MASTER FORMULA OF Ciprofloxacin, Fluocinolone and Clotrimazole Cream 

Ciprofloxacin, Fluocinolone and Clotrimazole Cream

Fluocinolone acetonide + Ciprofloxacin + Clotrimazole is a combination of three medicines: Fluocinolone acetonide , Ciprofloxacin and Clotrimazole. Fluocinolone acetonide is a steroid medicine. It blocks the production of certain chemical messengers (prostaglandins) that make the affected area red, swollen and itchy. Ciprofloxacin is an antibiotic. It kills bacteria by preventing them from reproducing and repairing themselves. Clotrimazole is an antifungal which stops the growth of fungi by preventing them from forming their own protective covering.

Clotrimazole is an antifungal with a broad spectrum and is structurally derived from imidazole and triazole. Fluocinolone acetonide is a corticosteroid that presents a high lipophilicity. It has been used extensively in dermatological preparations to provide relief of inflammatory dermatosis, dermatitis, psoriasis, hypertrophic
tissues, keloid tissues, and atopic dermatitis. Ofloxacin is an antibiotic of the fluoroquinolone family of medications useful for the treatment of a number of bacterial infections. Ofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.

Therapeutic Indication
● Atopic Dermatitis
● Psoriasis of the scalp
● Dermatosis
● Fungal and bacterial infection of the dermal
● Candidiasis

Pharmacology
Mechanism of Action:

Ofloxacin: DNA replication requires DNA gyrase and topoisomerase IV. DNA gyrase allows the untwisting required to replicate one DNA double helix into two.
Topoisomerase IV provides stability to the unwind DNA during replication. Ofloxacin inhibits these two and inhibits DNA replication thereby inhibiting normal cell division.
Fluocinolone acetonide is a synthetic anti-inflammatory corticosteroid. It can be inferred that it acts by inhibiting edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, collagen deposition, and scar formation. Fluocinolone acetonide presents a high binding
affinity for the glucocorticoid receptor. After binding the receptor, the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements in the promoter region of the target genes.
Clotrimazole inhibits fungus growth by inhibiting division. It alters the permeability of the fungal cell wall by inhibiting the biosynthesis of ergosterol and other sterols required for cell membrane production which eventually leads to cell death. It also inhibits the activity of enzymes within the cell.

EXPERT ADVICE FOR FLUOCINOLONE ACETONIDE + CIPROFLOXACIN + CLOTRIMAZOLE

• Fluocinolone acetonide + Ciprofloxacin + Clotrimazole must be applied as a thin layer on the affected area as prescribed by your doctor.
• Do not use this medicine more often or for longer than advised by your doctor.
• Before each application, wash the affected area with soap and water and dry well.
• Avoid getting it in the eyes, mouth or nose. Rinse with cold water if you accidentally get it in these areas.
• Do not cover the area being treated with airtight dressings such as bandages unless directed by a doctor, as this may increase the risk of side effects.
• Inform your doctor if the treated skin area does not improve after 2-4 weeks of treatment.

FAQ FOR FLUOCINOLONE ACETONIDE + CIPROFLOXACIN + CLOTRIMAZOLE

PURPOSE: This Master Formula is written to describe the formulae, manufacturing procedure, specifications, and packing details of the dosage form.

SCOPE: This MFR is performed and is applied during the manufacturing of dosage form.

RESPONSIBILITY / ACCOUNTABILITY: It is the responsibility of  Manufacturing Chemist to follow and adhere to this SOP. The Production Pharmacist, QC/QA Manager are accountable for the strict adherence to the master formula.

COPY ISSUED TO:

1. Master Copy: Manager Quality Assurance

2. Copy No.   1:     Production Pharmacist

3. Copy No.  2:     Manager Quality Control

4. Copy No.  3:     Ointment Section

COMPOSITION:

SPECIMEN OF UNIT CARTON: 

EQUIPMENTS TO BE USED: 

 RAW MATERIALS:-

 PACKING MATERIALS:-

 MANUFACTURING SPECIFICATIONS:

Average fill of each Tube is 10 grams.

Weight variation limit allowed in each filled Tube is + 200 mg.

Melt the ointment base at the maintained temperature 70˚ C.

Use accurate and weighed quantity of water to make up the final weight of cream.

Add Fluocinolone Acetonide to the bulk batch at room temperature.

Colloid the cream till uniform particle size is achieved.

The temperature of primary area should not exceed 30˚C.

Yield:

Theoretical Yield is 30000 Tubes.

Expected Practical Yield is 30000 + 2% Tube.

Packing Details:

Transfer the cream from storage tank to Aluminium Tube Filling & Crimping Machine and start filling and then Crimping of the tubes as per its SOP.

Pack the filled tubes in each unit cartons.

Pack such 12 tubes in one outer carton.

Seal the outer carton with cello tape.

Pack such 36 outer cartons in specified corrugated box  to give a pack size of 36 x 12 x 10g tubes.

Seal the each corrugated box with adhesive tape and label it properly by affixing the specified label.

MANUFACTURING PROCESS:

Melt 10 kg of Ceto Macrogol – 1000, 30 kg of Cetocetyl Alcohol, 15 kg of Liquid Paraffin Light, 48kg of White Petroleum Jelly in a Steam Heat Wax Melting Vessel by operating it as per its SOP at temperature 70˚C.

Heat 191.0kg water at 70˚ C in Water Vessel by operating it as per its SOP.

Filter and transfer the melted base through Stainless Steel Sieve no. 100 to the mixing vessel and start the machine as per its SOP.

Dissolve 0.600 kg of Methyl Paraben Sodium in 2 kg of hot water and transfer it to the bulk batch.

Dissolve 0.300 kg of Propyl Paraben Sodium in 1 kg of hot water and transfer it to the bulk batch.

Dissolve 0.300 kg of E.D.T.A. in 3 kg of hot water and transfer it to the bulk batch.

Dissolve 0.600 kg of Sodium Metabisulphite in 3 kg of hot water and transfer it to the bulk batch.

Take 30 kg of hot water and suspend 3.150 0kg of Clotrimazole and pass it through Colloidal Mill to achieve the slurry of uniform particle size by operating it as per its SOP and transfer it to the bulk batch.

Take 20 kg of hot water and suspend 1.830 kg of Ciprofloxacin Hydrochloride and pass it through Colloid Mill to achieve the slurry of uniform particle size by operating it as per its SOP and transfer it to the bulk batch.

Slowly add rest of water to the bulk batch.

Cool the cream to the room temperature by running the water in the jacket of Mixer vessel.

Triturate 78.000 g of Fluocinolone Acetonide in mortar-pestle with 2kg of Liquid Paraffin light by the gradually addition of the same. Add this to the bulk batch.

Mix the whole batch for 90 minutes while running the water in the jacket.

Send the sample to Quality Control Department for bulk testing.

After approval from Quality Control Department, transfer the cream to the storage tank. 

IN-PROCESS CONTROLS: 

The following in-process controls should be maintained during the processing:

Check Raw materials used for manufacturing purpose are all approved materials and have ‘Released’ labels fixed on it.

All weighed Raw materials should be counter-checked by Manufacturing Chemist. If any discrepancy is noticed, it should be immediately brought to the notice of Production Pharmacist and QC/QA Manager.

Physical characteristics of Raw material like colour, odour, and consistency are checked before compounding.

The total weight of bulk ointment / cream should be checked in the presence of Assistant Manufacturing Chemist and record the same in Batch Manufacturing Record.

pH of the bulk should be checked and it should be with in specified limits.

Bulk sample should be sent for analysis to Quality Control Department before starting the filling and sealing stage.

While the tube filling operation is on, the Assistant Manufacturing Chemist should check weight of net filled quantity per tube at the interval of 30 minutes by checking the tare weight of empty tube and gross weight of the filled tube. Record for the same should be kept in Batch Manufacturing Record.

The ‘fill weight’ of ointment or cream per tube should not be less than the labelled amount.

Limit for Weight Variation:  Weight claimed on the carton + 200 mg

Manufacturing Chemist will also ensure that the crimping of the filled Aluminium tubes, sealing of plastic tubes is appropriate and embossing of batch number and manufacturing date is conspicuous. Also the quality of embossing will be controlled by adjusting pressure exerted by the jaws, so that pinholes are not developed on the embossed letters / numbers.

The inner and outer cartons should be checked thoroughly for proper batch coding.

Manufacturing Chemist and Production Pharmacist should randomly check that the correct no. of inner cartons are being packed in each outer cartons and also the correct number of outer cartons in each shipper is exactly the same as that shown in proof.

Intimation should be sent to Quality Control Department for finished product sampling and testing.

After the completion of filling and packaging, the coded cartons should be accounted for and rejected printed material should be destroyed in the presence of QC/QA Manager. Maintain the destruction of the same in the Batch Manufacturing Record.

It will be ensure that filling or packaging equipment has been properly cleaned.

Filling or packaging of next product should be commenced only after getting the ‘Line Clearance’ of the previous product, from the Quality Control Analyst.

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