Incompatibilities in prescription, prescription Incompatibilities, pharmaceutics, prescription errors, important topic for pharmacist, how to remove error in the dispense and compound prescription

1. INCOMPATIBILITIES IN PRESCRIPTIONS
By
MR. RAJ KUMAR KUMAWAT
ASSISTANT PROFESSOR
BHARTI PHARMACY COLLEGE

2. Incompatibility –
Incompatibility occurs as a result of mixing of two or more
antagonistic substances and an undesirable product is
formed, which may affect the safety, efficacy, appearance and
stability of the pharmaceutical product.
It is of three types:-
1. Physical,
2. Chemical and
3. Therapeutic incompatibilities.

3. Incompatibilities occur during: -
 Compounding
 Formulation
 Manufacturing
 Packaging
 Dispensing
 Storage
 Administration of drugs
The incompatibilities may be detected by changes in the physical,
chemical, and therapeutic qualities of the medicine.

4. Physical Incompatibility - When two or more than two
substances are combined together, a physical change takes place and
an unacceptable product is formed.
Manifestations of physical incompatibility–
Insolubility:-insolubility of prescribed agents in vehicle
Immiscibility:-Immiscibility of two or more liquids
Precipitation:-It occurs due to solvent is insoluble when it is added to
solution
Liquefaction:-Liquefaction of solids mixed in a dry state (called eutexia)
Physical incompatibility may be corrected by–
1. Change the order of mixing of ingredients of the prescription
2. Emulsification
3. Addition of suspending agent
4. Change in the form of ingredients
5. By addition, substitution or omission of therapeutically nactive
substance to help in compounding of the prescription.

5. Physical Incompatibility –
Insolubility- It means the inability of material to dissolve in a
particular solvent system. The majority of incompatibilities is due to
insolubility of the inorganic as well as organic compounds in particular
solvents.
The following factors affect the solubility of prescribed agent in vehicle
and may render it less soluble:-
1. Change in pH
2. Milling
3. Surfactant
4. Chemical reaction
5. Complex formation
6. Co-solvent
To prevent this, it is important to study the insolubility of inorganic and
organic compounds used as ingredients in compounding and
dispensing of medicines.

6. Physical Incompatibility –
Immiscibility- When two such ingredients are combined resulting
in a non- homogenous product, such ingredients are called immiscible
to each other and the phenomenon is called immiscibility.
This manifestation appears clearly in emulsions, creams, lotions &
some types of ointments. Separation in two phases is noticed in this
pharmaceutical dosage form .
The following factors lead to immiscibility-
 Incomplete mixing
 Addition of surfactant with unsuitable concentration
 False time of addition
 Unsuitable for the type of emulsion
 Presence of microorganisms - Some bacteria grow on constituents
of mixture.
To overcome this incompatibility an emulsifying agent in case of
emulsion or a suspending agent in case of suspension is used to make
a good emulsion or suspension.

7. Physical Incompatibility -
Liquefaction- When certain low melting point solids are mixed
together, a liquid or soft mass know as eutectic mixture is produced.
This occurs due to the lowering of the melting point of the mixture to
below room temperature and liberation of hydrates.
The medicaments showing this type of behavior are camphor,
menthol, phenol, thymol, chloral hydrate, aspirin, sodium salicylates &
aspirin.
These substances can be dispensed by any of following methods-
i. Triturate together to form liquid and mixed with an absorbent like
light kaolin or light magnesium carbonate to produce free flowing
powder.
ii. The individual medicament is powdered separately & mixed with
an absorbent and then combined together lightly and filled in
suitable container.

8. Physical Incompatibility -
Precipitation- Solubilized substances may precipitate in solution
if a non-solvent for the substances is added to the solution.
E.g.:- Resins are insoluble in water, when tincture containing resinous
matter is added in water, resins agglomerates forming indiffusible
precipated . This can be prevented by slowly adding the undiluted
tincture with vigorous stirring to the diluted suspension or by adding
some suitable thickening agent.
Gum such as acacia, tragacanth, and agar, sugar and many other
hydrocolloids are precipitated from their aqueous solution by alcohol
or electrolytes through dehydration process.

9. Chemical Incompatibility - Reaction between two or more
substances which lead to change in chemical properties of
pharmaceutical dosage form as a result of this a toxic or inactive or
product may be formed.
Chemical incompatibilities occur due to the-
 Chemical properties of drugs and additives like, pH change
 Oxidation-reduction reactions
 Acid-base hydrolysis
 Double decomposition
 Complex formation
These reactions may be noticed by-
o Precipitation
o Effervescence
o Decomposition
o Color change
o Explosion

10. Types of chemical incompatibility –
1) Tolerated incompatibility: - In this type incompatibility, the
chemical interactions can be changing the order of mixing the
solutions in dilute forms, without or by changing the order of mixing.
2) Adjusted incompatibilities: - In this the chemical interaction can be
prevented by adding or substitution of one of the reacting
ingredients of a prescription with another of equal therapeutic value.
The chemical incompatibility may be:-
i. Intentional: When the prescriber knowingly prescribes the
incompatible drugs.
ii. Unintentional: When the prescriber prescribes the drugs without
knowing that there is incompatibility between the prescribed drugs.

11. Therapeutic Incompatibility- It may occur as a result of
prescribing certain drugs to a patient with the intention to produce a
specific degree of pharmacological action, but the intensity of action
produced is different from that intended by the prescriber.
It is divided into two groups-
1. Pharmacokinetics: It involves the effect of a drug on another from
the point of view that includes absorption, distribution, metabolism
and excretion.
2. Pharmacodynamics: These are related to the pharmacological
activity of the drugs. E.g., Synergism, antagonism, altered cellular
transport, effect on the receptor site.
Therapeutic incompatibilities occurs due to following reasons:-
a. Error in dosage
b. Wrong dose or dosage form
c. Contra-indicated drugs
d. Synergistic and antagonistic drugs
e. Drug interactions

12. ERROR IN DOSAGE- Many therapeutic incompatibilities result from
errors in writing or interpreting the prescription order. The most serious
type of the dosage error in the dispensing is overdose of a medication.
It becomes the duty of a pharmacist to check the prescription before
dispensing it. Pharmacist is often in a position to detect such errors
and help to avoid such problem.
WRONG DOSE OR DOSAGE FORM- There are certain drugs
which have quite similar names and there is always a danger of
dispensing the wrong drug. E.g., Prednisone and Prednisolone,
Digoxin and Digitoxin etc.
CONTRAINDICATED DRUGS- There are certain drugs which may
be contraindicated in a particular disease or a particular patient who is
allergic to it. E.g., Corticosteroids are contra-indicated in the patients
having peptic ulcers. The penicillin and sulphur drugs are contra-
indicated in the patients who are allergic. Vasoconstrictors are contra-
indicated in hypertensive patients. Barbiturates and morphine should
not be given to the asthmatic patients.

13. SYNERGISTIC & ANTAGONISTIC DRUGS- When two drugs are
prescribed together, they tend to increase the activity of each other
which is known as SYNERGISM.
When two drugs are prescribed together, they tend to decrease the
activity of each other which is known as ANTAGONISM.
E.g., A combination of aspirin and paracetamol increases the analgesic
activity. A combination of penicillin and streptomycin increases the
antibacterial activity. Amphetamines show its antagonists effect with the
barbiturates.
DRUG INTERACTIONS- The effect of one drug is altered by the
prior or simultaneous administration of another drug. The drug
interaction can usually be corrected by the proper adjustment of dosage
if the suspected interaction is detected.
E.g., Tetracycline is inactivated by calcium. So, it should not be taken
with milk. In this prescription, the therapeutic incompatibility is
unintentional. So, the prescription is referred back to the prescriber to
change the direction.

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