Theory Industrial Pharmacy-I [PY3CO19T]

Odd Semester (Aug-Dec 2021)

Unit –IV (Parenterals )

Sourabh Billore
Faculty of Pharmacy
E mail: Sourabh.Billore@medicaps.ac.in
Introduction
The term parenteral derives from the greek word Para (outside) Enteron (Intestine)

Parenteral dosage forms differ from all other drug dosage forms, because they are
injected directly into body tissue through the primary protective systems of the human
body, the skin, and mucous membranes.

Parenteral drugs are administered directly into the veins, muscles or under the skin or
more specialized tissues such as spinal cord by means of syringe and needles.

Sourabh Billore Sourabh.billore@medicaps.ac.in

Parenteral Routes of administration:

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore
Certain pharmaceutical agents, particularly peptides, proteins, and many
chemotherapeutic agents, can only be given parenterally, because they are
inactivated in the gastrointestinal tract when given by mouth.

Because medication administered parenterally bypass the intestinal tract,

the pharmacodynamic properties of such medications will differ depending
on the site of administration. This can results in advantages and
disadvantages that are unique to the parenteral formulations.

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ADVANTAGES
 It provides rapid onset of action
 It provides immediate therapeutic action
 It can be administered accurate dose.
 It can be given to patients who cannot take oral medication.
 It minimize the first pass effect
 It provides more bioavailability

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DISADVANTAGES
 It should be administered aseptically
 It produces pain at the site of injection
 The administered of drug through wrong route may prove fatal effect
 Self administration is not possible
 If pyrogenic preparations lead to very harmful effect.
Characteristics of parenteral dosage form
All products must be sterile, free from pyrogenic (endotoxin) contamination, free from
visible particulate matter, should be isotonic, must be stable, must be compatible.

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Classification
The United States Pharmacopoeia defines five main types of preparations intended for
parenteral administration.

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Classification based on volume
Small Volume Parenterals:

An injection that is packed in containers labelled as containing 100 mL or less. Examples:

Solution, Suspension, Emulsion, Dry Powders

Large Volume Parenterals (USP):

LVP as products in a container labelled as containing more than 100ml of a single dose
injection intended for administration by IV infusion. Electrolytes: 0.9 % NaCl Injection,
Multiple electrolyte, Lactated Ringer Injection • Carbohydrates: 5 % Dextrose Injection, 10
% Fructose Injection, 10 % Invert Sugar Injection Irrigating Solutions etc.
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Formulation Considerations
1. SOLVENTS AND VEHICLES
WATER AND AQUEOUS VEHICLES
 Water for injection
 Sterile water for injection
 Bacteriostatic water for injection
 Sodium chloride injection
 Bacteriostatic sodium chloride injection

Non-aqueous solvents
 Fixed vegetable oils
 Alcohol

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2. Preservatives
Agents containing mercury in concentration not more than 0.01%
- Cationic surfactants
- Alcohols up to 2%
- Phenols up to 0.5%
3. Antioxidants
Water solubleOil soluble
- Sulfurous acid salts - Propyl gallate
- Ascorbic acid isomers - Butylated hydroxyanisole
- Thiol derivatives - Ascorbyl palmitate
- a- Tocopherol
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4. BUFFER SYSTEMS

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 Role of tonicity in Parenterals
The osmotic pressure of blood is approximately 300 milliOsmoles/L

An isotonic solution is one that exhibits the same effective osmotic pressure as blood
serum.

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore
Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore
Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore
Advantages and Disadvantages of Parenteral Suspension
Advantages Disadvantages
*For insoluble & poorly soluble *Difficult formulation & manufacturing
drugs
*Risk of non‐uniformity of dose
*Increase chemical stability of drugs
(↑ resistance to hydrolysis & *Problems of physical stability
oxidation)
*Patient discomfort during injection
*More prolonged release from
injection site than solution (a depot
*Limited to SC and IM routes
effect)
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Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore
Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore
Aseptic area for preparation of Parenterals
Production of sterile products is carried out in a clean area which has strictly
controlled environmental quality of air particles, microbial contamination.

Some pharmaceutical products are not terminally sterilized (Packed, Sealed and
Sterilized) such products are meant to be prepared from sterile ingredients and are
sterilized by filtration before packing in sterile containers.

For manufacturing of such products strict aseptic measures need to be followed and
hence as Aseptic Area becomes an essential part of such manufacturing units.

An aseptic area is a premise in a clean area, designed, constructed, serviced and used
with an intention to prevent the microbial contamination of the product.
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The flow chart of the aseptic area

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Design and Construction:
Only authorized personnel can gain access to the clean and aseptic filling areas. 

The personnel enter the clean rooms by passing through the changing rooms where they put on and
remove their clean room uniform. 

A pass-Over (or cross-over) bench extends across the changing room to form a physical barrier for
separating the different areas for changing by the personnel. 

Surfacing Materials:
The floor, wall, and ceiling surface of clean rooms should be smooth, waterproof, and unbroken to reduce
the release and accumulation of contaminating particles and organisms. 

Minimum shelves, ledges, cupboards, and equipment should be present. 

Non opening and sealed windows should be present to prevent the entry of contaminants. 

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Laminar Flow Equipment (Laminar Airflow Hood)
 A Laminar Airflow Hood (LAFH)/ Laminar Aseptic Hoods, or a workbench, is a
primary engineering control device which provides the following services during
aseptic compounding

1) Clean air to the critical sites (immediate aseptic compounding area),

2) Constant flow of air out of the work area to prevent the entry of room air, and

3) Outward flow of air from the hood that suspends and removes contaminants which
have been introduced in the work area by personnel.

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A High Efficiency Particulate Air (HEPA) Filter is the most important part of a LAFH.
The air within the room is taken into this filter and passed through a pre-filter which
removes the gross contaminants (lint, dust, etc.).

HEPA filters provide:

1) A high air flow rate,

2) A high particulate holding capacity, and

3) A low-pressure drop across the filter.

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Classes of Clean Rooms and their Properties

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Air Particle Classification System for the Manufacturing of
Sterile Products

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Aseptic Parameters as per Grade area

For Aseptic Operation

For Terminally Sterilized Products

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Container & Closures
Packaging is the process by which the pharmaceuticals are suitably placed so that they
should retain their therapeutic effectiveness from the time of their packaging till they
are consumed.
“Packing is the art and science which involves preparing the articles for transport,
storage, display and use.”

Composition of package:
(a)Container
(b) Closure
(c) Carton or Outer
(d) Box

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SELECTION OF PACKAGING MATERIAL

They must protect the preparation from environmental conditions.

They must not be reactive with the product,
They must not impart tastes or odors to the products,
They must be non-toxic,
They must be FDA (Food & Drug Administration) approved,
They must meet applicable tamper-resistance requirements
They must be adaptable to commonly employed high-speed packaging equipment. and
They must have reasonable cost in relation to the cost of the product.

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Container & Closure for Parenterals
• Injectable formulations are packaged into containers made of glass or plastic.
Container systems include ampoules, vials, syringes, cartridges, bottles, and
bags.

Small volume Parenterals (SVPs)

• Ampoules
• Glass vials sealed with rubber stoppers
• Plastic ampoules (blow-fill-seal)
• Pre-filled syringes
• Needle-free injection

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Large volume Parenterals (LVPs)

• Glass bottles sealed with rubber stoppers

• Plastic bags

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

PACKAGING MATERIALS
The following materials are used for the construction of containers and closures

Glass: -

Type-I Borosilicate glass

Type-II Treated sodalime glass

Type-III Regular soda-lime glass

Type-NP General purpose soda lime glass

Coloured glass
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2. Plastics:
(a) Thermosetting resins: (i) Phenolics (ii) Urea
(b) Thermoplastic resins:
(i)Polyethylene,
(ii)Polypropylene,
(iii)Polyvinylchloride (PVC),
(iv) Polystyrene
(v)Polycarbonate
vi)Polyamide (Nylon)
(vii)Polyethylene terephthalate (PET)

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3. Metals:
(i) Tin (ii) Iron (iii) Aluminium (iv) Lead.

4. Rubber:
(i) Natural rubber
(ii) Neoprene rubber
(iii) Butyl rubber

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Parenteral filling techniques
BLOW FILL SEAL : for Aseptic filling

Blow-fill-seal technology is a manufacturing technique used to produce small, (0.1ml-

99ml) and large volume, (100ml and above) liquid filled containers.

History

Blow-fill-seal technology was originally developed in Europe in 1930s.

It was introduced for the first time in USA in 1960s by  ROMMELAG

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over the last 20 years, it has become moreprevalent technique in pharmaceutical
companies.

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore