liquids Flashcards
several reasons why liquids are used internally instead of other dosage forms (5)
Easier to swallow Only suitable dosage form Irritation Flexibility Immediate drug availability
Classification of liquids (2)
by types of system
by routes of administration
types of classification by system and example
Homogeneous – examples are solutions
Heterogeneous – examples are emulsions and suspensions
examples of classification by route of administration
oral solution
parenteral solution
opthalmic solution or suspensions
Topical solution or suspensions
Liquid preparation that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents.
pharmaceutical
pharmaceuticals are classified by ____ or ___. Examples are:
composition or use
syrup, elixir, spirits, aromatic waters, tinctures or fluid extracts
Aqueous solutions containing sugar
syrup
Sweetened hydroalcoholic (combinations of water and ethanol) solutions
Elixir
Alcoholic solutions of aromatic materials
Spirits
Aqueous solutions of aromatic materials
Aromatic waters
Solutions of prepared by extracting active constituents from crude drugs
Tinctures or Fluid extracts
pharmaceutical solutions can be aqueous or non-aqueous and do not necessary need to be in the ____ state
liquid
What are some Disadvantages of Solutions
- Relative chemical stability (vs. solids)
- Medium for microbial growth
- Bulky
- More pronounced distaste
- Potential dosing errors
the substance being dissolved
Solute
medium or vehicle in which solute is dispersed or dissolved
Solvent
important issue to address when considering ease of production is
dissolution
important issue to address when considering dosage uniformity is
there isn’t any important consideration
important issue to address when considering stability is
chemical pH, temperature, antioxidants
microbial preservation
important issue to address when considering patient acceptance is
palatability, appearance
important issue to address when considering drug release is
there isn’t any important consideration
process of dissolution (drug being dissolved in solvent) requires 3 main steps
Work is required to separate particles of solute in the crystal
Work is required to separate molecules of solvent
Energy is necessary with interaction
The Dissolution process involves:
Dipole-dipole interactions
Hydrogen bonding
Polarity
Three of polarity are:
Polar (water)
Semi-polar- (ketones, alcohol)
Non-polar (carbon tetrachloride, benzene, mineral oil)
Weak interactions, loose association orientation of positive and negative poles
Dipole-dipole interactions
Strong interaction between hydrogen atom and electronegative atom (F, O, N)
Examples are water, alcohol molecules, carboxylic acid, polypeptides
Hydrogen bonding
Solubility of drug due in large part to polarity of solvent
polarity
contains:
High dielectric constant
Break covalent bonds by acid-base reactions
Dipole interaction forces (hydrogen bonding)
Polar (water)
Induces polarity in nonpolar solvents
Semi-polar- (ketones, alcohol)
Used to increase aqueous solubility of weak electrolytes and non-polar molecules
Solute more soluble in mixture of solvents (alcohol/water mixture)
Co-solvents
Examples of co-solvents are
Glycerin
Alcohol
PEG
Propylene glycol
contain:
Low dielectric constant
Cannot reduce attraction, break covalent bonds or ionize weak electrolytes
Non-polar (carbon tetrachloride, benzene, mineral oil)
Measure of polarizability of a molecule -> “like dissolves like”
Dielectric constant
The reduction of particle size increases the total ____ ____ of the solid in contact with the solvent, and dissolution occurs more rapidly.
surface area
The rate of dissolution depends on many factors:
a. free surface energy and the shape of the particles
b. temperature
c. type of agitation
d. amount of material already in solution
e. viscosity and volume of the solvent
f. concentration of the dissolved solute
The exposure of new surfaces and the condition of the surface modifies the rate; if gas pockets or an insoluble coat form on the surface, the rate of dissolution will be _______.
decreased
sink conditions in Noyes and Whitney
if Ct (concentration at that instant) «_space;Cs (conc of saturated sln), then may omit Ct
_____ have different crystal forms and therefore have different energy contents.
So solubilities differ
Isomers
Fumaric acid forms a more stable crystal so is less ____ than Maleic acid
soluble
Many organic medicinal compounds are capable of existing in two or more crystalline
forms with different arrangements of the molecules in the crystal lattice and these are
referred to as ______
polymorphs
The X-ray diffraction patterns, densities, melting points, solubilities, crystal shape and electrical properties vary
with the ______ form. However, in the ___ or ____ state no difference is
discernible.
polymorphic
liquid
vapor
The _____ polymorph possesses a higher solubility and dissolution rate than does the
stable form, and this phenomenon may be used to advantage in biopharmaceutics
metastable
With poorly soluble drugs it is possible to increase the solubility simply by modifying their ____ nature
crystalline
Many organic medicinal agents are weak acids and weak bases which in many cases are ____ insoluble.
water
water soluble salts are formed by reaction with either ___ acids or ___ bases as the case may be.
strong
strong
What are the relative terms of solubility?
Very soluble < 1 Freely soluble 1 to 30 Soluble 10 to 30 Sparingly soluble 30 to 100 Slightly soluble 100 – 1000 Very slightly soluble 1000 to 10000 Practically insoluble, or insoluble 10000 and over
Solvent/Vehicles For Liquid Preparations (7)
Alcohol USP Diluted Alcohol USP Glycerin USP Propylene Glycol USP Isopropyl Rubbing Alcohol Oils water
Ethanol 94.9 to 96%
Miscible with water
Used as a cosolvent with water
Alcohol USP
Ethanol + water equal volume mixed together
Diluted Alcohol USP
Miscible with alcohol and water
More viscous; slower to dissolve substance
Preservative qualities
Glycerin USP
viscous
Miscible with water and alcohol
Substituted for glycerin
Propylene Glycol USP
70% by volume IPA
Remainder is water
Use externally only
91% solution used for preparing needles and syringes
Isopropyl Rubbing Alcohol
a. Vegetable
b. Fatty acid esters
c. Liquid paraffin
Are examples of ____
Oils
Always use the oil ___ form or ___ base of the drug to form an oil solution
Heavy liquid petrolatum or mineral oil is used as a ____
soluble
free
laxative
Fixed oils include
- Peanut
- Almond
- Sesame
- Soybean
- Cottonseed
Volatile oils (examples)
Wintergreen or turpentine
Note: Fixed oils used in I.M. produce a “____” action
depot
for orally administered pharmaceutical products, ___ Water, USP, is generally used.
Purified
Naturally occurring water is usually too impure, however, to be used for any pharmaceutical purpose.
Contains too many dissolved impurities which may react chemically with the medicaments.
tap water is also known as ____ water
potable
Purified Water may be prepared from potable water by any suitable process but the three processes mentioned specifically in the USP are:
- Distillation
- Ion-exchange
- Reverse osmosis
Purified water is intended for the formulation of all aqueous dosage forms except those intended to be administered by ____ or by the _____ route.
injection
ophthalmic
A variety of stills are available commercially for the preparation of Distilled or Purified Water.
In the distillation process the first __% to __% and the last ___ % of the water is usually discarded to avoid impurities.
10
20
10
Water purified by ion-exchange is known as ____ or ____ water
demineralized
de-ionized
What are water-insoluble synthetic polymerized resins with a high molecular weight?
- Phenolic
- Carboxylic
- Amino
- Sulfonated
Two types of resins are used:
Anionic and cationic
A reasonably new process when compared with the other two. Makes use of a semi-permeable membrane to remove impurities.
Reverse Osmosis
Although Purified Water can be used for general pharmaceutical purposes it must only be used for preparing solutions that are to be given ___ or applied _____.
orally
externally
USP specifies and has monographs on five other grades of water intended for special purposes. These are:
- Water for Injection USP
- Sterile Water for Injection USP
- Sterile Water for Irrigation USP
- Bacteriostatic Water for Injection USP
- Sterile Water for Inhalation USP
Differs from Purified Water in that it can only be prepared by Distillation or by Reverse Osmosis.
Water for Injection U.S.P.
small substances of bacterial origin which cause fever when injected
Pyrogens
There are ___ grades of Sterile Water which are all essentially modifications of Water for Injection USP.
- Differ only essentially in the manner of packaging.
- The Sterile Water for Injection U.S.P. and the Sterile Water for Irrigation, U.S.P. are both packaged in ___ dose container
But both must be packaged in containers made of Type __ or Type __ glass.
three
single
I
II
Both of these are glasses that are resistant to water and particularly to the leaching of alkali.
Type I - Highly resistant borosilicate glass.
Type II- Treated Soda-lime glass.
contains one or more anti-microbial agents.
- These must be stated on the label.
- Used for the preparation of small volume parenterals.
- Small volumes because of the presence of anti-microbial agents.
- In large volumes these could possibly cause toxicity
Bacteriostatic Water for Injection USP
Preserve in ___-dose or in ____ dose containers, preferably in Type I or Type II glass, but not larger than 30ml
single
multiple
The basic composition of any syrup is:
- Sugar or Sugar-substitute
- Preservatives
- Flavors
- Colors
Concentrated aqueous solutions of a sugar or sugar-substitute with or without added flavoring agents or medicaments
syrups
Syrups are traditionally prepared from ___.
Syrup NF contains 85g sucrose in 100ml of Syrup.
So it’s a very concentrated solution
Two very good reasons for this high concentration of sucrose are:
sucrose
- To give the desired sweetness and viscosity.
- To prevent microbial growth.
Syrup is quite resistant to microbial growth because there is little ___ present to support such growth
water
In some instances, sweeteners and viscosity inducing agents other than sucrose are used in preparing syrups.
Agents such as:
- Dextrose
- Glycerin
- Sorbitol
____ is often used to replace part of the sucrose to prevent crystallization of the latter around the cap of bottles.
Sorbitol
Syrups can be prepared by any of four general procedures:
- Solution with the aid of heat
- Solution by admixture in the cold
- Dissolution of sucrose in a medicated or flavored liquid.
- By percolation
When speed is required and the ingredients are not degraded by heat.
Sucrose is a di-saccharide and may be hydrolyzed by heat into the two mono-saccharides:
This reaction is known as inversion and the resulting combination of products as invert sugar.
- Dextrose (glucose)
2. Fructose (laevulose)
Clear, sweetened hydroalcoholic solutions intended for oral use.
Usually flavored for palatability
Elixirs
Percent alcohol varies from one ___ to another depending upon the solubility tendencies of the active components
elixir
The primary solvents or vehicles found in elixirs include:
water, alcohol, glycerin and propylene glycol
Classes of Elixirs
- Non-Medicated
2. Medicated
Non-medicated elixirs are used for the compounding of prescriptions because:
- Are a pleasant tasting vehicle
- For dilution of a medicated elixir - use an elixir of comparable
alcoholic strength in order to keep the alcohol content at a minimum.
Examples of Medicated Elixirs
- Antihistamine Elixirs (Diphenhydramine HCI Elixir, P.D., Benadryl Elixir, P.D.)
- Sedative and Hypnotic Elixirs (Phenobarbital Elixir)
- Expectorants (Terpin Hydrate Elixir)
- Cardiotonic Elixirs (Digoxin Elixir)
Oral Solutions
Can divide these into two categories:
- Colored and flavored aqueous solutions of medicaments.
2. Dry powder mixtures to which water is added at the time of dispensing.
Having a lower osmotic pressure than that of 0.9% sodium chloride
Passes water into cells in an attempt to establish an equilibrium concentration and could cause hemolysis of the cells.
Hypotonic
Having a greater osmotic pressure than 0.9% sodium chloride will have a tendency to draw water from cells and body tissues so could cause the crenation or shrinking of the cells.
Hypertonic
extraneous matter removed from tinctures and fluid extracts are:
The pectins, celluloses, and other extraneous ma
Two principle methods of extraction
- Maceration
2. Percolation
Method to be used for extraction depends on
- Nature of the material
2. The degree of extraction required-the purity of the extract
a process in which the ground drug is soaked in the solvent until the soluble constituents have been dissolved
Maceration
the extracting solvent - aqueous, hydroalcoholic or alcoholic.
Menstruum
A process where a powdered drug is extracted by the slow passage of a suitable solvent through a column of the drug
Percolation
the extraction vessel is called
Percolator
the residue remaining after extraction is called
Marc
the liquid extract
Percolate
Liquid preparations of vegetable drugs containing alcohol are
prepared by percolation using a long narrow percolator to ensure complete extraction
Fluid extracts
Examples of Fluidextracts USP XXII
- Cascara Sagrada Fluidextract
- Senna Fluid extract
- Aromatic Cascara Fluidextract
(all have cathartic action)
A solution of Pyroxylin dissolved in a mixture of ethanol and ether.
Pyroxylin is cellulose tetranitrate
Collodions
There are 3 USP Collodion Products:
a. Collodion USP
b. Flexible Collodion USP
c. Salicylic acid Collodion USP
