CHANDRA MOULI DUBEY M.Pharm.(PHARMACEUTICS) (1st SEM )

Under supervision of Mrs. Nimisha Srivastva

AMITY INSTITUTE OF PHARMACY

STERILE PRODUCTS

Sterile products are the dosage forms of therapeutic agents that are free of viable microorganisms. Principally, these include parenteral, ophthalmic and irrigating preparations of these parenteral products are unique among dosage forms of drugs because they are injected through the skin or mucous membrane into internal body compartments. Thus because they have circumvented the highly efficient first line of body defense ,i.e. the skin and mucous membrane, they must be free from microbial contamination and toxic components ,as well as possess an exceptionally high level of purity1. Although parenteral are comes under category of sterile products but all sterile products can’t say as parenterals.

EXAMPLE OF SOME STERILE PRODUCTS ARE:- Nasal & ear products

Ophthalmic solutions and ointments

Inhalation/ Aerosols.

Bladder irrigating solutions

Suppositories

PARENTERAL PRODUCTS:-

Parenteral (Gk, para enteron, beside the intestine) dosage forms differ from all other drug dosage forms, because they are injected directly into body tissue through the primary protective systems of the human body, the skin, and mucous membranes.

As per USP Parenteral articles are preparations intended for injection through the skin or other external boundary tissue, so that the active substance they contain are administered using gravity or force, directly into a blood vessel, organ, tissue or lesion.

Parenteral preparations are administered in systemic circulation by following:- INTRADERMAL OR INTRACUTANEOUS INJECTIONS INTRASYNOVIAL AND INTRA-ARTICULAR

INJECTIONS INTRATHECAL INJECTIONS(CSF) SUBCUTANEOUS AND INTRAMUSCULAR

INJECTIONS SUBCUTANEOUS INFUSIONS/PUMPS INTRA-ARTERIAL INFUSION ADMINISTRATION PERFUSION (EXTRA CORPOREAL OR ISOLATION

PERFUSION) ADMINISTRATION INTRAOSSEOUS INFUSION (IO)

PARENTERAL PRODUCTS MUST HAVE:- All products must be sterile. All products must be free from pyrogenic (endotoxin)

contamination. Injectable solutions must be free from visible

particulate matter. This includes reconstituted sterile powders.

Products should be isotonic, although strictness of isotonicity depends on the route of administration. Products administered into the cerebrospinal fluid must be isotonic .

ADVANTAGES OF PARENTERAL ADMINISTRATION:- An immediate physiological response can be achieved

if necessary, which can be of    prime consideration in clinical condition such as cardiac arrest, asthma and shock .

Parenteral therapy is required for drugs that are not

effective orally or that are destroyed by digestive secretions such as insulin other hormones and antibiotics.

ADVANTAGE CONT….

Drug for uncooperative, nauseous or unconscious

patients must be administered by injection.

When desirable, parenteral therapy gives the

physician control of the drug since the patient must

return for continued treatment, also in some cases the

patient cannot be relied upon to take oral administration.

Parenteral administration can results in local effect for

drugs when desired as in dentistry and anesthesiology.

FORMULATION OF PARENTERAL:-

Parenteral drugs are formulated as solutions, suspensions, emulsions, liposome, microspheres, nanosystems, and powders to be reconstituted as solutions.

WATER WATER-MISCIBLE VEHICLES NON-AQUEOUS VEHICLES SOLUTE ADDED SUBSTANCES

(SURFACTANTS,TONICITY ADJUSTER,ANTIOXIDANTS,PRESERVATIVE)

ANTIMICROBIAL AGENTS

QUALITY CONTROL OF PARENTERALS

Drug products administered by injection are characterized by three qualities possessed by no other type of pharmaceutical dosage form: sterility, freedom from pyrogenicity, and freedom from particulate matter. Method involved in quality control are –

STERILITY TEST SAMPLING

CULTURE MEDIA

Ex.- Fluid Thioglycollate Medium (FTM)

Soybean-Casein Digest (SCD)

COMPOSITION OF FTM

**pH after sterilization 7.1+ 0.2

Ingredients Quantity Property

L-C ysteine 0.5 g Antioxidant

Agar, granulated (moisture Nutrient and viscosity

content 15%)

0.75 g Nutrient and viscosity inducer

Sodium chloride 2.5 g Isotonic agent

Dextrose 5.5 g Nutrient

Yeast extract 5.0 g Nutrient

Pancreatic digest of casein 15.0 g Nutrient

Sodium thioglycollate or thioglycollic acid

0.5 g0.3 ml

Antioxidant

Resazurin sodium solution (1:1000), freshly prepared

1.0 ml Oxidation indicator

Purified water QS 1000 ml

A) DIRECT TRANSFER METHOD

The DT method is the more traditional sterility test

method. Basically, the DT method involves three steps:

1. Aseptically opening each sample container from a recently

sterilized batch of product.

2. Using a sterile syringe and needle to withdraw the required

volume of sample for both media from the container

3. Injecting one-half of the required volume sample into a

test tube containing the required volume of FTM and the

other half volume of sample into a second test tube

containing the required volume of SCD.

B) MEMBRANE FILTRATION METHOD

Five basic steps are involved in the use of the MF sterility test method:

1.The filter unit must be properly assembled and sterilized prior to use.

2.The contents of the prescribed number of units are transferred to the filter assembly under strict aseptic conditions.

3.The contents are filtered with the aid of a vacuum or pressure differential system.

4. The membrane is removed aseptically and cut in half.

5.One-half of the membrane is placed in a suitable volume (usually 100 ml) of FTM, and the other membrane half is placed in an equal volume of SCD.

 

PYROGEN TESTING

After a complete arrangement allow injecting the sample by following ways as USP:-

1. Rest the ear against the fingers of the left hand and hold the ear down with the thumb.

2. Introduce the needle with the bevel edge upward near the tip of the ear vein.

3. Slowly inject a small amount of sample to determine if the needle is within the vein. If not, a bubble will form or backpressure will be felt. Withdrawing the needle slightly and moving it forward again should place it in proper position.

4.Maintain steady pressure on the syringe plunger and complete the injection within 10 minutes. Usually, the time duration for infusion is much less than 10 minutes.

5. Withdraw the needle and apply pressure with the thumb at the site of injection to retard bleeding and scarring.

FIG NO. 01RABBITS SITUATED IN INDIVIDUAL RESTRAINING BOXES.

PARTICULATE MATTER TESTING

VISUAL INSPECTION: MANUAL METHODS

FIG NO. 02 VISUAL INSPECTION BY LIGHT BEAM

PACKAGE INTEGRITY TESTING

Pour the ampules in

1% Methylene Blue Solution

Rinsing well if leakage found

Color from the dye will be visible within a leaker

WATER USED IN PHARMACEUTICALS-

Purified water

Water for injection(WFI)

Sterile purified water

Sterile water for injection

Bacteriostatic Water for injection

Sterile water for irrigation

WATER FOR INJECTION

FIG NO 03 A SCHEMATIC OF A TYPICAL PROCESS USED TO CONVERT POTABLE WATER TO WATER FOR INJECTION

THERE ARE TWO BASIC TYPES OF WFI DISTILLATION UNITS:- VAPOR COMPRESSION DISTILLATION

FIG NO. 04 VAPOR COMPRESSION DISTILLATION

•THE MULTIPLE EFFECTS STILL

REVERSE OSMOSIS (RO)

FIG NO. 05 REVERSE OSMOSIS

ENVIORNMENTAL CONTROL OF PARENTERAL UNIT

Contaminants, such as dust, lint, and other particles and micro-organisms, are found floating in the air, lying on counters and other surfaces, attached to clothing and body surfaces of personnel, concentrated in the exhaled breath of personnel, and deposited on the floor. The design and control of an aseptic area is directed toward reducing the presence of these contaminants, so they are no longer a hazard to aseptic filling. The classifications used in pharmaceutical practice normally range from Class 100,000 (Grade D) for materials support areas to Class 100 (Grade A) for aseptic areas.

CLASSIFICATION OF GRADES-Grade Classification Pharm. Eng.

Description per m 3 >/= 0.5 μm

per m 3 >/= 5 μm

A 100 CRITICAL 3500 0

B 100 CLEAN 3500 0

C 10,000 CONTROLLED 35,000 2,000

D 100,000 PHARMACEUTICAL 3500000 20,000

ANY DOUBT THROW IT OUT

THANK YOU!..