as a soothing rub for bedridden patients, a germicide for instruments, and a skin cleanser prior to injection
It is also used a vehicle for topical preparations
The product is volatile and flammable and should be stored in tight containers away from fire hazards
Isopropyl Rubbing Alcohol
70% isopropanol
Water, color additives, stabilizers, fragrances
Commonly used for diabetics for the preparation of needles and syringes for insulin injection
Isopropyl Alcohol Solution
91% isopropanol
Commonly used for diabetics for the preparation of needles and syringes for insulin injection
Polyhydric Alcohols
Glycerin, USP (Glycerol)
Propylene Glycol, USP
Glycerin, USP (Glycerol)
Clear, viscous liquid with sweet taste
Miscible with water and alcohol
Solvent properties similar to ethanol
- Viscosity causes solutes to dissolve very slowly
- Heating reduces viscosity
Preservative, stabilizer
Propylene Glycol, USP
Clear, viscous liquid
Miscible with water and alcohol
Commonly substituted for glycerin
Purified Water, USP (H2O)
Water obtained by distillation, ion-exchange treatment, reverse osmosis of other suitable process. It is prepared from water complying with the regulations of the US
Environmental Protection Agency (EPA) with respect to drinking water. It contains no added substances
- nmt 0.001% total solids (1 mg in 100 ml)
- nmt 100 cfu/ml (guideline)
- pH between 5 and 7
- Less solid impurities than the drinking water
Purified Water, USP = intended for use in the preparation of aqueous dosage forms, EXCEPT those intended for parenteral administration (injections)
Distillation Method
The first portion of aqueous distillate (about the first 10 to 20%) must be discarded
- Contain many foreign volatile substances in the urban drinking water
The last portion of water (about 10% of the original volume of water) remaining in the distillation apparatus must be discarded and not subjected to further distillation
- Distillation to dryness will result in decomposition of solid substances and possible contamination
Ion-Exchange Method
On a large or small scale, the ion-exchange method for the preparation of purified water offers a number of advantages over the distillation method
- No heat is required, less energy consumption
The ion-exchange process permits ease of operation, minimal maintenance, and a more mobile facility
Cation Exchange
H-Resin + M+ + X- + H2O –> M-resin + H+ + X- + H2O (pure)
Anion Exchange
Resin-NH2 + H+ + X- + H2O –> Resin-NH2 (HX) + H2O (pure)
Cation & Anion Exchange
These two processes are successively or simultaneously employed to remove both cations and anions with water
Water purified in this manner is referred to as demineralized or de-ionized water
Osmosis
Diffusion of water molecules across semi permeable membrane from a solution with no or low concentration of solute to the solution with high concentration of solute
Membrane Filtration Processes
Cross-flow filter membranes can remove particles defined in the range of
- microfiltration (0.1 to 2 microns, e.g. bacteria)
- ultrafiltration (0.01 to 0.1 microns, e.g. virus)
- nanofiltration (0.001 to 0.01 microns, e.g., organic compounds in the molecular weight range of 300 to 1000)
Reverse osmosis (particles smaller than 0.001 microns)
Reverse Osmosis Removes Virtually All
Viruses
Bacteria
Pyrogens
Organic molecules
90-99% of all ions
Fixed Oils
Esters of glycerin and fatty acids derived from plants and animals
Used for solubilizing lipophilic drugs
- Can be used for IM depot formulations or for emulsions
Must remain clear when cooled to 10 degrees Celsius (USP requirement)
Toxicity is typically low but allergic reactions possible
Useful for the preparation of Oleaginous Solutions for Injection
- Corn Oil
- Cottonseed Oil
- Peanut Oil
- Sesame Oil
- Soybean Oil
- Castor Oil & Olive Oil (less common)
Why to use mixture of co-solvents?
Attain desired solubility without using high levels of any single cosolvent
Minimize toxicity in formulations
Minimize residual solvents in crystallizations
“Tune” solvent mix for crystal properties
