DISPERESE SYSTEM - Ease of swallowing

- Flexibility of doses
TYPES OF LIQUID DOSAGE FORM
SOLUTION Properties desired in pharmaceutical suspension
- 1 phase - Settle slowly and should be readily redispersed upon
- Solute, solvent gentle shaking
- Completely soluble - particles size should remain fairly constant
DISPERSED SYSTEM throughout long periods of undisturbed standing
- suspension and emulsions - Pour readily and evenly from its container
- 2 phases - Container: Wide-mouth Amber Bottle
- Not completely miscible
- SOLUTE (Dispersed phase, discontinuous phase or Sedimentation and Stoke’s Law
internal phase) - A flocculated suspension sediments faster and is
- SOLVENT (dispersing medium, continuous phase or easy to redisperse, whereas a deflocculated
external phase) suspension sediments slowly and is difficult to
redisperse. The rate of sedimentation of particles
Disperse System can be determined by Stoke’s law.
- Consists of dispersed phase and dispersion medium - Increase in particle size also increases velocity
- Particles of dispersed phase vary in size - Particle size
- 0.5µm to 10 µm fine dispersion: aerosols, inhalants - Density of the particle
- 1nm - 0.5µm colloidal dispersion: magmas, gels - Density of the medium
- 0.5 µm coarse dispersion (usually 10-50µm - Viscometer
suspension and emulsion) - Viscosity of the medium

SUSPENSION

- Refers to a two-phase system consisting of a finely

divided solid dispersed (suspended) in a liquid (the
dispersing medium)
- Preparations containing finely divided drug particles Dispersed phase
(the suspensoid) distributed somewhat uniformly - Particle size is considered - between 1 - 50µm
throughout a vehicle in which the drug exhibits a - Reduction is accomplished by the use of dry milling,
minimum degree of solubility micropulverization (10-50 um)
- Bentonite magma: common suspending agent - Finer: < 10 um by fluid energy grinding – Jet milling
- It is a disperse system in which solid, vehicle- (micronizing)
insoluble particles (internal phase) are uniformly o For parenteral or ophthalmic suspension
suspended by mechanical agitation and formulation - Spray drying – extremely small dimensions
design throughout the liquid vehicle (external phase) - Small particles reduce sedimentation rate but may
- The solid particles are greater than 1um pose a problem on forming hard sediment
- best pharmaceutical suspensions = 1 to 50 µm
Flocs
Classification of Suspension - AKA floccules
- According to route of administration - an aggregation of particles
- Oral suspensions - Form loose aggregate
- Topical/External suspensions - Rate of sedimentation is high
- Parenteral suspension - Sedimentation volume is high somewhat unsightly
- Sediment is formed rapidly
Advantages - Sediment is loosely packed –AVOIDS the problem of
- Provide palatable mixtures of an insoluble derivative CAKING
of a drug that in its soluble form has a highly
unpleasant taste
- Prolongs the action of drug
- Chemical stability
Deflocculated Suspensions Viscosity enhancers- reduce sedimentation rate in the
- In this system, solids as present as individual flocculated suspension (Hydroxypropylcellulose,
particles. They also exhibit aggregation but Hydroxypropylmethylcellulose)
comparatively low than flocculated. Preservatives - prevents the growth of microorganisms
- Pleasant appearance because of uniform dispersion (Benzoic acid, Methyl Paraben)
of particles Stabilizers - any additive used in substance and
- Particles exhibit repulsive forces compounds to keep them stable, retard deterioration
- Particles settle independently Wetting agents - increases penetration by the dispersion
medium (Alcohol, glycerin, propylene glycol, and other
Flocculated Suspensions hygroscopic liquids
- Solids are aggregate by forming chemical bridges
- A slightly sediment and supernatant layer is formed Preparation of suspension
- Particles exhibit attractive forces - Wet the powders using wetting agents like alcohol,
- They settle flocs glycerin, propylene glycol and other hygroscopic
agents
Flocculating agents - Use colloid mills or mortar and pestle to effect
- Bentonite, MC, sodium alginate, tragacanth, thorough mixing
- pH adjustment - Add the dispersion medium to which other soluble
- Electrolytes components are dissolve
- Surfactants
Extemporaneous preparation
Dispersion medium (Criteria) - Capsules or tablets are place in mortar and pestle
- Density of the suspensoid - Vehicle is added and mixed thoroughly to create a
- If suspensoid is flocculated paste
- Amount of the suspensoid - Diluted to volume using desired vehicle
- Caution on the use of alcohol, Benzyl alcohol and
Use of suspending agents Propylene glycol on neonates and geriatric patients
- (Methyl Cellulose, CarboxyMethyl Cellulose, - International Journal of Pharmaceutical
MicroCrystalline Cellulose,PVP, xanthan gum and Compounding
bentonite) at concentrations of 0.5% to 5
Apply Rheology Packaging and storage
- study of flow and formation of matter - Wide-mouth amber color bottles
- addresses the viscosity characteristics of powder and - Tight containers
fluid - Protected from freezing, excessive heat and light
Newtonian flow - Shake well instruction – Antacid oral suspensions,
- constant viscosity (e.g solutions) antibacterial, antiprotozoal and anti-inflammatory
Non-newtonian flow
- change in viscosity upon increasing the shear rates OTHER EXAMPLES
(e.g., dispersed system) Rectal suspensions
- Plastic, Pseudoplastic, dilatant flow - Barium sulfate for suspension, Mesalamine, Colocort
- Plastic: viscosity decrease upon applying sheer rate - Barium sulfate: employed or administered orally or
(ketchup) ―yield value rectally; used as diagnosis for diagnostic agents for
- Pseudoplastic flow: the substances begin to flow visualization of gastrointestinal tract
after sheering stress is applied - Mesalamine: aka 5-aminosalicylic acid; used as
- Dilatant flow: the materials increase in volume when treatment for Crohn’s Disease; for protitis
sheered; viscosity increases as shear rate increase - Colocort: cortico streiods used for ulcerative colitis;
(whip cream) antiinflamatory
Dry powders for suspension
Components of a suspension - for oral suspension
Flocculating agents or suspending agents - enhance
particle ―Dispersability‖
 EMULSIONS - plastic or interfacial film theory

- A thermodynamically unstable two-phase system SURFACE TENSION THEORY

consisting of at least two immiscible liquids, one of - tension lowering substances or wetting agent or
which is dispersed in the form of small droplets surfactant
throughout the other, and an emulsifying agent. - The use of these substances that used as emulsifiers
- Micro-emulsions: Thermodynamically stable or stabilizers to lower the interfacial tension to
- a dispersed system containing at least two penetrate the dispersing medium
immiscible liquid phases. The majority of - Reduce the repellent forces between the liquids and
conventional emulsions in pharmaceutical use have diminishing the liquid extraction for its own molecule
dispersed particles ranging in diameter from 0.1 to - Facilitate the breaking of large globules
100 um. ORIENTED-WEDGE THEORY
- assumes the monomolecular layers of emulsifying
Phases of Emulsion agents curved around a droplet of the internal phase
- The dispersed liquid - internal or discontinuous - Certain emulsifying agents orients themselves about
phase and within manner of their solubility
- The dispersion medium - external or continuous PLASTIC OR INTERFACIAL FILM THEORY
phase - Places the emulsifying agent interface between the
oil and water surrounding the droplets of the internal
Types of Emulsion phase as the thin layer of film absorbed on the
1. OIL-IN-WATER (O/W) EMULSIONS surface
- oils, petroleum hydrocarbons, and / or waxes are the
dispersed phase, and water or an aqueous solution is Preparing an emulsion: Select the suitable emulsifier
the continuous phase - Compatible with the other ingredients
- Oil is dispersed as droplets in an aqueous medium. - table and do not deteriorate
- formed if the aqueous phase constitutes >45% of the - Nontoxic
total weight and hydrophilic emulsifier is used - Little odor, taste or color
- O/W emulsions are used topically, orally, or - Capable of emulsifying
parenterally.
2. WATER-IN-OIL (W/O) EMULSION Emulsifying agents
- Water is dispersed as droplets in an oil or oleaginous 1. Natural emulsifying agents
medium - substances derived either form animal or plant
- Used for external preparations when emollient, sources
lubricating, or protective properties are desired. - Example: gelatin, casein, egg yolk, wool fat,
3. MULTIPLE EMULSIONS O/W/O OR W/O/W cholesterol, acacia, tragacanth, pectin, alginates,
4. MICROEMULSION - appear as translucent or starch
transparent and have droplet diameter in the 2. High–molecular-weight alcohols
nanometer range - Stearyl alcohol, cetyl alcohol, and glyceryl
monostearate
Advantages: - Employed primarily as thickening agents and
- dosage form of oral, rectal and topical administration stabilizers for o/w emulsions of certain lotions and
of oils and oil-soluble drugs ointments used externally.
- enhances palatability of oils when given orally 3. Finely divided solids
- increases absorption of oils and oil-soluble drugs - substances adsorbed in the water interface to form
through intestinal walls a coherent film. (Volcanic origin)
- dosage form for IM administered (vegetable oils) and - Example: Bentonite, veegum, magnesium hydroxide,
some water-soluble vaccines aluminum hydroxide and magnesium trisilicate
- dosage form for Parenteral Nutrition 4. Synthetic emulsifying agents
- or surface-active agents, they contain both the
THEORIES OF EMULSIFICATION lipophilic and hydrophilic groups.
- surface tension theory – tension lowering substances - Anionic agents
or wetting agent o these are organic salts which are ionized in the
- oriented-wedge theory presence of water.
 o They are widely used in external preparations as - G+W+O
o/w emulsifying agents 3. Bottle or Forbes bottle method
o Ex. Sodium lauryl sulfate - For the extemporaneous preparation of emulsions
- Cationic surfactants from volatile oils or oleaginous substances of low
o these are quaternary ammonium compounds, viscosities
which are inactivated by the presence of soaps. - 3:2:1 or 2:2:1
o Emulsions which used this type are generally 4. Auxiliary Methods
stable at acidic pH - An emulsion prepared by either the wet gum or the
o Ex. Benzalkonium chloride dry gum methods using hand homogenizer to
- Non-ionic surfactants facilitate emulsification
o these are the polysorbates and sorbitan series - The hand homogenizer is less efficient in reducing
which tend to be of low order toxicity, the particle size of very thick emulsions, and it should
nonirritating, tasteless and chemically stable not be employed for emulsions containing a high
and are compatible with ionic, anionic and non- proportion of solid matter because of possible
ionic drugs or adjuvant damage to the valve
o Ex. PEG 400, SPANS (sorbitan), TWEENS 5. In situ soap method
(polyoxyethylene derivatives) - The two types of soaps developed by this method are
calcium soaps and soft soaps. Calcium soaps are
HLB VALUES water-in-oil emulsions, which contain certain
vegetable oils, e.g., oleic acid, in combination with
- The type of emulsion formed is based on the limewater, and are prepared simply by mixing equal
hydrophiliclipophilic balance (HLB). volumes of the oil and limewater
- HLB system – logical means of selecting emulsifying
agents based on balance between the hydrophilic Factors that determine emulsion type
and lipophilic portions of an emulsifying agent. 1. Emulsifier
- Some emulsifiers form either w/o or o/w emulsion,
others form only one type
2. Phase ratio
- Phase present in greater concentration tends to be
external phase
3. Order of mixing
- The phase that is being added by portions tends to
be the internal phase

Identification of emulsion type

O/W and W/O
- Miscibility test
- Conductivity test
- HLB number usually between 1 and 20 are used as - Dye-solubility test
emulsifying agents o Oil soluble - Scarlet red C or Sudan III
- with values 8 –18 indicates hydrophilic molecule and o Water soluble - Amaranth
will produce o/w type of emulsion - Fluorescence test
- lower numbers in the range of 3 to 6 indicates o Oil fluoresces, when the whole field fluoresce –
lipophilic molecules and will produce w/o emulsions w/o

Methods of Preparation Microemulsion

1. Continental or dry gum method. - Thermodynamically stable, optically transparent
- “4:2:1”method isotropic mixtures of biphasic o/w system stabilized
- O+G+W with surfactants
2. English or wet gum method - With droplets having the size of 100Å - 1000Å
- same proportions of oil, water, and gum but the (angstron)
order of mixing is different. - Use for more rapid and efficient delivery of drugs
- Mucilage is prepared following oral or transdermal drug delivery system
Phenomena associated with the physical stability are: - Two-phase system – small distinct particles or
CREAMING MAGMAS
- Creaming is the upward movement of dispersed - Transparent or translucent semi-solid or solid
droplets relative to the continuous phase preparation, consisting of solution or dispersions of
- Downward creaming one or more active ingredients in suitable hydrophilic
- These phenomena are based on the densities of the or hydrophobic bases.
dispersed and continuous phase - It is non-greasy and generally applied externally.
AGGREGATION AND COALESCENCE - The gel contains small discrete particles - the gel is
- Aggregation (flocculation) is the coming together of called a two-phase system.
the dispersed droplets which results to creaming. - If it does not appear to have discrete particles it is
- Coalescence is the complete fusion of droplets. called as a one-phase system.
Aggregation precedes coalescence - Two-phase systems are thixotropic
CRACKING o e.g., they are semi-solid on standing but liquefy
- Irreversible when shaken.
- The coalescence of droplets results to separation of o Pseudoplastic
the dispersed phase as a separate layer
- Causes of emulsion to crack or cream Advantages
o Incorporation of excess dispersed phase - As a vehicle for the presentation of water-soluble
o Globule size – the smaller the better medicaments, it is ideal because of their high-water
o Storage temperature content.
o Potential for globule coalescence - Products tend to be smooth.
o Changes which affect the interfacial film formed - GELS are colloidal dispersion – 1 nm – 0.5 micron
by the emulsifying agent
PHASE INVERSION Terminologies
- when an emulsion changes from o/w to w/o. - Sol – general term that refers to the dispersion of
- the most stable range of dispersed phase solid substance to liquid, solid or gas; solid liquid
concentration is 30% to 60%. dispersed system
- If the amount of the dispersed phase approaches or - Tyndall effect – scattering of lights
exceeds a theoretical maximum of 74% of the total - Lyophilic – solvent loving
volume, then phase inversion may occur. - Lyophobic – solvent fearing
- Imbibition – taking up of certain amount of liquid
Dispensing of emulsion without increase in volume
- Emulsions can be extemporaneously prepared on a - Swelling- taking up liquid then increase in volume
small scale using mortar and pestle in such cases, - Syneresis – interaction between particles of the
proper labeling should be observed during dispersed phase becomes, it forms an unstable
dispensing. aqueous gel there will be shrinkage
- Emulsions are packed using tight, ambercolored - Thixotropy- the progressive decrease in viscosity
containers, preferably wide mouth for easy pouring. with time for a constant applied shear stress,
- Emulsions should be stored at room temperature, followed by a gradual recovery when the stress is
special labeling such as ―shake well before use‖ removed
should be attached to the container - Xerogel – framework; liquid is removed from the gel
- Emulsions are affected by heat, cold, light, air and and only the framework remains (e.g., tragacanth,
microorganisms acacia)

GELS Types
- Inorganic hydrogels
- Sometimes called jellies. - Organic
- Semisolid system consisting of either suspension - Hydrogels
made up of small inorganic particles or large organic - Organogels
molecules interpenetrated by a liquid.
- Single-phase - macromolecules are distributed so Method of preparation: Fusion and Dispersion
that no apparent boundaries exist
Gelling agents - 6 – 10% propellant, 35-55 psig
- acacia, alginic acid, bentonite, CARBOMER, CMC - Pet products and food products
sodium, cetostearyl alcohol, colloidal silicon dioxide,
ethylcellulose, gelatin, guar gum, hydroxy Advantages
ethylcellulose, hydroxypropyl cellulose, HPMC, - Minimum contamination
magnesium aluminum silicate, maltodextrin, MC, - Maximum stability
PVA, povidone, propylene carbonate, propylene - Reduces the irritation and provides cooling effect
glycol alginate, sodium alginate, sodium starch - Easy to control physical form: particles size and form
glycolate, starch, tragacanth, and xanthan gum, - A clean process requiring no wash-up
POLOXAMERS
Principle
MAGMAS AND MILKS - Product concentrate
- Propellant
- Aqueous suspensions of insoluble, inorganic drugs - Valve assembly
and differ from gels mainly in that the suspended - pressure of the propellant forces the liquid phase up
particles are larger the tube and out in the atmosphere →propellants
- USP indicates that the term MILK is sometimes used meet the air → evaporates due to drop in pressure
for suspension in aqueous vehicles intended for oral → leaving the product concentrate as airborne liquid
administration as compared to MAGMA, which is droplets or dry particles, as in powders 🡪 equilibrium
often used to describe suspensions of inorganic acids is reestablished
such as clay in water
Pressure
AEROSOLS - is controlled by a) type and amount of propellant b)
nature and amount of product concentrate
- pressurized dosage forms that upon actuation emit a
fine dispersion of a liquid and /or solid materials Aerosol system
containing one or more active ingredients in a - Propellants
gaseous medium. - Amount
- Designed to deliver drug systemically or topically - Reactivity - Trichloromonofluoromethane→ free HCl
with the aid of liquefied or propelled gas - Physiologic effect
- Colloidal system of very finely subdivided liquid or - Environmentally safe
solid particles dispersed in and surrounded by a gas - A ban was implemented (Montreal Protocol)
regarding the use of CFCs because of the negative
Classification impact to the ozone layer, temporary exceptions for
- Formulation of the product - Systemic or local effects CFCs in metered dose inhalers were granted and the
- Type of the valve assembly - Metered dose, dry use of acceptable hydrofluorocarbons
powder
Types of propellants
Space sprays Liquefiable gases
- Finely divided spray with particles not larger than 50 - include the saturated hydrocarbons,
um chlorofluorocarbons, hydroflurocarbons and
- 85% of propellant, 30- 45 psig (pound per square in dimethyl ether
gage) - CFCs - Propellant 114, 12, 11
- Insecticides, disinfectants, air deodorizer - HFCs – 134a, 152b
- Inhalational therapy: particles less than 6 µm or less
than 2 µm Compressed gases
Surface coating - include carbon dioxide, nitrogen, nitrous oxide
- Larger particles- coarse spray - higher initial pressures are used with compressed
- 30 – 70% of propellant, 25- 55 psig gas-based systems as compressed gas tends to lose
- Cosmetic/dermatological preparations, household pressure over time as the product is dispensed
products resulting to the drop in pressure
Foam spray/ Aerated spray - Nitrogen: Inert, tasteless, odorless, insoluble
- Foams, paste and creams - Carbon dioxide, nitrous oxide: Slightly soluble
Aerosol system DUAL VALVE MECHANISM
Two-phase - Actuator is closed 🡪 chamber is sealed from
- Liquid phase atmosphere but open to the container to be filled
- Vapor phase with the contents 🡪 Press the actuator 🡪 the chamber
Three-phase closes from the contents in the container and
- Water-immiscible propellant releases its pre-filled content
- Product concentrate NEBULIZER
- Vapor phase DRY POWDERED INHALER
MDI vs DPI
Container valve assembly - MDI’s energy for generating a dose relies on the
- Pressurized container – tin-plated, aluminum, device, DPI relies on energy provided by the patient’s
stainless steel, glass or plastic inspiratory effort
- Valve – expels the contents from the container in the
desired form at the desired rate Filling Methods
- Actuator – button that activates the system, COLD FILLING
contributes in the discharged product’s physical form - Both the product concentrate and the propellant
- Stem – supports the actuator and delivers the must be cooled to temperatures of -34.5°C and -40°C
formulation in the proper form to the chamber of the o Gas is liquefied
actuator - Metered into the cold container
- Gasket –prevents the leakage when the valve is - Not suitable for aqueous systems
closed o Ice
- Spring – holds the gasket in place and the mechanism PRESSURE FILLING
by which the actuator retracts when pressure is - Product concentrate is placed in the container and
released 🡪 valve in close position the propellant, liquefied gases, is metered into the
- Mounting cup – holds the valve in place valve stem.
- Housing – links the dip tube, the stem and the - This is the method commonly used in pharmaceutical
actuator aerosols
- Dip tube – the tube that delivers the content - Less danger of moisture contamination
- Less propellant is lost

Tests
- Tests for leaks and weakness at 130 F
- Proper functioning of the valve
- Particles size distribution
- Accuracy and reproducibility using metered valve

Packaging and Labeling

- Packaging is part of the manufacturing process
- Labeling uses the shrink wrap labels or peelaway
labels
- Use warning labels whenever required
- ‘Avoid inhaling except for preparations intended for
inhaling
- Do not puncture of incinerate container
Inhalation Devices - Storage condition: 15 and 30°C
METERED DOSE INHALER - Shake before use and proper angle and distance for
- metering valves are used for potent medication is use are also included in the label
required in inhalation therapy.
- In this device the amount of material discharged is Why a Curved Bottom?
regulated by an auxiliary valve chamber by virtue of - The shape strengthens the structure of the can
its capacity or dimension - The shape makes it easier to use up all the product
- Controlled by dual valve mechanism
 STERILE DOSAGE FORMS AND DELIVERY SYSTEMS - Placement of these devices is crucial to avoid
problems of extravasation or infiltration.
- Parenterals: outside the intestine Complications
- Biologicals - Extravasation – pass out of vessel into the tissue,
- STERILE: free from pyrogens (fever causing bacteria), blood, lymph
endotoxin - Infiltration – into a substance, cell or tissue
- VESICANTS: blistering
PARENTERAL PREPARATION Thrombosis
- Clotting within a blood vessel
- pharmaceutical dosage forms that are injected - Caused by factors: extremes in solution pH,
through one or more layers of skin. particulate material, irritant properties of the drug,
- Sterile preparation: pure, free from toxicity and free needle or catheter trauma, and selection of too small
from contamination of a vein for the volume of solution injected
- Pyrogen-free Phlebitis
- inflammation of the vein
Advantages - Caused by the same factors that cause thrombosis.
- Immediate action is provided Air emboli
- Modification of the formulation allowing the drug to - air is introduced into the vein
be administered slowly or with prolong duration of - a good practice is to purge all air bubbles from the
action formulation and administration sets before use.
- Therapeutic response is more readily controlled
- When administered by a professional can provide INTRAMUSCULAR
actual and accurate dose - The mid-deltoid area and gluteus medius are
- For drugs which cannot be administered or taken common injection sites.
orally - No more than 5 ml of a solution should be injected
by this route.
Disadvantages - Drugs intended for prolonged or delayed absorption
- Requires aseptic technique commonly are administered intramuscularly.
- Results to psychological pain factor - Patients generally experience more pain via IM
- Requires a professionally trained person to administration compared to intravenous
administer administration.
- Considered less hazardous and easier to use than the
PARENTERAL ROUTES OF ADMINISTRATION intravenous route.
Injection dependent routes (Sterility Demanding Route) - The onset of action is typically longer than with IV
- limited to solutions, suspensions, and emulsions administration, but shorter than with subcutaneous
- limited volumes of formulation that can be injected administration.
- excessive injection volumes will cause pain and cell - Needles used for the injections are generally 2 inch
necrosis. to 3 inches long and are generally 20 to 22 gauge in
- Injection independent size.
- intranasal, inhalation, and ophthalmic routes - The size of the needle must be chosen based on the
patient's deposits of fat.
PARENTERAL ROUTES - Maximum amount that can be used is 5 ml in gluteal
INTRAVENOUS region, 2 ml in the deltoid of the arm
- the veins of the antecubital area, and some of the
larger veins in the foot
- Provide the most rapid onset of action of any
parenteral route
- Johann Daniel Major in 1662
- Highest bioavailability
- Drugs that are too irritating for intramuscular or
subcutaneous administration (e.g., chemotherapy
agents) can be given by this route.
Complication INTRATHECAL
Abscesses - administration is injection into the spinal fluid; it
- is a collection of pus that has built up within the sometimes is used for antibiotics.
tissue of the body Needle Gauge
Cysts - the higher the gauge number, the smaller the
- sac-like structures, typically filled with liquid, diameter of the needle
semisolid, or gaseous material, very much like a - the higher the viscosity of the liquid, the lower the
blister. gauge size
- Other Complications: Embolism, Hematoma, Skin - the lower the gauge number, the stronger the
sloughing, Scar formation needle, resulting in less chance of bending or
breaking
SUBCUTANEOUS - the higher gauge number, the less pain or bruising
- beneath the skin layers-usually of the arm or thigh. experienced by patients
- it can be used for both short term and very long term
therapies Official Types of Injections
- loose interstitial tissues of the upper arm, the - Solutions ready for injection
anterior surface of the thigh, the lower portion of the - Dry, soluble product ready to be combined with a
abdomen vehicle just prior to use
- The site of injection is usually rotated when - Suspensions ready for injection
injections are frequently given. - Dry, insoluble products ready to be combined with a
- The maximum amount of medication that can be vehicle just prior to use
subcutaneously injected is about 1.3 mL. - Emulsions for injection
- Needles are generally 3/8 to 1 inch in length and 24
to 26 gauge. Parenteral solutions and suspensions
- Solvents or vehicles
INTRADERMAL - Added substances
- The usual site for intradermal injections is the - Specifications or standards
anterior surface of the forearm. - Production (facilities, areas)
- Needles are generally 3/8 inches long and 23 to 26 - Containers
gauge. - Labeling
- Drugs that are intradermally injected are agents for - Powders for reconstitution
diagnostic determinations, desensitization, or
immunization COMPONENTS
- 0.1 mL of solution is the maximum volume that can
be administered VEHICLES
INTRACARDIAC WATER
- administration is injection of a drug directly into the - is the vehicle of the greatest importance for sterile
heart. products and especially, for parenterals since it is the
HYPODERMOCLYSIS vehicle for all natural fluids
- refers to injection of large volumes of a solution into - It must meet the requirements for water for
subcutaneous tissue to provide a continuous, injection, USP.
abundant drug supply. - Water of highest quality is prepared distillation or by
- This route occasionally is used for antibiotic reverse osmosis.
administration in children WATER FOR INJECTION
INTRASPINAL - Meets requirements for Purified Water USP plus the
- administration refers to injection into the spinal USP "Pyrogen Test"
column. - Total dissolved solid nmt 1mg/100ml
INTRA-ARTICULAR - pH 5-7
- administration means injection into a joint space. - Contain no additives
INTRASYNOVIAL - Not necessarily sterile
- administration refers to injection into the joint fluid. - Used to prepare parenteral products which are then
sterilized after preparation (used within 24 hrs)
STERILE WATER FOR INJECTION Characteristics
- Meets requirements for Water for Injection USP plus - Perform its function throughout the useful life of the
passes the USP "Sterility Test" product
- Contains no additives - Must be non-toxic and non-irritating
- Used to prepare parenterals - no further sterilization - Must not exert any adverse effect on the products,
needed i.e., must be compatible with all the components of
- Packaged in single dose containers (Packaged in the formulation
container not larger than 1 L) - must not interfere with: Therapeutic efficacy, Assay
BACTERIOSTATIC WATER FOR INJECTION of the active therapeutic compound
- Sterile water with antimicrobialagents
- Packaged in container not more 30 mL ANTIBACTERIAL/ANTIFUNGAL AGENTS
- For multiple dosepreparation - The USP states that antimicrobial agents in
- Use for preparations administered in small doses bacteriostatic or fungi static concentrations must be
- Not to exceed 5ml added to preparation contained in multiple dose
- NOT USE FORNEONATES containers.
SODIUM CHLORIDE INJECTION - They must be present in adequate concentration at
- sterile, isotonic the time of use to prevent the multiplication of
- No antimicrobial agents microorganism inadvertently introduced into
- Approximately 154 mEq of Na and Cl per L solution preparation while with drawing portion of the
BACTERIOSTATIC SODIUM CHLORIDE contents with a hypodermic needle and syringe.
- Contains 1 or more antimicrobials - The most commonly used agents include:
- nmt 30 mL phenylmercuric nitrate and thimerosal (0.01%),
- Not for use in neonates phenol, benzyl alcohol and chlorobutanol, cresol
RINGER’S INJECTION (0.5%), sulfite, bisulfite or metabisulfite (0.2%)
- NaCl, KCl, CaCl2
- Sodium lactate (Lactated Ringer’s) ANTIOXIDANTS
- Oxidation is the primary pathway of degradation of
NON-AQUEOUS SOLVENTS which can be accelerated during thermal
- must not be toxic, irritating or sensitizing and must sterilization.
not exert adverse effect on the ingredients of the - To protect a therapeutic agent susceptible to this
formulation. reaction, antioxidants are required.
- most frequently used non-aqueous solvents are - Inert gas
glycerin, polyethylene glycol, propylene glycol, ethyl - Antioxidants
oleate, isopropyl myristate, dimethylacetamide, and - Antioxidants used in sterile products are classified
fixed oils. into:
- FIXED OILS are NOT used for IV route - Reducing agents- antioxidants which function by
- USED for IM to reduce irritation, produce longer DOA being preferentially oxidized; e.g.: ascorbic acid,
- Stability, pH, viscosity, fluidity, boiling point, sodium bisulfite, and metabisulfite, sodium
miscibility, vapor pressure, purity formaldehyde sulfoxylate, thiourea.
- Fixed oils - Blocking agents- antioxidants which block an
o they must remain clear when cooled to 10°C oxidative chain reaction in which they are not usually
(50°F). consumed; e.g.: ascorbic acid esters, butyl
o They must not contain mineral oil or paraffin – hydroxytoluene(BHT) and tocopherols.
The fluidity of a vegetable oil - Synergist- compounds increase the effectiveness of
o They must meet stated requirements of iodine antioxidants, particularly those blocking oxidative
number and saponification number. reactions; e.g.: ascorbic acid, citric acid, citraconic
acid, phosphoric acid and tartaric acid.
ADDED SUBSTANCES - Chelating agents- those that complex with catalysts
which otherwise would accelerate the oxidative
- solubilizers, antioxidants, chelating agents, buffers, reactions; e.g. ethylenediaminetetraacetic acid salts.
antimicrobial agents, tonicity contributors, - Inert gases like nitrogen and carbon dioxide have
hydrolysis inhibitors, antifoaming agents been used to displace oxygen from solution and
 reduced the possibility of the oxidative changes in - Exposure time must consider the penetration of
the formulation moist heat into the load
- Used for heat-stable materials
BUFFERS o Bulk solutions
- Buffers are added to maintain the required pH for o Glassware
many products; a change in pH may cause significant o Medical devices
alterations in the rate of degradation reactions o Surgical dressing
- Changes in pH may occur during storage as a result o Not for oils, fats, oleaginous preparations
of:
- Dissolving of glass constituents in the products. Dry heat sterilization
- Release of constituents from rubber closures or - Dry heat
plastic components in contact with the product. - 150 – 170 C, not less than 2 hours
- Dissolving of gases and vapors from the air spaces in - Dehydration followed by oxidation
the container or by diffusion through the rubber or - Temperature and time
plastic component. - Objects are subjected to a temperature of at least
- Reactions within the product. 160°C for 120 minutes (if higher temperatures can be
- The principal buffer systems used to stabilize pH are used, less exposure time is required).
the acetates, citrates and phosphates. - Oven
- Used for heat-stable materials which cannot be
TONICITY CONTRIBUTORS sterilized by moist heat
- Compounds contributing to the isotonicity of a o Fixed oils
product reduced the pain of injection in the areas o Glassware
with nerve endings. Buffers may serve as tonicity o Medical devices, instruments
contributors as well as stabilizers for the pH.
Sterilization by Filtration
STERILIZATION - Non thermal method based on the removal of
microorganisms by adsorption on filter medium
- Thermal – Moist and Dry heat - Filters with varying pore size
- Chemical - Millipore filter – 14 t0 0.025 um
- Radioactive - 6.5 um RBC
- Mechanical - 0.2 um Bacteria
- 0. 025 um poliovirus
Steam Sterilization (Moist heat) Depth filter
- Steam under pressure - usually consist of fritted glass or unglazed porcelain-
- Denaturation and coagulation substances that trap particles in channels.
- Temperature and time Screen Filter
- 10 lb pressure for 30 mins (115.5 C) - Membrane filter: Cellulosic materials (acetate,
- 15 lb pressure for 20 mins (121.5 C) nitrates, fluorocarbonate, acrylic polymers,
- 20 lb pressure for 15 mins (126.5 C) polyester, PVC, vinyl, nylon, polytef)
- Particulate filter remove particles of glass, plastic,
Moist heat Sterilization rubber,and other contaminants
- Moist heat sterilization is the most widely used and - Final Filter which may be either particulate or
reliable sterilization method. microbial, arein-line filters used to remove
- Microorganisms are destroyed by cellular protein particulates or microorganisms from an intravenous
coagulation. solution before infusion.
- The objects to be sterilized are exposed to saturated - Used for small quantity of solutions
steam under pressure at a minimum temperature of - Inexpensive
121°C for at least 15 minutes. - Allows removal of microorganisms
- Because it does not require as high a temperature, - Disadvantages include:
moist heat sterilization causes less product damage o Membrane tend to be fragile
compared to dry heat sterilization. o Requires validation of compatibility and
- Autoclave -commonly is used for moist heat integrity
sterilization. o Limited to small volumes
 o Nature of the filter - Endotoxins react with enzyme Limulus Amebocyte
o Particle size of the drug Lysate (LAL) forming gel-clot formation
- LAL are obtained from aqueous extracts of the
Gas sterilization circulating amebocytes of the horseshoe crab,
- In this method, ethylene oxide or propylene oxide is Limulus polyphemus
generally used in combination with heat and - The pyrogen test using rabbit is the Quantitative
moisture Fever response test
- used to sterilize surfaces and porous materials (e.g., o designed to limit to an acceptable level the risk
surgical dressings) that other sterilization methods of febrile reaction in the patient to the
may damage. administration, any injection, of the product
- Affected by time, temperature, gas concentration, concerned.
humidity
o Low temperature requires longer exposure Rabbit Test
- Residual gas must be allowed to dissipate after - Inject into an ear vein of each of three rabbits 10 mL
sterilization and before use of the sterile product of the product per kilogram of bodyweight,
- Interference with bacterial cell metabolism completing each injection within 10 minutes of the
- Used in medical devices and supplies, heat-labile start of administration. Record the temperature at
enzyme preparations, antibiotics 30-minute intervals 1 to 3 hours subsequent to the
injection.
Radioactive Sterilization - If no rabbit shows an individual rise in temperature
- Radioactive sterilization is suitable for the industrial of 0.5°C or more, the product meets the
sterilization of contents in sealed packages that requirements for the absence of pyrogens.
cannot be exposed to heat (e.g., prepackaged - If any rabbit shows an individual temperature rise of
surgical components and some ophthalmic 0.5°C or more, continue the test using five other
ointments). rabbits.
o This technique involves irradiation causing - If not more than three of the eight rabbits show
cellular destruction individual rises in temperature of 0.5°C or more and
- Accelerated drug decomposition sometimes results. if the sum of the eight individual maximum
temperature rises does not exceed 3.3°C, the
Validation of sterility material under examination meets the requirements
- Media fills are growth medium which support the for the absence of pyrogens.
growth of the contaminating microbe, and this
growth can be detected using a biologic indicator – Destroying pyrogens
resistant - may be destroyed or eliminated through physical,
- B. stearothermophilus – steam and gas sterilization chemical or a combination of both means.
- B. subtilis – dry heat Depyrogenation methods are as follows:
- B. stearothermophilus, subtilis and pumilus – - Adequate washing with detergent treatment
ionizing radiation followed by dry heat sterilization.
- P. diminuta – membrane filtration - Distillation is the most reliable method of eliminating
- Thermal death time for thermal sterilization (F value) pyrogens from water.
o Time required to kill a particular organism under - Removal of pyrogens by selected adsorbents has
specified conditions limited use because of the concurrent phenomenon
of adsorption of solute ions of molecules
PYROGEN Testing - Use of oxidizing agents
- Pyrogens are lipid substances associated with a
carrier molecule, which is usually a General Process of parenteral production
lipopolysaccharide but maybe a protein. - procurement and selection of the components
- product of a metabolism of microorganism such as - production facilities and procedure
most bacteria, many molds and viruses. - quality control
- ENDOTOXINS – gram (-) bacteria - packaging handling
- Bacterial Endotoxin test
- This is a test for estimating the concentration of
bacterial endotoxins
Parenteral solutions/ suspensions Sterilization by Filtration
- Solute → dissolved→ Filtration → packaged → - Depth Filter: matrix of randomly oriented fibers in a
sterilization maze of flow channels
- Particle size reduction → suspending the material → - Screen Filter: rigid, uniforms continuous mesh of
sterilization → packaging polymeric material with pore size precisely
- Dry solids → sterilized → packaged determined during manufacture

Production Packaging, labeling and storage

- A cleanroom is to be a separate room that contains - Parenteral solutions are packaged as large volume
laminar airflow hoods and meets certain standards parenteral (LVP) solutions and small volume
of airborne particle concentration. parenteral (SVP) solutions

Clean Room LVP

- Positive pressure airflow, uniform velocity - Common uses: 1) correction of electrolyte and fluid
- Counters as stainless steel balance disturbances; 2) nutrition; and 3) vehicle for
- Walls and floors are non-porous (epoxypainted), no administering other drug
cracks, no crevice and with rounded corners - Large volume parenteral solutions are packaged in
- Personnel wear special suit (cover-all gowns and containers holding 100 ml or more
shoe cap, mask and gloves) - Packaged in glass bottles or plastic bags

Maintenance Therapy
- When patients are unable to take oral nutrition or
fluids for slightly longer periods,
- If oral feeding must be deferred for
- TPN or TNAs- carbohydrates, protein, fat,
electrolytes, trace elements—mixed in a single
plastic IV bag for convenient administration

Replacement Therapy
- Heavy loss of water and electrolytes due to severe
diarrhea, vomiting
- Chrohn’s disease, AIDS, burns or trauma
- Class 100 – less than 100 particles of 0.5 micron size
per cubic foot – (HEPA) filter – air is filtered through Electrolytes
a high efficiency particulate air filter, removing - Potassium, the primary intracellular cation, is
99.97% of all particles 0.3 microns or larger particularly important for normal cardiac and
- DOP smoke test – efficiency of HEPA filters using skeletal muscle function.
anemometer and particle counters - The usual daily intake of potassium is about 100 mEq
- Vertical and Horizontal Laminar Flow hood and the usual daily loss is about 40 mEq
- Sodium, the principal extracellular cation, is vital to
Laminar flow hood maintain normal extracellular fluids.
- Laminar flow hoods are used to control airborne - Average daily intake of sodium is 135 to 170 mEq (8
contamination of sterile products during their to 10 g)
extemporaneous preparation - Chloride, the principal anion of the extracellular
fluid, is usually paired with sodium.
Filtration and Filters - Chloride is also important for muscle contraction,
- Filtration is used to remove particles from solutions. balancing the fluid levels inside and outside the cells,
- Filtration is not a "terminal sterilization" procedure and maintaining the acid-base balance of the
as are steam (moist heat), dry heat, ionized radiation, extracellular fluid
or gas sterilization. - Caloric requirement: Generally, patients requiring
- Filtration will sterilize the product, but after parenteral fluids are given 5% dextrose to reduce the
filtration, the sterile product is then aseptically caloric deficit that usually occurs in patients
combined with its packaging. undergoing maintenance or replacement therapy
Plastic bags ampules. Vials eliminate the risk of glass particle
Advantages over glass bottles: contamination during opening
- they do not break; they weigh less - Disadvantages: The rubber stopper may become
- they take up less storage space cored causing a small bit of rubber to enter the
- they take up much less disposal space. solution. Multiple withdrawals (as with multiple-
Disadvantages dose vials) may result in microbial contamination.
- Adsorption of drugs into the plastic. Some drugs that are unstable in solution are
- Leaching of a plasticizer out of the plastic packaged in vials unreconstituted and must be
- Plastic bags are available in different sizes. The most reconstituted with sterile water or sterile sodium
common sizes are 250, 500, and 1,000 m chloride for injection before use.

Glass bottles Prefilled syringes

- The major advantage of glass bottles is to administer - A cartridge type package, is a single syringe and
drugs that are incompatible with plastic bags. needle unit which is to be placed in a special holder
- Glass intravenous bottles are packaged with a before use. Once the syringe and needle unit is used,
vacuum, sealed with a solid rubber closure, and the they are discarded but the holder is used again with
closure is held in place by an aluminum band a new unit.
- Glass tube closed at both ends with rubber stoppers.
SVP The prefilled tube is placed into a specially designed
- Small volume parenteral (SVP) solutions are usually syringe that has a needle attached to it. After using
100 ml or less and are packaged in different ways this type or prefilled syringe, all of the pieces are
depending on the intended use. discarded.
- If the SVP is a liquid that is used primarily to deliver
medications, it is packaged in a small plastic bag Ready-to-mix systems
called a minibag of 50 - 100 ml (minibags look like - Mix – O – Vial (Pharmacia)
small plastic LVP bags). o Example: Solu-Medrol
- SVPs can also be packaged as ampules, vials, and - ADD Vantage System (Abbott)
prefilled syringes.
QUALITY CONTROL
Ampule
- Ampules are sealed glass containers with an Aseptic technique - defined as the sum total of
elongated neck that must be broken off. methods and manipulations required to minimize the
- Most ampules are weakened around the neck for contamination of sterile compounded formulations
easy breaking or if not, it must first be scored with a - Conduct all manipulations inside a properly
file maintained and certified laminar flow hood. Allow
- Filtration is done when using solutions from ampule the laminar flow hood to operate for at least 30
- In addition, it is useful to wrap an alcohol wipe or minutes before use in order to produce a particle
small piece of gauze around the top of the ampule free environment. Maintain a designated "clean"
before breaking it. area around the hood.
- Types: Pull seal, Tip seal - Remove all jewelry and scrub hands and arms to the
- Disadvantages: Their unsuitability for multiple-dose elbows with a suitable antibacterial agent. Sterile
use, the need to filter solutions before use, and other gloves are worn in addition to scrubbing.
safety considerations have markedly reduced - Wear lint-free clothing or clothing covers, head and
ampule use. facial hair covers, and a mask.
- Clean all flat surfaces of the hood with 70% isopropyl
Vials alcohol, or other antibacterial scrub such as
- Vials are made of glass or plastic and are sealed with benzalkonium chloride solution, working from top to
a rubber stopper. bottom, then from back to front.
- Vials may be designated for single-dose or multidose
use. Sterility Test
- Advantages: Vials can be designed to hold multiple 1. Sterility tests are intended primarily as a check test
doses (if prepared with a bacteriostatic agent). It is on the probability that a previously validated
easier to remove the product from vials than from sterilization procedure has been repeated.
2. The USP provides two basic methods - direct
introduction method and membrane filtration
method.
3. A product is deemed to pass the sterility test if all
media vessels incubated with product sample reveal
no evidence of microbial growth (turbidity).
4. The time for incubation for sterility testing by
membrane filtration is 7 days, less than that for
testing by direct inoculation (14 days).

Pyrogen testing
1. Pyrogens, or bacterial endotoxins, are metabolic
products of living microorganisms, or the dead
Needles
microorganisms themselves, causing a specific
- A needle has three parts, the hub, the shaft, and the
pyretic response upon injection (chemically, they are
bevel.
considered to be lipopolysaccharides).
- The hub is at one end of the needle and is the part
2. The USP pyrogen test is a qualitative fever response
that attaches to the syringe.
test in rabbits.
- The shaft is the long slender stem of the needle that
3. A more recent test is the Limulus amebocyte lysate
is beveled at one end to form a point.
(LAL) test for the presence of bacterial endotoxins,
- The hollow bore of the needle shaft is known as the
i.e., the USP Bacterial Endotoxins test
lumen.
- Needle size is designated by length and gauge.
Test for particulate matter
- The gauge of a needle, used to designate the size of
1. Light Obscuration Particle Count test
the lumen, ranges from 27 (the finest) to 13 (the
2. Microscopic Particle Count test
largest).
- There are two considerations when choosing a
DEVICES FOR ADMINISTRATION
needle size; the viscosity of the solution, and the
nature of the rubber closure on the parenteral
- The basic parts of a syringe are the barrel, plunger,
container
and tip.
- The barrel is a tube that is open at one end and
IV Infusion Pumps
tapers into a hollow tip at the other end.
- The set contains a spiked plastic device to pierce a
- The plunger is a piston-type rod with a slightly cone-
port on the IV container
shaped top that passes inside the barrel of the
- This connects to a sight or drip chamber that may be
syringe.
used to set the flow rate
- The tip of the syringe provides the point of
- Heparin lock is a short piece of tubing attached to a
attachment for a needle
needle or intravenous catheter
- Syringes come is different sizes
Dialysis solution
There are three common types of syringe tips:
- Dialysis – separation of substance from one another
1. Slip-Tips® allow the needle to be held on the syringe
in solution by taking advantage of their differing
by friction. The needle is reasonably secure, but it
diffusibility through membrane
may come off if not properly attached or if
- Peritoneal dialysis
considerable pressure is used.
- Hemodialysis
2. Luer-Lok® tips incorporate a collar with grooves that
lock the needle in place.
Radiopharmaceuticals
3. Eccentric tips, which are off-center, are used when
- These agents also represent an environmental
the needle must be parallel to the plane of injection
hazard and must be handled carefully. In addition to
such as in an intradermal injection.
adhering to the guidelines set forth for cytotoxic
agents, one may further reduce his exposure to these
agents by working with them in protective lead vial
shields
Cytotoxic Agents - Albert Sabin polio developed the oral polio vaccine
- These agents present an environmental hazard. It is few years later
now known that prolonged exposure to these agents
may lead to the development of cancers. For this Vaccines
reason special precautions must be taken to - Active immunization is where the actual microbe is
minimize the exposure of pharmacy personnel to taken in by a person. Antibodies are created by the
these agents. These agents should be prepared in a recipient and are stored permanently
shielded vertical flow hood, so that materials are not - Natural active immunization - when an untreated
blown into the operators face microbe is received by a person who has not yet
come into contact with the microbe and has no pre-
Antibiotics made antibodies for defense.
- Due to the allerginicity of the penicillins, it is - Artificial active immunization - where the treated
desirable to work with them in a shielded vertical microbe is injected into the person before they are
flow hood to avoid environmental contamination. able to take it in naturally.
When working with any of the antibiotics, it is - Passive immunization is where pre-made antibodies
important to remember that prolonged exposure are given to a person.
may lead to infections of exposed areas by o Immunization begins to work very quickly, but it
nonsusceptible bacteria and fungi is short lasting, because the antibodies are
naturally broken down, and not stored for later
Irrigation solutions use.
- To bathe or wash wounds, surgical incisions or body - Natural passive immunization - when antibodies are
tissues being transferred from mother to fetus during
pregnancy, to help protect the fetus before and
BIOLOGICS shortly after birth.
- Artificial passive immunization - given by injection
- are substance derived from a living organism and and is used if there has been a recent outbreak of a
used for the prevention or treatment of disease. particular disease or as an emergency treatment to
- include antitoxins, bacterial and viral vaccines, blood poisons.
products and hormone extracts.
Types of Vaccines
Immunity - Live attenuated vaccines contain bacteria or viruses
- State of relative resistance to a disease that develops that have been altered so they can't cause disease.
after exposure to the specific disease-causing agent - Killed vaccines contain killed bacteria or inactivated
- Natural immunity viruses.
- Acquired Immunity - Toxoid vaccines contain toxins (or poisons)
- Active immunity produced by the germ that have been made
- Passive immunity harmless.
- Component vaccines contain parts of the whole
Immunization bacteria or viruses.
- is the process by which an individual is exposed to an
agent that is designed to fortify his or her immune Live attenuated vaccines
system against that agent. - usually are created from the naturally occurring
- The material is known as an immunogen germ itself.
- human immune system 🡪 expose to an immunogen - Viruses are weakened by growing them over and
in a controlled way 🡪 body will then be able to over again in a laboratory under nourishing
protect itself from infection conditions called cell culture.
- Substance used to produced immunization are - The process of growing a virus repeatedly-also
known as vaccines known as passing serves to lessen the disease-
- Edward Jenner originated vaccination procedure causing ability of the virus.
- Dr. Raymond Parker defined a chemical nutrient Examples of live attenuated vaccines include:
medium in which cells can grow and replicate - Measles vaccine (as found in the MMR vaccine)
- Jonas Salk developed polio vaccine - Mumps vaccine (MMR vaccine)
- Rubella (German measles) vaccine ( MMR vaccine)
- Oral polio vaccine (OPV) - Adjuvants – enhances the immune response of the
- Varicella (chickenpox) vaccine antigen (alum, aluminum hydroxide, aluminum
sulfate)
Inactivated (killed) vaccines - Stabilizers – increase the storage life (2-
- cannot cause an infection, but they still can stimulate phenoxyethanol)
a protective immune response. - Preservatives – allow the use of multiple dose vials
- Viruses are inactivated with chemicals such as (Thimerosal (49.6%) is the common preservative)
formaldehyde. - Dispensed in units of
Examples of inactivated (killed) vaccines o Total # of organism/ml or dose
- Inactivated polio vaccine (IPV), which is the shot o mcg of immunogen/ml or dose
form of the polio vaccine o For toxoids – in flocculating units
- Inactivated influenza vaccine - Biologicals are sensitive to extreme temperature
- These are kept in a biological refrigerator or an
Toxoid vaccines insulated container
- made by treating toxins produced by germs with - Diagnostic skin biologics
heat or chemicals, such as formalin, to destroy their o Contains antigen
ability tocause illness. o Multiple Skin Antigens
- o not cause disease but they stimulate the body
toproduce protective immunity just like the germs' RADIOPHARMACEUTICAL
natural toxins.
Examples of toxoid vaccines - chemical containing a radioactive isotope for use in
- Diphtheria toxoid vaccine (may be given alone or as humans, for the diagnosis, mitigation, or treatment
one of the components in the DTP, DTaP, or dT of a disease
vaccines) - Products should meet requirements of state agency,
- Tetanus toxoid vaccine (may be given alone or as part FDA and NRC
of DTP, DTaP, or dT)
Isotopes
Component vaccines - Any of two or more forms of chemical element,
- made by using only parts of the viruses or bacteria. having the same number of protons in the nucleus,
Examples of component vaccines: but having different number of neutrons in the
- Haemophilus influenzae type b (Hib) vaccine nucleus
- Hepatitis B (Hep B) vaccine Occurrence in Nature
- Hepatitis A (Hep A) vaccine - All isotopes are not equally abundant in nature
- Pneumoccocal conjugate vaccine - For example, naturally occurring isotopes of
hydrogen (hydrogen-2 is the only common isotope
PRODUCTION which has its own name, and is generally called
deuterium)
- Extraction – culture, isolation
- Chemical synthesis Radioactive isotopes
- GENETIC ENGINEERING - Radioactive isotope or radioisotope, natural or
- Uses a bioreactor artificially created isotopes of a chemical element
having an unstable nucleus that decays, emitting
Bioreactor is defined as a vessel that carries out alpha, beta, or gamma rays until stability is reached.
a biological reaction and is used to culture aerobic cells - The stable end product is a nonradioactive isotope of
for conducting cellular or enzymatic immobilization another element, i.e., radium- | 226 decays finally to
lead-206.
Genetic engineering is the artificial alteration of
the genetic composition of cells or organisms. Gene Stable isotopes
cloning is fundamental to genetic engineering. - Stable isotopes are chemical isotopes that may or
- A segment of DNA from any donor organism is joined may not be radioactive, but if radioactive, have half
in the test tube to a second DNA molecule, known as lives too long to be measured.
a vector, to form a "recombinant " DNA molecule. - Only 90 nuclides from the first 40 elements are
energetically stable .
- there are 255 known stable nuclides of the 80 - Spontaneous fission
elements which have one or more stable isotopes.
Types of Radioactivity
Related Terms - An alpha particle is a helium nucleus.
- An beta particle is an electron.
- Isotope — substances that have the same number of
- A gamma particle is a high energy photon.
protons but have varying numbers of neutrons
- Radioisotope — an isotope of an element that emits
ALPHA
alpha, beta or gamma radiation during its decay into - Spontaneously throw off an alpha particle.
another element - An alpha particle is made up of two protons and two
- Radioactive — substance that emit energy in the neutrons bound together
form of alpha, beta or gamma rays. Naturally - Composition: identical to helium nucleus
occurring radioactive elements include radium and - Velocity: low velocity, 1/10 the speed of light or
uranium 10,000 miles per second
- Penetrating power: low
RADIOACTIVE DECAY - How to stop penetration: paper or layer of human
skin
- Half-life - the time required for a radioisotope to
- Hazards to the body: not hazardous unless
decay to 50% of its original activity
swallowed or inhaled
- dis transformation or decay constant ~ HALF-LIFE of
a particular radionuclide is PARTICULAR to that Alpha decay(a)
radionuclide 0 IDENTITY - In alpha decay, the nucleus emits an alpha particle;
an alpha particle is essentially a helium nucleus, so
it's a group of two protons and two neutrons. A
helium nucleus is very stable.

BETA
- Positron
- In beta decay, a neutron in the nucleus
Units of Measure spontaneously turns into a proton, an electron, and
- Curie — defined as radionuclide decaying ata rate of a third particle called an antineutrino
3.700 x 10'9 nuclear transmission per second - Composition: identical to electron
- Becquerel — equal to one disintegration per second - Velocity: greater velocity than alpha
- Radioactive dose — amount of radiation absorbed - Penetrating power: moderate
by the body tissue in which a radioactive substance - How to stop penetration: wood block, aluminum
resides (rad, Gray) plate
- Hazards to the body: cause damage to skin and eyes
History Beta Decay(f)
- Henri Becquerel (1852-1908) discovered the - A beta particle is often an electron, but can also be a
existence of multiple masses for the same element positron, a positively-charged particle that is the
when he realized a product of uranium's radioactive anti-matter equivalent of the electron. If an electron
decay, ionium, was unable to be retrieved again by is involved, the number of neutrons in the nucleus
chemical means from the element thorium. decreases by one and the number of protons
- Because chemical uniqueness is a defining increases by one.
characteristic of an element, it had to be concluded
that ionium was not a new element, just a different GAMMA
variation of thorium. - Atom actually splits instead of throwing off an alpha
or beta particle: Neutron radiation
Types of Decay - Composition: high energy radiation
- An atom of a radioactive isotope will spontaneously - Velocity: equal to velocity of light (3 x 101° cm/s)
decay into another element through one of three - Penetrating power: high
common processes: - How to stop penetration: several layers of blocks of
- Alpha decay Pb
- Beta decay
- Hazards to the body: affect the genes causing THERAPEUTIC RADIOPHARMACEUTICALS
mutations - are radiolabeled molecules designed to deliver
therapeutic doses of ionizing radiation to specific
Gamma Decay (ry) diseased sites (ex. Using MABs)
- The third class of radioactive decay is gamma decay, - The concept explains that certain radionuclides
in which the nucleus changes from a higher-level possessing particulate emission such as alpha and
energy state to a lower level. Similar to the energy beta radiations or low-energy, low-range electrons
levels for electrons in the atom, the nucleus has (Auger electrons) possess the ability to destroy
energy levels. diseased tissues
Effect of Radioactive Decay
Types of Radiation - Ionizing radiation- uranium atoms break into smaller
- Nuclear medicine depend on radiopharmaceuticals atoms and particles, which enter a human cell, strike
that decay by gamma emission e the nucleus, and damage the DNA, causing it to
- Radiopharmaceuticals are produced by the process divide in uncontrolled way- cancer
of nuclear activation in a nuclear reactor
- Uses of radiopharmaceuticals include: Radioisotopes may be used internally or externally.
o diagnosis of disease or evaluation of progression - externally or as implants in sealed capsules in a
of disease, evaluation of drug induced toxicity tissue, the dose could be terminated by removal of
o used therapeutically the sources.
- internally as unsealed source: the dose cannot be
DIAGNOSTIC RADIOPHARMACEUTICALS stopped by removal of the source.
- are used to derive detailed description of the
morphology and dynamic functioning of the various The total dose in therapeutic applications may be
internal organs of the body. calculated on the ff. basis:
- The radiopharmaceutical accumulated in an organ of 1. effective half- life of the isotope
interest emit gamma radiation which are used for 2. concentration of the isotope
imaging of the organs with the help of an external 3. type and energy of radiation emitted.
imaging device called gamma camera. - lodine 131 — is used both as diagnostic agent and
therapeutic agent
PRINCIPLE OF NUCLEAR IMAGING TECHNIQUE
The Stepwise Procedure of Nuclear Imaging: Methods of manufacturing radionuclide
- Radionuclides are administered via vein or mouth - Nuclear Fission — Uranium iodine, molybdenum or
- They distribute in the body according to their affinity xenon
for particular tissues so called target tissues - Charged particle bombardment- charged particles
- Radionuclides emit gamma radiations - Neutron bombardment — neutron (Cyclotron)
- Detected by y-scintillation camera - Radionuclide generator system- parent nuclide:
- Which forms images showing location of short half life radionuclide.
radionuclides in the body
CYCLOTRON - an apparatus in which charged atomic and
Examples subatomic particles are accelerated by an alternating
- Tc 99 —- ‘ideal” radionuclide for imaging electric field while following an outward spiral or circular
- Abscess and infection—Gallium Citrate Ga 67, path in a magnetic field.
Indium In 111 Oxyquinoline
- Appendicitis—Technetium (99m Tc) Fanolesomab Positron emission tomography (PET)
- Biliary tract blockage—Technetium Tc 99m - Anuclear medicine medical imaging technique which
Disofenin, Technetium Tc 99m Lidofenin, produces a threedimensional image or map of
Technetium Tc 99m Mebrofenin functional processes in the body.
- Blood volume studies—Radioiodinated Albumin, - The technique was first developed by Michel
Sodium Chromate Cr 51 (Michael) Ter-Pogossian, Michael E. Phelps and
- Blood vessel diseases—Sodium Pertechnetate Tc others at the Washington University school of
99m Medicine in 1975
PET principle - Dispensing and distribution
- Short-lived radioactive isotope are introduced to the - Implementation of basic radiation protection
body emit positron After travelling up to ajfew mm. procedures
the positron encounters and annihilates with an - Consultation and education
electron, producing a pair of annihilation gamma
photons moving in almost opposite directions. These RADIOPHARMACEUTICALS USED IN MEDICINE
are detected when they reach a scintillator material - Albumin Microspheres Tc 99m, In 111, In 113m, Pb
in the scanning device, creating a burst of light which 203 — used for lung imaging.
is detected by photomultiplier tubes or silicon - Chromated Cr 51 Albumin Injection - detection and
avalanche photodiodes (Si APD). quantitation of gastrointestinal protein loss and
placental localization.
Radioisotopes used in PET - lodinated | 125 Albumin Injection — diagnostic aid
- carbon-11 (~20 min) in the determination of total blood and plasma
- nitrogen-13 (~10 min) volumes.
- oxygen-15 (~2 min) - Iodinated I 131 Albumin Injection – diagnostic aid in
- fluorine-18 (~110 min) the determination of total blood and plasma
- These radionuclides are incorporated into volumes, circulation times or cardiac output and as
compounds normally used by the body such as adjunct to other diagnostic procedures in the
glucose, water or ammonia and then injected into detection and localization of brain tumors, in
the body to trace where they become distributed. placental localization and in cisternography.
Such labelled compounds are known as radiotracers - Iodinated I 131 Albumin Aggregated Injection –
diagnostic study of the lungs (pulmonary embolism)
Drug Antidote for Radiation Exposure by radioisotope scanning.
- Prussian Blue (ferric hexacyanoferrate) - Chlormerodrin Hg 197 Injection — diagnostic aid for
- Initially used for Thallium and Cesium poisoning scanning the brain for suspected lesions and the
- Acts by trapping the ions and preventing kidneys for anatomical and functional abnormalities.
reabsorption - Chlormerodrin Hg 203 Injection — same uses as
above.
Drugs used as interventional pharmaceutical drugs - Chromic Phosphate P 32 Injection – neoplastic
- Acetazolamide (used in cerebral perfusion studies) suppressant for palliative treatment of pleural and
- Captopril (used in renovascular hypertension peritoneal effusions.
studies) - Cobalt Co 60 and Iridium Ir 192 Sources – 60 Co has
- Dipyridamole and Adenosine (used for cardiac replaced radium, which is relatively expensive for
imaging) many radiation uses of the latter element.
- Furosemide (used in renograms) - Cyanocobalamin Co 57 and Co 60 Capsules and
- Cimetidine (in diverticulum imaging) Solution – diagnostic aid to study the absorption and
deposition of Vit. B12 in normal individuals and in
NUCLEAR PHARMACY patients with megaloblastic anemias.
- Ferric hydroxide In 113m – diagnostic agent for lung
- Nuclear Pharmacy is the patient-oriented service imaging.
that embodies the scientific knowledge and - Ferrous nitrate Fe 59 Injection – diagnostic aid for
professional judgment required to improve and the evaluation of the kinetics of iron metabolism.
promote health through the assurance of the safe - Ferrous Hydroxide Tc 99m – diagnostic aid in
and efficacious use of radioactive drugs for diagnosis pulmonary scintigraphy.
and treatment - Fibrinogen I 125 Injection – diagnosis and
- Nuclear pharmacy is the first specialty in pharmacy localization of deep-vein thrombosis, the
recognized by the Board of Pharmaceutical accumulation of fibrinogen in clots is observable by
Specialties use of a radiation detector pressed to the surface of
the limb.
The practice is composed of the following areas: - Gallium Citrate Ga 67 Injection – diagnosis of lesions
- Procurement of the lungs, breast, maxillary sinuses and liver by
- Compounding using scanning and organ-imaging techniques. A
- Routine quality control procedures positive 67 Ga uptake is a potential indicator of
 certain malignancies such as lymphomas, glands, imaging placental localization and blood pool
bronchogenic carcinoma, and Hodgkin’s disease. imaging.
- Indium Chloride In 113m Injection – blood-pool - Sodium Phosphate P 32 Solution – neoplastic and
studies, including visualization, aneurysms, and in polycythemic suppressant, diagnostic aid for
placental scintigraphy. localization of ocular tumor.
- Indium Hydroxide In 113m Injection – for liver, - Strontium Sr 85 Injection – diagnostic aid for
spleen and bone marrow scintigraphy. scanning bones to detect and define lesions and to
- Insulin I 125 and I 131 - in vitro assay of circulating study bone growth and abnormal formation.
insulin either free or bound. - Technetium Tc 99m Etidrenate Injection – best
- Iodohippurate Sodium I 131 Injection – for kidney agent for bone imaging.
function. - Technetium Tc 99m Iminodiacetic acid (TIDA) or
- Krypton Kr 81m – lung function, ventilation and Hepatobiliary Iminodiacetic acid (HIDA) –
perfusion and radiocardiology. hepatobiliary imaging agent.
- Liothyronine I 125 and I 131 – in vitro evaluation of - Technetium Tc 99m Ferpentate Injection – kidney
thyroid function. imaging.
- Levothyroxine I 125 and I 131 – study metabolism of - Technetium Tc 99m Pentetate Injection – brain and
endogenous thyroxine, supplementing other tests of kidney visualization, for vascular dynamic studies for
thyroid function. measurement of glomerular filtration and lung
- Oleic acid I 125 and I 131, Trinolein I 125 and I 131 – ventilation studies.
diagnostic agents for measuring fat absorption in - Technetium Tc 99m Pyrophosphate Injection –
suspected pancreatic disease and other skeletal imaging agent used to demonstrate regions
gastrointestinal dysfunction. of altered osteogenesis.
- Pentetate Indium Trisodium In 113 Injection – - Technetium Tc 99m Sulfur Colloid Injection –
diagnostic aid for brain scanning, for studies of diagnostic aid for liver scanning.
glomerular filtration and for kidney imaging. - Technetium Tc 99m Gluceptate Injection – a renal
- Pentetate Indium Disodium In 111 Injection – imaging agent and localization of brain, lung and gall
diagnostic aid for studies of cardiac output, for bladder lesions.
cisternography, for evaluation of glomerular - Technetium Tc 99m sodium phosphates Injection –
filtration and in renal scintigraphy. bone and renal imaging.
- Pentetate Ytterbium Trisodium Yb 169 Injection – - Technetium Tc 99m Sodium Phytate Injection – for
for brain and kidney imaging and for cisternographic liver and spleen imaging.
diagnosis of CSF rhinorrhea. - Thallium Tl 201 chloride Injection – myocardial
- Potassium Chloride K 42 Injection – tumor perfusion imaging for diagnosis and localization of
localization and studies of renal blood flow. myocardial ischemia and infarction.
- Potassium Chloride K 43 Injection – for heart - Xenon Xe 133 Injection – as gas for lung imaging to
imaging. detect alveolar blockage.
- Rose Bengal Sodium I 131 Injection – diagnostic aid
(liver function), especially for differential diagnosis of Products of Biotechnology
hepatobiliary diseases. Techniques used:
- Selenomehtionine Se 75 Injection – scintigraphy of 1. rDNA
the pancreas and parathyroid glands. 2. Monoclonal antibodies
- Sodium chloride Na 22 Injection – determining 3. Polymerase chain reaction
circulating times, sodium space and total 4. Gene therapy
exchangeable sodium. 5. Antisense or Nucleotide blockade
- Sodium chromate Cr 51 Injection – biological tracer
to measure circulating red-cell volume, red-cell MEDICAL DEVICES
survival time and whole blood volume.
- Sodium Fluoride F 18 Injection – bone imaging, - A medical device is an instrument, apparatus, in vitro
especially to define area of altered osteogenic reagent , implant or other similar or related article,
activity. which is intended for use in the diagnosis of disease
- Sodium Iodide I 123, I 125, I 131 – thyroid function. or other condition, or in the cure, mitigation ,
- Sodium Pertechnetate Tc 99m Injection – detection treatment , or prevention of disease or intended to
and location of cranial lesion, thyroid and salivary affect the structure or any function of the body and
 which does not achieve any of its primary intended
purposes through its chemical action within or on the
body
- Diagnosis, prevention, monitoring, treatment or
alleviation of disease
- Diagnosis, monitoring, treatment, alleviation of or
compensation for an injury or handicap
- Investigation, replacement or modification of the
anatomy or of a physiological process
- Control of conception
- And which does not achieve its principal intended
action in or on the human body by pharmacological,
immunological or metabolic means, but which may
be assisted in its function by such means

Classification
- Medical Devices are classified as per their risk level
and intended use

MDD-Risk Based Classification

- Class A (Class-I) – Devices involving low risk levels
- Class B (Class-II a) – Devices involving low to medium
risk
- Class C (Class-II b) – Devices involving moderate to
high risk
- Class D (Class-III) – Devices involving high risk

By USFDA
- Class-I : Elastic bandages, Examination Glove, Adult
Incontinence Pad
- Class –II: Catheter Cannula, Dialyzer , Piston syringe ,
Needle, Infusion Pumps, Bone fixation screw, Blood
pressure kit
- Class-III: Pacemakers, Dental Lasers, Heart Valves.

Registration of Medical Devices – United States

- FDA ‘APPROVAL PROCESS’ BY CLASS OF DEVICE
- Note: Approval of Class-3 Devices is complicated and
involves clinical trials. Less than 10% of devices are
considered Class-3 by the FDA
- CLASS 1: NO FDA APPROVAL NEEDED. Must register
device and company on FDA website
- CLASS 2: FDA CLEARANCE REQUIRED. Typically, via
510 K premarket notification submission
- CLASS 3: FDA APPROVAL REQUIRED. Typically via
premarket (PMA) approval process