by MULTIMEDIA DISSOLUTION PROTOCOL
OF
CITALOPRAM 20 MG AND 40 MG TABLETS
| Department | : | Quality Control |
| Product Name | : | Citalopram 20 mg and 40 mg Tablets |
| Study | : | Multimedia Dissolution Profile |
| Protocol No. & Revision No. | Effective date | Reason |
| New Document |
Table of contents :
| Sr. No. | Subject | Page No. |
| Protocol Approval | ||
| Objective | ||
| Scope | ||
| Responsibility | ||
| Product Profile | ||
| Background | ||
| Product Detail | ||
| Methodology | ||
| Incident/Deviation | ||
| Summary/Final conclusion/Recommendation | ||
| Abbreviation |
- Protocol Approval:
Prepared By:
| Functional Area | Name | Designation | Signature / Date |
| Quality Control |
Reviewed By:
| Functional Area | Name | Designation | Signature / Date |
| Quality Assurance | |||
| Head Quality Control |
Approved By:
| Functional Area | Name | Designation | Signature / Date |
| Head QA |
Customer Approved By:
| Functional Area | Name | Designation | Signature / Date |
- Objective:
The objective of this protocol is to perform the multimedia dissolution profile of Citalopram 20 mg and 40 mg tablets on single validation batch (test product).
- Scope :
Multimedia dissolution profile study of Citalopram 10 mg, 20 mg and 40 mg were already performed with R & D sample against the reference sample as per protocol. This dissolution profiling study now shall be performed on single validation batch for Citalopram 20 mg and 40 mg. This protocol is applicable for the presentation of analytical results of dissolution profile to be performed in QC laboratory.
- Responsibility of Team:
| Departments | Responsibilities |
| QC | Preparation & Review of Protocol. |
| Analysis of samples and recording of data. | |
| Compilation and checking of data | |
| Preparation of Summary Report. | |
| To impart training of protocol to concerned department/persons. | |
| QA | Review and approval of protocol. |
| Co-ordination with QC to carryout multimedia dissolution study | |
| Review of data and summary report. |
- Product Profile:
| Category | Antidepressant |
| Active Ingredient | Citalopram Hydrobromide |
| Strength | Each coated tablet contains: Citalopram Hydrobromide 20 mg & 40 mg |
| Method Reference |
- Back Ground:
- Multimedia dissolution profiling was performed on R & D batches as per protocol. This dissolution profile study now shall be performed on single validation batch.
- As mentioned in this protocol multimedia dissolution study shall be performed in QC laboratory.
- Multimedia dissolution study shall be performed for Citalopram 20 mg and 40 mg tablets.
- At least 12 dosage units (e.g. tablets) of each batch shall be tested individually, and mean and individual results reported.
- The batches are tested using the same apparatus and, if possible, on the same day.
- Suitable spaced time points (excluding zero time point) to provide a profile for each batch 20 mg & 40 mg) are at 05, 10, 20, 30 and 45 minutes.
- The Multimedia dissolution study of Citalopram Hydrobromide tablets shall be performed on medium as follows.
- Purified water
- pH 6.8, Phosphate buffer.
- pH 1.2, Acid,0.1M Hydrochloric acid
- pH 4.5, Acetate Buffer
- The percent release of dissolved drug shall be calculated at each time interval.
- Product Details:
Sample Manufacture at Galpha Laboratories Limited
| Product Name | Batch No. | Manufacture date | Expiry date |
| Citalopram 20 mg Tablets | |||
| Citalopram 40 mg Tablets |
- Methodology:
Chemical, reagents and filters:
Table 1.0: Chemical, reagents and filters
| Sr. No | Material /Chemicals/Filters | Grade |
| 1. | Potassium dihydrogen phosphate (KH2PO4) | AR Grade |
| 2. | Ortho phosphoric acid | HPLC Grade |
| 3. | Water | HPLC Grade or Milli Q water |
| 4. | Methanol | HPLC Grade |
| 5. | Acetonitrile | HPLC Grade |
| 6. | 0.45 µm membrane filter | Millipore or Equivalent |
| 7. | 0.45 µm Nylon filter | Millipore or Equivalent |
| 8. | Hydrochloric Acid | AR Grade |
| 9. | Sodium Hydroxide Pellets | AR Grade |
| 10. | Sodium Acetate | AR Grade |
Dissolution Parameters:
Apparatus : With paddles
Agitation speed : 75 rpm
Mean volume per vessel : 900 ml
Temperature of the medium : 37 ± 0.5ºC
Duration of test : 30 minutes
Sampling time point : 05, 10, 20, 30 and 45 minutes,
Preparation of Dissolution median as follows: (as per BP/USP/Ph. Eur. pharmacopoeia)
- Purified Water
- Phosphate buffer solution pH 6.8:
Dissolve 27.22 g of potassium dihydrogen phosphate in water and dilute with water to 1000 ml. Place 50 ml of the monobasic potassium phosphate solution in a 200 ml volumetric flask, add the 22.4 ml of 0.2 M NaOH, then add water to volume.
- 0.1 M Hydrochloric acid: (Principal medium)
Dilute 8.5 ml of hydrochloric acid with sufficient water to produce 1000 ml. adjust the volume as per required volume.
- Acetate buffer solution pH 4.5:
Dissolve 77.1 g of ammonium acetate in water. Add 70 ml of glacial acetic acid and dilute to 1000 ml with water.
Blank: Dissolution medium.
Sample Preparation Procedure:
Transfer 900 ml dissolution medium into each of the vessels and warm to 37ºC ± 0.5ºC.
Prepare a Citalopram calibration curve with 7 different concentration points between 0.0067 mg/ml and 0.044 mg/ml, using Citalopram Hydrobromide WS (with the knowledge that 1 mg of Citalopram base is equivalent to 1.249 mg of Citalopram Hydrobromide).
Linearity solutions
Stock linearity solution 1:
Accurately weigh 85.0 mg of Citalopram Hydrobromide WS and dilute to 50.0 ml with dissolution medium.
Stock linearity solution 2:
Accurately weigh 69.0 mg of Citalopram Hydrobromide WS and dilute to 50.0 ml with dissolution medium.
Linearity solution 1:
(Citalopram base concentration: 0.0068 mg/ml). Dilute 5.0 ml of linearity stock solution 1 to 100.00 ml with dissolution medium. Dilute 1.0 ml of this solution to 10.0 ml.
Linearity solution 2:
(Citalopram base concentration: 0.0088 mg/ml). Dilute 2.0 ml of linearity stock solution 2 to 25.0 ml with dissolution medium. Dilute 5.0 ml of this solution to 50.0 ml.
Linearity solution 3:
(Citalopram base concentration: 0.011 mg/ml). Dilute 1.0 ml of linearity stock solution 2 to 100.0 ml with dissolution medium.
Linearity solution 4:
(Citalopram base concentration: 0.0176 mg/ml). Dilute 5.0 ml of linearity stock solution 2 to 25.0 ml with dissolution medium. Dilute 4.0 ml of this solution to 50.0 ml with the dissolution medium.
Linearity solution 5:
(Citalopram base concentration: 0.027 mg/ml). Dilute 2.0 ml of linearity stock solution 1 to 100.0 ml with dissolution medium.
Linearity solution 6:
(Citalopram base concentration: 0.034 mg/ml). Dilute 5.0 ml of linearity stock solution 1 to 100.0 ml with dissolution medium. Dilute 10.0 ml of this solution to 20.0 ml with the dissolution medium.
Linearity solution 7:
(Citalopram base concentration: 0.0442 mg/ml). Dilute 4.0 ml of linearity stock solution 2 to 100.0 ml with dissolution medium.
Procedure:
Place one film coated tablet from the batch to be tested in each of the vessels. All standard and test solutions are previously filtered through 0.45 µm filter paper.
Determine the UV-VIS absorbance of the samples, filtered into 0.5 cm cells, at wavelength 238 nm and calculate the concentration of Citalopram base dissolved in the samples by extrapolation in the calibration curve.
Calculations:
From the extrapolated concentration, the percentage of solution is calculated using the following formula:
900 x C x 100
% dissolved Citalopram = ————————-
S
In which:
C: concentration, in mg/ml, of Citalopram base in the test solution
S strength of Citalopram per tablet
- Incident /Deviation:
Any incident or deviation observed during multimedia dissolution study shall be recorded and reported in comparative study report.
Summary/ Conclusion:
Final summary and conclusion shall be given in report.
Abbreviation
MSP : Miscellaneous study protocol
MDC : Multimedia dissolution Citalopram
SD : Standard deviation
HPLC : High performance liquid chromatography
RT : Retention Time
ml : Milliliter
mg : Milligram
min. : Minutes
QA : Quality Assurance
QC : Quality Control
% : Percentage
ºC : Degree centigrade
hrs : Hours
µm : Micrometer
µl : Microlitre
RSD : Relative standard deviation
NLT : Not less than
NA : Not applicable
NMT : Not more than
WS : Working standard
AS : Standard Area
AT : Test Area
