Description:DESCRIPTION

TECHNICAL FIELD
The invention belongs to the field of drug preparation for the Iron Deficiency and the process patent of Ferric Carboxymaltose Lyophilized Injection.The invention belongs to the field of drug synthesis and preparation processes, and relates to a preparation process of a carboxyl ferric maltose injection in the lyophilized form which is the novel preparation of the applicant.

BACKGROUND
Iron Deficiency causes variety of diseases in the human body for example: Anemic. It is clear that in the human body the blood carries molecule hemoglobin, a protein in RBCS which carries blood to the various parts of the human body, which mainly constituted of the Iron(Fe) pigment to which the heme group comprises an iron atom at the centre with the help of complex formed by nitrogen atoms the oxygen is capable of binding to the above said heme group.
PRIOR ART:-
Carboxymaltose ferric iron (FCM) is an iron-carbohydrate complex that is very commonly used to treat patients with ID or IDA who are not undergoing dialysis. It is marketed under the trade name Injectafer® in the United States and under the trade name Ferrinject® in the EU and many other countries. A typical treatment regimen for FCM is a two dose of 750 mg elemental iron administered as an intravenous infusion at weekly intervals (this is an approved use according to the US label), or 1000 mg elemental. It consists of either an iron infusion or an additional dose of 500-1000 mg one week later, which is the approved usage according to the EU label.

USES OF THE INVENTION:-ADVANTAGE OF THE INVENTION
The use of the injection as the lyophilized form improves the therapeutic value of the drug. By virtue of its lyophilized form the affinity of the oxygen molecules to bind to the heme protein group also increases substantially in the RBC's.

DETAILED DISCRIPTION:-
1.1 RAW MATERIAL

S. No. Ingredient Spec. Label Claim Each ml
Std.
Qty./ 1000 Nos
Rqd. Qty.
A.R.N Issued Qty.
( In Kg ) Wt.
by
Store Ckd.
by
QA
Ckd.
By
PRD.
Gross
wt. Tare wt. Net wt.
1. Ferric Carboxymaltose. Eq. to Iron IH 50 mg 2.22 kg 2.22 kg
3. Meglumine IH 0.0125 mg 0.125 kg 0.125 kg
4. Hydrochloric acid IP qs
5 Sod. Hydroxide IP qs
6. Water For Injection IP q.s. ---- q.s to 5.0ltrs

Note: 1.Meglumine is an organic base used as a pH-adjusting agent and solubilizing agent.
2. If API soluble clearly in WFI in that case pH will set by NaOH /HCl.
3. Fill volume for Lyo 5.0 ml

1.2 CALCULATIONS:(EXAMPLE)

(i) FerricCarboxymaltose. (10 ml)
Required Quantity of Ferric Carboxymaltose

Each ml contains: 50 mg elemental iron as Ferric Carboxymaltose

1.3 Label Claim Calculations:

Claim amount× Batch Size×100×100
Qty. of Drug =_______________________________
Assay X (100-Y) X 1000 X 1000

Where:

X: Assay/Potency
Y: LOD/Water contains

=500 × 1000×100×100
24.1 ×(100-6.6) x 1000 x 1000

= 2.2219 kg

2.0 DESCRIPTION OF MANUFACTURING PROCESS

Sr. No. Manufacturing Process Qty. Time Done by Checked by/ date
From To
2.1 Preparation of Bulk Solution:
2.1.1 Take Water for injections upto 80 to 90 0C in a clean and sterilized solution preparation tank and cool upto room temp. With continuous N2 purging (0.5 – 1.0 Kg/cm2).
2.1.2 Adjust WFI temp between 25 0C to 300C Add partial qty. of Meglumineand add dispensed qty. ferric Carboxymaltose and mix with continuous N2 pursing and stirring (at 3000 – 5000 rpm).
2.1.3 Add required qty.of Maglumine to adjust the pH of the solution with NaOH/HCl 3.1.2between 6.0 to 7.0
2.1.4 Make up the solution volume upto 5.0ltrs.
5.0ltr.
2.1.5 Send the sample to QC for bulk analysis and start filtration after the batch is released by QA. 10ml
2.1.6 Filter the solution using sterilized 293 mm stainless steel filtration assembly fitted with pre filter 0.45 micron and 0.45 micron PVDF membrane filter at nitrogen pressure of 1-2 Kg /cm2. Adjust the fill volume and Fill 5.0ml solution into 10 ml vial and do the half bunging and load the filled Vials into Lyo.

2.1.7 Lyophilisation Process:

Ferric Carboxymaltose Injection 50 mg/ml fill volume 5 ml for lyophilization (reconstituted volume 10 ml)
Self temp 5
1 Freezing Process -10 15 30 Not required Not required
-20 15 30 Not required Not required
-35 30 60 Not required Not required
-45 60 180 Not required Not required
2 Primary Drying -35 60 480 150
-20 60 360 150
-10 30 240 150
3 Secondary drying 0 30 240 150
10 30 300 100
25 30 240 100
35 30 180 100
Total duration in minute 390 2340
2730
Total cycle process time in hrs 45.5

2.3 Sealing
2.3.1 Carry out sealing of Vials under LAF. Ensure the sealing should be smooth.

2.4 Optical Inspection
2.4.1 Optical Inspection shall be carried out by manual method

2.4.2 Trained operators shall carry out the visual optical inspection

2.4.3 The presence of colored particles shall be detected by viewing the Vials against the white background

2.4.4 Keep the rejected vials with respect to the rejection type in designated place till accountability

2.4.5 Collect the accepted/rejected vials in different crates, pre-labeled showing the status

3.4.6 Optical Inspection supervisor shall carry out random test for 5% quantity of the total inspected good vials

2.4.7 The inspected vials shall be finally counter checked randomly by IPQA chemist for 10% quantity of the total inspected good vials

, Claims:CLAIMS
We hereby claim as under
1. A process for preparing Iron Carboxymaltose in the Lyophilized Form by using Ferric Carboxymaltose (Equal to Iron), Meglumine, Hydrochloric Acid, Sodium Hydroxide, Water For Injection as a raw material. The PH is maintained at 3.0 to 5.0 of FCM & methods comprises of following steps:
Take Water for injections upto 80 to 90 0C in a clean and sterilized solution preparation tank and cool upto room temperature with continuous N2 purging (0.5 – 1.0 Kg/cm2) than adjust WFI temp between 25 0C to 300C Add partial quantity of Meglumineand add dispensed quantityferric Carboxymaltose and mix with continuous N2 pursing and stirring (at 3000 – 5000 rpm) than add required quantity of Maglumine to adjust the pH of the solution with NaOH/HClbetween 6.0 to 7.0Make up the solution volume upto 5.0liters and send the sample to QC for bulk analysis and start filtration after the batch is released by QA than filter the solution using sterilized 293 mm stainless steel filtration assembly fitted with pre filter 0.45 micron and 0.45 micron PVDF membrane filter at nitrogen pressure of 1-2 Kg /cm2 and adjust the fill volume and Fill 5.0ml solution into 10 ml vial and do the half bunging and load the filled Vials into Lyophilized. Where we carry out sealing of Vials under LAF and ensure that the sealing is smooth and thereafter Optical Inspection shall be carried out by manual method and then trained operators shall carry out the visual optical inspection thereafter the presence of colored particles shall be detected by viewing the Vials against the white background and keep the rejected vials with respect to the rejection type in designated place till accountability and collect the accepted/rejected vials in different crates, pre-labeled showing the status.Optical Inspection supervisor shall carry out random test for 5% quantity of the total inspected good vials.The inspected vials shall be finally counter checked randomly by IPQA chemist for 10% quantity of the total inspected good vials.

2. The process for preparing Lyophilized Form as claimed in Claim 1 followed by the Freezing Process whereby the temperature is set in the range of -10 to -45 and ramp duration varies from 30 to 60 and soak duration varies is set from 60 to 180.

3. The process for preparing Lyophilized Form as claimed in Claim 1 is followed by Primary Dying whereby the temperature is set in the range of -35 to -10 and ramp duration varies from 60 to 120 and soak duration is setfrom 480 to 600.

4. The process for preparing Lyophilized Form as claimed in Claim 1 is followed by Secondary Dying whereby the temperature is set in the range of 10 to 30 and ramp duration varies from 60 to 90 and soak duration is setfrom 600 to 900.