Types of Parentrals

DIVYA BANSAL

CLASSIFICATION OF PARENTERALS
Based on Volume: 1. Small Volume Parenterals(SVP), 2. Large Volume Parenterals(LVP).

Based On State Of Product According to USP (SVP)

1. 2. 3. 4. 5.

Solution Or Emulsion of medicament, Dry Solids or Liq. Concentrate without additives, Dry Solids or Liq. Concentrate with additives, Suspension of solids not for IV or Intra Spinal use, Dry solids on reconstitution become suspension

Small Volume Parenterals

USP Defn: An Injection that is packed in containers labeled as containing 100 mL or less

Components of SVP
1. Vehicle:
Sr. No. Type 1. 2. 3. 4. Aqueous Water Miscible Non-Aqueous Synthetic Example Purified Water,WFI,Sterile WFI,etc PEG, Glycerin, etc Vegetable Oils Ethyl oleate, Isopropyl Myristate

Component

Example

Usual Conc.
0.01% 1-2% 0.1-0.2% 0.1% 0.1% 0.1% pH 3-6 pH 6-8 pH 8-10 0.5-0.9% 4-5 % 0.1-0.5% 0.05-0.25%

2.Antimicrobial Benzalkonium Cl, Preservative Benzyl Alcohol, etc. 3. Antioxidants Water soluble : Sulfurous & Ascorbic a. Thiol derivative Water Insoluble: Propyl Gallate BHT & BHA Acetate Buffer & Citrate Buffer Phosphate Buffer Glutamate Buffer Electrolyte : NaCl Non-Electrolyte : Dextrose Poly-oxy ethylene : Tween & Pluoronic Sorbitan mono oleate : Spans

4. Buffers

5.Tonicity Adjusting 6.Surfactant

7.Chelating A.
8. Bulking agents

Di Sod. EDTA
Lactose Mannitol & Sorbitol

0.01-0.05%
1-8% 1-10%

Formulation of SVPs
Aqueous vehicle : Water For Injection(WFI) USP : Highly purified water used as a vehicle for injectable preparations which will be subsequently sterilized. USP requirement include not more than 10 parts per million of total solids. pH of 5.0 to 7.0 WFI may prepared by either distillation or reverse osmosis. Stored for less than 24hr at RT or for longer times at specific temperatures. Should be meet USP pyrogen test It may not contain any added substances. Stored in chemically resistant tank.
5

Bacteriostatic Water for Injection (BWFI) :

This type of water used for making parenteral solutions prepared under aseptic conditions and not terminally sterilized. Need to meet USP sterility test. It can contain an added bacteriostatic agent when in containers of 30ml or less

Sterile Water for Injection USP (SWFI) It contains one or more suitable bacteriostatic agents. Multiple-dose containers not exceeding 30 ml. They are permitted to contain higher levels than WFI because of the possible leaching of glass container. Sterile Water for Irrigation. Wash wounds, surgical incisions, or body tissues
7

Official Types of Injections:

1. Drug Injection Liquid preparations that are drug substances or solutions thereof. Example: Insulin Injection, USP 2. Drug for Injection Dry solids that, upon the addition of suitable vehicles, yield solutions conforming in all respects to the requirement for Injections Example: Cefamandole Sodium for Injection

3.Drug Injectable Emulsion- Liquid preparations

of drug substances dissolved or dispersed in a suitable emulsion medium Example: Propofol

4.Drug

Liquid preparations of solids suspended in a suitable liquid medium Example: Methylprednisolone Acetate Suspension upon the preparations conforming in all respects to the requirements for Injectable Suspensions Example: Imipenem; Cilastatin for Injection Suspension,
9

Injectable

Suspension

5. Drug Injectable Suspension - Dry solids that,

CHARACTERISTICS OF COMPONENTS USED IN COMPOUNDING

1. Therapeutically effective when used as the active ingredients 2. Provide maximum safety 3. Function efficiently (when used as excipient) 4. Free from contamination 5. Physically and chemically stable even after thermal sterilization 6. Produce little or no tissue irritation at site 10 of administration

Nonaqueous Vehicles Selected Vehicles must be

1. 2. 3. 4. 5. Nonirritating Non toxic in the amounts administered Nonsensitizing It must not exert a pharmacologic activity May not adversely affect the activity of the medicinal agent.

11

Other Considerations Of Selecting Nonaqueous Solvents:

1. Physical and chemical stability 2. Its viscosity (syringeability) and its fluidity 3. Its boiling point (it should be high to permit heat sterilization) 4. Its miscibility with body fluids 5. Its low vapor pressure to avoid problems during heat sterilization 6. Constant purity or ease of purification and standardization.
12

Examples of Nonaqueous Solvents:

1. Fixed vegetable oils 2. Glycerin 3. Polyethylene glycols 4. Propylene glycol 5. Ethyl oleate 6. Isopropyl myristate 7. Methylacetamide 8. Alcohol
13

Nonaqueous Vehicles
Examples of Fixed Oils Commonly Used in Injections are: 1. Corn Oil 2. Cottonseed seed Oil 3. Peanut Oil 4. Sesame Oil 5. Castor Oil and Olive Oil (occasion)

14

Compounding
Processing of sterile preparations follow normal manufacturing procedures which must be done in aseptic condition. All equipment and materials used whenever possible must be sterile

15

Filtration
Membrane filters are used for clarification when a highly polished solution is desired. The process removes particulates matter down to at least 3 microns in size. Sterilization by filtration is achieved when viable microorganisms and spores of approximately 0.3 microns are removed. Membranes with porosity ratings of 0.22 or 0.45 microns are usually specified for sterile filtration.
16

Filling and Sealing

Bulk preparations are subdivided into unit dose containers during filling. This process forces a measured volume of the preparation through the orifices of a delivery tube designed to enter the constricted opening of a container by means of gravity, vacuum or with the aid of a pressure pump. Sealing is done to retain the contents of a sterile product and will assure a tamper-proof presentation.
17

Large Volume Parenterals

Defn: LVP are Parenterals designed to provide -Fluid(water), -Calories(Dextrose soln), -Electrolytes(Saline soln), or -Combination of these. Volume 101-1000mL per day by slow intravenous infusion with or without controlled-rate infusion systems IV infusion technique is termed as Venoclysis.

18

Requirements for LVP

1. Sterile, Non Pyrogenic, Free from Particulate matter 2. Volume 101-1000mL, 3. Single dose unit, 4. No Preservative, 5. Clear solution except Fat Emulsion, 6. Isotonic, but Hypertonic also administered in TPN.

19

Types of Large Volume Parenterals

20

1.Hyperalimentation Solution
Adm. Of large amt. of nutrients to patients who unable to take food orally, at caloric intake of 4000 kCal/day. Subclavian vein cannulation : Infusion of Hypertonic soln. Formulation : mix. Of Dextrose, Amino acids, Lipids, Electrolytes, & Vitamins. Use: 1.Adm. of Life saving/sustaining drug to Comatose patient. 2.Patient undergoing t/t of GI disease
21

Total Parenterals Nutrition

Modified term for Hyperalimentation Defn: IV adm. Of Caloric, Nitrogen, & other nutrients in sufficient qt. to achieve tissue synthesis & anabolism
Content 1.Calories Sources Dextrose,

2.Nitorgen
3.Electolyte 5.Vitamin 6.Elements

Crystalline amino Acids

Na, K, Mg, Cl, Po4 Water soluble & Fat soluble Traces of Zn, Cu, Mn, Cr

22

Indication For Use of TPN

1. 2. 3. 4. 5. 6. 7. 8. GI disease, Major trauma, Septicemia, Major Abdominal Surgery, Malignancy of Small Bowel, Radiation Enteritis, Chemotherapy & Radiotherapy, Bone Marrow Transplantation, Prolonged Coma.

23

2. Cardioplegic Solutions
Are LVP used in Heart surgery to prevent injury to myocardium during reperfusion, as well as to maintain bloodless operating field. Maintains the Diastolic arrest. Adm. In cold form. Slightly alkaline to compensate Metabolic acidosis, Hypertonic Use: To minimize reperfusion injury resulting from tissue edema
24

3. Peritoneal Dialysis Solution

Infused continuously into abdominal cavity, bathing peritoneum & are then continuously withdrawn. Formulation:- Glucose , - Antibiotics as Prophylactic Use: 1. Removal of toxic substances from body. 2. To aid & accelerate excretion normal. 3. To treat acute renal insufficiency

25

4.Irrigating solutions
To irrigate, flush & aid in cleansing body cavities & wounds. Certain IV soln(Normal Saline) may be used as irrigating soln, but soln designed as Irrigating soln should not be used Paretentrally. Use: treatment of serious wounds infused into blood stream.

26

Examples Of LVP fluids

Sr. No LVP 1. 2. 3. Dextrose Inj NaCl Inj. Ringers Soln Common Name Glucose Normal Saline Soln Ringers Soln Conc. % 5,10, 20,50, 0.9, 3.5 Nacl 0.86 KCl 0.03 CaCl2 0.033 Therapeutic Use Fluid & Caloric Supplement Fluid & Electrolyte Supplement Fluid & Electrolyte Supplement

4.

Lactate Ringer Inj.

Hartmanns

Nacl-0.6, KCl-0.03 Systemic Alkaliser, CaCl2 - 0.02 Fluid & Electrolyte Na.Lactate -0.3 Replishner

5.
6.

Mannitol Inj.
IV fat emulsion

_
_

5, 10, 15, 20.

10, 15, 20

Osmotic Diuresis
Caloric

27

Difference Between SVP & LVP

PARAMETER Volume Routs Dosage Unit Technique Needle SVP 100 mL or Less IV, IM, & SC Single or Multiple( USP=max. size 30mL) Vein Puncture 1, 20-22 Gauge LVP 101-1000mL IV-LVP Single Venoclysis 1, 18-19 Gauge & Non-IV-LVP

Preservative
Buffers Formulations

Used
Used Soln, Emulsion, Suspension.

Not Used
Not Used Soln, & o/w Nutrient Emulsion

28

Continued.. PARAMETER Isotonicity Pyrogenicity Use SVP Not Essential Not Essential As Therapeutic agent, As Diagnostic agent, LVP Must Must As Nutrition, In Detoxification, Aid during surgery.

29

Quality control of parenterals:

1. Leaker test/container or closure integrity test: This is done whether the contents may leak to outside and spoil the package, when micro-organisms or other contaminants may enter. Changes in temp during storage cause expansion and contraction of glass/plastic and contents will accentuate interchange if passageway exists, even of microscopic 30 size.

The sealed containers are dipped in coloured soln of 0.5%-1% methylene blue and vaccume applied, the soln inside the leaked container shows blue colour. 2. Particulate evaluation/clarity testing: The parenteral preparations should be free from particulate matter in the range of 30-40micrometers and larger size particles. USP states that all containers should be visually inspected for visible particles and if present they are discarded. 31

In LVPs the permitted limits of particulate matter is maximum of 50 particles of 10 micrometer and larger per ml. and 5 particles of 25 micrometer and larger per ml. and no particle should have a size of 50 micrometer or more .
Clarity is tested by visual inspection of containers under light and viewed against a black and white background.
32

Instrumental methods of evaluation is based on the principles of light scattering, light absorption and electrical resistance which are used to count particle and particle size distribution. Coulter-counter method and filtration method are used for monitoring particulate matter.
33

3. Pyrogen testing: pyrogens are the metabolic products of gm-ve micro-orgs. pyrogens are lipopolysaccharides and are thermo stable. This testing is done by 2 ways: In vivo testing In vitro testing In vivo testing: The test involves the measurement of the rise in body temp of rabbit following IV injection of a sterile soln of a substance being examined.
34

The soln under test is injected into 3 healthy rabbits slowly through an ear vein in a vol of 0.5 to 10ml/kg body weight, record the temp of each rabbit in an interval of 30min for 3 hours after the injection. If the response of any rabbit is 0.6 or more ,or if the sum of the responses of the rabbits exceeds 1.4,continue the test using 5 other rabbits, if not more than 3 of 8 rabbits show individual responses of 0.6 or more, and if the sum of the responses of the group of 8 rabbits does not exceed 3.7,then the preparation passes the test.
35

Invitro testing/LALtest:
LAL is cell lysate of blood cells of horse shoe shaped crab. Blood cells of crab are called as amoebocytes as they do not have perfect shape. Soln of the preparation is made with WFI and LAL reagent is added to it ,then incubate it at 370C for 1hour-gelly consistency indicates presence of pyrogens and no gel formation indicates absence of pyrogens.

36

4. Sterility testing/microbiological tests:

Sterility testing is done to know the sterility of the sterilised material. The medium selected for culturing should extremely support the growth of the microbes. The protocol contains +ve control to check

the ability of the medium to support growth and ve control to ensure sterility of the media.
5. Safety testing: This test is essential particularly for biological products to provide additional assurance that the product does not have unexpected toxic properties.

37

38