This document provides an overview of parenteral dosage forms, including definitions, advantages and disadvantages, preformulation considerations, and types of small and large volume parenterals. Parenterals refer to routes of administration other than the gastrointestinal tract, such as intravenous, intramuscular, and subcutaneous. Preformulation studies examine the drug's physicochemical properties, solubility, stability, and compatibility with excipients. Small volume parenterals are formulated with water for injection, buffers, antimicrobial preservatives, antioxidants, tonicity agents, and surfactants. Large volume parenterals provide intravenous nutrition through protein, energy, electrolyte, and vitamin substrates. Finished products are tested for content uniformity, leakage,

1. By
Mrs. B. S. BHANAGE
Assistant Professor
Dept. of Pharmaceutics
Parenterals

2. Content
• Definition
• Advantages and Disadvantages
• Preformulation
• Formulation considerations
• SVP
• LVP
• Evaluation

3. Parenterals
Parenteral dosage forms are those administered directly into body
tissues rather than via the alimentary canal.
“Parenteral” is derived from the Greek words para (beside) and
enteron (the intestine). Parenterals refers to various routes such as
IV, IM, SC etc.

4. Advantages
• The parenteral route provides an effective way to dose patients
who are unconscious or those who cannot take oral
medications.
• A drug administered parenterally generally produces an
immediate therapeutic effect. Therefore desirable in emergency
situations.
• Parenteral administration also provides a mechanism for dosing
drugs that are not bioavailable via parenteral routes such as
many protein and peptides.
• Total parenteral nutrition can be provided for seriously ill patients
where tube feeding is not an alternative.

5. • Large amounts of fluid and electrolytes can be given relatively
quickly via the IV route to patients with serious fluid loss from
dehydration or gastrointestinal infections.
Disadvantages
• Once a drug has been dosed it is difficult to reverse its effect.
• The risk of infection is always present with parenteral dosing
both in the hospital/clinic setting as well as home administration.
• Costly as compared to oral medications.

6. Intramuscular Intradermal
Subcutaneous
Intravenous Intraarticular
Intrathecal
Intraepidural
Intracisternal
Intraperitonial
Intraplular Intracardiac
Parenteral Routes

7. Preformulation
Physicochemical properties of Drug:
1. Molecular Properties
2. Material Properties
3. Bulk Properties.
Molecular Properties: These properties defined by molecular
structre. In that molecular weight, Partition coeficient, Ionization
contants etc has been studied.
Partition coefficients which are descriptions of the lipophilicity of a
compound, are often correlated to the ability of a compound to cross
biological membranes as well as their ability to dissolve in
formulation vehicles.

8. • The pKa is an important determinant in the pH dependence of
ionization and hence solubility as well as salt formation ability of
a molecule
Solubility:
• Solubility is the concentration of drug in solution at equilibrium
with excess solid.
• .Aqueous solubility is of particular relevance to biological activity,
bioavailability, and formulation strategy.
• Solubility is experimentally measured by placing an excess solid
in a test tube in contact with a particular solvent with mild
agitation and determining the concentration of the drug in a
supernatant solution over a period of time using appropriate
analytical techniques such as UV spectrophotometry or high-
performance liquid chromatography (HPLC)

9. • During preformulation studies, it is common to determine
solubility of the drug compound in aqueous and nonaqueous
vehicles used in pharmaceutical formulations.
• Aqueous systems include, surfactants solutions, buffers,
complexant solutions.
• Nonaqueous systems includes, cosovents such as ethanol,
glycerol, polyethylene glycol etc.
• Stability and Degradation:
• In addition to solubility, stability of the active drug compound is a
key determinant in the viability of parenteral drug product.
• It is essential for a drug product to maintain potency relative to
label claim over the shelf life to deliver an accurate dose.
Second, degradation in the drug product can result in changes in
appearance (color, precipitation) or bioavailability.
• Understanding the degradation pathways, kinetics, and
mechanisms leads to development of a stable drug product.

10. Generally, HPLC with UV detection is used in preformulation
studies, but techniques such as LC-MS and NMR spectroscopy
could often aid in the identification of degradation products.
Modes of Degradation:
1. Hydrolysis
2. Oxidation
3. Photolysis.
Drug Excipient Compatibility.

11. Small Volume Parenterals

13. • Formulation Principles:
1. Influence of Routes of Administration
2. Isotonicity
3. Selection of Vehicle
4. Solubility and solubilization

14. USP Requirments for WFI
1. Not more than 10 ppm of total solids
2. pH 5-7
3. It should be prepared by Distillation method or reverse osmosis
method.
4. Stored in chemical resistant tank.
5. It should be pyrogen free.

15. Antibacterial Agents
1. Added in multiple dose containers
2. To prevent growth of microorganisms.
Antibacterial preservatives
1. Benzalkonium chloride 0.01
2. Benzethonium chloride 0.01
3. Benzyl alcohol 1–2
4. Chlorobutanol 0.25–0.5
5. Chlorocresol 0.1–0.3
6. Metacresol 0.1–0.3
7. Phenol 0.5
8. Phenylmercuric nitrate and acetate 0.002
9. Methyl p-hydroxybenzoate 0.18
10. Propyl p-hydroxybenzoate

16. Buffers
1. To maintain the Ph of formulation
2. To prevent chemical degradation in the formulation
• Acetic acid and a salt, pH 3.5–5.7 1–2
• Citric acid and a salt, pH 2.5–6 1–5
• Glutamic acid, pH 8.2–10.2 1–2
• Phosphoric acid salts, pH 6–8.2 0.8–2

17. Antioxidants
• Acetone sodium bisulfite 0.2
• Ascorbic acid 0.01
• Ascorbic acid esters 0.015
• Butylhydroxyanisole (BHA) 0.02
• Butylhydroxytoluene (BHT) 0.02
• Cysteine 0.5
• Nordihydroguaiaretic acid (NDGA) 0.01
• Monothioglycerol 0.5
• Sodium bisulfite 0.15

18. Surfactants as solubilizers
1. Surfactants are effective solubilizing agents because of their
wetting properties and association tendencies as they are able
to disperse water-insoluble substances
2. Surfactants helps to enhance the solubility of poorly soluble
drugs.
3. Most widely used water-soluble nonionic surfactants in
injectable products are polyethylene oxide (PEO) sorbitan fatty
acid esters, or Polysorbates.

19. Tonicity Agents

20. 1. Formulation should be isotonic with the boold to avoid cell
damage.
2. prevent electrolyte imbalance upon administration of small-
volume parenterals, the product should be isotonic.
3. Isotonic solutions exert the same osmotic pressure as blood
plasma.
4. In isotonic solutions (e.g., 0.9% sodium chloride) the cells
maintain their “tone” and the solution is isotonic with human
erythrocytes
5. NACl, KCl, Dextrose, Mannitol etc.

21. Large volume Parenterals:

22. 1. LVPs or injections are primarily used for IV nutritional therapy
which is when normal enteral feeding is not possible or is
inadequate for nutritional requirements.
2. To meet IV nutritional requirements, one or more of the
following nutrients may be required:
• Protein substrates: These include various amino acids
formulation used for general replacement purpose, for hepatic
failure, for encephalopathy, and for metabolic stress conditions.
• Energy substrates: These include dextrose and IV fat emulsion.
• Electrolytes: Saline, ringer’s solution, etc.
• Vitamins and trace metal supplements

23. Types of LVP
• Hyperalimentation solutions
• Cardioplagic solutions
• Peritoneal dialysis solutions
• Irrigating solutions

24. Finished Product QC test
1. Content Uniformity
2. Leackage test
3. Pyrogen testing
4. Sterility test
5. Clarity test

25. References:
• Pharmaceutical Dosage Forms: Parenteral Medications Third
Edition Volume 1,Formulation and Packaging, Informa
Healthcare.
• Theory and Practice of Industrial Pharmacy by, Lachman and
Liberman. Verghese Publications.

26. Thank You