sterile dosage forms

1. Azerbaijan medical university
Department of Pharmaceutics
Faculty of Pharmacy
Department of pharmaceutical technology
1
presentation of STERILE DOSAGE FORMS
student albuissa muhammed hamed
3rd
course 887b
2016

2. CONTENTS
2
 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

3. Introduction
3
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.

4. Routes of parenteral
administration
4
Intravenous injections and infusions
Subcutaneous injections
Intramuscular injections
Intradermal injections
Intra-arterial injections
Intracardic injections
Intraspinal injections
Intra-articular injections

5. Routes of parenteral
administration
5

6. Components of parenteral
products
6
Vehicles
Stabilizers
Buffering agents
Tonicity factors
Solubilizers
Wetting, suspending, emulsifying agents
Antimicrobial compounds

7. Antioxidants
7
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.

8. Antibacterial
8
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.

9. Buffers
9
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.

10. Chelating agents
10
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.

11. Inert gases
11
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.

12. Surfactants
12
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.

13. Surfactants
13

14. Solvents systems
14
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.

15. Non-aqueous vehicles
15
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.

16. Containers and closures
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

17. Containers and closures
17

18. Containers
18
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.

19. Closures
19
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.

20. Containers and closures
20

21. Formulation of parenterals
(solution)
21
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

22. Formulation of parenterals
(solution)
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 IV solutions can also be multivitamins or trace
elements

23. Solution
23
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

24. Suspension
24
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.

25. Suspensions
25
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

26. Suspensions
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

27. Emulsions
27
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.

28. Emulsions
28
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

29. Dry powders
29
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.

30. Sterilization
30
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.

31. Radiopharmaceuticals
31
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)

32. Radiopharmaceuticals
32
Diagnostic radiopharmaceuticals may be classified into
two types:
1. Radiopharmaceuticals used in tracer techniques for
measuring physiological parameters (e.g. 51
Cr-EDTA
for measuring glomerular filtration rate)
2. Radiopharmaceuticals for diagnostic imaging (e.g.
99m
Tc-methylene diphosphonate (MDP) used in bone
scanning).

33. Radiation protection
33
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.

34. Ophthalmic preparations
34
 Eye drops
 Eye lotions
 Eye ointments
 Ophthalmic inserts
 Contact lenses and their solutions
 Solutions
 Suspensions
 Emulsions
 Ointment
 Gels
 Erodible inserts
 Non-erodible inserts

35. Ophthalmic preparations
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

36. Packaging of ophthalmic products
36
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.

37. THANK YOUalbuissa muhammed hamed
37