2. • Drug–drug or drug–excipient interactions can take place
before administration of a drug
• These may result in precipitation of the drug from
solution, loss of potency or instability
• An incompatibility occurs when one drug is mixed with
other drugs or agents, producing a product unsuitable for
administration
• Reasons might be some modification of the effect of the
active drug, such as an increase in toxicity or decrease in
activity through some physical change such as decrease in
solubility or stability
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3. chelating – in which a chelator binds with a metal
ion to form a complex
adsorption to excipients and containers causing
loss of drug
interactions with plastics and loss of drug
Protein binding to plasma proteins through
which the free plasma concentration of drugs is
reduced.
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4. PH effects in vitro and in vivo
In vitro pH effects
• PH changes often follow from the addition of a
drug substance or solution to an infusion fluid.
• An increase or decrease in pH may then
produce physical or chemical changes in the
system:
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5. • Chemical, as well as physical, instability may
result from changes in pH, buffering capacity,
salt formation or complexation.
• Chemical instability may give rise to the
formation of inactive or toxic products
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6. In vivo pH effects
Gastric effects
• Fluids have a pH of 1–3 in normal subjects
• Changes in the acid–base balance have a marked
Influence on the absorption and thus on the
activity of drugs
• Ingestion of antacids and food will change the pH
of the stomach
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8. .
Incompatibility is the result of mixing two or
more antagonistic substances and it is
detected by changes in physical, chemical or
therapeutic qualities.
• It may affect the safety, efficacy and
appearance of a medicine
Classification
1. Physical
2. Chemical
3. Therapeutic
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9. .
Physical
• This can be expressed by:
1. Precipitation e.g. gums will precipitate in alcoholic
solutions
2. Color change e.g. change of color of alkaloids with PH
change.
3. Recrystallization
• To improve their pharmaceutical property crystalline
forms may be converted to powder (non crystalline)
form, but some substances may facilitate the
recrystallization of the powdered form through time.
4. Leaching out of containers by some substances
5. Salting out – e.g. aromatic water + salt
- The presence of salt facilitates the separation of the
two phases
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10. .
Chemical
• This type of incompatibility is generally caused
by PH change, decomposition reaction or
complex formation.
Can be expressed by:
• Precipitation
• Change of color
• Salting out
• Leaching
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11. .
Chemical incompatibility could be intentional or
none intentional
• Intentional: -
example
- Production of CO2 to produce effervescence. -
effervescent granules
Complexation between cyclodextrin and
drugs
- done for insoluble drugs to increase their
solubility.
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12. .
• Therapeutic
Causes decrease in the efficacy or increase in
the activity to toxic effect.
Can be expressed by
– Synergistic effect
– Contra indication
– Adverse effect
• Synergistic: - One potentiates the activity of
the other.
Eg. Aspirin + Parcetamol
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13. .
• Contraindication: - the opposite action may
happen.
Eg. Stimulant + hypnotic
• Adverse effect- drug may increase the adverse
effect. So such drugs should not be given in
combination
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14. .
Containers and closures
Containers
• According to the USP, a container is “that
which holds the article & is or may be in direct
contact with the article.”
• The immediate container is “that is in direct
contact with the article at all times”.
• The closure is part of the container
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15. .
• Desirable properties
1. The container must be rigid enough to
prevent damage to the content.
2. The material of construction must not react
with the content.
3. The closure must prevent
– Access of moisture
– Loss of moisture from creams and from water
containing ointments and pastes
– Un intentional escape of the content and
– Entry of dirt or other contaminants such as
odorous vapors that might cause tainting
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16. .
4. The closure must be easily removed and
replaced.
5. It must not be difficult to abstract the contents or
to empty the container completely
6. For many products, protection from light must be
given.
7. Medicaments or additives must not be absorbed
by the container materials nor must diffusion
through the walls be possible
8. It must be easy to label the container correctly.
9. It must have a pharmaceutically elegant
appearance.
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17. .
• Glass: - It has been widely used & continues to be
the preferred packaging material for many
pharmaceutical products.
Advantages:- 1. Inert to most medicinal
products
2. Impervious to air & moisture
3. Allows easy inspection
4. Can be colored to protect
from harmful light.
5. Easy to clean & sterilize by
heat
6. Available in different shaped
containers
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18. .
Disadvantages:- 1. Fragile
2. Certain glasses may
release alkali
3. Expensive compared to
plastic
4. Heavy resulting in
increased transport costs
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19. .
Constitution of official glass types
• Type General Description
I highly resistant, Borosilicate
glass , neutral
II Treated soda lime glass (silica)
III Soda – lime glass , silica (more
leachable oxide).
IV General purpose soda – lime
glass with a low hydrolytic
resistance.
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20. .
Examples:-Bottles, dropper bottles, jars, containers for
parental products (Ampoules, vials)
Plastics
– can be used as container & carton (20 packaging).
In recent times, it is used for packaging of parental
products (infusion fluids & small volume injections)
Advantage:- Flexible & not easily broken
- Low density & light in weight
- Easily molded in to various shapes
- Suitable for use as container, closure &
as secondary packaging.
- Cheap
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21. .
Disadvantage:- Not inert as type – I glass
- Cracking & distortion with some
chemicals
- Some are very heat sensitive
- Not impermeable to gas & vapor
as glass.
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22. Closures
• Any closure system should provide an
effective seal to retain the container contents
& exclude external contaminants.
• Child – resistance containers (CRCs)
commonly consist of a glass or plastic vial or
bottle with a specially designed closure.
• Closures are made of using natural rubbers or
synthetic rubbers
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23. .
• Injection containers are hermetic containers
which are sterile used to hold preparations for
parentral administration.
• A hermetic container is impervious to air or
any other gas under the ordinary or customary
conditions of handling shipment, storage &
distribution.
• A single dose container is one in which the
quantity of drug contained is intended as a
single dose & when opened can’t be resealed.
Ex. Ampoules , pre – filled syringes.
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24. .
• A multiple – dose container is a hermetic
container that permits withdrawal of
successive portions of the contents without
changing the strength, quality or purity of the
remaining portion. Ex. Vials
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25. .
Re-packaging
• Is the process by which the dispenser transfer, a
medication manually or automated system from
manufacturers original container to another type
of containers
• Repackaging is performed
- In community pharmacy for dispensing purpose
and in hospital pharmacy
- Bulk medicines are repackaged into smaller
quantities in dispensing containers for
distribution to hospital wards, clinics and so on.
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26. .
The containers used in repackaging process
must protect the product from
- Physical damage
- Chemical and microbial contamination
- Light, moisture and air (oxygen)
• Repackaging is limited for volatile drug
• Sterile products are not easily repackaged and
require sterile procedure
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27. .
Material used for repackaging
• Glass bottles
• Plastic bottles
• Collapsible tubes
• Paper envelops
• Plastic envelops
Paper has least value in primary packaging in
term of maintaining safety, quality and stability of
packaged drug
• In Ethiopia commonly used repackaging material
is ordinary paper and also labeling is incomplete
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