Physcal incompatibilities Flashcards by Kim Grace

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

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Two classes of incompatibility (from viewpoint of compounder):

(1) Desirable
(2) Undesirable

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Problems arise during:

compounding (extemporaneous)
dispensing
administration of pharmaceuticals (oral and
parenteral route)

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Problems develop as a result of:

using two or more drugs
use of only one drug such as dosage errors

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Three classes (based on cause and
manifestations):

(1) Physical incompatibilities
(2) Chemical incompatibilities
(3) Therapeutic incompatibilities
(4) Combination of Types

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physical or chemical interaction
between 2 or more ingredients that
lead to a visibly recognizable change

Physical incompatibilities

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involves a reaction in which change is
not visible

Chemical incompatibilities

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involves an undesirable
interaction between 2 or
more ingredients.

Therapeutic incompatibilities

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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

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Consequences of Incompatibility to patient

may not receive the full therapeutic effect of the medication
adverse effect due to the formation of toxic
products

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the assurance that the product
retains its original physical properties, including
appearance, palatability, uniformity, dissolution and
suspendability, during its shelf-life.

Physical stability

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When two or more substances are combined, they do
not give a homogenous product

Incomplete solution

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danger of forming a clear solution (at high temp.) but
will deposit crystals on cooling.

Use of heat

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usually objectionable (except to make slowly soluble
substances dissolve more rapidly).

Use of heat

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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

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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

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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

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Efflorescent powders examples

alums
ferrous sulfate
terpin hydrate

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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.

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solids that absorb moisture from the air, which
may or may not dissolve to form a solution

Hygroscopic & Deliquescent powders

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Hygroscopic & Deliquescent powders example

calcium chloride
ephedrine sulfate
phenobarbital Na

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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

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refer to 2 or more substances that may liquefy
when intimately mixed at room temperature

Pharmaceutical eutectic mixtures of drugs

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Pharmaceutical eutectic mixtures of drugs example

acetaminophen
aspirin
camphor
menthol

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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