PARENTRALS

By.
Manohar
ASPECTS OF FORMULATIONS:

 Vehicle in which the drug dissolved (Or) dispersed

 Adjustment of Is tonicity
 Concentration Units
 Adjustment of specific gravity
 Adjustment of PH
 Stabilizers
 Preservatives
 VEHICLES:--- a)Water for injection
 Water is the preferred injection vehicle Since the Aq.Prepartions
are well tolerated by the body and easy to administrator
b)Water Miscible vehicles for injections
EX:
Ethanol:- Rarely used because of it pharmacological activity
and also Co solvent

c)Water Immiscible vehicles for injections

Ex:
Fixed Oils
Fattyacid esters
Alcohols
Benzyl benzoate
 Adjustment of Is tonicity
 Various methods may be used to estimate amount of adjusting
substances required to render a particular solution is tonic with plasma

 Calculation is based on freezing point depression, on sodium chloride

equivalents , on molar concentration or on Osmolarity
 Concentration of Units
 Weight per unit volume Ex: Atropine sulphate Injection 600
Micro gram/Ml

 Percentage weight per volume Ex: Lignocaine Injection 0.5%

 Millimole per unit volume Ex: Potassium chloride solution

2mmol each of K+ and Cl-/ml
 Adjustment of specific gravity

 Specific gravity of the solution determine the region of anesthesia

Hypobaric (lower density) Solutions tend to rise
Hyperbaric (Higher density) Solutions to sink relative to the
cerebrospinal fluid.
Adjustment of PH
 PH solubility and PH verses Stability are needed for solution
and suspension formulation to assure physical and chemical
stability as well as to max or min solubility
 It also voluble for predicting the compatibility of the drugs
with various infusion fluids
 Physical and chemical data that should be obtained
 Molecular structure
 Melting point
 Particle size and shape
 PH solubility
 PH stability
 Optical activity
 Solvate formation
 Stabilizers:
 Antioxidant and reducing agents
a) Aq.Injections:
Ex: Sodiummetabisulphite,Sodiumsulphite,Sodiumthiosulphate,Ascorbic
dextrose

b) Oily-Injections
Ex: Propyl gallate,Butylated hydroxy toluene,Bh-anisole and Tocophero

 Chelating agents
Ex: Disodium edetate, Calcium edetate , citric acid and tartaric acid

 Other Stabilization methods includes:

Use of buffers to optimum PH
 Preservatives

Ex 1: Aq.Injections-phenol 0.5%, Chlorocresol 0.1%, O-cresol

0.3%, benzyl alcohol 1%,phenylmercuricsalts 0.002%

Ex 2: For Oily Injections – phenol, O-cresol or Chlorocresol

In the pilot plant, a formulae is transformed into a
viable, robust product by the development of a
reliable and practical method of manufacture that
effect the orderly transition from laboratory to
routine processing in a full – scale production
facility.
So pilot plant is the miniature, intermediate plant
between the laboratory scale and the production
plant.
Working Area:
Incoming goods stored in special areas for
quarantine.
Temperature sensitive products stored in cold
room.
Sampling and weighing of raw materials in
sampling area.
Final product stored in designated area/
Production area ensure full quality compliances.
Technical area for formulation development
EX:
Parenteral Nutrition Mixture
Total energy supplied in 24 hrs is …………………………………..KCAL is…………………ML.
Contents:
Nitrogen g
Carbohydrates kcals
Sodium mmol
Potassium mmol
Phosphate mmol
Magnisum mmol
Calcium mmol
Trace Elements:
Cu:Zn:Cr:Mn:F:I:Fe
Vitamins:
A:B Co:C:E:Folate:Biotin
Final Volume ml
Patient ward
Expiry Date:
Date:
Prepared By Batch no
Warning: protect from light contains approx 20%
W/V dextrose,donot infuse to rapidly .refregirate until
Ready for use.
Donot make any further additions to this container
Scale-up for parenterals
Lay-out of the pilot-plant
 Facility Design

To provide the control of microbial, pyrogen and

particles controls over the production environment
are essential.
Warehousing:
All samples should be aseptically taken, which
mandates unidirectional airflow and full operator
gowning.
These measures reduce the potential for
contamination ingress into materials that are yet to
receive any processing at any site.
 Preparation Area:
The materials utilized for the production of the
sterile products move toward the preparation area
through a series of progressively cleaner
environments.

First the materials are passed through class 100,000 i.e. grade D
environment for presterilization.

Transfer of materials are carried out in air-locks

to avoid cross contamination
The preparation areas are supplied with HEPA filters.
There should be more than 20 air changes per hour

The preparation place is Class 100 area.

Production area
Compounding area:
The manufacture of parenterals is carried out in
class 10,000 (Grade C) controlled environments in
which class 100 unidirectional flow hoods are
utilized to provide greater environmental control
during material addition.
These areas are designed to minimize the
microbial, pyrogen, and particulate contamination to
the formulation prior to sterilization.
 Aseptic filling rooms:
The filling of the formulations is performed in an
Class 100 environment.
Capping and Crimp sealing areas:
The air supply in the capping line should be of
Class 100
Corridors:
They serve to interconnect the various rooms. Fill
rooms, air locks and gowning rooms are assessed
from the corridor.
Aseptic storage rooms.
Air-locks and pass-throughs:
Air locks serve as a transition points between one
environment and another.
They are fitted with the UltraViolet lights, spray
systems, or other devices that may be effectively
utilized for decontamination of materials.