Technology-III

 1. Active Pharmaceutical Ingredients (API’s)

 2. Vehicle
 3. Added Substances
a) Antimicrobials or Preservatives
b) Antioxidants
c) Buffers
d) Chelating agents
e) Stabilizers
f) Tonicity- adjusting agents
Active Pharmaceutical Ingredients (API’s) for parenteral products:
Developing a stable and safe parenteral dosage form , evaluation of properties of API
is essential.
Factors affecting of API :
Solubility and rate of solution: Important factor that affect the dissolution or aqueous
solubility.
Physical state of the drug-
Crystal - Chalosporines,
Salt – Ceftriaxone Na ,
Prodrug – Metronidazole phosphate, chloramphenicol.
Particle size and shape.
Molecular weight and structure.
Physical state of the drug-
• Particle size and shape.
• Molecular weight and structure
• Chemical modification of drug
• Polymorphism
• Melting point.
• Thermal profile of API.
• Ionization constant.
• Light stability.
• Optical activity.
 Matters to be considered :
1. Solubility of drug (in case of solutions)

2. Physical and chemical Stability

3. Pharmacologically inert

4. Compatible with blood

5. Non-sensitizing

6. Non-irritants

7. Not affected by formulation and manufacturing conditions

(e.g. sterilization)
Most widely used: Because it is
Non-toxic & Non-irritant
Widely available
Tastelessness
Easy to store
Physiologically compatible to the body
Wide range of materials dissolve in water
Lack of pharmacological activity
Water for injections in bulk - Water for the preparation of
medicines for parenteral administration.

Prepared from purified by distillation or reverse osmosis.

 Maximum allowable viable aerobic count - 10 microorganisms per 100 ml.
 Electrical conductivity is monitored as a method to ensure the quality.
 Free from pyrogen.
 Should be stored properly to inhibit growth of microorganism and to prevent
contamination. Stored at 60-90˚C for 24 hr.
Water for dissolving or diluting substances or preparations for
parenteral administration(SWFI)
SWFI is Water for injections in bulk that has been distributed into
suitable containers, closed and sterilized by heat.
It is sterile as well as pyrogen free.
Sterilized water for injections is free from any added substances.
Sterilized WFI with one or more antimicrobial agents.
Not more than 30ml
Label must contain the name of antimicrobial agents.
Applied in SV injectables.
Must pass the pyrogen test
Colorless and usually odorless. Sometimes may have the odor of
the bacteriostatic agent

Nacl injection
Bacteriostatic Nacl injection
The word means - fever producing
Comes from bacteria, molds, yeasts.
Most potent are gram negative endotoxins.
Chemistry – lipids associated with proteins or polysaccharides.
Have high M.W. ( > 10,00,000 )
Effects in body : rise in body temperature (fever), pain, itching,
rise in blood pressure due to peripheral vasoconstriction
 :
Source of pyrogen
• Vehicle
• Solutes
• Containers
Removal of pyrogenic materials is difficult because they are :
 Water soluble  Thermostable
Pyrogens are Important to control in -
Single dose injections volume greater than 15 ml.
Intravenous infusions
 Non aqueous solvents
Non aqueous solvents are required
• To increase solubility of the drug ( used as cosolvent )
• To enhance stability of the drug ( hydrolysis may cause loss of
potency )
• To alter biopharmaceutical properties ( onset of action,
duration of action )
 Criteria of Non aqueous solvents

• Non toxic, Non irritating and non sensitizing

• Must not adversely affect the API
• Pharmacologically inert
• Administered by IM
• Must maintain its fluidity over a wide temp
• Should have high boiling point
• Should have lower vapor pressure
• Should have proper miscibility with body fluids.
 Non aqueous solvents
• Non aqueous solvents may be two types:

• Water miscible – Propylene glycol, alcohol, glycerol, PEG 400

& 600. They are used in combination with water at a safe
concentration

• Water immiscible – Vegetable oils ( arachis oil, almond oil,

popyseed oil ), organic esters (Isopropyl myristate,benzyl
benzoate,ethyl oleate)
• May be too viscous, particularly at low temperature
• Often cause pain
• Can be given only by IM routes
• They contaminate the syringe and needle, difficult to clean.
Limitations of water immiscible solvents