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STABILITY STUDY PROTOCOL

STABILITY STUDY PROTOCOL

THIS PROTOCOL IS: Lisinopril and Hydrochlorothiazide tablets 10+12.5 mg
CONTENTS: Each uncoated tablet contains:

Lisinopril dihydrate equivalent to Lisinopril 10mg

Hydrochlorothiazide                                           12.5mg

SHELF LIFE: 24 months
DOSAGE FORM: Tablet
MANUFACTURED AT:  
TYPE OF STABILITY STUDIES: Accelerated stability studies 40 + 20C / 75 + 5 % RH 6 months

 

Long term stability studies

 

25 + 20C / 60 + 5 % RH 36 months

 

Zone IVb. Long Term Stability 30 + 20C / 75 + 5 % RH 36 months

Protocol Approval

Prepared by : 

Name Job Title Signature Date
       

 Checked by : 

Name Job Title Signature Date
       

 Approved by : 

Name Job Title Signature Date
       

 LIST OF CONTENTS:

S.No. CONTENTS PAGE NO.
1.0 Objective  
2.0 Scope  
3.0 Responsibility  
4.0 Accountability  
5.0 Selection of Batches for Stability  
6.0 Sampling  
7.0 Stability Conditions  
8.0 Charging & Withdrawal of Samples  
9.0 Product Details  
10.0 Stability Attributes & Specifications  
11.0 Acceptance Criteria  
12.0 Stability Testing Schedule  
13.0 Stability Commitments  
14.0 Documentation & Reporting  
15.0 Conclusion  
16.0 References  
17.0 Revision History  
18.0 Annexures  

 

1.0 OBJECTIVE
  The objective of this protocol is to define procedure for carrying out Stability study Lisinopril and Hydrochlorothiazide tablets 10+12.5 mg.

The quality of drug product is likely to be influenced during storage. There are various factors involved, such as temperature, humidity, primary packing etc. for influencing drug product quality. Therefore it is necessary to evaluate the influence of these factors on product quality, establish the shelf life or evaluate storage conditions of the Drug Product (for new products). The stability is also carried out to ascertain that the existing products are stable till the end of their shelf life when studied as per defined schedule/interval & stability conditions.

2.0 SCOPE
  The scope of this Protocol is applicable to Lisinopril and Hydrochlorothiazide tablets 10+12.5 mg

The stability studies will be carried out to ensure the stability of the product till the end of its shelf life.

3.0 RESPONSIBILITY
  The responsibility for conducting Stability studies will be as follows:

Preparation & Approval of Stability Protocol – QA

Sampling – IPQA Chemists

Charging & Withdrawal of Samples – QС Chemist

Monitoring Temperature & Humidity Conditions of Stability Chambers – QС Chemist

Analysis of Stability Samples – QC Chemist

Documentation & Reporting – Head QC

OOS Results if any – Head QC & Head of QA

Review of Data, Documentation & Reports & Conclusion – Head of QA

4.0 ACCOUNTABILITY
  Head of QC

Head of QA

5.0 SELECTION OF BATCHES FOR STABILITY
  Samples required for stability studies are taken by IPQA supervisors on packing line and sent to QC department.

Sample quantity of any subjected batch contains samples for following requirements:

·         Sample required for one complete analysis for each time point.

·         Total quantity for all time points

·         One additional pack for any unforeseen event like OOS.

·         Placebo sample for each time point analysis.

6.0 SAMPLING
  Sampling required for Stability Studies are to be drawn by IPQA Chemist on Packing Line.

The samples to be taken should be in market equivalent container i.e

In case of Lisinopril and Hydrochlorothiazide tablets 10+12.5 mg : it will be packed in Alu-Alu blister in a printed carton.

The sample quantity will be calculated to 1 pack extra in addition to the packs required for single analysis.

The samples will be drawn by IPQA Chemists & then handed over to QC department. This will be recorded.

7.0 STABILITY CONDITIONS
  The products manufactured in formulation plant and will be subjected to 3 conditions:

Long Term Stability Studies at 25 + 20C / 60 + 5 % RH.

Accelerated Stability Studies at 40 + 20C / 75 + 5 % RH.

Zone IVb. Long Term Stability at 30 + 20C / 75 + 5 % RH.

In case of breakdown / non functioning of any stability chamber; the samples will be shifted to the spare stability chamber after setting it to the required stability conditions.

8.0 CHARGING & WITHDRAWAL OF SAMPLES
  The samples will be charged after putting the sticker labels on each pack.

The samples will have to be charged in the Stability chambers within 5 days of completion of Initial Analysis.

As per the Calendar the samples are withdrawn within 5 days of the due date of analysis for Long Term Stability Studies and Long Term Stability Studies for Zone IVb and 3 days of the due date of analysis for Accelerated Stability Studies.

The analysis of the samples will have to be done within 15 days from the due date of analysis.

In case of any deviation, this will be documented with justification & with approval from QA.

9.0 PRODUCT DETAILS
  Lisinopril and Hydrochlorothiazide tablets 10+12.5 mg contains Lisinopril dihydrate equivalent to Lisinopril 10 mg Hydrochlorothiazide 12.5mg

The Product is packed in Alu-PVC/PVdC Blister is packed in cartons.

10.0 STABILITY ATTRIBUTES & SPECIFICATIONS
  The specifications and stability attributes for Lisinopril and Hydrochlorothiazide tablets 10+12.5 mg  are at the table below:

S.No Tests Specifications
1
Description
White to off-white, round, flat, uncoated tablet, plain on both side.
2

 

Identification

 

 

 

 

In the Assay, the principal peak in the chromatogram obtained with the test solution has the same retention time as the principal peak in the chromatogram obtained with reference solution
3
Disintegration
NMT 15 minutes
4 Dissolution NLT 80 % (Q) in 30 min for Lisinopril & NLT 80% (Q) in 45 min for Hydrochlorothiazide.
5 Assay Between 95% to 105%
6
Uniformity of dosage units
AV ≤ L1 (L1=15.0)
7 Related substances Lisinopril related compound A: NMT 2.0%

Benzothiadiazine related compound A: NMT 1.0%

8 Microbiological purity

 

 

 

 

Total aerobic microbial count

(ТАМС): NMT 103 CFU/g.

Total combined yeasts/moulds count (TYMC):

NMT 102 CFU/g.

Escherichia coli must be absent per 1 g.

11.0 ACCEPTANCE CRITERIA
  The Product is considered to be stable if it passes all the criteria for the Specifications mentioned above or there is no significant change.

Significant change means:

a.       A 5% change in assay form initial value or failure to meet the acceptance criteria 90 % to 110 % of labeled amount.

b.      Related substances fail to meet the acceptance criteria.

c.       Fails to meet the microbial purity.

d.      Failure to meet the acceptance criteria for other parameters likes Description, DT, Dissolution, Assay, Chromatographic Purity & Microbial Purity & any other characteristics.

12.0 STABILITY TESTING SCHEDULE
  Stability Testing Schedule for Lisinopril and Hydrochlorothiazide tablets 10+12.5 mg is as follows:

S.

No.

Tests Initial Accelerated Long Term Stability

Zone IVb.

 
3

M

6

M

3

M

6

M

9

M

12

M

18

M

24

M

36

M

 
1 Description                    
2 Identification                    
3 Disintegration                    
4 Dissolution                    
5 Assay                    
6 Uniformity of dosage units                    
7 Related Substances                    
8 Microbial Purity                    
13.0 STABILITY COMMITMENT
  The product has been tested at development stage (lab trial batches) for stability to determine the shelf life of the product. Besides, it the first three commercial batches are kept for accelerated, long and Zone IVb. long term stability. If required, accelerated stability study data shall be used for submission to authorities & Long term stability data will be provided as & when complete.
14.0 DOCUMENTATION & REPORTING
  The analyst will enter the data obtained in the Stability Summary Report & at the end of completion of Stability Study, a proper Report will be made with conclusions.

All the analytical Raw data carried out for stability will be retained in QC along with COA made for each sample from each station.

15.0 CONCLUSION
  After completion of Long Term Stability, Accelerated Stability Studies Stability, conclusion about the assigned shelf life to be drawn whether it can remain the same or it needs to be changed.
16.0 REFERENCES
  ICH Guidelines Q1A (R2)
17.0 REVISION HISTORY
   

Version Number Effective Date Changes
0              – New
18.0 ANNEXURES
I All the entries of samples received for Stability analysis will be made in the documents as mentioned in SOP for Stability Studies.

 

 Accelerated stability study chart:

Product Details Stability study Details
Product name/ Lisinopril and Hydrochlorothiazide tablets 10+12.5 mg Protocol No. Temperature/ 40 ± 2°C
Batch. No.: Mfg.Date Exp. Date Pack Size

 

RH 75 ± 5%
Pack profile Blister in duplex board carton Date of sample charging Stability Chamber No.
Tests Specifications Initial 3M 6M
Completion date of analysis        
Observations        
Conclusions        

Long term stability study chart: 

Product Details Stability study Details
Product name Lisinopril and Hydrochlorothiazide tablets 10+12.5 mg Protocol No. Temperature 25 ± 2°C
Batch. No.: Mfg.Date Exp. Date Pack Size

 

RH 60 ± 5%
Pack profile Blister in duplex board carton Date of sample charging Stability Chamber No.
Tests Specifications Initial 3M 48M
Completion date of analysis          
Observations          
Conclusions          

Long term stability Zone IV b study chart: 

Product Details Stability study Details
Product name Lisinopril and Hydrochlorothiazide tablets 10+12.5 mg Protocol No. Product name 30 ± 2°C
Batch. No.: Mfg. Date Exp. Date Pack Size RH 75 ± 5%
Pack profile Blister in duplex board carton Date of sample charging Stability Chamber No.
Tests Specifications Initial 3M 48M
Completion date of analysis          
Observations          
Conclusions          

 

 

 

About Pharmaceutical Guidanace

Mr. Shiv Kumar is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 14 years of rich experience in pharmaceutical field. During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube

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