Industrial pharmacy assignment Formulation of injections

1. Formulation of
Injections

2. INTRODUCTION
 Injection are the sterile solution or suspensions
of drugs in aqueous or oily vehicle meant for
introduction into the body by means of an
injectable needle under or through one or more
layers of the skin or mucous membrane.
 Injections should be sterile, isotonic and free
from foreign particles, such as dust, fibres etc.

3. Formulation of injections (Solution
and suspension) :
 Solution : A range of excipients may be
included in parenteral solutions, including
antioxidants, antimicrobial agents, buffers,
chelating agents, inert gases, and substances
for adjusting tonicity. Antioxidants maintain
product stability by being preferentially oxidized
over the shelf life of the product.
 Antimicrobial preservatives inhibit the growth of
any microbes that are accidentally introduced
while doses are being withdrawn from multiple-
dose bottles and act as adjuncts in aseptic
processing of products

4. Suspension :
A suspension for injection consists of
insoluble solid particles dispersed in a liquid
medium, with the solid particles accounting
for0.5-30% of the suspension. The vehicle
may be aqueous, oil, or both.
 Caking of injectable suspensions is minimized
through the production of flocculated systems,
comprising clusters of particles (flocs) held
together in a loose open structure.

5.  Excipients in injectable suspensions include
antimicrobial preservatives, surfactants,
dispersing or suspending agents, and buffers.
 Surfactants wet the suspended powders and
provide acceptable syringe ability while
suspending agents modify the viscosity of the
formulation.

6. Ingredients :
Example : Diazepam 5mg/ml injection .

7. Method of Preparation:
 This formulation should be prepared
according to strict aseptic compounding
technique in a laminar airflow hood in a
clean room or via isolation barrier
technology by a compounding
pharmacist validated in aseptic
compounding. This is a high-risk
preparation.

8.  Diazepam injection USP is a sterile
solution of diazepam in a suitable
medium. It has a pH between 6.2 and
6.9, contains not more than 11.6 USP
Endotoxin Units per mg of diazepam,
and has an osmolality of about 7,775
mOsm/kg.1 Because of the cosolvent
system used to solubilize the diazepam,
care should be taken when diluting this
injection.

9. Propylene glycol :
 Propylene glycol (C3H8O2) occurs as a clear,
colorless, viscous, practically odorless liquid
with a sweet taste, somewhat resembling
glycerin. It has a specific gravity of 1.038
g/mL, and it is miscible with 95% ethanol,
glycerin, and water.5

10. Ethyl alcohol :
 Ethyl alcohol, ethanol, grain alcohol,
C2H5OH, MW 46.07) is a clear, colorless,
mobile, volatile liquid with a slight,
characteristic odor and a burning taste.
Alcohol USP refers to 95% ethanol, and
dehydrated alcohol refers to 99.5% alcohol.
Its specific gravity is between 0.812 and
0.816, and its boiling point is 78.15°C.
Alcohol is miscible with glycerin and water.

11. Sodium benzoate :
 Sodium benzoate (C7H5NaO2, MW 144.11)
occurs as a white granular or crystalline,
slightly hygroscopic powder. It is generally
odorless and has an unpleasant sweet and
salty taste. Sodium benzoate is soluble 1 g
in 1.8 mL of water and 75 mL of 95%
ethanol. It is used as an antimicrobial
preservative.

12. Benzoic acid :
 Benzoic acid (C7H6O2, MW 122.12)
occurs as white crystals, scales, or
needles with a slight odor. It is somewhat
volatile at warmer temperatures, slightly
soluble in water, and freely soluble in
alcohol.

13. Benzyl alcohol :
 Benzyl alcohol (C7H8O, MW 108.14) is an
antimicrobial preservative, disinfectant, and
solvent that occurs as a clear, colorless, oily
liquid that has a faint, aromatic odor and a
sharp, burning taste. Benzyl alcohol has a
specific gravity of about 1.045. It is soluble 1
g in 25 mL of water at 25°C and is miscible
with ethanol.

14. Uses :
 Diazepam injection is used to treat anxiety
disorders, alcohol withdrawal symptoms,
or muscle spasms. Diazepam injection is
also used to treat a seizure emergency
called status epilepticus. Diazepam
injection is sometimes used as a sedative
to help you relax before having surgery or
other medical procedure.

15. Common side effects of diazepam
injection include:
 drowsiness,
 dizziness,
 nausea,
 poor coordination,
 unsteadiness,
 headache,
 sleep disturbances,
 low blood pressure,

16. Example : Amikacin for 250 mg/ml
injection

17. Method of Preparation:
 This formulation should be prepared
according to strict aseptic compounding
technique in a laminar airflow hood in a clean
room or via isolation barrier technology by a
compounding pharmacist validated in aseptic
compounding. This is a high-risk preparation.

18.  Amikacin sulfate (Amikin, C22H43N5O13.2H2SO4,
MW 781.76) occurs as a white, crystalline powder
that is freely soluble in water. It contains the
equivalent of not less than 674 mcg and not more
than 786 mcg amikacin per mg, calculated on the
dried basis. On drying, it loses not more than
13.0% of its weight. It is important to check the
label of the bulk amikacin sulfate powder to
determine the equivalent amount to be used.
Amikacin sulfate should be preserved in a tight
container. The injection is colorless to light straw-
colored and has a pH ranging from 3.5 to 5.5.

19. Sodium citrate :
 Sodium citrate (trisodium citrate, C6H5Na3O7, MW 258.07,
anhydrous; dihydrate, MW 294.10) occurs as colorless
crystals or as a white, crystalline powder. The hydrous form
is freely soluble in water (1 g in 1.5 mL), highly soluble in
boiling water (1 g in 0.6 mL), and insoluble in alcohol.
Sodium citrate is stable and can be sterilized by
autoclaving. When sodium citrate is stored in a glass
container for a period of time, separation of small, solid
particles may occur. The bulk material should be stored in
an airtight container in a cool, dry place. Each gram of
dihydrate represents approximately 10.2 mmol sodium and
3.4 mmol citrate; each gram of anhydrous represents about
11.6 mmol sodium and 3.9 mmol citrate.

20. Sodium bisulfite :
 Sodium bisulfite (sodium hydrogen sulfite,
NaHSO3, MW 104.07) occurs as a white,
crystalline powder. It is soluble 1 in 3.5 parts of
water and in 70 parts of 95% alcohol. Most
substances sold as sodium bisulfite contain
significant but variable amounts of sodium
metabisulfite; sodium metabisulfite is less
hygroscopic and more stable during storage and
shipment. Sodium bisulfite generally is used as
an antioxidant in solutions of intermediate pH

21. Sulfuric acid :
 Sulfuric acid (oil of vitriol, H2SO4, MW 98.08)
occurs as a clear, colorless, oily liquid that is
miscible with water and alcohol with the
generation of heat. It is highly caustic and
corrosive. Sulfuric acid has an SG of about 1.84
and is used as an acidifying agent. It is
hygroscopic and contains not less than 95%
and not more than 98% of H2SO4 by weight, the
remainder being water. Sulfuric acid is a
powerful oxidizer; it may ignite or explode upon
contact with numerous materials.

22. Uses :
 Amikacin 250mg Injection is an antibiotic
used to prevent or treat a wide variety of
bacterial infections. These may include
infections of the urinary tract, bones, and
joints, lungs (eg. pneumonia), brain, blood,
among others. It is also used in hospitalized
patients to prevent infections.

23. Side effects of Amikacin
Injection :
 Increased blood urea.
 Injection site reactions (pain, swelling,
redness).

24. Reference :
1.) U.S. Pharmacopeia 34/NF 29. Rockville, MD:
U.S. Pharmacopeial Convention, Inc;
2011:330-336,336-373,1009,2533-2536.
2.) McEvoy GK, ed. ASHP Drug Information
2011. Bethesda, MD: American Society of
Health-Systems Pharmacists; 2011:2620-2623.
3.) Niazi SK. Handbook of Pharmaceutical
Manufacturing Formulations, Volume 6—Sterile
Products. Boca Raton, FL: CRC Press;
2004:73.
4.) USP Pharmacists’ Pharmacopeia. 2nd ed.
Rockville, MD: US Pharmacopeial Convention,
Inc; 2008:775-779,779-831,1463.