Sterile Dosage Forms

1. STERILE DOSAGE FORMS
Dr. Basavaraj K. NanjwadeM. Pharm., Ph. D
Department of Pharmaceutics
Faculty of Pharmacy
Omer Al-Mukhtar University
Tobruk, Libya.
E-mail: nanjwadebk@gmail.com
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Faculty of Pharmacy, Omer Al-Mukhtar University,
Tobruk, Libya.

2. CONTENTS
• Introduction
• Routes of parenteral administration
• Components of parenteral products
• Antioxidants
• Antibacterial
• Buffers
• Chelating agents
• Inert gases
• Surfactants
• Solvents systems
• Non-aqueous vehicles
• Containers and closures
• Formulation of parenterals (solution)
• Suspensions
• Emulsions
• Dry powders
• Sterilization
• Radiopharmaceuticals
• Radiation protection
• Ophthalmic preparations
• Packaging of ophthalmic products
• References
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3. Introduction
• The human eye is a remarkable organ and the ability
to see is one of our most treasured possessions. Thus
the highest standards are necessary in the
compounding of ophthalmic preparations and the
greatest care is required in their use. It is necessary
that all ophthalmic preparations are sterile and
essentially free from forign particle.
• Parenteral preparations are sterile preparations
intended for administration by injection, infusion or
implantation into the human or animal body.
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4. Routes of parenteral
administration
• Intravenous injections and infusions
• Subcutaneous injections
• Intramuscular injections
• Intradermal injections
• Intra-arterial injections
• Intracardic injections
• Intraspinal injections
• Intra-articular injections
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Routes of parenteral
administration

6. Components of parenteral
products
• Vehicles
• Stabilizers
• Buffering agents
• Tonicity factors
• Solubilizers
• Wetting, suspending, emulsifying agents
• Antimicrobial compounds
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7. Antioxidants
• Many drugs in aqueous solutions are easily degraded
by oxidation. Small-volume parenteral products of
these drugs often contain an antioxidant.
• Bisulphites and metabisulphites are commonly used
antioxidants in aqueous injections.
• Antioxidants must be carefully selected for use in
injections to avoid interaction with the drug.
• Antioxidants have a lower oxidation potential than
the drug and so are either preferentially oxidized or
block oxidative chain reactions.
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8. Antibacterial
• Antibacterials may be divided into two groups
according to their speed of action and residue
production:
• The first group contains those that act rapidly to
destroy bacteria, but quickly disappear. E.g. alcohols,
chlorine, peroxides, and aldehydes.
• The second group consists mostly of newer
compounds that leave long-acting residues on the
surface to be disinfected and thus have a prolonged
action. E.g. triclocarban, and benzalkonium chloride.
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9. Buffers
• The ideal pH of parenteral products is pH 7.4.
• If the pH is above pH 9, tissue necrosis may result,
whilst below pH 3 pain and phlebitis in tissues can
occur.
• Buffers are included in injections to maintain the pH
of the packaged product.
• pH changes can arise through interaction between the
product and the container.
• Acetate, citrate and phosphate buffers are commonly
used in parenteral products.
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10. Chelating agents
• Chelating agents such as disodium edetate may be
included to chelate the metal ions and thus enhance
stability.
• It is seen that disodium edetate is a very useful
adjuvant to ophthalmic preparations at concentrations
of up to 0.1 % w/v to enhance antibacterial activity
and chemical stability.
• It has also been used at higher concentrations as an
eye drop for the treatment of lime burns in cattle.
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11. Inert gases
• An inert gas is a gas which does not undergo
chemical reactions under a set of given conditions.
• Inert gases are used generally to avoid unwanted
chemical reactions degrading a sample.
• The term inert gas is context-dependent because
nitrogen gas and several of the noble gases can be
made to react under certain conditions.
• Purified nitrogen and argon gases are most commonly
used as inert gases.
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12. Surfactants
• Certain compounds, because of their chemical
structure, have a tendency to accumulate at the
boundary between two phases, such compounds are
termed surfactants.
• The adsorption at the various interfaces between
solids, liquids and gases results in changes in the
nature of the interface which are of considerable
importance in pharmacy.
• Surfactants are generally classified according to the
nature of the hydrophilic group.
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Surfactants

14. Solvents systems
• The drug is generally present in an injection in low
concentration.
• The vehicle provides the highest proportion of the
formulation and should not be toxic nor have any
therapeutic activity.
• The first choice of solvent is obviously water.
• However, although the drug may be freely soluble, it
may be unstable in aqueous solution.
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15. Non-aqueous vehicles
• Water-miscible co-solvents, such as glycerin and
propylene glycol are used as vehicle in small-volume
parenteral fluids.
• They are used to increase the solubility of drugs and
to stabilize drugs degraded by hydrolysis.
• Metabolizable oils are used to dissolve drugs that are
insoluble in water. E.g. Steroids, hormones and
vitamins are dissolved in vegetable oils.
• These formulations are administered by intramuscular
injection.
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16. Large-volume parenteral fluids are packed into:
• Glass bottles
• PVC collapsible bags
• Semi-rigid polythene containers
The containers and closures that are used for packaging
parenteral products must;
• Maintain the sterility of the packed fluids
• Withstand sterilization
• Be compatible with the packed fluid
• Allow withdrawal of the contents
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Containers and closures

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Containers and closures

18. Containers
• Parenteral preparations are usually supplied in glass
ampoules, bottles or vials, plastic bottles or bags, and
prefilled syringes, which are coloured in the case of
light-sensitive substances.
• Containers should be made from material that is
sufficiently transparent to permit the visual inspection
of the contents.
• They should not adversely affect the quality of the
preparation, allow diffusion of any kind into or across
the material of the container.
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19. Closures
• Closures for parenteral preparation containers should
be equipped with a firm seal to prevent entry of
microorganisms and other contaminants.
• They should not be made of components that react
with the contents, nor should they allow foreign
substances to diffuse into the preparation.
• Plastic materials or elastomers of which the closure is
composed should be sufficiently firm and elastic to
allow the passage of a needle with the least possible
shedding of particles.
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Containers and closures

21. Formulation of parenterals
(solution)
• Aqueous solutions
– High viscosity solutions
• For compound with mol. wt. more than 750
• For water solution drugs
• Gelling agents or viscosity enhancers are used
– Complex formulations
• Drug forms dissociable complex with macromolecule
• Fixed amount of drug gets complexed
• Given by I.M. route
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22. • Oil solutions
– Drug release is controlled by controlling partitioning of
drug out of oil into surrounding into aqueous medium
– For I.M. administration only
– No. of oils are limited
• LVP usually contains one or more electrolytes
– Potassium chloride is the most common additive
– Other salts of potassium, magnesium, or sodium can be
added
• Additives to I. V. solutions can also be multivitamins or trace
elements
Formulation of parenterals
(solution)
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23. Solution
• The vehicles most commonly used for IV infusions
are:
– Dextrose in water
– NS solution
– Dextrose in saline solution
• The two main types of IV solutions are:
– small-volume parenterals (SVPs) of 50 or 100 mL
– large-volume parenterals (LVPs) of more than 100
mL
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24. Suspension
• Suspension for injection contain less than 5% of drug
solids with a mean particle diameter within the range
5-10µm.
• During the manufacture of suspension for injection,
the components are prepared and sterilized
separately, then aseptically combined.
• The final product cannot be filter sterilized owing to
the presence of particles in the formulation.
• Powders for use in sterile suspensions can be
sterilized by gas residues must be avoided.
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25. Suspensions
• Aqueous suspensions
– Given by I.M. or S.C. routes
– Concentration of solids should be 0.5 to 5 %
– Particle size should be < 10 μm
– Drug is continuously dissolving to replenish the lost.
– For oil soluble drugs
– Only crystalline and stable polymorphic drugs are given by
this form
– Viscosity builders can be used.
– E.g., Crystalline zinc insulin
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26. • Oil suspensions
– Given by I.M. route.
– Process of drug availability consists of dissolution
of drug particles followed by partitioning of drug
from oil solution to aqueous medium.
– More prolong dug action as compared to oil
solution and aqueous suspension.
– E.g., Penicillin G procaine in vegetable oil
Suspensions
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27. Emulsions
• Can be given by I.M., S.C., or I.V. routes
• O/w systems are not used due to large interfacial area
and rapid partitioning.
• W/o emulsions are used for water soluble drugs.
• Multiple emulsions are used generally such as w/o/w
and o/w/o since an additional reservoir is presented to
the drug for partitioning which can effectively retard
its release rate.
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28. Emulsions
• Release of water soluble drugs can be retarded by
presenting it as oil suspension and vice versa.
Aqueous phase
Oil phase
Water soluble drug
e.g., 5-Fluorouracil
Oil soluble drug
e.g., lipidol
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29. Dry powders
• Dry sterile powder is aseptically added to a sterile
vial.
• The dry drug powder is reconstituted with a sterile
vehicle before use.
• Powders for injections are solid substances,
distributed in their final containers and which, when
shaken with the prescribed volume of the appropriate
sterile liquid, rapidly form either clear and practically
particle-free solutions or uniform suspensions.
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30. Sterilization
• Products to a process to a process whereby all viable
life forms are either killed or removed.
• The sterilization process is usually the final stage in
the preparation of the product.
• The methods of sterilization in regular use include
exposure to: saturated steam under pressure, dry heat,
ionizing radiation, ethylene oxide or passage through
a bacteria retaining filter.
• When possible, exposure to saturated steam under
pressure is the sterilization method of choice.
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31. Radiopharmaceuticals
• Radiopharmacy is concerned with the manufacture of
radioactive medicines known as radiopharmaceuticals.
• These have two main applications in medicine:
1. As an aid to the diagnosis of disease (diagnostic
radiopharmaceuticals)
2. In the treatment of disease (therapeutic
radiopharmaceuticals)
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32. • Diagnostic radiopharmaceuticals may be classified
into two types:
1. Radiopharmaceuticals used in tracer techniques for
measuring physiological parameters (e.g. 51
Cr-EDTA
[Ethylenediaminetetraacetic acid] for measuring
glomerular filtration rate)
2. Radiopharmaceuticals for diagnostic imaging (e.g.
99m
Tc-methylene diphosphonate (MDP) used in bone
scanning).
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Radiopharmaceuticals

33. Radiation protection
• There are three basic principles to radiation
protection:
1. Shielding: By placing shielding around the
radioactive source the radiation dose rate may be
reduced.
2. Distance: The radiation dose from a radioactive
course is inversely proportional to the square of the
distance.
3. Time: Minimizing the time spent handling a
radioactive source will reduce the radiation dose.
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34. Ophthalmic preparations
• Eye drops
• Eye lotions
• Eye ointments
• Ophthalmic inserts
• Contact lenses and their solutions
• Solutions
• Suspensions
• Emulsions
• Ointment
• Gels
• Erodible inserts
• Non-erodible inserts
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35. • Eye drops including solutions and suspensions of active
medicaments for instillation into the conjunctival sac.
• Eye lotions for irrigating and cleansing the eye surface, or for
impregnating eye dressings.
• Eye ointments, creams and gels containing active ingredients
for application to the lid margins and/or conjunctival sac.
• Contact lens solutions to facilitate the wearing and care of
contact lenses.
• Parenteral products for intracorneal, intravitreous or
retrobulbar injection
• Ophthalmic inserts placed in the conjunctival sac and
designed to release active ingredient over a prolonged period
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Ophthalmic preparations

36. Packaging of ophthalmic
products
• Contact lens solutions are usually packed in plastic
containers.
• It is imperative that the low concentrations of
antimicrobials present in these products are not
reduced to ineffective levels due to sorption effects
with the plastic.
• Contact lens storage cases are also of importance to
the contact lens wearer.
• It is important that these containers are kept in a
hygienic conditions.
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37. THANK YOUe-mail: nanjwadebk@gmail.com
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Tobruk, Libya.