by DISSOLUTION PROFILING STUDY PROTOCOL OF
CETIRIZINE DIHYDROCHLORIDE TABLETS
| Protocol No. & Rev. No | Effective date | Reason for revision |
| New Document |
Table of contents :
| Sr. No. | Subject | Page No. |
| Protocol Approval | ||
| Objective | ||
| Scope | ||
| Responsibility | ||
| Product Profile | ||
| 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 |
Authorized By:
| Functional Area | Name | Designation | Signature / Date |
| Head Quality |
- Objective:
The objective of this protocol is to perform the additional testing to describe and specify the scientific and technical handling of dissolution data. This study shall be to compare the initial results of dissolution. This study shall be performs only on principal media.
- Scope :
This protocol is applicable for the dissolution profiling of Cetirizine dihydrochloride tablets.
- Responsibility of Validation 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 Validation. | |
| Review of data and summary report. | |
| Head Quality | Authorization of protocol. |
- Product Profile:
| Category | Antihistamine |
| Reason for Validation | First Validation |
| Active Ingredient | Cetirizine Dihydrochloride |
| Strength | Each coated tablet contains: Cetirizine Dihydrochloride 10 mg |
| Method Reference | In House |
| Specification Limits | Not less than 80% (Q) of the labeled amount. |
- Methodology:
Chemical, reagents and filters:
Table 1.0: Chemical, reagents and filters
| Sr. No | Material /Chemicals/Filters | Grade |
| 1.0 | Potassium dihydrogen phosphate (KH2PO4) | AR Grade |
| 2.0 | Ortho phosphoric acid | HPLC Grade |
| 3.0 | Water | HPLC Grade or Milli Q water |
| 4.0 | Methanol | HPLC Grade |
| 5.0 | Acetonitrile | HPLC Grade |
| 6.0 | 0.45 µm membrane filter | Millipore or Equivalent |
| 7.0 | 0.45 µm Nylon filter | Millipore or Equivalent |
Dissolution Parameters:
Apparatus : Paddle (II)
Dissolution Medium : Purified Water
Dissolution Medium volume : 900 ml
Speed : 50 rpm
Temperature : 37°C ± 0.5 °C
Sampling Time : 5, 10, 15, 20, 30, 45 minutes.
Chromatographic conditions (By HPLC):
Instrument : High Performance Liquid Chromatography (UV Visible/DAD Detector)
Column : ACE 5C18, 150 mm X 4.6 mm, 5 μm
Flow rate : 1.5 ml/min
Detector : 230 nm
Column Temperature : 40ºC
Injection Volume : 20 µl
Run time : 6.0 minutes (Cetirizine RT Approximately 3.0 min)
Program : Isocratic Method
Mobile Phase : Mixture of Phosphate Buffer: Methanol: (350:650 V/V)
Diluent : Water: Methanol: (50:50) filtered through 0.45μ filter
Preparation of Phosphate Buffer:
Weigh accurately about 6.8 g of Potassium dihydrogen phosphate (KH2PO4) in 1000 ml of water. Adjust pH with dilute ortho-phosphoric acid to 2.6 ± 0.05.
Standard Preparation:
Weigh accurately about 56 mg of Cetirizine dihydrochloride working standard, transfer into a 100 mL volumetric flask. Add 60ml of diluent and sonicate till dissolve and dilute to volume with diluent.
Pipette out 10.0 ml of this solution and transfer into 50 ml of volumetric flask and make up the volume with dissolution media and mix. Further pipette 5.0 ml of this solution and transfer into 50 ml of volumetric flask, make up the volume with dissolution media and mix.
Sample Preparation:
Perform the test on six tablets. Place the 1 tablet in each dissolution vessels containing 900.0 ml of dissolution medium, previously maintained specified temperature (37°C ± 0.5 °C) and run the instrument for 45.0 minutes. After specified time interval mention, withdraw specified volume of aliquot from each vessel and filter through 0.45 µm Nylon Syringe filter, discard first 2-3 ml of the filtrate.
Evaluation of System Suitability:
- Area % RSD : Should not be more than 2.0 % for peak area due to Cetirizine dihydrochloride from 6 replicate injections of standard solution.
- Tailing factor : Should not be more than 2.0 for peak due to Cetirizine dihydrochloride.
- Theoretical plates : Should not be less than 2000 for peak due to Cetirizine dihydrochloride.
Procedure:
Equilibrate the HPLC Column with mobile phase. Inject as per the following sequence or as per requirement.
Sequence of Injections:
Table 2.0: Sequence of Injection of dissolution
| Preparation | No. of Injections | Action |
| Blank Solution | 1 | Record the blank Chromatograms |
| Standard solution 1 | 6 | Check for system suitability Criteria (i), (ii) and (iii) |
| Sample solution 1 to 6 | 1 | Inject the individual solution, Maximum 6 in a set. |
| Standard solution 1 (Bracketing standard) | 1 | %, Area RSD of total 7 injections ≤ 2.0% (6 Injection of standard solution + 1 injection of bracketing standard) |
Calculation for Dissolution (% labeled amount):
Correction factor is used to calculate results at different time interval
AT WS 10 5 900 P
% Released Content = ——- x ——- x —— x —— x —— x —— x 100
AS 100 50 50 LC 100
Where,
AS = Average peak area due to Cetirizine Dihydrochloride obtained from six replicate
injections of standard solution.
AT = Peak area due to Cetirizine Dihydrochloride obtained from sample Solution
WS = Weight of Cetirizine Dihydrochloride RS/WS taken in mg.
LC = Label claim of Cetirizine Dihydrochloride in mg/tablet (10).
P = Potency of Cetirizine Dihydrochloride RS/WS in %, on as basis.
As per method of analysis, record the area on testing data sheet and calculate the % released, mean, standard deviation and % relative standard deviation. Obtained results will be report in tabulated manner as given below.
Dissolution profiling performed on three different batches.
- Incident /Deviation:
Any incident or deviation observed during dissolution profiling should be recorded and reported.
- Summary/ Conclusion / Recommendation:
Final conclusion should be drawn from analytical dissolution profiling.
- Abbreviation
MSP : Miscellaneous study protocol
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
BP : British Pharmacopoeia
RSD : Relative standard deviation
NLT : Not less than
NMT : Not more than
Vol : Volume
AS : Standard Area
AT : Test Area
