Industrial pharmacy assignment

1. MAHARSHI DAYANAND
UNIVERSITY
INDUSTRIAL PHARMACY
AVISHEK
1407 5TH SEM

2. Formulation of Large Volume Parenterals
Large vo lume parenterals are sterile aqueous solutions or emulsions having water for
injection as its main component. They are formulated as single -dose injections
administered by intravenous infusion. They are packed and administered in large volumes.
They should be free of par ticles. Before administration, sometimes ad ditional drugs are
added to them by either injecting small volume parenterals to the administration sets or
by the piggyback method (smaller volume infusion of an additional drug is added to the
intravenous delivery system).

3. Large-volume parenteral products include:
• 1) Infusion fluids,
• 2) Total Parenteral Nutrition (TPN) solutions,
• 3) Intravenous antibiotics,
• 4) Patient-controlled analgesia,
• 5) Dialysis fluids, and
• 6) Irrigation solutions.

4. CHARACTERISTICS
• Sterile,
• ✓ Pyrogen-Free,
• ✓ Essentially free of particulate matter,
• ✓ No anti-microbial agents/ free of preservatives,
• ✓ Isotonicity,
• ✓ The LVP is supplied in sizes appropriate to label claims
facilitating use ofthe contents promptly following initial entry.

5. Formulation of Large Volume Parenterals
Large volume parenterals should be terminally heat sterilised . Apart from
water for
injection as the main component, other ingredients that should be included
are
carbohydrates (e.g., dextrose, sucrose and dextran ), a mino acids, lipid
emulsions
(containing vegetable or semi -synthetic oil ), electrolytes (e.g., sodium
chloride ), and
polyols, including glycerol, sorbitol and mannitol

6. Formulation considerations
Drug-Excipient Compatibility:
✓ The main challenge of all the different parenteral dosage forms is
to achieve a good compatibility of the drug substances with the
excipients (no formation of new impurities either by degradation of
the drug substance or formation of new chemical entity between
the drug substance and the excipients).

7. Formulation considerations
Selection of suitable containers:
✓ The compatibility of the preparations with the primary container
(no leachable or adsorption to container) is always a prime concern.
✓ Plasticizers used to keep plastic flexible may leads to leaching as
it mayinteract with some drugs and solutions.

8. Formulation considerations
✓ Solubility of drug solvent/vehicle:
✓ When drug substances are not soluble, dissolution can be
achieved by the use of co-solvents, surfactants, or a soluble pro
drug, or eventually the use of solubility enhancers such as
cyclodextrins to the formation of inclusion complex.

9. Formulation considerations
pH:
✓ The pH is one of the critical aspects of parenteral preparations which
shouldhave a pH close to the physiological one.
✓ In certain cases, a compromise should be found between the pH ensuring
stability of the drug substance (such for peptides requiring alkaline pH or
proteins at pH close to the isoelectric point) and the physiological one.
✓ In all cases, large volume preparations (LVP, i.e. more than 100 ml as
definedin pharmacopeia) should not contain a pH buffer as the blood has
already abuffer effect property that could enter into competition with the
injecteddrug product.

10. Formulation considerations
Drug stability:
✓ The stability of the drug substance is another critical point that a formulator
can face during the development of the formulation.
✓ Unstable drug substances will lead to the formation of new impurities
jeopardizing the safety of use of the preparations.
✓ When the use of a stabilizer is justified (for instance the use of mannitol as
free-radical scavenger or cysteine in paracetamol solution for injection), it
should be included at the minimum concentration demonstrated to be efficient
at release and during the entire shelf-life

11. Formulation considerations
Suitable sterilization method:
✓ Finally the process of the sterilization should be selected according to the
characteristics of the parenteral preparations (for instance, heat steam
sterilization for aqueous solutions and dry heat for non-aqueous solutions),
but in any case it can be justified by the nature of the primary containers.