Master Formula Record

1. PREPARATION, REVIEW & APPROVAL

Following personnel are involved in various activities like preparation, review & approval of this
Master Manufacturing Formula Record.

Specimen
Name Department Function Designation
Signature

Production Deptt MFR Preparation Chemist

Production Deptt MFR Review Asst. Manager

Quality Assurance MFR Review Asst. Manager

Quality Assurance MFR Approval Manager

2. INDEX

S.No. Process Stage Page No.

1 Preparation, Review & Approval 1
2 Index 2
3 Product Details 3
4 Dispensing of Raw Material 4
5 Bill of Raw Material 5
6 Calculation Sheet for API 6-7
7 Pre Manufacturing Instructions 8
8 Equipment / Machines Detail for Manufacturing 8
9 Manufacturing Operation 9-10
10 Sample Analysis 10
11 Batch Release 10
12 Inprocess Specifications 10
13 Bulk Reconciliation 11
14 Revision History 11
3. PRODUCT DETAILS:

Product Name
:
(Brand)
Generic Name : Clotrimazole & Hydrocortisone Acetate Cream BP
Composition:
Clotrimazole BP 1.0 % w/w
Claim :
Hydrocortisone Acetate BP 1.0 % w/w
Cream Base q.s.
Standard Batch Size : 400.00 Kgs.

Pack Size : 1 X 15 g

Shelf Life : 24 Months

Mfg. Lic. No. :

Description : Off White soft Cream packed in collapsible lami tube.

Storage Condition : Store at temperatures below 30 °C, Do not freeze.

Other Details (If any) :

4. DISPENSING OF RAW MATERIAL:

 Environmental Monitoring: Temperature and RH shall be recorded at start, end and at

1-hour interval during dispensing of Raw material.
 Environmental should within the specified limits i.e. Temperature: NMT 27 ℃, RH: NMT
60%
 Line Clearance: Take line clearance before starting in activity from QA.
 During line clearance ensure proper cleaning of area, equipment, utensils etc.
 Follow dispensing procedure as defined in the SOP.
  Warehouse person shall issue the material and QA person shall verify the material during
dispensing for material AR No., labels, quantity etc. after receiving material production
person shall verify the quantity.
 Verify AR No. before dispensing of material.
 Record the detail of each material & put the label with each material.
 During dispensing store person & QA person shall verify material details & weight of each
dispensed material.

5. BILL OF MATERIAL & DISPENSING DETAIL:

Std. Qty
Label
S. No Ingredients Spec Overages For 400 Unit
Claim
.00 kg

1 Clotrimazole BP 1.0% 5% 4.200 KG

2 Hydrocortisone Acetate BP 1.0% 5% 4.200 KG
3 Propylene Glycol IP 28.000 KG
4 Light Liquid Paraffin IP 72.728 LTR
5 Hard Paraffin Wax IP 10.800 KG
6 Micro crystalline Wax IP 10.800 KG
7 Cetomacrogol-1000 IP 8.400 KG
8 Cetostearyl Alcohol IP 33.600 KG
9 Methyl Paraben IP 0.400 KG
10 Propyl Paraben IP 0.100 KG
11 Disodium Edetate IP 0.400 KG
12 Butylated hydroxytoluene IP 0.400 KG
13 Butylated hydroxyanisole IP 0.400 KG
14 Sodium Phosphate IP 0.400 KG
15 Sodium Acid Phosphate IP 0.020 KG
16 Purified Water IP q.s. KG

 Use Clotrimazole on 100% assay basis.

 Use Hydrocortisole Acetate on 100% assay basis.
 5 % Overages added of Clotrimazole included under standard quantity.
 5 % Overages added of Hydrocortisole Acetate included under standard quantity.
 *
Make up Volume to required quantity with Purified Water quantity sufficient (q.s.).
 Ware house shall dispense material & put an identification tag in each container.
 QA shall verify the material & other details at the time of dispensing.
 Production shall check the gross weight of each material container before taking into production.
 Do not open cable ties in case of discrepancy & inform to QA immediately.

AR 6. API CALCULATION
No.1- 6.1. Clotrimazole:
AR
No.2-
Calculation for Required API:
AR
No.3-
For 400.000 Kg. of batch size, Std. Qty. is 4.200 Kg.
For …….……Kg. of Actual Batch Size, Std. Qty. is …………… Kg. (In case change in batch
size)

Required Batch Qty. (A) For AR1= Std. Qty. x100

Assay (AR1)

(A) =
……………..kg.

In case Qty. of AR1is not sufficient then.

Required Batch Qty. (A) - Available Qty. of AR1= (B)

(B) =
……………..kg.

For AR2 = Qty.Req. (B) x Assay (AR1)

 Assay (AR2)

(C) =
……………..kg.

Qty. Req. (C) - Available Qty. of AR2= (D)

(D) =
……………..kg.

For AR3 = Qty.Req. (D) x Assay (AR2)

Assay (AR3)

(E) =
……………..kg.

Total Dispensed Qty. =…………………………………………………………………

= ……………….Kg.

6.2. Hydrocortisone Acetate:

AR
No.1-
AR
No.2-
AR
No.3-

Calculation for Required API:

For 400.000 Kg. of batch size, Std. Qty. is 4.200 Kg.

For …….……Kg. of Actual Batch Size, Std. Qty. is …………… Kg. (In case change in batch
size)

Required Batch Qty. (A) For AR1= Std. Qty. x100

Assay (AR1)

(A) =
……………..kg.

In case Qty. of AR1is not sufficient then.

Required Batch Qty. (A) - Available Qty. of AR1= (B)
 (B) =
……………..kg.

For AR2 = Qty.Req. (B) x Assay (AR1)

Assay (AR2)

(C) =
……………..kg.

Qty. Req. (C) - Available Qty. of AR2= (D)

(D) =
……………..kg.

For AR3 = Qty.Req. (D) x Assay (AR2)

Assay (AR3)

(E) =
……………..kg.

Total Dispensed Qty. =…………………………………………………………………

= ……………….Kg.

7. Pre-Manufacturing Instructions:

 Read the MFR thoroughly before proceeding with operation and follow it strictly.
 Carry out all the activities related to equipment cleaning and material handling strictly as
per respective standard operating procedures.
 Label all the materials of process stages.
 Label all equipment and area with status and product label and display prominently.
 All Raw Materials labels and Equipment Cleaning status labels to be retained with the Batch
manufacturing Record.
 Get line clearance before beginning of every operation from QA.
 Ensure that environmental conditions are achieved.
 Protective mask, surgical gloves and any other safety provisions must be followed.
 Any deviation from the BMR must be done with prior approval of QA.
 Record all time in 24 Hrs format & Date DD/MM/YY or DD/MM/YYYY format.
 8. Equipment/Machines details for Manufacturing:

S.No. Equipments/Instruments Name Capacity

01 Manufacturing vessel 600.000 Ltr.
02 Oil Heating/ Wax Melting Tank 400.000 Ltr.
03 Water Heating Tank 400.000 Ltr.
04 Weighing Balance 100.000 Kg.
05 Weighing Balance 2000.000 Kg.
06 Storage Tank 500.000 Ltr.

9. MANUFACTURING:
9.1. Environmental Monitoring: Temperature and RH shall be recorded initially & at an
interval of 2 hour, during manufacturing. In mfg. area the materials are holded in the same
area therefore environmental conditions are recorded in routine general format also.

9.2. Line Clearance: Take line clearance before starting in activity.

9.3. MANUFACTURING PROCESS (A):

9.3.1. Preparation of Cream -

Process Description
STEP 1: WAX MELTING TANK (OIL PHASE):
Take all following Raw Materials together into the wax melting tank having capacity of 400
Ltr. And heat up to 80 to 90 ºC for at least 45 minutes.
Transfer the melted wax phase into the Jacketed mixing tank by passing through filter # 200
mesh size.

Ingredients Quantity
Hard Paraffin Wax 41.800 Kg
Light Paraffin Wax 329.68 LTR
Microcrystalline Wax 62.000 Kg
Cetomacrogol-1000 4.000 Kg
Cetostearyl Alcohol 4.000 Kg
B.H.T. 0.400 Kg
B.H.A. 0.400 Kg
Clotrimazole 4.200 Kg
 Add Clotrimazole into melted Wax Phase at continuous Stirring at temperature 80 ℃.

STEP 2: Heat the purified water up to the temperature 80 ℃. after this, add Sodium
Phosphate, Sodium Acid Phosphate.
Ingredients Quantity
Disodium Edetate 0.400 Kg
Sodium Phosphate 0.400 Kg
Sodium Acid Phosphate 0.020 Kg
Purified Water 238.000 Kg

STEP 3: Transfer the step 1 and step 2 into mixing tank at the temperature of 70 ± 2 ℃ of
both phases under vacuum continuous the mixing 30 minutes. After that continue cooling
and mixing till temperature reaches to 50 ℃.

STEP 4: Take propylene Glycol in a S.S. Container and dissolve methyl Paraben and Propyl
Paraben then transfer into the manufacturing.

Ingredients Quantity
Propylene Glycol 10.000 Kg
Methyl Paraben 0.400 Kg
Propyl Paraben 0.100 Kg

STEP 5: Take Propylene Glycol in SS container and titrate Hydrocortisone Acetate until
smooth slurry is formed. Then transfer the slurry into the manufacturing tank.
* Keeping approximate 1.0 kg Propylene Glycol aside for rinsing purpose.

Ingredients Quantity
Propylene Glycol 18.000 Kg
Hydrocortisone Acetate 4.200 Kg

10. SAMPLE ANALYSIS:

QA will collect the sample and send to QC for analysis.

11. BATCH RELEASE:

On the basis of review of manufacturing process, in-process checks & analytical data, QA
shall release the batch for further processing.

12. INPROCESS SPECIFICATIONS:

S.
PARAMETER SPECIFICATION LIMITS FREQUENCY
No.
1 Description White to white off soft mass filled in lamitube 2 hrs.
2 Average wt. of Net filled 15 g 91 % to 109% 30 min
3 Net wt. filled of 10 Tubes NLT 15 g NLT Label claim 2hrs.
4 Leak Test Not Permitted Not permitted 2 hrs.
5 Batch Details on Crimp Legible and clear Legible and clear 30 min

13. BULK RECONCILIATION:

Actual Weight of Final Bulk

% Yield = --------------------------------------- X 100
Theoretical batch size

(LIMIT: NLT- 99.50 %)

14. REVISION HISTORY:

S.No. Revision Number Reason

1 00 New Introduction

Ref: http://guidelines4pharma.blogspot.com/2018/07/master-formula-record.html