Formulasi Dan Teknologi Sediaan Steril-6

FORMULASI DAN TEKNOLOGI SEDIAAN
STERIL
3/28/2018 TEKNOLOGI FARMASI UNIVERSITAS BUANA PERJUANGAN KARAWANG 2018 1

“METODE PREPARASI PRODUK STERIL”
OVERVIEW OF STERILE
COMPOUNDING
When drugs need to be injected, any one of several routes can be used to administer the
drug. The most common injectable routes of administration are intravenous (in the vein),
intramuscular (in the muscle), and subcutaneous (in the skin).
The compounding of sterile preparations is an integral part of any health-system setting.
While the majority of perenteral products are prepared using commercially available
medications and diluents solutions, pharmacy departments still perform intravenous
manufacturing.

OVERVIEW OF STERILE
COMPOUNDING
The reasons for this vary greatly, but can include:
• Special patient populations such as pediatrics, geriatrics, or the terminally ill (pain
management). For these patients, the appropriate strengths for certain drugs may not be
available.
• Some patients might be allergic to the diluents and preservatives in commercially
available products.
• Some drugs are unstable and require preparation to be dispensed every few days.

• A combination therapy that a prescriber desires, but that is not currently commercially
available.
INTRAVENOUS ADMINISTRATION
Intravenous administration of drugs has advantages over other routes of
administration because it provides the fastest route to the bloodstream. There
are no barriers like skin or muscle to absorb the drug first, which allow the most
rapid onset of action.
If someone cannot take medication by mouth because he is unconscious or
vomiting, then intravenous administration is the best route. Since the inner lining of
a vein is relatively insensitive to pain, drugs that can be irritating if given by
another route can be given intravenously as a slow rate without causing pain.

Drugs that can be diluted to reduce irritation can be given only intravenously
because the tissue and skin around the other routes of administration cannot
accommodate large volumes.
There are two types of intravenous administration. The first is an intravenous
injection in which the prepared medication is drawn up into a syringe and
administered immediately.
The amount of medication is usually a small volume pushed through an IV line
that is already in place on the patient.

The second type of administration is an IV infusion. Infusions are given to
overcome dehydration, to build up depleted blood volumes, and to serve as
an aid for the administration of medications.
An infusion allows a larger volume to be given at a constant rate, depending
on the drug to be administered. Infusions can be administered continuously or
intermittently. Continuous infusions are used to administer larger
volumes of solutions over several hours at a slow, constant rate. Intermittent
infusions are used to administer a relatively small volume over a shorter time
at specific intervals.

STERILE PREPARATION FORMULATIONS
The objective of formulating and compounding sterile preparations is to
provide a dosage form of a labeled drug, in the stated potency, that is safe
to use if administered properly.
This section will explore the professional standards and operating procedures
that should be followed during formulation and compounding. The
components, containers, and closures also are described, as well as the
physiologic and physical norms of preparing formulations for parenteral and
ophthalmic use.
Stability, incompatibility of drugs, sterilization methods, labeling,
documentation, and end preparation evaluation is discussed in later sections.

THE TECHNICIAN ENSURES THAT THE STERILE COMPONENTS
UNDER HIS
SUPERVISION MEET ACCEPTABLE CRITERIA OF STABILITY AND
STERILITY
1. Storing components under the environmental conditions stated in the individual monographs
and/or in the labeling.
2. Observing components for evidence of instability. Although chemical degradation ordinarily
cannot be detected by the naked eye, some physical changes not necessarily related to chemical
potency, such as change in color and odor, or formation of a precipitate, or clouding of solution,
may alert the technician of a stability problem. If a component has undergone a physical
change not explained in the labeling, such a preparation is never to be dispensed.
3. Observing components for evidence of lack of sterility. The presence of microbial contamination
in sterile components cannot be detected visually, but color change, cloudiness, surface film, or

gas formation is sufficient reason to suspect possible contamination. Evidence that the integrity
of the seal has been violated should make the component suspect of microbial contamination.
THE TECHNICIAN ENSURES THAT THE STERILE COMPONENTS

UNDER HIS
SUPERVISION MEET ACCEPTABLE CRITERIA OF STABILITY AND
STERILITY
4. Properly handling and labeling preparations that are repackaged, diluted, or mixed
with other products.
5. Using the oldest stock first and observing expiration dates
6. Dispensing the proper container with the proper closure.

7. Sterile compounding equipment must be appropriate in design, size, and composition so
that surfaces contacting components are not reactive, additive, or adsorptive. These
surfaces should not alter the required safety, identity, strength, quality, and purity of
the components.
8. As a technician, your work must be checked by a licensed pharmacist. Dispensing
pharmacist must inspect and approve or reject all formulas, calculations, substances,
containers, closures, and in-process materials.
VEHICLES
Vehicles for most liquid sterile preparations have no therapeutic activity or
toxicity. Rather, they serve as solvents or mediums for the administration of
therapeutically active ingredients. For parenteral preparations, the most
common vehicle is water. Vehicles must meet USP (United States
Pharmacopeia) requirements.

WATER FOR INJECTION
Water for injection is purified by distillation or reverse osmosis and is free of
pyrogens (bacterial substance that can produce fever). Sterile water for
injection USP is sterilized and packaged in single-dose containers not
exceeding 1000 ml. Bacteriostatic water for injection is sterilized and contains
one or more bacteriostatic agents in a container no larger than 30 ml.
AQUEOUS ISOTONIC VEHICLES

Aqueous isotonic vehicles are often used in sterile preparations. A common vehicle is
sodium chloride injection, a 0.9% solution (also known as normal saline) that is sterilized
and packaged in single-dose containers no larger than 1000 ml.

Bacteriostatic sodium chloride injection is a 0.9% sodium chloride injection that contains
one or more bacteriostatic agents in a container no larger than 30 ml.
Sodium chloride irrigation also is a 0.9% solution; however, it has no preservatives
and may be packaged in a container larger than 1000 ml.
STERILE PREPARATIONS
Other isotonic vehicles include Ringer’s injection, dextrose injection 5%, and
lactated Ringer’s injection. None of these components is available in
containers larger than 1000 ml.

WATER-MISCIBLE SOLVENTS
A water-miscible solvent is a solution that can be thoroughly mixed with water.
Several water-miscible solutions are used as a portion of the vehicle in sterile
preparations (cosolvents).
These solvents, such as ethyl alcohol, liquid polyethylene glycol, and propylene
glycol) dissolve drugs with low water solubility. Preparations compounded
with these components are usually administered intramuscularly.
Examples of drugs in cosolvent formulations include some barbiturates,
antihistamines, and cardiac glycosides.

NONAQUEOUS VEHICLES
Nonaqueous vehicles, such as fixed oils, can be used to formulate parenteral
preparations, USP specifies that fixed oils must be vegetable in origin and
odorless and also have no rancid taste.
Examples include peanut, cottonseed, corn, and sesame oils. Some vitamins
and hormones can only be solubilized in these oils. Also, oil-based parenterals
can only be given intramuscularly.

SOLUTES
A solute is a component of a solution. In a solution, the dissolving substance is called the
solvent, whereas the dissolved substance is called the solute. Solute chemicals dissolved
in vehicles should be USP grade or better since their contaminants can:
• Alter solubility and compatibility of other solutes
• Cause catalytic chemical reactions
• Cause toxicity of patients
Solutes may be active ingredient or added substances. Added substances can
increase stability or usefulness if they are harmless in their administered amounts and
do not interfere with therapeutic efficacy.

ANTIMICROBIAL PRESERVATIVES
If a concentration is considered bacteriostatic (preventing bacteria from growing and
multiplying, but not really killing them) a antimicrobial preservative may be added.
Some preservatives, however, have innate toxicity within these concentrations and are
used mostly in ophthalmics and seldom in injectables.
Examples include phenylmercuric nitrate 0.01%, benzalkonium chloride 0.01%, and
phenol 0.5%). Benzyl alcohol (usually 0.9%) is commonly used in injectables. In oleaginous
(oily) preparations, no antimicrobial is highly effective.
An antimicrobial agent may be effective in one formula of ingredients but not in
another. To select a preservative, an appropriate reference should be consulted and
its effectiveness should be verified. USP provides a test for the efficacy of
antimicrobial preservatives.

PH BUFFERS
Buffering agents stabilize a solution against degradation. Buffering agents
are formulated at the lowest concentration needed for stability so that they do
not disturb the body’s natural pH. Acid salts such as citrates, acetates, and
phosphates are commonly used as buffers.
ANTIOXIDANTS
Antioxidants help to prevent oxidation of the component drug. Oxidation is
defined as the interaction between oxygen molecules and all the different
substances. Technically, however, with the discovery of electrons, oxidation
came to be more precisely defined as the loss of at least one electron when
two or more substances interact.

Those substances may or may not include oxygen. This can work to degrade
the drug/drugs with in the solution. The most common antioxidants are the
sodium and potassium salts of metasulfite and sulfite ions. However, the choice
of salt depends on the pH of the system to be stabilized. Metabisulfite is used
for low pH values, bisulfite for intermediate pH values, and sulfite for high pH
ranges.
CHELATING AGENTS
Chelating agents enhance the effectiveness of antioxidants. They form
complexes with trace amounts of heavy metals, thereby eliminating the
catalytic activity of metals during oxidation. The most commonly used
chelating agent is edenate sodium.

TONICITY AGENTS
The tonicity agents are used to adjust the composition of the formulation to the
desired isotonic range. Some examples include glycerin, mannitol, sorbitol,
sodium chloride, and other electrolytes.

SOLUBILIZERS
When performing sterile compounding, technicians must know the solubility
characteristics of drug substances, since they must possess some solubility to
elicit a therapeutic response.
Polyethylene glycols 300 and 400, and propylene glycol, glycerin, and ethyl
alcohol frequently are used. However, toxic levels of these solvents must be
avoided as well as amounts that make the preparation too viscous (thick or
sticky) for parenteral use.

EMULSIFIERS
Some drugs are minimally soluble in water. Emulsifiers are used to suspend
tiny oil globules in water to create an emulsion that contains a uniformed
concentration of the active drug throughout the volume of the liquid.
One example is a soybean oil and water emulsion manufactured with egg
yolk. An example of an active drug is propofol that is dissolved in soybean oil
which is emulsified into a concentration.

CONTAINERS
Containers are defined as “that which holds the article and is or may be indirect contact
with the articles. The closure is part of the container.” All containers for sterile
preparations must be sterile, free of both particulate matter and pyrogens.
These containers should not interact physically or chemically with formulations to alter
their required strength, quality, or purity. Containers must also permit inspection of
their contents.

SINGLE OR MULTIPLE DOSE
CONTAINERS
Sterile, single-dose containers are intended for parenteral, inhalation,
irrigation, octic, and ophthalmic administration. Examples are prefilled
syringes, cartridges, ampuls, and vials (when labeled as single-use).
Multiple-dose containers permit withdrawal of successive portions of their
contents without changing the strength, quality, or purity of the remaining
portions. Sterile, multiple-dose containers may be used for preserved
parenterals, ophthalmics, and octics.

GLASS
Glass is the most popular material for sterile preparation containers. USP classifies
glass as Type I (borosilicate glass), Type II (soda-lime-treated glass), Type III (sodalime
glass), or NP (soda-lime glass unsuitable for parenteral containers).
Different glass types vary in their resistance to attack by water and chemicals. For
pharmaceutical containers, glass must meet the USP test for chemical resistance.
Because most pharmacy personnel do not have the time or facilities to perform glass
chemical interaction studies, they should use only Type I glass to minimize sterile
preparation compatibilities.

PLASTIC
Plastic polymers can be used as sterile preparation containers but present three problems:
1. Permeation of vapors and other molecules in either direction through the container.
2. Leaching of constituents from the plastic into the preparation.
3. Sorption of drug molecules onto the plastic.
Plastics must meet USP specifications for biological reactivity and physiochemicals.
Most plastic containers do not permit ready inspection of their contents because they are
unclear. Most plastics also melt under heat sterilization.

CLOSURES
Rubber closures must be rendered sterile, free from pyrogens and surface
particles. To meet these specifications, multiple washings and autoclavings are
required. An autoclave heats sterilizing solutions above their boiling point to
sterilize medical instruments.
Closures are made of natural, neoprene, or butyl rubber. Thus, the rubber
sealing of a vial or the plug in a syringe is a complex material that can
interact with the ingredients of a formula.
Rubber closures also are subject to coring. Therefore, you should consult the
literature standards when selecting a rubber closure for sterile preparations.

PARENTERAL FORMULATIONS
Pharmacists and technicians will compound a wide variety of sterile formulations in different
settings. These formulations will include products administered by injection, such as:
• Intravenous (IV) – medication is injected directly into the vein
• Intramuscular (IM) – medication is injected directly into a large muscle
• Subcutaneous (SC) – also know as hypodermic injection; medication is injected into the tissue
under the skin
• Intradermal (ID) – medication is injected into the substance of the skin
• Intrathecal – medication is injected into the spinal canal
• Epidural – medication is injected through a catheter placed in the “epidural space”, which is
the outermost part of the spinal canal.

PARENTERAL PREPARATIONS ARE CLASSIFIED
INTO SIX GENERAL CATEGORIES:
1. Solutions read for injection.
2. Dry, soluble preparations ready to be combined with solvent before use.
3. Suspensions ready for injection.
4. Dry, insoluble preparations ready to be combined with a vehicle before use.
5. Emulsions.
6. Liquid concentrates ready for dilution prior to administration.

LARGE VOLUME PARENTERAL
SOLUTIONS
Large-volume parenteral (LVP) solutions are commonly stored in plastic or glass.
Solutions for injection must be sterile, and contamination must be prevented by using
aseptic techniques. LVP solutions are available in a variety of sizes (250 mL, 500 mL,
1000 mL).
Examples of LVP solutions with additives, manufactured in standard concentrations,
include:
• Aminophylline
• Dopamine
• Lidocaine
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SOLUTIONS
• Nitroglycerin
• Potassium
In some cases, the preparation of LVPs by the pharmacist or technician depends on
the drug and intended use. The preparation of LVPs in the pharmacy must always
follow aseptic technique (discussed later). Common examples of LVPs in use include:
• Dextrose Injection, USP
• Dextrose and Sodium Chloride Injection
• Amino Acid Injection

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SOLUTIONS
• Mannitol Injection, USP
• Ringer’s Injection, USP
• Lactated Ringer’s Injection, USP
• Sodium Chloride Injection, USP
These solutions are usually administered by intravenous infusion to replenish
body fluids, electrolytes, or provide nutrition. They are usually administered
in volumes of 100 mL to 1 liter amounts (and more) per day by slow
intravenous infusion with or without controlled-rate infusion systems.

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SMALL-VOLUME PARENTERAL
SOLUTIONS
Small-volume parenteral (SVP) solutions can be either directly administered to a
patient or added to another parenteral formulation. Additive parenteral solutions
are called “admixtures.” SVP solutions can be supplied in different forms :
• Prefilled syringes
• Glass or plastic vials sealed with a rubber closure
• Ampules

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PHYSIOLOGICAL NORMS
• Plastic minibags or “piggybacks”
1. pH
The term pH is used to describe the degree of acidity of a solution. pH values
range from 0 to 14, with values below 7 representing greater acidity of the solution,
while values above 7 represent less acidity or greater alkalinity.
A solution having a pH of 7 is neither acid, nor alkaline; it is considered neutral.
Plasma in our body is about 7.4, and solutions should try to stay around that number,
pH is another characteristic that cannot be seen, but can be tested after it is
prepared.

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PHYSIOLOGICAL NORMS
Normal human serum pH, a logarithmic measure of the hydronium ion concentration in
solution, is 7.4. Drugs that are acids or bases or their salts sometimes must be
buffered to a pH near normal (e.g., 3-8) to prevent pain or tissue damage.
2. Tonicity
Another characteristic that also cannot be seen is isotonicity. An isotonic solution has
the same concentration as red blood cells. Isotonic IV solutions minimize patient
discomfort and damage to red blood cells.
Stinging caused by either a hypertonic (shrinking of red blood cells) or hypotonic
(swelling of red blood cells) solution is not experienced with an isotonic solution. IV
solutions should be as close to isotonic as possible.

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PHYSIOLOGICAL NORMS
A good reference point to remember is that 0.9 percent sodium chloride injection and
5 percent dextrose injection are both approximately isotonic.
2. Tonicity
Any chemical dissolved in water exerts a certain osmotic pressure, which is the
pressure exerted by a solution necessary to prevent osmosis into that solution when it
is separated from the pure solvent (i.e., a solute concentration related to the number
of dissolved particles per unit volume).
Blood has an osmotic pressure corresponding to sodium chloride 0.9%; thus, its
common name is normal saline. Normal saline is said to be “isosmotic” with blood ad
other physiologic fluids.

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PHYSIOLOGICAL NORMS
2. Tonicity
In the medical setting, the term “isotonic” is used synonymously with isosmotic. A
solution is isotonic with a living cell if no net gain or loss of water is experienced by
the cell and no other change is present when the cell contacts that solution.
Very hypotonic (containing a low concentration of solute relative to another solution)
IV preparations can cause hemolysis (the destruction or dissolution) of red blood cells.
Very hypertonic (contains a high concentration of solute relative to another solution)
injections can damage tissue and cause pain on injection. The greater the volume of
solution to be injected, the closer the parenteral preparation should be to isotonicity.

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PHYSIOLOGICAL NORMS
3. Pyrogenicity
Pyrogens are contaminants that are unacceptable in final compounded sterile
preparations. Pyrogens are fever-producing endotoxins from bacteria. As
large proteins, pyrogens are not removed by normal sterilization procedures
and can exist for years in aqueous solution or dried form.
The sources of pyrogens in sterile preparations are:

• Aqueous vehicles
• Equipment
• Containers and closures
• Chemicals used as solutes
• Human touch
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PHYSICAL NORMS
1. Particulates
Parenteral solutions must be free of particulate matter – mobile, undissolved
solids not intended for sterile preparations. Examples include lint, cellulose12
and cotton fibers, glass, rubber, metals, plastics, undissolved chemicals, rust,
diatoms, and dandruff.
Sources of particulate matter are:
• Vehicles and solutions
• Environment
• Containers and closures
• Personnel
A careful choice of components, containers, and closures can minimize
particulate contamination. Also, filtration can remove particles and bacteria
from sterile preparations.
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PHYSICAL NORMS
2. Stability
Stability of parenteral preparations must be assured so that patients receive the
intended dose. Hydrolytic (decomposition of a chemical compound) and oxidative
degradations are the most common forms of instability but rarely show as cloudiness
or color changes. The rate of hydrolysis13 may be affected by storage temperature
or pH of the solution.
Oxidation is affected by temperature, pH, exposure to light, oxygen concentration of
the solutions, and impurities. Because numerous factors affect the stability of drug
molecules, parenterals from bulk chemicals should use a short beyond the use date.
The choice of packaging also is important for perenteral drug stability.

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PHYSICAL NORMS
3. Impurities
Heavy metals (like lead and mercury) are also to be minimized in sterile
preparations. Heavy metals can be toxic and can catalyze the degradation of active
ingredients and preservatives. Introduction of these impurities is most likely when non-
sterile; raw materials are used in compounding.
STERILE PREPARATION FACILITIES AND

EQUIPMENT
The following equipment is essential for sterile compounding:
• Syringes and needles • Alcohol pads • Large-volume parenteral (LVP) solutions. •
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Small-volume parenteral (SVP) solutions • Ampules or vials • Laminar airflow hoods •
Refrigerators (with thermometers) • Freezers • Sinks with hot and cold water •
Automated compounding devices • Disinfectant cleaning solutions • Disposable,
lintfree towels or wipes • Disposable gowns, caps, masks, and sterile gloves • Sharp
containers • Computer systems • Shelving • Carts • Stainless steel furniture
LAMINAR FLOW HOODS

Sterile products should be prepared in Class 100 environments, which can contain no
more than 100 particles (a small piece or portion of anything, such as
microorganisms) per cubic foot. These particles are 0.5 microns (or larger) in size.
Laminar flow hoods are commonly used to achieve a Class 100 environment.
Laminar flow hoods are designed to reduce the risk of airborne contamination during
the preparation of IV admixtures by providing an ultra-clean environment. The most
important part of a laminar flow hood is a high-efficiency, bacteria-retentive filter,
commonly called a HEPA (high-efficiency particulate air) filter.
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LAMINAR FLOW HOODS
Room air is taken into the unit and passed through a pre-filter to remove relatively
large contaminants such as dust and lint. The air is then compressed and channeled
up behind and through the HEPA filter, where virtually all bacteria are removed.
The purified air then flows out over the entire work surface in parallel lines at a
uniform velocity. The orientation of the direction of airflow can be horizontal or
vertical.
Great care must be exercised to prevent cross-contamination from one operation to
another, especially with horizontal laminar airflow. Vertical laminar airflow hoods
are used to prepare drugs for chemotherapy.

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VERTICAL LAMINAR AIRFLOW
HOODS
With vertical flow, room air enters at the top of the unit and is channeled through the
bacteria-retentive filter (which forms the ceiling of the unit) and down vertically across
the work surface area.
As with the horizontal flow hood, this type of vertical flow hood is not suitable for
chemotherapy drugs. Although they protect the drug product from microbial
contamination, they do not protect personnel or the environment from the hazards of
the drug agents.
These laminar flow hoods blow air across the work surface toward the operator and
into the work environment. Drug particles or aerosols of these hazardous agents can
easily contaminate both workers and the work environment.
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BIOLOGICAL SAFETY CABINETS
Since horizontal laminar-airflow hoods blow air toward the operator, vertical
laminar airflow hoods are preferred when working with hazardous substances.
Vertical flow hoods are part of a family of equipment called biohazard
cabinets or biological safety cabinets.
BIOLOGICAL SAFETY CABINETS

Three types of biohazard cabinets are available:
1. Class I cabinets have a HEPA filter on their exhaust outlet but not for inward
airflow. The protect personnel and the environment but do not prevent contamination

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of compounded preparations. This class of hoods has no application in compounding
sterile preparations.
2. Class II cabinets have HEPA filtered inward air for protection of compounded
preparations and HEPA filtered exhaust air to protect personnel. They are suitable
for compounding sterile preparations. Class II cabinets are classified according to
how their exhaust air is vented.
CLASS II CABINETS ARE CLASSIFIED ACCORDING

TO HOW THEIR EXHAUST AIR IS VENTED
a. Type A cabinet: i. Maintains a minimum calculated average inflow air velocity of

75 ft/min through the work area access opening. ii. Has HEPA filtered air from a
common plenum (some air is exhausted from the cabinet and some is supplied to the

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work area). iii. May have air exhausted back into the controlled area. iv. May have
positive-pressure-contaminated ducts and plenums.
b. Type B cabinet exhausts some or all air outside the controlled area. These
cabinets are further classified as B1, B2, or B3:
i. B1 cabinet: 1. Maintains an average air velocity of 100 ft/min. 2. Has HEPA
filtered down flow air composed largely of uncontaminated, recirculated inflow air?
3. Exhausts most contaminated air to the atmosphere through a dedicated duct and
HEPA filter 4. Has all contaminated ducts and plenums under negative pressure?

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CLASS II CABINETS ARE CLASSIFIED
ACCORDING TO HOW THEIR
EXHAUST AIR IS VENTED
ii. B2 cabinet, sometimes called a total exhaust cabinet, differs from B1 cabinet in
that it: 1. Has all down flow air drawn through a HEPA filter from the controlled area
or outside, not recirculated from the cabinet. 2. Exhausts all air to the atmosphere
after HEPA filtration, not to recirculation in the cabinet controlled area. iii. B3 cabinet,
sometimes referred to as a convertible cabinet: 1. Has HEPA filtered air that is a
portion of the mixed down flow and inflow air from a common exhaust plenum? 2.
Exhausts all air to the atmosphere after HEPA filtration. 3. Can be converted from a
Type B to a Type A cabinet if desired.
Class III cabinets are totally enclosed, vented, and gastight units.
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Operations are conducted through attached rubber gloves, and the
cabinet is maintained under negative pressure. These cabinets
have limited applications in the preparation of sterile products and
are intended for the handling of extremely hazardous substances
ASEPTIC TECHNIQUE
Aseptic technique is carrying out a procedure under controlled conditions in a manner
that minimizes the chance of contamination. Contamination can be caused by the
following factors:
• Environment – controlling the air where the compounding is being performed.
• Equipment – all objects that come in contact with the drug(s) must be sterile.
• Personnel – touch contamination is the most frequent cause of contamination.

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ASEPTIC TECHNIQUE
Aseptic technique refers to the procedures used during preparation that maintains the
sterility of pharmaceutical dosage forms. Sterilization is an essential concept in the
preparation of sterile pharmaceutical products. Its aim is to provide a product that is
safe and that eliminates the possibility of introducing infection.
Aseptic technique describes the methods used to manipulate sterile products so that
they remain sterile. Technique is a separate element in compounding of sterile
preparations, independent from equipment and the environment. Proper technique
does not eliminate the need for good equipment and a proper environment.
Conversely, good equipment and an ideal environment do not change the need for a
good technique.

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CLEAN ROOM
A clean room is an area that is specially constructed and maintained to reduce the
probability of environmental contamination of sterile products during the
manufacturing process.
USP 797 requires that the surfaces of all floors, wall, ceilings, cabinets, shelving, and
work surfaces in the buffer room should be soft and smooth. These surfaces must also
be free from crevices or cracks, making them easy to clean and sanitize.
Because air is one of the greatest potential sources of contaminants in clean rooms,
special attention must be given to air being drawn into clean rooms by the following
systems:
• Heating • Ventilation • Air conditioning

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CLEAN ROOM
Personnel entering the aseptic area should enter only through an airlock. They
should be attired in sterile coveralls with sterile hats, masks, goggles, and foot
covers. Traffic flow into the room should be minimized and in-and-out
movement rigidly restricted during a filling procedure.
Clean rooms sometimes have an anteroom that is used for non-aseptic
activities related to the clean room operation such as:
• Gowning
• Handling stock
• Order processing

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PROCEDURES FOR COMPOUNDING
OF SOLUTIONS
A sterile product contains no living microorganisms. The need for sterility is based on
the fact that through injection, the major body defense mechanisms are bypassed. In
the hospital, a majority of patients will receive a medication that is administered by
injection.
Examples of ophthalmic preparations that must be sterile include ointments, solutions,
and suspensions. Sometimes pharmacy technicians must compound two solutions that
are not commercially available. An example is the compounding of two materials that
are both liquid in nature.

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THE PROCEDURE FOR STERILE COMPOUNDING OF SOLUTIONS
MUST BE PERFORMED IN THE CLEAN AIR SPACE BY USING
PROPER ASEPTIC TECHNIQUE, AS FOLLOWS:
• Prepare all materials needed for the procedures.
• Swab the rubber tops of vials with alcohol and wait for them to dry.
• Pull the plunger back on the syringe slightly, and then pull the amount needed to by
drawn up.
• Insert the needle through the stopper.
• Push the air from the syringe into the vial.
• Withdraw the desired amount of medication.
• Withdraw the needle.
• Add the medication into the IV bag.
• Gently shake the bag of solution.
• Label the product of compounded solution.
• Store the product in the refrigerator.
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COMPATIBILITY
Not all drugs are compatible with each other. The incompatibility may be between
two drugs or between a drug and an IV solution. The possibility of an unexpected or
undesirable combination is relatively low compared with the number of IV admixtures
prepared, but it is always possible.
An incompatibility can lead to a patient not receiving the full therapeutic dose of a
medication or, even worse, can lead to an adverse reaction. Some incompatibilities,
such as a color change or hazy appearance, can be seen.
Precipitate can form in the solution, or an evolution of a gas may even be smelled.
Be aware that sometimes when drugs are combined and a visible change occurs, it
could be expected and harmless.
Reading the package insert or checking with the pharmacist can confirm the reason
for this change in appearance.

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TO MINIMIZE INCOMPATIBILITIES, THE
FOLLOWING GUIDELINES NEED TO BE
FOLLOWED WHENEVER POSSIBLE:
1. Use solutions promptly after preparation in order to ensure administration of the
most stable product; drugs tend to degrade in a relatively short time. If a newly
made admixture is not immediately used, it should be placed in the refrigerator.
2. Minimize the number of drugs added to a solution. As the number of drugs
added increases, the chance of an incompatibility rises. It becomes increasingly
difficult to find information on compatibilities when more than two drugs are added
to a solution.
3. Check incompatibility resources to verify which drugs have a very high or very
low pH. Since most drugs are acidic, their combination with a drug having a very high
pH is more likely to result in an incompatibility.
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BEYOND-USE DATE
This date is the last date that the sterile preparation can be used by the patient and
should be consistent within each health care setting. Beyond-use dating should be
based on known stability information and sterility considerations. The specific
beyond-use date of a preparation should be based on published data, appropriate
testing, or USP-NF standards.
STORAGE CONDITIONS
Storage instructions can be put on the primary label or added as an auxiliary label.
Preparations must be stored in accord with the condition stated on the label to ensure
the preparation’s sterility and stability.

56
This can include, but is not limited to, whether the preparation should be refrigerated,
kept at room temperature, protected from light, or not shaken. If the sterile
preparation requires refrigeration, it should be separated from food to avoid
contaminating the outside of the container.
DAFTAR PUSTAKA
Anderson RJ. Pharmacy technician survey in the state Georgia. Ga J Hosp Pharm. 1993:7(summer):179.
Turco SJ. Composition. In: Turco SJ, ed. Sterile Dosage Forms, Their Preparation and Clinical Application, 4th
ed. Philadelphia, PA: Lea & Febiger; 1994:1127.
Food and Drug Administration. Chap 32, Division of Field Regulatory Guidance. Hospital pharmacies status as
drug manufacturer, FDA Guide 7132.06. Washington, DC: Oct 1, 1980.
National Association of Boards of Pharmacy. Good compounding practices applicable to state licensed
pharmacies. Model State Pharmacy Act and Model Rules of the National Association of Boards of Pharmacy.
http://nabp.net ; accessed September 9, 2003.
Standard operating procedure: Certificates of analysis of materials used for pharmaceutical compounding.
Internat J Pharma Compound. 2001 (Mar/Apr): 5:147.

57
Avis KE. Levchuk JW. Chapter 41. Parenteral preparations In: Gennaro AR, ed, Remington: the Science and
Practice of Pharmacy, 20th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2000. p 780-806.
United States Pharmacopeial Convention. Chapter 1 Injections. In: United States Pharmacopeia 27th
rev./National Formulary 22nd.
United State Pharmacopeial Convention. General notices and requirements. In: United States Pharmacopeia,
27th.
Avis KE, Levchuk JW. Chapter 41. Parenteral preparations. In: Gennaro AR, ed. Remington: The Science and
Practice of Pharmacy, 20th ed. Baltimore, MD: Lippincott Williams & Wilkins: 2000. p. 780806.

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Formulasi Dan Teknologi Sediaan Steril-6

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FORMULASI DAN TEKNOLOGI SEDIAAN

3/28/2018 TEKNOLOGI FARMASI UNIVERSITAS BUANA PERJUANGAN KARAWANG 2018 1

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3/28/2018 TEKNOLOGI FARMASI UNIVERSITAS BUANA PERJUANGAN KARAWANG 2018 8

THE TECHNICIAN ENSURES THAT THE STERILE COMPONENTS

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AQUEOUS ISOTONIC VEHICLES

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3/28/2018 TEKNOLOGI FARMASI UNIVERSITAS BUANA PERJUANGAN KARAWANG 2018

3/28/2018 TEKNOLOGI FARMASI UNIVERSITAS BUANA PERJUANGAN KARAWANG 2018

3/28/2018 TEKNOLOGI FARMASI UNIVERSITAS BUANA PERJUANGAN KARAWANG 2018

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3/28/2018 TEKNOLOGI FARMASI UNIVERSITAS BUANA PERJUANGAN KARAWANG 2018

3/28/2018 TEKNOLOGI FARMASI UNIVERSITAS BUANA PERJUANGAN KARAWANG 2018

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The sources of pyrogens in sterile preparations are:

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STERILE PREPARATION FACILITIES AND

LAMINAR FLOW HOODS

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BIOLOGICAL SAFETY CABINETS

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CLASS II CABINETS ARE CLASSIFIED ACCORDING

a. Type A cabinet: i. Maintains a minimum calculated average inflow air velocity of

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