ACTIVITY 5: PREPARATION OF ASCORBIC ACID INJECTION (LABORATORY)

• ● Nasal Solutions

• Otic, Ophthalmic

• Irrigating Solutions

  • Wash or bathe surgical inclusions, wounds, or body tissues. ○ "Not for injection, For Irrigation only"

GENERAL FORMULATION OF STERILE PREPARATIONS (3)

1. WATER (SPECIFICALLY WFI) 

2. NONAQUEOUS SOLVENTS

2 types of vehicle

Water (Specifically WFI)

• Most frequently employed vehicle.

• Total solids content: 10 ppm.

• Electrolytic measurement of conductivity: not more than 1 micromho (1 megohm, approx. 0.1 ppm NaCl).

Nonaqueous Solvents

Polyethylene glycol, Propylene glycol, Fixed oils.

1. Tonicity adjusters 

2. Active/s

3. Solvent/vehicle

4. Antimicrobials

5. Preservatives

6. Buffers 

COMPONENTS (6)

Tonicity adjusters

reduce the pain of injection in areas with nerve endings.

Buffers

to maintain the required pH.

TRUE

TRUE OR FALSE

A change in pH affects stability.

Slight acidic (4-6)

Required PH in PREPARATION OF ASCORBIC ACID INJECTION

To avoid drug degradation and will not have reaction with the container.

Why acidic?

Clean rooms

Room in which concentration of airborne particles are controlled.

positive pressure air flow

Filtered air supplied: ?

HEPA filter

removes 99.97% of particles (≥0.3 µm) from air.

Diocylphthalate Test

QC test for HEPA filter.

Airlocks for entry

space with interlocked doors.

1. Compounding

2. Filtration

3. Filling

4. Sealing

GENERAL STEPS IN THE MANUFACTURE OF STERILE PREPARATIONS (4)

Spray Drying

Produces finely divided particles by spraying a mist of liquid through a heated chamber, drying immediately and collecting the dried powders in a clean receptacle.

1. Spray Drying

2. Freeze Drying

2 types of Compounding

Freeze Drying

Involves the removal of water content of an aqueous preparation.

Lyophilization

Technical term of freeze drying.

2-3 microns

Membrane filter?

0.2-0.3 microns

Sterilization by filtration?

Nitrogen gas

used in filling ampules (inert).

1. Gravity Filling – hand-operated.

2. Pressure filling – semi-automatic.

3. Vacuum Filling – fully automated.

1. hand-operated.

2. semi-automatic.

3. fully automated.

Tip/bead seal and Pull seal.

High temperature gas-oxygen flame?

1. Tip Sealing / Bead Sealing - melt top of ampule.

2. Pull Sealing - melt top of ampule and pull to seal.

3. Leaker's test (0.5 to 1% methylene blue) – not for vials and bottles.

1. melt top of ampule.

2. melt top of ampule and pull to seal.

3. not for vials and bottles.

0.5 to 1% methylene blue

Leaker's test is composed of?

Terminal Sterilization

Method of choice whenever possible in Sterilization.

1. High level of Sterility.

2. Low chance of contamination.

3. Less costly and complex

ADVANTAGES OF TERMINAL STERILIZATION (3)

1. Not for heat sensitive products causing heat degradation.

DRAWBACKS/DISADVANTAGES OF TERMINAL STERILIZATION (1)

Aseptic Processing

Components are sterilized separately and assembled.

1. Compatible for heat sensitive materials.

ADVANTAGES OF ASEPTIC PROCESSING (1)

1. Has more chance of contamination in the process.

DRAWBACK/DISADVANTAGES OF ASEPTIC PROCESSING (1)

1. Moist Heat (Steam)

2. Dry Heat

3. Ionizing Radiation

4. UV Light

5. Membrane Filtration

6. Gas

7. Tyndallization/ Intermediate Sterilization

8. Surface disinfection

STERILIZATION METHODS (8)

1. Autoclave or steam under pressure (121°C, 15psi, 15-20 minutes).

2. MOA (Mechanism of Action): protein coagulation.

3. BI (Biological Indicator): Bacillus stearothermophilus.

MOIST HEAT 

1. Autoclave or steam under pressure?

2. MOA (Mechanism of Action): ?

3. BI (Biological Indicator): ?

1. Oven (160-170°C for 2-4 hours).

2. MOA: oxidation.

3. BI: Bacillus subtilis.

DRY HEAT

1. Oven?

2. MOA: ?

3. BI: ?

1. Membrane filters (0.22 µm); for heat-labile solutions.

2. MOA: physical separation.

3. BI: Brevudimonas diminuta.

MEMBRANE FILTRATION

1. Membrane filters?

2. MOA: ?

3. BI: ?

Alkylation 

addition of alkyl groups

• also, changes in DNA, which disrupt the system of bacteria causing to inhibit growth.

1. Ethylene oxide, formaldehyde or β-propiolactone.

2. MOA: alkylation.

3. BI: Bacillus subtilis

GAS

1. Examples?

2. MOA: ?

3. BI: ?

1. Gamma or cathode rays.

2. MOA: DNA mutation.

3. BI: Bacillus pumilus.

IONIZING RADIATION

1. Examples?

2. MOA: ?

3. BI: ?

TRUE

TRUE OR FALSE

The Biological Indicator used in each method is the high level of their kind. If the highest level of bacteria is killed, it can kill all those low level bacteria under it.

Pyrogens

Lipid substances associated with a carrier molecule, usually a polysaccharide but may be a protein.

Pyrogens

Product of microbial metabolism (produces febrile reactions about an hour after injection).

1. Bacterial Endotoxin Test

2. Pyrogen Test

OFFICIAL TESTS (2)

Bacterial Endotoxin Test

Uses Limulus Amebocyte Lysate (LAL) from the horseshoe crab, Limulus polyphemus.

Endotoxin Units (EU).

In Bacterial Endotoxin Test quantities defined in?

Pyrogen Test

Done in rabbits. and nmt 10ml/kg IV within a period of nmt 10 minutes.

no rabbit shows individual rise in temp 0.6°C or above, sum does not exceed 1.4°C.

Pass in Pyrogen Test if: ?

Depyrogenation Method

Adequate washing with detergent + dry heat sterilization for glasswares and equipment.

1. Distillation

2. Adsorbents

DEPYROGENATION METHOD

1, for water. 

2. for antibiotics.