Transcript PHARMACEUTICAL DOSAGE FORMS & DRUG DELIVERY …

PARENTERALS
PARENTERAL
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The term parenteral
derived from the Greek words:
para (outside) and
enteron, (intestine)
denotes routes of administration other than oral route.
refers to the injectable routes administration.
sterile
PARENTERAL INJECTIONS
 pyrogen free preparations
 intended to be administered parenterally.
Based on the route of administration,
sterile products are classified into:
1.
2.
3.
4.
Parenteral preparations
Ophthalmic preparations - for the eye
Otic preparations
- for the ear
Nasal preparations
- for the nose
& throat
5. Irrigating solutions - for washing wounds
or abraded mucous
membrane
Parenteral Routes of
Administration
1. Intra-articular
–joints
2. Intraspinal
–spinal column
3. Intra-arterial
–arteries
4. Intravenous
–veins
5. Intradermal
–shin
6. Intrasynovial
–joint fluid
7. Intrathecal
–spinal fluid
8. Intracardiac
–heart
9. Intramuscular
–muscles
10. Subcutaneous
–under the skin
ROUTES
PARENTERALS
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Injections- (1874) Earliest injectible drug:
Mophine solution
Preparation intended to be administered
parenterally
Sterility is important because they are placed in
direct contact with internal body tissues or fluids,
Sterile
Pyrogen- free
PARENTERALS ARE
ADMINISTERED BY:
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Physician
 Physician’s assistant
 Nurse
PARENTERALS ARE
ADMINISTERED AT:
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Hospitals
 Clinics
 Extended care facilities
Antirheumatic injectables
Brand Name: Enbrel
Generic name:: Etanercept
Manufacture: Immunex
Form::Injectable
Recommended initial dose: 25mg (1 vial) twice a week
injected subcutaneously
Botulinum toxin
Brand name: Botox
Generic name: Clostridium botulinum ( type A neurotoxin
complex)
Form: Powder for solution for injection
Botulinum toxin
Brand name: Myobloc
Generic name: Botulinum toxin Type B
Form: Injection, solution [single-dose vial]: 5000 units/mL (0.5 mL, 1
mL, 2 mL) [contains albumin 0.05%]
Intravenous Route (IV)
Intravenous Route (IV)
Advantage:
 May be a life-saving procedure because of the placement of the
drug directly into the circulation and the prompt actions which
ensues.
Disadvantage:
 Once the drug administered, it cannot be retrieved.
 In the case of adverse reaction to the drug, for instance, the
drug cannot be easily removed from the circulation.
Precautions:
 Strict aseptic precautions must be taken at all times to avoid
risk of infection.
 The syringes and needles used must be sterilized and to the
point of entrance must be disinfected to reduce chance of
carrying bacteria from the skin into the blood via the needle
Intravenous Route (IV)
Flow Rates:
 Generally, the flow rates of IV are expressed in mL/hour,
 Range from 42 to 150 mL/hour.
 Lower rates are used for keep-open (KO, KVO)
 Great care must be taken to prevent overdosing or
underdosing.
Example:
 Metoprolol (beta blocker)
– 3 bolus injections of 5 mg each
at about 2-minute intervals;
– oral dosing (100 mg/day)
Intravenous Route (IV)
NOTE:
 Not only are the injectable solutions sterile,
syringes, needles must also be disinfected to
reduce the chance of carrying bacteria
 A backflow of blood into the administration set or
syringe indicates proper placement of the needle
in the vein
 Intravenous drugs ordinarily must be aqueous
solution;
they must mix with the circulating blood and not
precipitate from solution. Such an event can
lead to pulmonary micropillary occlusion and
blockage of blood flow.
Intravenous Route (IV)
Intravenous fat emulsions
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–
–
–
Intralipid, 10,20,30%
Clintec
Liposyn 11,10, 20%
Abott Liposyn 111, 10,20,30%
 as a source of calories and essential fatty acids for
patients requiring parenteral nutrition for extended
period, usually more than 5 days.
 The product contains up to:
30% soybean oil emulsified with eggyolk
phospholipids in a vehicle of glycerin in water
injection
INTRAVENOUS
Different lengths of needles
Intravenous Route (IV)
Hazard Of Intravenous Injection

The possibility of thrombus formation
– induced by the touching of the wall of the vein by
the catheter or needle.
 Thrombus
– is a blood clot formed within the blood vessel (or
heart) due usually to a slowing of the circulation
or to an alteration of the blood or vessel wall.
 Once such a blot circulates, it becomes an Embolus
– carried by the blood stream until it lodges in a
blood vessel, obstructing it, and resulting in
blockage or occlusion referred to as an
Embolism.
INTRASYNOVIAL / INTRASPINAL
INTRATECAL: SPINAL FLUID
INTRAARTERIAL: ARTERIES
Intravenous Route (IV)
Example: Automated IV delivery system
- Self administration analgesics
Advantages:
1. Patient Controlled Analgesia (PCA) used to control
pain
2. Allows greater degree of ambulation and independence
3. Typical PCA contains analgesic drug, syringe and
programmable electromechanical unit, which might
be compact enough to be worn on a belt or carried in a
pocket
Example: WalkMed PCA
4. Ability to provide constant and uniform analgesia
5. Can prevent pharmacokinetics and
pharmacodynamic differences between
patients from interfering with the
effectiveness of analgesia
6. Also permits patients to medicate
themselves when there is breakthrough
pain.
7. Minimizes various side effects
8. PCA devices can be used for IV, SC or
epidural administration
9. These devices are either, demand dosing
(fixed dose of drug is injected
intermittently) or constant-rate infusion
plus demand dosing
Intramuscular (IM)
Intramuscular (IM)
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Intramuscular injections of drugs provide effects
that are less rapid, but generally of greater duration
than those obtained from intravenous
administration
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IM are performed deep into the skeletal muscles.
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The point of injection should be as far as possible
from major nerves and blood vessels.
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Injuries to patients from IM injection usually are
related to the point at which the needle entered and
where the medication was deposited.
Intramuscular (IM)
Such injuries include:
1.
2.
3.
4.
5.
6.
7.
Paralysis resulting from neural damage
Abscesses
Cysts
Embolism
Hematoma
Sloughing of the skin
Scar formation
Adult – upper outer quadrant of the gluteus maximus
Infants – gluteal area is small, composed primarily
fats not muscle, so not recommended
Infants and Young children
– deltoid, muscles of the upper arm or the
midlateral muscles of the thigh
Intramuscular (IM)
Volume of Administration:
 limited :
– 5 mL in the gluteal region
– 2 mL in the deltoid of the arm.
 Injection is 2 to 3 inches deep
 20 to 22 gauge needle.
 To avoid staining: it must be injected
only into the muscle mass of the upper
outer quadrant of the buttock.
Intramuscular (IM)
The
skin is displaced laterally, then needle inserted
and syringe aspirated, and injection performed
slowly and smoothly. The needle is then
withdrawn and the skin release. This create a
“Z” pattern that blocks infiltration of medication
into subcutaneous tissue.
The Z-Track Injection techniques is useful for IM
injections of medications that stain upper tissue.
Examples:
Iron dextran injection –irritate tissues
Diazepam (Valium) – by sealing in the lower
muscle
Subcutaneous Route (SC)
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May be utilized for
– the injection of small amounts of medication or
of drugs beneath the surface of the skin of the
1. upper arm,
2. the anterior surface of the thigh, and the
3. lower portion of the abdomen.
 The site of injection is usually rotated when
injections are frequently given, as with daily
insulin injection.
 The maximum amount of drug given SC is about
1.3 mL
 Amounts greater than 2 mL will most likely cause
painful pressure.
Subcutaneous Route (SC)
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Syringes: up to 3 mL capacities
 Utilizing needles: 24 to 26 gauges
 SC insulin needles:
– gauge between 25 to 30
– needle length between 5-16 to 5-8 inch.
 Upon insertion, if blood appears in the syringe,
a new site should be selected.
 Irritating drugs and those in thick suspension
may produce
– induration, sloughing, or abscess and may
be painful. Such preparations are not
suitable for subcutaneous injection
Intradermal Route
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Substances may be effectively injected into the
corium, the more vascular layer of the skin just
beneath the epidermis.
These substances include:
– diagnostic determinations, desensitization, or
immunization.
Usual site: anterior surface of the forearm.
Needle:
– A short (3-8 inch) and narrow gauge (23 to 26).
– is inserted horizontally into the skin with the bevel
facing upward. The injection is made when the
bevel just disappears into the corium.
Volume: Usually about 0.1 mL
Specialized Access
 Devices
that provide continued access
and reduce pain associated with
administration (Repeated injections
over time)
 Several catheters of central venous
are used for a variety of parenteral
medications.
Example: cancer chemotherapy,
long term antibiotic therapy,
TPN solutions
The
use of indwelling plastic catheters
reduces the need for multiple
punctures during intravenous
therapy.
Composed of
–polyvinyl chloride,
–Teflon, and
–Polyethylene,
these should be radiopaque to ensure
that they are visible on radiographs.
Specialized Access
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Usually, these must be removed within 48
hours after insertion.
 The choice of catheter depends on several
factors
1. Length of time of the infusion
2. Purpose of the infusion
3. Condition and availability of the veins
Types of Catheter
1. Plain plastic
2. Catheter over needle or outside needle
3. Catheter inside needle
Official Types of Injections
1. Drug Injection
- Liquid preparations that are drug
substances or solutions thereof.
Example: Insulin Injection, USP
2. Drug for Injection
- Dry solids that, upon the addition of
suitable vehicles, yield solutions
conforming in all respects to the
requirement for Injections
Example: Cefamandole Sodium for
Injection
Official Types of Injections
3. Drug Injectable Emulsion
- Liquid preparations of drug substances
dissolved or dispersed in a suitable
emulsion medium
Example: Propofol
Official Types of Injections
4. Drug Injectable Suspension
- Liquid preparations of solids suspended in a
suitable liquid medium
Example: Methylprednisolone Acetate Suspension
5. Drug Injectable Suspension
- Dry solids that, upon the preparations conforming
in all respects to the requirements for Injectable
Suspensions
Example: Imipenem;
Cilastatin for Injection Suspension, USP
Official Types of Injections
INSULIN INJECTION, USP
PROPOFOL
METHYLPREDNISOLONE
ACETATE SUSPENSION
Injections
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Generally, if a drug is unstable in solution, it may be
prepared as a dry powder intended for reconstitution
with the proper solvent at the time of administration
If the drug is unstable in water, the solvent may be
replaced in part or totally by a solvent in which the
drug is insoluble
If the drug is insoluble in water, an injection may be
prepared as an aqueous suspension or as solution in a
suitable nonaqueous solvent, such as a vegetable oil
If an aqueous solution is desired, a water soluble salt
form of the insoluble drug is frequently prepared
Aqueous or blood miscible solutions may be injected
directly into the blood stream
Injections
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Blood immiscible liquids, such as
oleaginous injections and suspensions
can interrupt the normal flow of blood,
and their use is generally restricted to
other than intravenous administration
 Often times long action is desired to reduce
the frequency of injections.
 These long acting injections are called
respiratory or depot preparations
Following differences with other
preparations
1. Solvents or vehicles used must meet special purity
and other standards assuring their safety by injection
2. The use of added substances, as buffers, stabilizers,
and antimicrobial preservatives, fall under specific
guidelines of use and are restricted in certain
parenteral products. The use coloring agents is strictly
prohibited.
3. Parenteral products are always sterilized and meet
sterility standards and must be pyrogen free.
4. Parenteral solutions must meet compendial standard
for particulate matter.
5. Parenteral products are packaged in special hermetic
containers of specific and highly quality.
Following differences with other
preparations
6. Each container of an injection is filled to a volume in slight
excess of the labeled “size” or volume to be withdrawn. This
overfill permits the ease of withdrawal and administration of
the labeled volumes
7. Parenteral products must be prepared in environmentally
controlled areas, under strict sanitation standards, and by
personnel specially trained and clothed to maintained the
sanitation standards.
8. There are restrictions over the volume of injection permitted
in multiple-dose containers and also a limitation over the
types of containers (single-dose or multiple- dose) which may
be used for certain Injections.
9. Specific powders intended for solution or suspension
immediately prior to injection are frequently packaged as
lyophilized or freeze-dried powders to permit ease of solution
or suspension upon the addition of the solvent or vehicle.
Solvents and Vehicles for Injections
1. Water for Injection, USP
• This water is purified by distillation or by reverse
osmosis.
• Water for Injection is not required to be sterilized, it
must be pyrogen free.
2. Purified water, USP
• may not contain other substances and
• meets standard for the presence of total solids
3. Sterile Water for Injection, USP
• is water for injection which has been sterilized and
packaged in single-dose containers of not greater than
I L size.
• as water for Injection, it must be pyrogen free and
may not contain an anti-microbial agent or other
added substance.
Solvents and Vehicles for Injections
4. Bacteriostatic Water for Injection, USP
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is sterile water for injection containing one or more
suitable anti-microbial agents.
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it is packaged in pre-filled syringes or in vials
containing not more than 30 mL of the water. Label
must state, “Not for Use in Newborns”.
Example: benzyl alcohol - not good for neonates and
the toxicity of the bacteriostat.
5. Sodium Chloride Injection, USP
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a sterile isotonic solution of sodium chloride in
Water for Injection. It contains no antimicrobial agents
Solvents and Vehicles for Injections
6. Bacteriostatic Sodium Chloride Injection
– is a sterile isotonic solution of sodium chloride in Water for
Injection. It contains one or more suitable antimicrobial
agents which must be specified in the label.
–
Sodium chloride concentration is 0.9% to render isotonic
solution. It is also used to flush a catheter or IV line to
maintain its patency.. “Not for Use in Newborns”.
7. Ringer’s Injection, USP
– is a sterile solution of sodium chloride, potassium chloride,
and calcium chloride in water for injection.
– It is used as electrolyte replenisher and a systemic alkalizer.
– Lactated R = Na lactate
BACTERIOSTATIC
WATER SODIUM
CHLORIDE
INJECTION, USP;
POTASSIUM
CHLORIDE
SODIUM CHLORIDE
INJECTION, USP
BACTERIOSTATIC
WATER FOR
INJECTION, USP
STERILE WATER
FOR INJECTION,
USP
DEXTROSE INJECTION
Characteristics Of Components used
in Compounding
1. Therapeutically effective when used as the
active ingredients
2. Provide maximum safety
3. Function efficiently (when used as excipient)
4. Free from contamination
5. Physically and chemically stable even after
thermal sterilization
6. Produce little or no tissue irritation at site of
administration
Nonaqueous Vehicles Selected
Vehicles must be:
1.
2.
3.
4.
Nonirritating
Non toxic in the amounts administered
Nonsensitizing
It must not exert a pharmacologic
activity
5. May not adversely affect the activity of
the medicinal agent
Other Considerations Of Selecting
Nonaqueous Solvents
1. Physical and chemical stability
2. Its viscosity (syringeability) and its fluidity
3. Its boiling point (it should be high to
permit heat sterilization)
4. Its miscibility with body fluids
5. Its low vapor pressure to avoid problems
during heat sterilization
6. Constant purity or ease of purification and
standardization.
Examples of Nonaqueous Solvents
1.
2.
3.
4.
5.
6.
7.
8.
Fixed vegetable oils
Glycerin
Polyethylene glycols
Propylene glycol
Ethyl oleate
Isopropyl myristate
Methylacetamide
Alcohol
Nonaqueous Vehicles…
Examples of Fixed Oils Commonly Used in
Injections
1.
2.
3.
4.
5.
Corn Oil
Cottonseed seed Oil
Peanut Oil
Sesame Oil
Castor Oil and Olive Oil (occasion)
SOLVENTS AND VEHICLE FOR INJECTIONS

Water for Injection
 solvent
 purified by distillation or by reverse
osmosis
 stored in tight container with temperature
below or above the range of microbial
growth
 must be pyrogen free
Added Substances

Additives are essential for almost every product to
enhance its stability. They must exhibit the
following characteristics:
1. Perform its function throughout the useful life of
the product
2. Must be non-toxic and non-irritating
3. Must not exert any adverse effect on the product
4. Must be compatible in all components of the
formulation
5. Must not interfere with:
a. Therapeutic efficacy
b. Assay of the active therapeutic compound
Such substances include:
1.
2.
3.
4.
5.
6.
7.
8.
Solubilizers
Chelating agents
Anti-microbial agents
Hydrolysis Inhibitors
Antioxidants
Buffers
Tonicity contributors
Antifoaming agents
Antifungal/Antibacterial

must be present in adequate concentration at
the time of use to prevent the multiplication
of microorganism.
Examples:
agents containing mercury and the cationic,
surface active compounds - 0.01%; for
agents like chlorobutanol, cresol, and
phenol - 0.5%
Antioxidants
 Oxidation
is one of the pathways of
degradation which can be accelerated
during thermal sterilization.
 To protect a therapeutic agent
susceptible to this reaction,
antioxidants are required.
Example: Sulfur dioxide - 0.2%
Classification of Antioxidants
Used In Sterile Products
1. Reducing agents - antioxidants which functions by
being preferentially oxidized
Examples: ascorbic acid
sodium bisulfite
metabisulfite
thiourea
sodium formaldehyde sulfoxylate
2. Blocking agents - antioxidants which block an
oxidative chain reaction in which they are not usually
consumed
Examples: ascorbic acid esters
butyl hydroxytoluene (BHT)
tocopherols
Classification of Antioxidants
Used In Sterile Products
3. Synergists - compounds increase the effectiveness of
antioxidants, particularly those blocking oxidative
reactions
Examples: ascorbic acid
citraconic acid
phosphoric acid
citric acid
tartaric acid
4. Chelating agents - those that complex with catalysts
which otherwise would accelerate the oxidative
reaction
Examples: ethylenediaminetetraacetic acid salts
5. Inert gases like nitrogen and carbon dioxide have
been used to displace oxygen from a solution and
reduce the possibility of oxidative changes in the
formulation
Buffers

are added to maintain the required pH for many
products; a change in pH may cause significant
alterations in the rate of degradation reactions.
Changes in pH may occur during storage as a result
of:
1. Dissolving of glass constituents in the product
2. Release of constituents from rubber closures or
plastic components in contact with the product
3. Dissolving of gases and vapors from the air space
in the container or by diffusion through the rubber
or plastic component.
4. Reactions within the product
The principal buffer systems used to stabilize
pH are the
1. Acetates
2. Citrates
3. Phosphates
Tonicity
Contributors
Compounds contributing to the isotonicity
of a product reduce the pain of injection
in areas with nerve endings.
Buffers may serve as tonicity contributors
as well as as stabilizers for the
Containers

Containers for sterile products are made of
glass or plastic.
 Glass is still preferred for injectable products.
 Glass is composed principally of the
– silicon dioxide tetrahedron
– modified physicochemically by such oxides
as those of sodium, potassium, calcium,
magnesium, aluminum, boron and iron.
 Two general types of glass
(1) soda-lime
(2) borosilicate
Containers

Based on its chemical resistance, glass compounds
are classified into 4 types:
1.
2.
3.
4.
Type I - highly resistant borosilicate glass
Type II - treated soda-lime glass
Type III - soda lime glass
NP (nonparenteral) - general purpose soda-lime
glass
Glass containers like ampule cartridges and vials
may be manufactured from glass tubings or blow
molding.
Rubber closures
are used to seal
the openings of catridges, vials
and bottles, providing a material
soft and elastic enough to permit
entry and withdrawal of a
hypodermic needle without loss
of the integrity of the sealed
container. Accessories used in
conjunction with closures are
aluminum caps with or without
flif-off seals.
Examples of Some Injections in Oil
Injections
Oil
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Dimercaprol Injection
Peanut
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Estradiol Cypionate Injection
Estradiol Valerate Injection
Fluphenazine Decanoate Inj.
Fluphenazine Enanthate Inj.
Hydroxyprogesterone Caproate
Progesterone in OilInjection
Testosterone Cypionate
Testosterone Cypionate and
Estradiol Cypionate
Testosterone Enanthate Inj.
Testosterone Enanthate and
Estradiol Valerate
Cottonseed
Sesame/Castor
Sesame
Sesame
Castor
Sesame/Peanut
Cottonseed
Antidote to As ,Au, Hg
poisoning
Estrogen
Estrogen
Antipsychotic
Antipsychotic
Progestin
Progestin
Androgen
Cottonseed
Sesame
Sesame
Androgen and Estrogen
Androgen
Andragen and Estrogen
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Category
METHODS OF STERILIZATION
Sterilization

defined as the complete destruction or elimination of
microbial life.
The choice of the most effective sterilization procedure
is dependent on:
1. Compatibility of the process with the
preparation; (sterilization process must not
have significant adverse effect upon the
preparation)
2. The successful validation of the process ( the
parameters must prove to be lethal to the most
resistant spores of microorganism normally
encountered)
5 GENERAL METHODS
1.
2.
3.
4.
5.
Steam distillation
Dry-heat sterilization
Sterilization by filtration
Gas sterilization
Sterilization by ionizing radiation
2 MAIN DIVISIONS OF STERILIZATION
1. Physical Processes of Sterilization
A. Thermal Method
Microorganisms are killed by heat by what is
thought to be coagulation of the protein of a
living cell. The lethal effectiveness of heat is
dependent on:
1. The degree of heat
2. The exposure period
3. The moisture present
Steam sterilization is conducted in an
autoclave and employs steam under
pressure
The usual steam pressures, the temperatures
obtainable under these pressures, and the
approximate length of time required after the
system reaches the indicated temperatures are
as follows:
1. 10 pounds pressure (115.50C), for 30 min.
2. 15 pounds pressure (121.50C), for 20 min.
3. 20 pounds pressure (126.50C), for 15 min.
2 MAIN DIVISIONS OF STERILIZATION
Dry-Heat Sterilization
 usually carried out in sterilizing ovens
specifically designed for this purpose.
The ovens may be heated either gas or
electricity and generally
thermostatically controlled.
 conducted at temperatures of 1600C to
1700C for periods not less than 2 hours.
B. Nonthermal Methods
1. Ultraviolet light - is commonly
employed to aid in the reduction of airborne
contamination and to attempt to sterilize surfaces
within the processing environment. The
germicidal light produced by mercury vapor
lamps is emitted at a wavelength of 2537
Angstrom units (253.7 millimicrons)
The lethal mechanism of UV light works
when this energy is absorbed by orbital electrons
within the molecules of the microorganisms or of
their essential metabolites causing excitation and
alteration of activity. Thus the organism dies or
is unable to reproduce.
2 MAIN DIVISIONS OF STERILIZATION
2. Ionizing Radiations - are highly
radiations emitted from radioactive
isotopes such as cobalt-60 (gamma
rays) or produced by mechanical
acceleration of electrons to very high
velocities and energies (cathode rays,
beta rays). Ionizing radiations destroy
microorganisms by stopping
reproduction as a result of lethal
mutations.
3. Filtration - This is a nonthermal method for
the sterilization of select solutions by
removing microorganisms from the solution
while permitting the passage of all the
desired components of the solution and
imparting no undesirable components from
the filter.
–They are available in pore sizes from 14 to
0.025 um.
–The size of the smallest particle visible to the
naked eye is about 40 um, a red blood cell is
about 6.5 um, the smallest bacteria, about
0.2 um, and a polio virus, about 0.025 um
2 MAIN DIVISIONS OF STERILIZATION
2. Chemical Processes of Sterilization
A. Gas Sterilization - Ethylene oxide
believed to exert its lethal effect upon
microorganisms by alkylating essential
metabolites, affecting particularly the
reproductive process. Ethylene dioxide
sterilization is the acceptable practical
method for sterilizing plastic. Other gases
used are beta propiolactone,
formaldehyde and sulfur dioxide
2 MAIN DIVISIONS OF STERILIZATION
B. Surface Disinfection
Disinfectants do not sterilize a
surface. However, as adjuncts to
thoroughly cleaning of surfaces,
disinfectants properly used may be
expected to provide an aseptic
condition of the surfaces involved
Validation of Sterility
 Regardless
of the method of
sterilization employed, Pharmacutical
preparations must undergo sterility
tests to confirm the absence of
microorganisms.
 A biologic indicator is characterized
preparation of specific microorganisms
resistant to a particular sterilization
process
2 main forms
1. Spores are added to a carrier, as a strip of
filter paper, packaged to maintain physical
integrity while allowing the sterilization
effect.
2. The spores are added to representative units of
the product being sterilized, with sterilization
assessed based on these samples
In moist heat (steam) - Bacillus
stearothermophilus
In dry heat
- Bacillus subtilis
In ionizing radiation - Bacillus pumilus,
stearothermophilus,
subtilis
Pyrogens and Pyrogen Testing
 Pyrogens
are fever producing organic
substances arising from microbial
contamination and responsible for
many of the febrile reactions which
occur in patients following injections.
 Are lipid substances associated with a
carrier molecule which is usually a
polysaccharide but may be a protein.
2 Official Tests for Detecting and Measuring
Pyrogens
1. Bacterial Endotoxins Test
Using Limulus Amebocyte Lysate (LAL) which
has been obtained from aqueous extracts of the
circulating amebocytes of the horseshoe crab,
Limulus polyphemus, and which has been
prepared and characterized for use as an LAL
reagent for gel-clot formation.
The procedure include incubation for a preselected
time of reacting endotoxins and control solutions
with LAL Reagent and reading of the
spectrophotometer light absorbance at suitable
wavelength
2 Official Tests for Detecting and Measuring
Pyrogens
2. Pyrogen Test
The test involves measuring the rise in temperature of
rabbits following the intravenous injection of a test
solution and is designed for products that can be
tolerated by the test rabbit in a dose not to exceed 10
mL per Kg injected intravenously within a
period of not more than 10 minutes
If no rabbit shows an individual rise in temperature
0.60C or more above its respective control
temperature, and if the sum of the 3 individual
maximum temperature rises does not exceed 1.400 C,
the product meets the requirements for the absence of
pyrogens.
Depyrogenation Method are as follows:
1. Adequate washing with detergent treatment followed
by dry heat sterilization is recommended for
glasswares and equipment. Optimum temperature is
2500C for 45 minutes.
2. Distillation is the most reliable method of eliminating
pyrogens from water. Pyrogenic substances are not
volatile and thus will remain in the distilland.
3. Removal of pyrogens by select adsorbents has limited
use because of the concurrent phenomenon of
adsorption of solute ions of molecules. It is of interest
in the production of antibiotics where heavy pyrogen
contamination results from fermentation.
PRODUCTION of a sterile preparation
 consists
1.
2.
3.
4.
5.
of the following steps:
Compounding
Filtration
Filling
Sealing
Sterilization
Compounding
Processing of sterile preparations
follow normal manufacturing
procedures which must be done in
aseptic condition. All equipment and
materials used whenever possible
must be sterile
Filtration
Membrane filters are used for
clarification when a highly polished
solution is desired. The process removes
particulates matter down to at least 3
microns in size. Sterilization by filtration
is achieved when viable microorganisms
and spores of approximately 0.3 microns
are removed. Membranes with porosity
ratings of 0.22 or 0.45 microns are
usually specified for sterile filtration.
Filling
Bulk preparations are subdivided into
unit dose containers during filling. This
process forces a measured volume of the
preparation through the orifices of a delivery
tube designed to enter the constricted opening
of a container by means of gravity, vacuum or
with the aid of a pressure pump.
Sealing
Sealing will retain the contents of a
sterile product and will assure a tamper-proof
presentation.
Containers

should be sealed in an aseptic area adjacent to
the filling machine. Ampuls are sealed by
heating with a high temperature gas-oxygen
flame to form
1. Tip-seals: those made by melting sufficient
glass at the tip of the ampul neck to form a
bead of glass and close the opening
2. Pull-seals: those made by heating the neck
of a rotating ampul below the lip, then
pulling away the tip to form a small, twisted
capillary just prior to being melted closed.
A leakers test
is
a useful method for evaluating the efficiency of
the sealing process.
the test consists of immersing completely the
sterile sealed ampuls in an aqueous dye bath
(0.5 to 1.0% of methylene blue) within a
vacuum chamber.
ss negative pressure of 27 inches Hg or more is
created, a tiny drop of dye solution can
penetrate an opening of an incompletely
sealed ampul.
the colored ampuls are sorted out during washing
and 100% inspection that follows after.
Examples of Sterile Drugs prepared and packaged
without the presence of phamaceutical additives as
buffers, preservatives, stabilizers, tonicity agents,
and other substances
1.
2.
3.
4.
5.
6.
7.
8.
9.
Sterile Ampicillin Sodium
Sterile Ceftazidime Sodium
Sterile Kanamycin Sulfate
Sterile Penicillin G Banzathine
Sterile Tobramycin Sulfate
Sterile Ceftizoxime Sodium
Sterile Cefuroxime Sodium
Sterile Nafcillin Sodium
Sterile Streptomycin Sulfate
Examples of Sterile drugs
formulated with pharmaceutical additives and
intended to be reconstituted prior to Injection
1. Cephradine for Injection
2. Dactinomycin for Injection
3. Erythromycin Lactobionate for Injection
4. Oxytetracycline Hydrochloride Injection
5. Nafcillin Sodium for Injection
6. Hydrocortisone Sodium Succinate for Injection
7. Cyclophosphamide for Injection
8. Hyaluronidase for Injection
9. Mitomycin for Injection
10. Penicillin G Potassium for Injection
11. Vinblastine Sulfate for Injection.
Containers…
1. Mix-O-Vial - that incorporates the cover as part
of the plunger. Once mixed, the small circle of
plastic that covers the injection site is removed.
This reduces the touch contamination
2. Add-Vantage System IVPH - is other example
of ready-to-mix sterile IV product designed for
intermittent IV administration of potent drugs that
do not have long term stability in solution. Two
components:
(a) A flexible plastic IV container partially filled
with diluent
(b) Glass vial of powdered or liquid drug
The
vials containing the medication and
the piggybacks (50-250 mL of
Dextrose 5% in Water Injection) or
Normal Saline Solution are specially
designed to be used together.
The ADD-Vantage System can be used
within 30 days from the date that the
diluent container was removed from
the overwrap.
Containers…
3. Monovial Safety Guard - This is new system
integrated device (drug transfer mechanism) with a
protective shield surrounding the attached transfer
needle. The reconstitution and transfer of the drug into
an infusion bag is accomplished safely, quickly, and
necessitates fewer materials. The needle is inserted
into the port of the infusion bag and then the transfer
set is pushed down toward the vial until a “Click” is
heard. With Monovial upright, the infusion bag is
squeeze several times to transfer liquid into the
Monovial. The Monovial is then shaken to reconstitute
the drug. It is then inverted, the minibag is squeezed
and release to transfer the drug back into the infusion
bag. This process is repeated until the vial is empty.

Packaging, Labeling, and Storage of Injections
Containers for injections, including closures, must not
interact physically and chemically with the
preparation.
 Single-dose container - A single dose container is a
hermetic container holding a quantity of sterile drug
intended for parenteral administration as a single dose,
and which when opened cannot be re-sealed with
assurance that sterility has been maintained.
 Multiple-dose container - A multiple-dose container
is a hermetic container that permits withdrawal of
successive portions of thecontents without changing
the strengths, quality, or purity of the remaining
portion.
Note: Recall type I,II,III containers
The Labels on containers of parenteral
products must state:
1. The name of the preparation
2. For liquid preparation, the percentage content
of the drug or amount of the drug; for dry
preparation - the amount of the active
ingredient present and the volume of liquid
to be added to the dry preparation to
prepare a solution or suspensions.
3. The route of administration
4. Statement of storage conditions and expiration
5. The name of the manufacturer and distributor
6. The identifying lot number
General Precautions required with the use of
microwave ovens for thawing frozen premixed
products include
1. Being aware that the possibility of radiation leakage does
exist. However, manufacturers of microwave ovens are
required by law to comply with federal standards
2. Safeguarding pharmacy personnel who are exposed to these
ovens, especially those with cardiac pacemakers.
3. The possible leaching of rubbers material when the rubber
material on the container is exposed to microwave heating.
4. A possible explosion that may result from the increase in
internal pressure as a result of placing a closed or sealed
container into the microwave oven.
5. Developing protocols to ensure that the final solution
temperature does not exceed room temperature
Examples of some Injections Usually
Package and Administered in Small Volume
1. Butorphanol Tartrate Injection
- Narcotic Agonist- Antagonist
Analgesic
2. Chlorpromazine HCl Injection
- Antipsychotic drug with antiemtic
3. Cimetidine HCl Injection - Histamine H2 antagonist
4. Dalteparin Sodium Injection
- Prophylaxis against deep vein
thrombosis
5. Dexamethasone Sodium Phosphate Injection Glucocorticoids
6. Digoxin Injection
- Cardiotonic
Examples of some Injections Usually
Package and Administered in Small Volume
7. Dihydroergotamine Mesylate Injection
- Alpha-adrenergic blocking agent
8. Diphenhydramine HCl Injection
- An ethanolamine, non selective
antihistamine
9. Furosemide Injection - Loop diuretic
10. Granisetron HCl Injection - Prevention of nausea
and vomiting
11. Heparin Sodium Injection - Anticoagulant (IV or
SubQ)
12. Hydromorphone HCl Injection - Narcotic analgesic
Examples of some Injections Usually Package
and Administered in Small Volume
13.
14.
15.
16.
17.
Ibutilide Fumarate Injection
- An antiarrhythmic drug
Iron Dextran Injection
- Hematinic agent
Isoproterenol HCl Injection
- Adrenergic (bronchodilator)
Ketorolac Tromethamine Injection
- NSAID
Lidocaine HCl Injection
- Cardiac depressant as an
antiarrhythmic
18. Magnesium Sulfate Injection
- Anticonvulsant/Electrolyte
19. Meperidine HCl Injection
- Narcotic analgesic
20. Metoclopramide Monohydrochloride Injection
- Gastrointestinal stimulant
Examples of some Injections Usually
Package and Administered in Small Volume
22. Midazolam HCl
22.
23.
24.
25.
26.
27.
28.
29.
- Short acting benzodiazepine CNS
depressant
Morphine Sulfate injection - Narcotic analgesic
Naloxone HCl Injection - Narcotic antagonist
Nalbuphine HCl Injection - Narcotic Agonist-Antagonist
Analgesic
Oxytocin Injection
- Oxytoxic
Phenytoin Sodium Injection - Anticonvulsant
Phytonadione Injection - Vitamin K (prothrombogenic)
Procaine Penicillin G Injection - Anti-infective
Prochlorperazine Edisylate Injection - Antidopaminergic
Single-dose
unit
2 mL
Single-dose
vials
BUTORPHANOL
TARTRATE
INJECTION
8 fl oz
8 mL
Multi-dose
vials
TAGAMET
300 mg/2 mL
Product Classification: RX
Manufacturer: SMITHKLINE
BEECHAM PHARM
LANOXIN
FUROSEMIDE
INJECTION
HEPARIN SODIUM
INJECTION
BENADRYL
CIMETIDINE HCL
INJECTION>>>>
SODIUM
BICARBONATE
INJECTION
>>>IRON
DEXTRAN
INJECTION
LIDOCAINE<<
HCL
INJECTION
MIDAZOLAM HCL
INJECTION>>>>
>>PROCAINE
PENICILLIN G
INJECTION
>>NALBUPHIN
HCL
INJECTION
MAGNESIUM SULFATE
PHYTONADIONE
Examples of some Injections Usually
Package and Administered in Small Volume
30. Propranolol HCl Injection
- Beta adrenergic receptor blocking agent
31. Sodium Bicarbonate Injection
- Electrolyte
32. Sumatriptan Succinate injection
- treat acute migraine attacks
33. Verapamil HCl Injection
- Calcium channel blocking agent
INSULIN
1. Insulin Injection (regular)
Insulin Injection is a sterile aqueous solution of insulin.
It is prepared from beef or pork pancreas or both or
through biosynthetic means (Human Insulin). With apH
of 2.8 to 3.5. Insulin Injection is prepared to contain
100 or 500 USP Insulin Units in each mL.
Expiration: Not to be later than 24 months after the
date of distribution.
Preservative: Glycerin (1.4 to 1.8) for stability
Phenol or Cresol (0.1 to 0.25%)
Storage:
Cold place, preferably the refrigerator
2. Human Insulin
It is produced by utilizing a special
nondisease-forming laboratory strain of Escherichia
coli and recombinant DNA technology.
Two formulations:
(1) Neutral Regular Human Insulin (Humulin
R) - consists of Zinc-insulin crystals in solution. It
has a rapid onset of action and relatively short
duration of action (6 to 8 hours);
(2) NPH Human Insulin (Humulin N) - is a
turbid preparation that is intermediate acting, with a
slower onset of action and longer duration of action
(slightly less than 24 hours) than regular insulin
3. Lispro Insulin Solution
Insulin solution consists of Zinc-insulin lispro crystals
dissolved in a clear aqueous fluid. It is created when
the amino acids at positions 28 and 29 on the Insulin Bchain are reversed
Compared to regular insulin, however, peak serum
levels of lispro insulin occur earlier, (within 0.5 to 1.5
hours) are higher, and are shorter acting ( 6 to 8 hours)
Lispro insulin are administered fifteen minutes before
meals has decreased the risk of hypoglycemic episodes
and improve postprandial glucose excursions when
compared to conventional regular insulin.
Storage: Refrigerator; room temperature - 28 days
Note: If accidentally frozen, it should not be used
4. Isophane Insulin Suspension (NPH Insulin)
Is a sterile suspension, in an aqueous vehicle buffered with
dibasic sodium phosphate to between pH 7.1 and 7.4, of
insulin prepared from zinc-insulin crystals modified by the
addition of protamine so that the solid phase of the suspension
consists of crystals composed of insulin, zinc, and protamine.
Protamine is prepared from the sperm or the mature testes of
fish belonging to the genus Oncorhynchus.
Expiration date: 24 months
Dosage: dosage range subcutaneously is 10 to 80 USP Units
NPH used in some product names stands for “Neutral
Protamine Hagedorn”; the pH is 7.2 and developed by
Hagedorn. The term “isophane” is based on the Greek: iso and
phane, meaning “equal” and “appearance” and refers to
equivalent balance between the protamine and insulin.
5. Isophane Insulin Suspension and Insulin Injection
A premixed formulation of of isophane insulin suspension
and Insulin injection.
2 Formulations:
1. Humulin 70/30
- combination that consists of 70% isophane insulin
suspension and 30% insulin injection
2. Humulin 50/50
- combination that consists of 50% isophane
insulin suspension and 50% insulin injection
They contain zinc of 0.01 to 0.04 mg/100 units. Neutral
in pH and phosphate buffered
Preservatives: m-cresol and phenol
6. Insulin Zinc Suspension





modified by the addition of zinc chloride so that the
suspended particles consists of a mixture of
crystalline and amorphous insulin
in a ratio of approximately 7 parts of crystals to 3
parts of amorphous material.
Buffered to pH 7.2 to 7.5 with sodium acetate:
0.7% sodium chloride for tonicity; 0.10%
methylparaben as preservatives
Expiration: 24 months after the immediate
container was filled.
Storage: Refrigerator with freezing being avoided
7. Extended Insulin Zinc Suspension

Is a sterile suspension of zinc insulin crystals
in an aqueous medium buffered to between
pH 7.2 and 7.5 with sodium acetate.
 Present also are 0.7% sodium chloride for
tonicity and 0.1% methylparaben as
preservatives
 Dosage: The usual dosage range is 10 to 80
USP Units
 Expiration: 24 months after the immediate
container was filled
8. Prompt Insulin Zinc Suspension
 The sterile suspension of insulin in
Prompt Insulin Zinc Suspension is
modified by the addition of Zinc
chloride so that the solid phase of
the suspension is amorphous
 The suspension is available in 100
USP Insulin Units per mL in vials
of 10 mL
 Expiration: not more 24 months
9. Insulin Infusion Pumps





Insulin infusion pumps allow the patients to achieve
and maintain blood glucose at near-normal levels
on a constant basis.
The main objective of pump therapy is the strict
control of the blood glucose level between 70 to
140 mg/dL
These systems utilize microcomputers to regulate the
flow of insulin from a syringe attached to a
catheter (usually 18 gauge) connected to a 27 to
28 gauge needle inserted in the patient.
The insulin may be delivered SubQ, IV, IP
Patients who used infusion pumps for the continuous
subcutaneous administration of insulin may
develop hard nodules at the site of injection
10. Humalog Mix
Manufactured premix insulin
consisting
lispro and neutral protamine lispro (NPL)
in afixed ratio
Humalol Mix 50/50 consists of 50% insulin
NPL suspension and 50% insulin lispro
injection
Humalog Mix 75/25 contains 75% insulin
NPL suspension and 25% insulin lispro
injection
It is estimated that these premixed
combinations are used by more than 40%
of diabetes patients who inject insulin
twice daily
11. Insulin Glargine

It is a long acting (up to 24 hours) basal insulin
preparation intended for once daily
subcutaneous administration at bedtime in
the treatment of type 1 diabetes mellitus in
adult and children
 In can be used by adults with type 2 diabetes
who require long-acting insulin
 It is created when the amino acids at position
21a of human insulin are placed by glycine
and 2 arginines are added to the C terminus
of the B chain
Types of Insulin: Approximate effect/action *
Onset
Peak
Duration
Short/Fast-Acting 5 - 30 mins
(clear)
1 - 3 hrs
4 - 8 hrs
IntermediateActing (milky)
1 - 2 hrs
4 - 12 hrs
16 - 24 hrs
Premixed (Short
& Intermediate)
1/2 hr
2 - 12 hrs
16 - 24 hrs
Long-Acting
(milky)
4 hrs
8 - 24 hrs
28 - 36 hrs
Characteristics
Insulin Activity Prof iles and Comp at ib ility
Insulin Preparat ions
mixed with
Onset (hr)
Peak (hr)
Duration (hr) Compatible
Rapid acting
Insulin I nj (reg ular)
Insulin Z inc
0.5 to 1
8 to 12
1 to 1.5
5 to 10
12 to 16
all Lente
Prompt
Suspension(semilente)
Lispro Insulin Sol’n
0.25
0.5 to 1.5
6 to 8
Ultralente, NPH
1 to 1.5
4 to 12
24
regular
7 to 15
24
regular, semilente
PZI (Protamine Zinc Insulin) 4 to 8
14 to 24
36
regular
Extended Insulin Zinc
10 to 30
>36
regular, semilente
2 to 12
18 to 24
Intermediate
Isophane Insulin
Suspension (NPH)
Insulin Zinc Suspension(lente) 1to 2.5
Long acting
4 to 8
Isophane Insulin Suspensio n
Premixed 50% and Insulin Inj 50%
insulin Isophane Insulin Susp.
70% and Insulin Inj, 30%
0.5
regular, NPH
Examples of Some Injections Administered in Large Volume by IV t hat may be Administered
in Volumes of 1 Liter or More, Alone, or With Other Drugs Added
Injection
Usual Content
Category/Comments
Amino Acid Injection 3.5,5,5.5,7,8.5,10% crystalline amino
Fluid /Nutrient replenishe r
acids with or without varying
concentrations of electrolytes or glycerin
Dextrose Injection,USP 2.5,5,10,20% dextrose, other strengths
Fluid/Nutrient replenishe r
Dextrose and sodium Dextrose varying from 2.5 to 10% and
Fluid/Nutrient/Electrolyte
chloride Injection,USP sodium chloride from 0.11 (19 mEq Na)
electrolyte
to 0.9% (154 mEq sodium)
Mannitol Injection, USP 5,10,15,20 and 25% mannitol
f unction determinatio ns;
diuret ic. Fluid/Nut rient
Diagnostic aid in renal
Ringers’ Injection, USP 147 mEq sodium, 4 mEq potassium
calcium, and 156 mEq chloride/ liter
Fluid/electrolyte
Lactated Ringer’s
2.7 mEq calcium, 4 mEq potassium,
Systemic alkalinizer; Injectio n,
USP
130 mEq sodium and 28 mEq
f luid and electro lyte
lactate per liter
replenisher
Sodium Chloride
USP
vehicle
0.9% sodium Chloride
Fluid and electrolyte Injection,
replenisher, isotonic
INSULIN INJECTION
SITES
Large Volume Parenterals
(LVPs)

These solutions are usually
administered by IV infusion to
replenish body fluids, electrolytes, or
to provide nutrition. They are usually
administered in volumes of 100 mL to
liter amounts and more per day by
slow intravenous infusion with or
without controlled-rate infusion
systems
USES:
1. Employed as Maintenance therapy for
the patient entering or recovering
from surgery, or for the patient who
is unconscious and unable to obtain
fluids, electrolytes, and nutrition
orally.
2. Utilized as Replacement therapy in
patients who have suffered a heavy
loss of fluid and electrolytes.
 Maintenance Therapy
Is given to the patient being maintained on
parenteral fluids only several days, simple
solutions providing adequate amounts of water,
dextrose and small amounts sodium and
potassium generally suffice.
Total Nutrient Admixtures also may be
given (TNA) include all substrate necessary for
nutritional support ( carbohydrates, protein, fat,
electrolytes, trace elements and others).
These admixtures are very useful for
patients undergoing chemotherapy, and for
gastrointestinal patients, and anorexic patients
Replacement Therapy
Is given to the patient in which there
is heavy loss of water and electrolytes, as
in severe diarrhea or vomiting, greater
than usual amounts of these materials
may be initially administered and
maintenance therapy provided. Patients
with Crohn’s disease, AIDS, burn
patients, or those experiencing trauma are
candidates for replacement therapy.

Water Requirement
The daily water requirement is that amount needed to
replace normal and expected losses. Normal
requirement adult -25 to 40 mL/kg of body weight or
an average of about 2,000 mL per square meter of
body surface area
Estimate guidelines in normal daily
requirement for water
1. <10 kg: 100 mL/kg/day
2. 10-20kg: 1000 mL plus 50 mL/kg/day for
weight over 10 kg
3. >20 kg to maximum of 80 kg: 1500 mL
Plus 20 mL/kg/day for weight over 20 kg
Electrolyte Requirement
1. Potassium - important for cardiac and skeletal
muscle function. The usual daily intake is
about 100 mEq and the usual daily loss is
about 40 mEq
Potassium can be lost through:
excessive perspiration, repeated enemas,
trauma (such as severe burns), uncontrolled
diarrhea, diseases of intestinal tract, surgical
operations and others.
Low potassium levels - Hypokalemia, can lead
to death
Symptoms of potassium loss :weak pulse, faint
heart sounds, falling blood pressures and
generalized weakness
Excess potassium is not good either :
Hyperkalemia can cause kidney failure
Symptoms : diarrhea, irritability, muscle
cramps, and pain
2. Sodium - is vital to maintain normal extracellular fluids.

Average daily intake of sodium:
135 to 170 mEq (8 to 10 g of Sodium chloride)

Sodium loss/deficit:
3 to 5 g sodium chloride (51 to 85 mEq of sodium) is
administered daily

Symptoms: excessive sweating, fatigue, muscle weakness,
convulsions

Symptoms (excess): Dry, sticky mucous membranes,
flushed skin, elevated body temperature, lack of tears, and
thirst
3. Chloride - the principal anion of the extracellular
fluid usually paired with sodium. Chloride is also
important for muscle contraction, balancing the
fluid levels inside and outside the cells and
maintaining the acid-base balance of the
extracellular fluid.
 Caloric Requirements
Basic caloric requirements may be estimated by body
weight; in the fasting state, the average daily loss
of body proteins is approximately 80g/day for a
70 kg man.
Daily ingestion of at least 100 g of glucose reduces
this loss by half.
Generally patients requiring parenteral fluids are
given 5% dextrose to reduce caloric deficit
Parenteral
hyperalimentation
This is the infusion of large
amounts of basic nutrients sufficient to
achieve active tissue synthesis and
growth. It is employed with a long term
intravenous feeding of protein solutions
containing high concentration of
dextrose (approximately 20%),
electrolytes, vitamins, and sometimes
insulin.
Components of Parenteral Nutrition
Solutions

Electrolytes
1. Sodium…………. 25 mEq
2. Potassium …….. 20 mEq
3. Magnesium …… 5 mEq
4. Calcium ……….. 5 mEq
5. Chloride ……….. 30 mEq
6. Acetate ………… 25 mEq
7. Phosphate …….. 18 mM
Vitamins






Vitamin A – 3300 I.U.
Vitamin D – 200 I.U.
Vitamin E – 10 I.U.
Vitamin C – 100 mg
Niacin – 40 mg
Vitamin B2 – 3.6 to
4.93
mg






Vitamin B1 – 3 to 3.35 mg
Vitamin B6 – 4 to 4.86 mg
Pantothenic Acid – 15 mg
Folic Acid – 400 mcg
Vitamin B12 – 5 mcg
Biotin – 60 mcg
Components of Parenteral Nutrition solutions
 Amino Acids: Essential Amino Acids
1. L - Isoleucine……… ……..590 mg
2. L - Leucine ……………… 770 mg
3. L - Lysine acetate ………..870 mg
(free base………….. 620 mg)
4. L - Methionine …… ……..450 mg
5. L - Threonine …………….340 mg
6. L - Tryptophan ………….. 130 mg
7. L - Valine ………………. 560 mg
8. L - Phenylalanine ……….. 480 mg
Nonessential Amino Acids
1.
2.
3.
4.
5.
6.
L - Alanine …………….. 600 mg
L - Arginine …………… 810 mg
L - Histidine …………… 240 mg
L - Proline ……………… 950 mg
L - Serine ………………. 500 mg
Aminoacetic acid ……….. 1.19 g

Enteral Nutrition
Enteral nutrition products may be administered orally, via
nasogastric tube, via feeding gastronomy, or via needle-catheter
jejunostomy.
These products are formulated to contain vitamins, minerals,
carbohydrates, proteins, fats and caloric requirements to meet
specific needs of the patient.
The formula diets may be monomeric or oligomeric ( amino
acids or peptides and simple carbohydrates) or polymeric ( more
complex protein and carbohydrates sources.
Example: Protein
- ProMod Powder, Propac Powder
Carbohydrates - Moducal Powder
Fat
- Lipomul Liquid
Fewer calories - Ensure HN, Sustacal, and Osmolite
HN
Intravenous Infusion Devices
 Advances
in infusion technology and
computer technology have resulted in
devices with extremely sophisticated
drug-delivery capabilities
Example: Multiple-rate programming,
pump or controller operation)
Special Considerations Associated with
Parenteral Therapy


Adsorption Of Drugs
Some drugs are adsorbed onto the inner lining of
IV containers and tubing or administration sets.
Examples of drugs that have implicated with this
phenomenon:
1. Chorpromazine HCl
6. Diazepam
2. Insulin
7. Promazine HCl
3. Promethazine HCl
8. Thiopental sodium
4. Trifluoperazine HCl
9. Warfarin sodium
5. Thioridazine HCl
Another Example:
Nitroglycerin - should always be prepared
in glass containers, and is adsorbed (40
to 80% of total dose) to
polyvinylchloride (PVC), a plastic
commonly used in administration
components and some infusion
containers, therefore, it should be
packaged with special non-PVC tubing
to avoid loss <5% of the drug into the
tubing during administration.
Selected Infusion Devices Used in Parenteral
Nutrition Support
1. Volumetric Infusion Pumps
AVI 2000 #200: Flo-Gard 8100; IMED
2. Multiple-rate Programmable Pumps – CADD-TPN
3. Volumetric Infusion Pumps - Provider one; Quest 521
Intelligent
4. Multiple-solution Programmable Pumps
Gemini PC –2; Life Care 5000 Plum;Omni-Flow 4000
5. Others- Breeze Lifecare 175, Coleague 3, Horozon Nxt,
Sabratek 600
NOTE: All these devices have their own features like: safety
alarm, flow rate error, alarm for air in line, door open, low
battery, occlusion, malfunction, invalid rates and others
Handling/Disposal of
Chemotherapeuticc Agents for Cancer
In theory, “correct and perfect preparation and
handling techniques will prevent drug particles
or droplets from escaping from their containers
while they are being manipulated”.
Basic Steps in handling Chemotherapeutic
Agents
1. Utilizing vertical laminar flow hoods (or bacteriological
gloves boxes) for the preparation and reconstitution of
cytotoxic drugs.
2. Wearing protective gloves and mask during product
preparation
3. Handling and disposing of cytotoxic drugs centrally utilizing
specially designed waste containers and incineration.
4. Periodic monitoring of personnel involved with handling
admixtures of cytotoxic drugs (CBC, blood chemistry
screen, differential cell count)
5. Informing personnel handling cytotoxic drugs that a
potential risk to their health exists.
6. Instituting specialized labeling of containers to ensure
proper handling and disposal of the cytotoxic agent.
Other Injectable Products
Pellets or Implants
 are sterile, small, usually cylindricalshaped solid objects
 about 3.2 mm in diameter and 8 mm in
length,
 prepared by compression and intended
to be implanted subcutaneously for the
purpose of providing the continuous
release of medication over prolonged
period of time
The pellets - implanted under the skin (thigh
or abdomen) with special injector or by
surgical incision - used for potent
hormones.
The implanted pellets, which might contain
100 times the amount of drug.
Example: (desoxycorticosterone, estradiol,
testosterone) given other routes are
release slowly into general circulation
Pellets were formulated with no binders,
diluents, or excipients, to permit total
dissolution and absorption of the pellets.
Example: Levonorgestrel
 Levonorgestrel Implants
These are a set of six flexible, closed capsules of a
dimethylsiloxane/methylvinylsiloxane copolymer,
each containing 36 mg of the progestin levonorgestrel
These are found in an insertion fit to facilitate
surgical subdermal implantation through a 2 mm
incision in the mid-portion of the upper arm about 8 to
10 cm above the elbow crease.
These are implanted in a fan like pattern, about
150 apart, for a total of 750. Removal after the end of
the 5th year.
The dose of levonergestrel is about 85 mcg/day by
9 months, and to about 35 mcg/day by 18 months,
with a further decline thereafter to about 30 mcg/day.
Irrigation
and Dialysis Solutions
Solutions for irrigation of body
tissues and dor dialysis resemble
parenteral solutions in that they are
subject to the same stringent standards.
These solutions are not injected
into the vein, but employed outside of
the circulatory system.
 Irrigation
Solutions
Irrigation solutions are intended to
bathe or wash wounds, surgical incisions,
or body tissues.
 Dialysis
Solutions
May be defined as a process whereby
substances may be separated from one
another in solution by taking advantage
of their differing diffusibility through
membranes
Peritoneal Dialysis
Solutions allowed to flow into the peritoneal
cavity, are used to remove toxic substances
normally excreted by the kidney
The solutions are made to be hypertonic
(with dextrose) to plasma to avoid absorption of
water from the dialysis solution into the circulation
Hemodialysis
Is employed to remove toxins from the blood.
In this method, the arterial blood is shunted through
a polyethylene catheter through an artificial
dialyzing membrane bathed in an electrolyte
solution. Following the dialysis, the blood is
returned to the body circulation through a vein.
 Examples of Irrigation Solutions
1. Acetic acid Irrigation, USP - This solution
is employed topically to the bladder as a
0.25% solution for irrigation. It is
administered to wash blood and surgical
debris away while maintaining suitable
conditions for the tissue.
2. Neomycin and Polymixin B Sulfate
Solution for Irrigation, USP - Employed
as a topical antibacterial in the continuous
irrigation of the bladder.
Examples
of Irrigation Solutions
3. Ringer’s Irrigation, USP - It is used topically as an
irrigation and must be labeled “not for injection”. The
solution is sterile and pyrogen free.
4. Sodium Chloride Irrigation, USP - This solution is
employed topically to wash wounds and into body
cavities where absorption into the blood is not likely.
The solution also employed rectally as an enema for
simple evacuation and also for colonic flush.
5. Sterile Water for Irrigation, USP - The label designations
“for irrigation only” and “not for injection” must appear
prominently on the label. The water must not contain
any antimicrobial or other added agent.