Sterile Dosage forms

Sterile Products

Dosage forms of therapeutic agents that are free of viable microorganisms

• Parenteral injections

• Opthalmic preparations

• Irrigating solutions

Sterile dosage products examples:

Parenteral injections

Injections are sterile, pyrogen-free (endotoxin units limited) preparations intended to be administered parenterally.

• Intravenous

• Subcutaneous

• Intramuscular

• Intradermal

Examples of Parenteral injections

• Sterile

• Pyrogen-free

• High purity

• Safe

Characteristics of a Parenteral Injection:

Pyrogen

Fever producing substance are termed as?

• Bacterial endotoxin (from outermembrane of gram - bacteria)

Examples of Pyrogens

• Fevers

• Chills

• Low blood pressure

Pyrogens can cause what:

• 25 degree

• Vein

Angle and Target of Intravenous

• 90 degrees

• Muscles

Angle and Target of Intramuscular

• 45 degree

• under the skin

Angle and Target of Subcutaneous

• 10-15 degree

• Into the dermal

Angle and Target of Intradermal

Insulin

Common examples of drugs administered subcutaneously

• IV fluids

• Antibiotics

• Emergency medications

Examples of drugs that are administered via intravenously

• Vaccines

• Depot medication

Examples of drugs that are administered via Intramuscularly

• Tuberculin skin test

Examples of drugs administered intradermally

Opthalmic preparations

Applied topically to the eye to treat surfaceor intraocular conditions.

• Bacterial, fungal and viral infections of eye or eyelid

• Allergic or infectious conjunctivitis or inflammation

• Elevated intraocular pressure or glaucoma

• Dry eyes

Surface or intraocular contions include:

Irrigating solutions

Fluids intended to bathe or wash body wounds, surgical openings, or body tissues, and dialysis solutions

• Wound irrigation

• Surgical irrigation

• Body tissue irrigation

• Dialysis solutions

Types of irrigation solutions

• Sterile

• Low microbial contamination

• Controlled endotoxin/pyrogens

• High purity

Irrigation solutions must be

• Contaminated water, container, equipment, solute

• Innaccurate and non-aseptic manufacturing methods

• Endotoxins

Sources and elimination of Pyrogen Contamination:

• Sterily = microorganism killed

• Pyrogen free = no badterial endotoxin left after microorganism is killed

Difference between sterility and pyrgoen free

• heating

  • 180C for 4 hours

  • 250 C for 45 mins

  • 650 C for 1 min

• Adsorbents

• Ultrafiltration

Decontamination processes

Sterilization

Process of killing microorganisms

Depyrogenation

Process of removing pyrogens

• Solute (API)

• Vehicle (solvents)

• Antimicrobial

• Tonicity adjusters

• Buffers
  
  

• Solubilizing

• Antioxidants

• Antifoaming agents

• Hydrolosis inhibitors

Formulation of Parenteral Preparations

WFI

Common vehicle (solvents for parenteral products)

Sodium chloride

Common tonicity adjusters in parenteral solutions

Buffers

Helps maintain the desired pH of the formulation

• aqueous solvents

• non aqueous solvents

2 types of solvent systems

• Purified Water, USP

• Water for Injection, USP

• Sterile Water for Injection, USP

• Bacteriostatic Water for Injection, USP

• Sterile Water for Irrigation, USP

• Ringer’s Injection

• Lactated Ringer’s injection

Aqueous solvents enumerate

• Fixed oils

• Polyethylene glycol

• Propylene glycol

Non-aqueous solvents enumerate

Purified water

what type of AQ solvent: purified by distillation, reverse osmosis and ion-exchange resin?

Water for Injection, USP

what type of AQ solvent: Same standards with purified water but is pyrogen-free.

Sterile Water for Injection

what type of AQ solvent: Pyrogen free but does have an allowable endotoxin level of nmt 0.25 USP EU/mL

Bacteriostatic Water for Injection

Sterile water for injection containing one or more suitable antimicrobial agents

Sterile water for irrigation

what type of AQ solvent: Not for injection

Ringer’s injection

what type of AQ solvent: Sterile solution of NaCl, KCl and CaCl in water for injection

Lactated Ringer’s Injection

Sterile water for injection containing NaCl, KCl, CaCl and sodium lactate in water for injection

Neonates

Bacteriostatic Water for injection is contraindicated to?

Benzyl alcohol

Common antimicrobial agent that is suitable for bacteriostatic water for injection

May cause Gasping syndrome

What happens when bacteriostatic water for injection, USP is administered to a neonate

0.25 USP EU /mL

Sterile water for injection does not allow endoxin level of nmt ?

• Physical interaction

• Chemical interaction

A container can affect a product in two main ways?

Glass

What containers are traditionally used for sterile products, many which are closed with rubber stoppers

Plastic

Generally lighter and less fragile than glass

Containers

Are direct contact with the druh

• Protect the drug

• not contaminate the drug

• not interact with the drug

Container must:

• Highly resistant borosilicate glass (I)

• Treated soda-lime glass (II)

• Soda-lime glass (III)

• General-purpose soda-lime glass (NP)

Enumerate the USP glass types

Powdered glass

Type of test for Highly resistant borosilicate glass

Water attack

Type of test for Treated soda-lime glass

Powdered glass

Type of test for general-purpose Soda-lime glass

Powdered glass

Type of test for General-purpose soda-lime glass

I

What type of glass: buffered and unbuffered aq solutions

II

What type of glass:

• Buffered aq solutions with pH below 7.0

• Dry powders, oleaginous solutions

Soda-lime glass

What type of glass: Dry powders, oleaginous solutions

NP

Not for parenterals. for tablets, oral solutions and suspensions, ointments and external liquids

1.0

mL of 0.02N H2SO4: I

• 0.7

• 0.2

mL of 0.02N H2SO4: II

8.5

mL of 0.02N H2SO4: III

15

mL of 0.02N H2SO4: NP

Standard operating procedures

Production: SOP means

Master Formula

Production: Ingredients are compounded according to what formula?

Specifications

Production: Process equipment and container components are cleaned thoroughly according to required what?

Explain the diagram of flow of materials through the production department

• Airlock

• Materials and support area

• Compounding area

• Aseptic filling

Facilities for sterile dosage manufacturing

• ante room

• Pass through hatch

Airlock is classified into two areas

• Cleaning

• Compounding

• Filtration

• Fillinf

• Sealing

• Sterilization

Procedure of preparing sterile dosage forms

• Tip sealing (bead sealing)

• Pull sealing

two types of the sealing of ampules

Tip sealing

Are made by melting sufficient glass at the tip of the ampule neck to form a bead glass and close the opening

Pull sealing

Is made by heating the neck of a rotating ampoule below the tip, then pulling the tip away to form a small, twisted capillary just prior to being melted closed

• Halogenation

• Siliconization

Sealing of bottles, cartridges and vials (two types)

Halogenation

Chemical treatment of the rubber surface, modifies surface properties and reduce friction

Siliconization

Application of the silicon base material, reduce friction and improve sliding

• Steam sterilization

• Dry heat

• Filtration

• Gas

• Ionizing radiation

Methods of sterilization: General methods

Steam sterilization

Sterilization method: Conducted in an autoclave at 121 C for 15-30 minutes and employs steam under pressure

• 121

• 15-30

Steam sterilization is conducted in an autoclave at ___ celsius for how many mins

Dry heat sterilization

Sterilization method: Conudcted in an oven at 150 170 celsius for not less than 2 hours

• 150

• 170

• 2 hours

Dry heat sterilization if conducted in an oven at ___ to ___ for not less than ___

Sterilization by filtration

Sterilization method: Depends on the physical removal of microorganisms by adsorption on the filter medium or by sieving mechanism

Gas sterilization

Sterilization method: Conducted by exposing materials to ethylene oxide or propylene oxide gas

Sterilization by ionizing radiation

Sterilization method: Techniques are available for sterilization of some types of pharmaceuticals by gamma rays and by cathode rays

• Ethylene oxide

• Propylene oxide gas

What gases are materials exposed to in gas sterilization?

• gamma rays

• cathode rays

what rays are used in sterilization by ionizing radiation

denaturation and coagulation

Mechanism of Steam sterilization

dehydration and slow oxidation

Mechanism of dry heat sterilization

Filtration

mehcanism of sterilization by filtration

Interfering with the metabolism of the bacterial cell

Mechanism of Gas sterilization

Leaker test

Quality control of parenteral products: Intended to detect incompletely sealed ampoules by producing a negative pressure within an incompletely sealed ampule, usually in a vacuum chamber while the ampule is entirely submerged in a deeply colored dye solution.

Clarity test

Quality control of parenteral products: Instrumental methods of evaluation for particulate matter in liquids utilizing the principle of light scattering, light absorption and electrical resistance

Sterility test

Quality control of parenteral products: Samples are subjected to test tube inoculation test and filtration test methods

Rabbit

Animal used in pyrogen test

3 hours

Elevation of temperature occurs within a period of how many hours when pyrgoen test is tested on a rabbit

Horseshoe crab

Limulus polyphemus is the scientific name of?

Limulus Amebocyte Lysate

LAL test means