Codeine Phosphate and Chlorpheniramine Maleate Syrup

Codeine Phosphate and Chlorpheniramine Maleate Syrup

Dosage Form – Oral Liquid Dosage Form

Average fill – 100 ML

Label Claim – Each 5 ml contains:

Codeine Phosphate IP             10 mg

Chlorpheniramine Maleate IP   4 mg

In a pleasantly flavored syrupy base

Colour: – Sunset Yellow FCF.

Product Generic Name: Codeine Phosphate and Chlorpheniramine Maleate Syrup.

Category: Antihistamine & Cough Suppressant

Document Checklist

1. Index
2. Batch manufacturing activity

• Attachment with BMR (Handwritten entries can be made in the table given below, in case of any extra attachments)
• Flow Chart

3. General instructions/Precautions in the dispensing area
4. Standard bill of raw material
5. Dispensing area

• Line clearance for dispensing area
• Dispensing of raw materials (in case if required, fill manually)
• Calculation sheet: (calculation for codeine phosphate, Chlorpheniramine maleate) (API)

6. General instructions/precautions in mfg. area

• Equipment cleaning record
• Wash water /rinse/swab sample analysis report (Attach if any)

7. Sugar mfg. area

• Line clearance for sugar mfg. area
• Verification of Dispensed Material
• Dispensed material label attach
• Sugar manufacturing process

8. Weighing & Checking
9. Sugar manufacturing process

• Equipment cleaning record
• Wash water /rinse/swab sample analysis report (Attach if any)
• Environmental Monitoring Of Liquid Mfg. Area

10. Liquid manufacturing area

• Line clearance of liquid mfg. area
• Verification of Dispensed Material
• Dispensed material label attach
• Manufacturing Process

11. Weighing and Checking
12. Bulk Preparation
13. in process control

• Sampling

14. Transfer to Storage Tank
15. Batch Yield
16. Batch Summary Sheet
17. Batch Release for Packing

BATCH MANUFACTURING ACTIVITIES

• Line Clearance for Dispensing
• Dispensing of Raw material
• Line Clearance for Sugar Mfg. Area.
• Sugar Mfg. Process
• Line Clearance for Liquid Mfg. Area.
• Batch Mfg. Process
• Batch Summary Sheet
• Batch Release for Packing

Flow Chart 

• Approved raw materials
• Dispensing
• Weighing Verification
• Sugar manufacturing process
• Sugar preparation with Liquid Glucose
• Transfer & filtered Sugar syrup to Mfg. tank
• Manufacturing process
• Addition of Sodium Benzoate
• Addition of Di Sodium Edetate
• Addition of Glycerin
• Addition of Saccharin Sodium
• Addition of Sodium Citrate
• Addition of Codeine Phosphate
• Addition of Chlorpheniramine Maleate
• Addition of Colour (Carmoisine & Sunset Yellow)
• The addition of Menthol dissolve in Propylene Glycol
• Addition of Liquid Flavour Raspberry
• PH adjustment with Citric Acid (Monohydrate)
• Volume makeup with purified water
• Flavour Raspberry
• In-process check of Bulk
• Bulk Sampling
• QC Analysis
• Release for packing

VERIFICATION OF DISPENSED MATERIAL

Before starting the manufacturing operation cross check the quantity of dispensed material & record the weight.

SUGAR MANUFACTURING PROCESS:   

Check the weights of all the raw materials as per the formulations sheet also check the AR No. of all the materials as per the issuance sheet.

(i) Take 400.00 Ltr. Purified water in S.S. jacketed tank and heat it to maintain a temperature up to 60 – 70°C.

ii) Take 10.0 Ltr. Purified water in a suitable S.S. container & dissolve 300 kg of Sodium Methyl Paraben & add into step no. (i) with a continuous stirrer.

Take 5.00 Ltr. purified water in a suitable S.S. container & dissolve 0.255 kg of Sodium Propyl Paraben & add into step no. (i) with continuous stirring.

Add 1026.300 kg of Sucrose into step no. (i). After the dissolution of sucrose, take 10.00 Ltr. Purified water in a suitable S.S. container & dissolve 1.080 kg of Citric Acid Monohydrate & add into step no. (i) With continuous stirring.

 Now add 400 kg of Liquid Glucose with continuous stirring in sugar syrup. Maintain the temperature up to 90 – 100°C for 30 minutes. Cool down the sugar syrup to temperature______ (45 – 55°C.).

Transfer & filter (pass through Nylon cloth 200#.) Sugar syrup to Sugar Syrup storage tank.

LINE CLEARANCE OF LIQUID MFG AREA

BMR is available & complete till Stage.

Check the “Status Board” of the area for the following details: Product Name, Batch No., Mfg. Date, Exp. Date, Batch Size, and match with BMR.

Verification of cleaning of light fixtures, return air risers, & supply air risers during line clearance at the Liquid manufacturing area.

The waste bin is emptied out and cleaned.

Line Clearance for Liquid mfg. area, verification of Preventive maintenance & Qualification status of the Manufacturing tank, Paste Preparation Kettle, Manufacturing tank, Storage tank, Transfer pump, Filter press, and Sugar syrup storage tank.

All personnel are in required apparel viz. gowning, gloves, mask, and goggles. Pieces of jewelry etc. are removed

Status label of Equipment, the material is updated and released from QC. All required utensils and area are visually cleaned

No activity (i.e. maintenance or other product handling) is being carried out in the area except mentioned in BMR/SOP.

Ensure the Room Temperature: NMT 27 ⁰C & Differential Pressure should be within NLT +6   Pascal’s.

No activity (like maintenance or another product handling) is being carried out in the area except mentioned in BMR/BPR or SOP.

Sodium Lamp is available for light-sensitive Material and is in working condition.

DATE (Date required in case of LC to be done in shift change or day of working change) 

VERIFICATION OF DISPENSED MATERIAL

Before starting the manufacturing operation cross check the quantity of dispensed material & record the weight

MANUFACTURING PROCESS

Check the weights of all the raw materials as per the formulations sheet also check the AR No. of all the materials as per the issuance sheet.

Bulk Preparation

Transfer the filtered sugar syrup from the Sugar Syrup storage tank to the Manufacturing tank (Again pass through Nylon cloth 200#.)

Take hot Purified water (60-70°c) in an S.S. container & dissolve Sodium Benzoate & add into the main bulk of step No.1 with continuous stirring

Take Purified water in an S.S. container & dissolve. Disodium Edetate & add it to the main bulk with continuous stirring.

Add Glycerin to the main bulk of mfg. tank with continuous stirring Take Purified water in a suitable S.S. container & dissolve Saccharin Sodium & add in to the main bulk with continuous stirring.

Take Purified water in a suitable S.S. container & dissolve Sodium Citrate & add into the main bulk with continuous stirring.

Take Purified water in a suitable S.S. container & dissolve Codeine Phosphate & add into the main bulk with continuous stirring.

Take Purified water in a suitable S.S. container & dissolve Chlorpheniramine Maleate & add it to the main bulk with continuous stirring.

Take Purified water in a suitable S.S. container & dissolve Colour Carmoisine Supra & add into the main bulk with continuous stirring.

Take Purified water in a suitable S.S. container & dissolve Colour Sunset Yellow & add it to main bulk of step No.1 with continuous stirring

Take Propylene Glycol in a suitable S.S. container & dissolve Menthol & add it to the main bulk with continuous stirring.

Add Liquid Flavour Raspberry flavor into main bulk with continuous stirring

pH Adjustment (If required): Take 5.00 lit. of Purified water in an S.S container & dissolve Citric Acid (Monohydrate)

Initial pH ___________

Volume consumed for pH adjustment__________

Final pH____________(pH 4.0 – 6.0)

Volume makeup with purified water up to 1500 Ltr. (STOP THE STIRRER DURING VOLUME MAKEUP). After volume makeup start the mixing for 30 minutes.

IN PROCESS CONTROL – Appearance, pH  

Sampling: SAP requisition was given by production to IPQA to collect the sample Bulk for analysis as per current specification. 

Attachments

• Rinse water/Swab Sample intimation cum analysis report (BMR copy)
• Additional material requisition slip
• Additional material dispensing slip
• Bill of raw Material requisition slip sheet generated by SAP
• Dispensing tag raw material generated by SAP
• Bulk/ intimation
• Bulk COA
• All in-process Label
• Rejection Note (if any)
• Preventive & breakdown record (if any)
• Deviation & change control record (if any)
• The calculation sheet attached was generated by SAP

BATCH RELEASE FOR PACKING

The batch manufacturing record is reviewed, all process parameter & in-process specification Comply / does not comply with the specification, and therefore batch is released/Not Released for Packaging.