80 Handbook of Pharmaceutical Manufacturing Formulations: Sterile Products

Amoxicillin–Clavulanic Acid Injection

Bill of Materials (Batch Size 1000 Vials)

Scale/Vial Item Material Quantity UOM
1.00 g 1 Amoxicillin as sterile Amoxicillin Sodiuma 1.225 kg
200.00 mg 2 Clavulanic Acid as sterile Potassium Clavulanateb 269.00 g
a Quantity of sterile amoxicillin sodium is calculated on the basis of assay 85% of amoxicillin (C 16H19N3O5S) on the anhydrous
basis and 4.0% for water compensation.
b Quantity of sterile potassium clavulanate is calculated on the basis of assay 75.5% of clavulanic acid (C H NO ) on the
8 9 5
anhydrous basis and 1.5% for water compensation.

MANUFACTURING DIRECTIONS 4. Sterilize the stopper and filling equipment.

5. Mix aseptically amoxicillin sodium sterile pow-
1. Clean the vials and rubber closure in automatic der and clavulanate potassium sterile powder in
machine. a suitable mixer.
2. Clean the filling accessories related to filling 6. Aseptically fill the mixed powder into the vials
machine. automatically with purging of N2 gas, to get
3. Sterilize and depyrogenize the clean, empty labeled amount of active ingredient per vial.
vials, using sterilizer. 7. Close the vials and cap with flip-off cap.

Amoxicillin Powder for Injection

Bill of Materials (Batch Size 1000 Vials)

Scale/mL Item Material Quantity UOM
250.00 mg 1 Amoxicillin as Sodium Amoxicillin equivalenta (276.88 ¥ 4), 1107.53 g
3% excess
aFor 500 mg, use 553.76 g; for 1000 mg, use 1107.53 g. Actual weight (adjusted according to potency) = weight above ¥
930/potency.

MANUFACTURING DIRECTIONS a. Wash West Compound 888 stoppers by

using rubber cycle (slow tumbling) with Tri-
Caution: Amoxicillin sodium is sensitive to moisture. This ton X-100 detergent.
powder is sterile and must be handled aseptically in a dry, b. Dry in dryer at 55∞C. Rack, inspect, and
dust-free atmosphere. RH NMT 25% at 27∞C. wrap the stoppers for autoclaving.
c. Sterilize in an autoclave for 1 h at 121∞C
1. Preparation. Wipe outer surface of each bottle
and vacuum dry with heat for a minimum
with 3A alcohol and deliver immediately to
of 4 h at a temperature not exceeding 90∞C.
sterile area.
d. Deliver to sterile area for filling.
2. Preparation of vials.
4. Filling.
a. Wash and dry Type I 20-mL or 10-mL (for
a. Sterile-fill required grams of powder (see
500 and 250 mg, respectively) glass vials
formula in table) equivalent to labeled
and load in appropriate containers for ster-
amount of amoxicillin into each clean, dry,
ilization.
sterile vial. Check fill weight of vials at ca.
b. Sterilize by dry heat at 200∞C (-0, +50°C)
5-min intervals.
bottle temperature, for 225 min (-0, +360
b. Insert sterile stopper and apply sterile over-
min). Maintain oven temperature at 225∞C
cap.
(±10∞C) for the duration of the cycle (or an
c. Remove from sterile area and pack into bulk
equivalent heat input).
containers and label each container with
c. Deliver to the sterile filling area.
product lot number.
3. Preparation of stoppers.
d. Sample for testing.
5. Finishing. Sample for testing.

© 2004 by CRC Press LLC

Sterile Pharmaceutical Formulations 81

Amphotericin B Cholesteryl Sulfate Complex for Injection

Bill of Materials (Batch Size 1000 Vials)

Scale/mL Item Material Quantity UOM
50.00 mg 1 Amphotericin B 50.00 g
26.40 mg 2 Sodium Cholesteryl Sulfate 26.40 g
5.64 mg 3 Tromethamine 5.64 g
0.372 mg 4 Disodium Edetate Dihydrate 0.372 g
950.00 mg 5 Lactose Monohydrate 950.00 g
QS mL 6 Hydrochloric Acid for pH adjustment QS

Note: This is a 1:1 molar ratio complex of amphotericin B and cholesteryl sulfate. For 100-mg dose, use 52.8 mg of cholesteryl
sulfate, lyophilized powder.

© 2004 by CRC Press LLC