Physcal incompatibilities Flashcards
Inability of a substance to maintain its identity
or to exercise its inherent properties when
brought into contact with or into the sphere
of influence of another substance or a
physical force
INCOMPATIBILITIES
Two classes of incompatibility (from viewpoint of compounder):
(1) Desirable
(2) Undesirable
Problems arise during:
- compounding (extemporaneous)
- dispensing
- administration of pharmaceuticals (oral and
parenteral route)
Problems develop as a result of:
- using two or more drugs
- use of only one drug such as dosage errors
Three classes (based on cause and
manifestations):
(1) Physical incompatibilities
(2) Chemical incompatibilities
(3) Therapeutic incompatibilities
(4) Combination of Types
physical or chemical interaction
between 2 or more ingredients that
lead to a visibly recognizable change
Physical incompatibilities
involves a reaction in which change is
not visible
Chemical incompatibilities
involves an undesirable
interaction between 2 or
more ingredients.
Therapeutic incompatibilities
The ff. is essential from a theoretical as well as practical
viewpoint:
Solubility (correct diluent eg. For parenteral route NSS)
* Chemical reactivity
* Drug stability (stability based on manufacturer’s testing)
* Therapeutic activity
Consequences of Incompatibility to patient
- may not receive the full therapeutic effect of the medication
- adverse effect due to the formation of toxic
products
the assurance that the product
retains its original physical properties, including
appearance, palatability, uniformity, dissolution and
suspendability, during its shelf-life.
Physical stability
When two or more substances are combined, they do
not give a homogenous product
Incomplete solution
danger of forming a clear solution (at high temp.) but
will deposit crystals on cooling.
Use of heat
usually objectionable (except to make slowly soluble
substances dissolve more rapidly).
Use of heat
Remedy for incomplete solution (use of heat and wrong solvent):
for ___________ material, if not beneficial or objectionable, remove it by __________
for undissolved material, if not beneficial or objectionable, remove it by filtration
Remedy for incomplete solution (use of heat and wrong solvent):
For doubtful cases: physician should be __________ & an
_____________ should be secured before radical steps are taken.
advised; approval
contain water of hydration that may be
released when powders are triturated or stored
in a low humidity environment which may
cause powders to become damp or pasty, or
become powdery
Efflorescent powders
Efflorescent powders examples
alums
ferrous sulfate
terpin hydrate
Efflorescent powders
Remedies:
≈ Store & dispense in ___________
containers.
≈ Use ____________ form
with appropriate dose
correction.
≈ Store & dispense in tight
containers.
≈ Use anhydrous drug form
with appropriate dose
correction.
solids that absorb moisture from the air, which
may or may not dissolve to form a solution
Hygroscopic & Deliquescent powders
Hygroscopic & Deliquescent powders example
calcium chloride
ephedrine sulfate
phenobarbital Na
Hygroscopic & Deliquescent powders
Remedies:
≈Store and dispense in __________ containers.
≈Add an _________, powdered ingredient that will
preferentially absorb water, like ________ or
___________________
≈Store and dispense in tight containers.
≈Add an inert, powdered ingredient that will
preferentially absorb water, like lactose or
light magnesium oxide
refer to 2 or more substances that may liquefy
when intimately mixed at room temperature
Pharmaceutical eutectic mixtures of drugs
Pharmaceutical eutectic mixtures of drugs example
acetaminophen
aspirin
camphor
menthol
Desirable Eutexia:
__________(High/Low) concentration of lidocaine and
prilocaine in EMLA Cream is achieved
by forming a _________(solid/liquid) eutectic mixture of
the components.
High; liquid
Desirable Eutexia:
Used to facilitate reduction in particle
size of crystal without need for
__________________.
pulverizaton by intervention
Pharmaceutical eutectic mixtures of drugs
Remedies:
Force the liquid eutectic to form, then sorb the liquid onto an ________, _____________, _________solid.
inert; high-melting; finely-divided
Pharmaceutical eutectic mixtures of drugs
Remedies:
_________ potential eutectic former separately with an inert powder like ___________, then mix by gentle spatulation.
Triturate; MgO
Pharmaceutical eutectic mixtures of drugs
Remedies:
Triturate until _____________ then encapsulate & place in tightly __________ containers.
homogeneous; stoppered
Pharmaceutical eutectic mixtures of drugs
Remedies:
Divided the ___________ between the reacting ingredients. These are combined with _____________ & the remainder of
the ingredients are then incorporated.
diluent; gentle trituration
is readily overheated and solidifies
as one of the lower melting polymorphs, which
may melt at room temp
Cocoa butter
T/F: Changes in crystal form need specific remedy depends on what caused the
change in crystal form
True
Remedy for Cocoa butter
melt cocoa butter slow and carefully,
at temperatures below 340C
- precipitated from alcoholic
solutions when water is added
Resins
frequently
precipitated from aqueous solution when
alcohol is added.
Mucilaginous and albuminous substances
& some metallic salts
Precipitation from solution (Solvent Effects) Remedies:
≈ Choose appropriate _________ system.
≈ Follow _______________ when diluting
preparations using cosolvent system.
≈ ____________ the drug concentration so the drug is
soluble in the solvent system.
≈ For oral or topical products, a suspension may
be prepared by adding a ___________.
Include “shake well” label.
solvent; manufacturer’s instruction; Decrease; suspending agent
Most drugs are _________ electrolytes and their
degree of ionization depends on the _______ of the
solution
weak; pH
Precipitation from solution (pH effects) what to consider:
Check ___________ of all drugs in the solvents
to be used
Determine the _________of the drug, whether salt
of a neutral weak acid or a neutral weak base.
Estimate the resultant ________ of the solution
Calculate the pH of the ___________ as a
function of the pKa and _________.
Control the pH at a desirable level using pH
adjusting agents or ________
Keep drug solutions with incompatible pH’s
separate.
solubilities; salt type; pH; precipitation; drug solubility; buffers
pH Insolubles
→ codeine and morphine
→ ephedrine and ephedrine HCl
→ phenobarbital Na and
phenobarbital
T/F: For IM injections that are pH incompatible, draw solutions in
separate syringes and give in different sites.
True
T/F: For IV injections that are pH incompatible, give at different times and flush the IV line between additions of incompatible drug
solutions.
True
Precipitation from solution
(b) pH effects:
With oral or topical solutions, a ___________
may be used if a suitable one that is
available will keep the free form of the drug
in solution. Or check possibility of making a
suspension.
cosolvent
Precipitation from solution
(b) pH effects
Remedies:
≈ ___________ the final solution so that drug
concentration is ___________ the precipitation
concentration of the neutral free form.
≈ For injectable drugs, like _________ Inj. and
____________ Inj., that are sensitive to pH
changes caused by absorption of CO2, use _______
expiration times.
Dilute; below; Phenytoin Na; Aminophylline; short
Solutions of hydrophilic polymers such as
methylcellulose and acacia depend on
hydration through _____________ . These polymers may be
dehydrated and precipitated by
concentrated _______________
hydrogen-bonding and iondipole interactions; electrolyte solutions or phenolic
compounds.
Precipitation from solution
(c) Colloids and polymers
Remedies:
≈ ___________ concentration of electrolyte.
≈ Substitute with __________ that is not
easily ________
Decrease; polymer gum; dehydrated
T/F: For some viscosity-increasing polymers,
interactions are required to form the desired gel.
true
Sodium alginate is gelled with
calcium ions
Carbomer is gelled by addition of an
inorganic
(e.g.NaOH) or organic (e.g. Triethanolamine)
base.
Solubility of most drugs ___________ with decrease
in the temperature of the solution
decreases
Effect of temperature Remedy:
For injectable solutions, check _________
concerning temperature effects. If an
extemporaneously prepared sterile product
cannot be refrigerated, the ___________
should be adjusted.
warnings; beyond-use date
Effect of temperature
Remedies:
For oral or topical solutions, be aware of possible
problems when handling solutions near the
__________ point. If such a solution must be stored
or used at temperatures different from that at
which it was made, steps to prevent or handle
precipitation should be undertaken.
saturation
“salted out” of aromatic
waters when salts or metals are dissolved in the liquid.
Camphor & volatile oils
is precipitated from a solution when
tragacanth is dissolved in the liquid
Boric acid
show precipitation on the addition
of electrolytes
Colloidal solutions
T/F: Ethyl nitrite spirit with a substantial proportion of potassium citrate - separates & floats as a layer.
True
dependent on the hydrophilic/ lipophilic
nature of the drug and the binding site or the material
in the capillary space of the interface.
Sorption
Drugs that are poorly water-soluble or lipophilic have
a _________ (lower/greater) tendency to sorb to PVC or dissolve in its
plasticizer.
greater
Example of drugs that is affceted by sorption and leaching
lorazepam, amiodarone, diazepam,
isosorbide dinitrate, vitamin A
Remedies for sorption:
≈ Special tubing or containers may be used.
≈ Use __________ run-times for IVs containing drugs with
potential sorption problems.
≈ Add the drug just before the time of administration.
≈ Consider giving the drug by __________, if possible
shorter; IV push
Remedies for sorption:
≈ Use ________ administration-set
tubing (with less binding sites).
≈ Store product in the
____________ until
administration.
short; refrigerator
Drug solutions containing ____________are
more at risk, because some of these have been found
to extract plasticizer from the plastic and
contaminate the drug solution.
surfactants or cosolvents
Remedies for leaching:
Containers, administration sets
and device components that
do not contain _____________
materials, like glass, polyolefin,
ethylene vinyl acetate, silicone,
polyethylene and
polyurethane, can be used.
DEHP-plasticized
