Defination of Lvps and Svps Formulation of Lvps and Svps Evaluation

1. RAJIV GANDHI UNIVERSITY OF HEALTH AND SCIENCE
BANGALORE
Large and small volume parentrals

2. Content
■ Introduction
■ General requirement for parenteral dosage form
■ Parenteral Routes
■ Advantages and Disadvantage
■ Classification
■ Small volume parenterals (SVPs)
■ Large volume parenterals (LVPs)

3. Introduction
■ The term derived from Greek word ‘Para’ outside & ‘Enterone’ intestine.
■ Parenterals are sterile solutions or suspension of drug in aqueous or oily
vehicle
■ Parenteral drugs are administered directly in to the veins, muscles or under
the skin, or more specialized tissues such as spinal cord.
■ Term parenteral used for any drug/fluid whose delivery doesn’t utilize the
alimentary canal for entering in to the body tissues.

4. General requirements for parentrals dosage form
■ Stability
■ Sterility
■ Free from pyrogens & toxins
■ Free from foreign particles
■ Isotonic
■ Chemical purity

5. Parentrals routes
■ The term parenteral literally means to avoid the gut (gastrointestinal tract) and refers to any
route of administration outside of or beside the alimentary tract.
■ Thus, parenteral are injectable drugs that enter the body directly and are not required to be
absorbed in the gastrointestinal tract before they show their effect.
■ Parenteral routes of administration usually have a more rapid onset of action than other routes of
administration.
■ 1. Intravenous
■ 2. Intramuscular
■ 3. Subcutaneous
■ 4. Intradermal
■ 5. Intrathecal
■ 6. Intraarterial

6. Advantages
■ Rapid onset of action .
■ Useful for emergency situation.
■ Avoid first pass metabolism.
■ Complete bioavailability.
■ Useful for patients who cannot take drugs orally

7. Disadvantages
■ Painon injection.
■ Trained person is required.
■ Difficult to reserve an an administered drugs effects. Sensitivity or allergic
reaction at the site of injection.
■ Requires strict control of sterility.
■ Require specialized equipment, device.

8. Classification
■ Based on volume
■ Small volume parenterals (SVPs)
■ Large volume parenterals (LVPs)

9. Difference between LVP and SVP
■ Small Volume parenteral
■ Volume- upto 100 ml
■ Route – any other parenteral route
■ Containers- small glass containers like ampoules and vials
■ Use –multiple dose
■ Example- Drugs in solution, emulsion and suspension
■ Large volume parenterals
■ Volume- More than 100ml
■ Route- only by IV
■ Container- Large glass/plastic containers of capacity upto 1lit
■ Use –single dose
■ Example- Saline solution (NS)

10. Small volume parenterals (SVPs)
■ The volume is generally less than or equal to 100ml.
■ They are supplied in single or multiple dose.
■ They are used to dispense most of the drugs.
■ Examples: Ampoules and vials
■ Types of Small volume parenterals
■ 1. Solution
■ 2. Suspensions
■ 3. Emulsions
■ 4. Dry Powder

11. Large volume parenterals (LVPs)
■ These are supplied for single dose having more than 100ml.
■ These are delivered through IV route.
■ These generally provides electrolyte, nutrition to the body
■ Example Normal saline.
■ Types of LVPs
■ 1. Hyper alimentation solution
■ 2. Cardiolplegic solution
■ 3. Peritoneal dialysis solution
■ 4. Irrigating solution

12. HyperalimentationSolutions
■ Administration of large amtof nutrients to patients who unable to take food
orally.
■ Formulation: Mix of dextrose,aminoacids, lipids, electrolytsand
vitamins.TotalParenteral Nutrition

13. Cardioplegic solutions
■ LVPs are used in heart surgery to prevent injury to myocardium during
reperfusion,as well as to maintain bloodless operating field.
■ Maintain the diastolic arrest.
■ Administered in cold form.
■ Slightly alkaline to compensate metabolic acidosis.
■ Hypertonic
■ Use
To minimize reperfusion injury resulting from tissue edema

14. Peritoneal dialysis solution
■ Infused continuously into abdominal cavity,bathing peritoneum & are then
continuously withdrawn.
■ Use
■ 1. Removal of toxic substances from body
■ 2. To aid and accelerate excretion normal.
■ 3. To treat acute renal insufficiency.

15. Irrigating Solutions
■ To irrigate,flush,and aid in cleaning body activities and wounds.
■ Certain IV solutions (normal saline) may be used as irritating solution, but
solution designed as irritating solution should not be used parentrally.
■ Use Treatment of serious wounds infused in to blood stream.

16. Formulation aspects
■ Therapeutic agents. Ex: Insulin, Antibiotics, Vaccines, Antipyretics, Analgesics,
Dextrose, Nacl, Electrolytes.
■ • Vehicles.
■ 1) Water. ■WFI, BWFI, SWFI.
■ 2) Aqueous vehicles. “E.g.: Ethyl alcohol, Propylene Glycol.
■ 3) Non-aqueous vehicles. E.g: Fixed oils (corn oil, peanut oil, cotton seed oil.)

17. Other Additives
1. Antimicrobial agent Ex phenol and cresol,Phenyl mercuric nitrate and
thiomersol.
2. Buffers Ex Sodium bezoate and benzoic acid
3. Antioxidants Ex Reducing agent-Ascorbic acid,Thiourea . Blocking agent-
Tocophenol, Phosphate buffer . Synergists-Ascorbic acid,Tartaric acid .
Chelating agent-EDTA
4. Stabilizers Ex Glycerine, Sodium saccharine
5. Surfactants Ex Lecithin, Propylene glycol

18. 6. Tonicity Adjuster Ex Glycerine,Lactose, Mannitol
7. Chelating agents Ex Tetrasodium edetate, Ethylene diamine tetraacetic acid
8. Co solvents Ex Alcohol
9. Bulking agent Ex Mannitol, Lactose, Sucrose, Dextran
10. Suspending agent Ex CMC,Methyl cellulose, Gelatin, Sorbitol
11. Emulsifying agents Ex Lecithin,Polysorbate 80,Gelatin

19. Physiological Consideration
■ Requirements for parenteral preparation
■ Sterile
■ Apyrogenic
■ Pure
■ Stable
■ Isohydric
■ Isotonic
■ The most convenient and simplest form of an parenteral product is an isotonic aq. Solution
which have the pH close to that of blood and body tissues i.e pH 7.4 Aqueous solution which
given through IM the release of drug may be controlled by- Increasing the vehicle viscosity
by using MC,CMC or PVP and thus decreasing the molecular diffusion and localising injected
drug.

20. ■ pH consideration
■ To adjust the pH to the physiological one (mineral or organic acids or salts) are
used.
■ The generation of pH/stability is the main step in the selection of pH in a
formulation.
■ Tolerability of formulation depends on its buffering capacity.
■ Tonicity Consideration
* An isotonic solution is one that exhibit the same effective osmotic pressure as
blood serum.
• To make the preparation isotonic with respect to blood (Glucose, Mannitol) are
used.
• For LVPs isotonicity is very essential.
• To avoid the tissue damage parenteral formulation should be isotonic with human
plasma.

21. Formulation consideration
■ Choice of excipients In pharmaceutical products the formulation should developed
by using excipients.
In parenteral products the quality, particularly in microbial terms of excipients
should be considered.
The excipients have pharmacopoeial grade.
Excipients are important to assure safety to minimise pain and irritation on
injection and to control or prolonged drug delivery.
Pharmacokinetic of drug
Pharmaceutics also affects the drug dose and the dosage regimen. A drug having a
rapid pharmaceutic profile there is a need of development of modified release dosage
formulation

22. ■ Absorption rate is depend on type of formulation.
Distribution, metabolism and excretion of drug have effect on route of
administration.
Drug solubility
. The formulation must contain a co-solvent for maintain drug in solution,if the drug
is insufficiently soluble in water.
. Solubility is the major factor that gives the concentration in the dosage form.
A dispersed system dosage form developed when simple formulation additives do
not result in the solution.
Drug stability
If the drug possesses significant degradation problems in the solution,then sterile
solid dosage form should be developed.

23. ■ Sometimes drug concentration affects the stability, affects size and the
packaging system used also. Stability determines the storage condition since it
indicates the drug expiration date.

24. Manufacturing
■ Manufacturing process (Based on the requirements of sterility)
■ Production of parenterals
■ 1. Cleaning
■ 2. Preparation of bulk production
■ 3. Filtration
■ 4. Filling of solution in ampoules or vials
■ 5. Sealing
■ 6. Sterilization and quality control test

25. Filtration
■ If product is a solution,after its compounding it should filter This process
employed for clarify solution and removing particulate matter. It is
accomplished by cold sterilization.
■ Types :-
■ Screening / Sieving-
■ Entrapment or Impaction-
■ Electrostatic attraction
■ Membrane filters are used for parenteral preparation because they have high
effective in particle retention,non-shedding property,non reactivity and have
disposal characteristics.

26. Filling
■ The solution which sterilized through filtration are to be filled under the
aseptic condition.
Filling is important for the prevention of contamination. Aseptic fill and by
using media fills it is validated.
The liquid is more easily exposed uniformly into the container. Liquid are easier
to transfer than the viscous or sticky fluids.
Filling types of liquid
1. Volumetric filling
2. Time/pressure filling
3. Netweight filling

27. Sealing
■ The filled containers should be sealed as soon as possible to prevent
contamination.It represents the final aseptic procedure.
■ Ampoules : Sealing of ampoules are done by melting of the portion of the
neck. Methods
■ 1. Pull seals method
■ 2. Tip seals
■ Vials and Bottles : By closing the opening using the rubber closure (stopper)
the glass or the plastic vials are sealed properly.

28. Sterilization
■ Sterilization of parenteral products should be done after sealing to the final
container that is called as terminal sterilization.
■ 1.Heat sterilization
*Moist heat
*Dry heat –Hot air oven-Incineration
2.Filtration sterilization
■ 3.Radiation
*Non-ionizing radiation
*Ionization radiation
■ 4.Gaseous Sterilization

29. Packaging of parenterals
■ Packaging of parenterals are done by
■ A. Glass containers
■ Type-I: Highly Resistant Borosilicate Glass
■ Type II: Treated Soda lime Glass
■ Type III: Regular Soda Lime Glass.
■ Type IV: N.P (Non-parenteral) Glass Type 4 is not used for parenteral
packaging, others all are used for parenteral packaging.

30. Plastic
■ Plastic containers are used but they face following problems
■ Permeation
■ Sorption
■ Leaching
■ Softening
■ Rubber: To provide closure for multiple dose vials, IV fluid bottles, plugs for disposable syringes and
bulbs for ophthalmic pipettes, rubber is the material of choice. Problems associated with rubber
closures are
■ Incompatibility
■ Chemical instability
■ hysical instability

31. Evaluation of parenterals
■ Sterility test method
■ Membrane filtration method method
■ Direct inoculation method
■ Clarity test
■ Leaker test
■ Pyrogen test Types a.Rabbit test b.Limulus amebocyte lysate (LAL) test