Comparative Dissolution profile protocol

This article contains information about Comparative Dissolution profile protocol for various formulations like Tablet/capsule etc.                                                                                                    

Comparative Dissolution profile protocol

Team Approval:

	Designation	Name	Signature	Date
Prepared By	Executive -QC
Reviewed By	Manager-QC
	Head-QC
Approved By	Head-QA

 Protocol Content for comparative dissolution profile Protocol :

Sr. No	Contents Name	Page No
I	Purpose	3
II	Scope	3
III	Reference	3
IV	Site of the Study	3
V	Responsibility	3
VI	Materials and instrument	3 => 4
VII	Profiling Medium	4
VIII	Method of Analysis	5  => 6
IX	Acceptance Criteria	7
X	Results	7
XI	Conclusion	7
XII	Attachments	7

I:  Purpose:

The purpose of comparative dissolution profile protocol testing in the four media is to access dissolution performance of Reference Sample of drug product against the Test Sample (Innovator sample) across the physiologically relevant pH range in consideration of multiple time points.

 II: Scope:  

The comparative dissolution profile protocol study is applicable to drug product which is manufactured at site

III: Reference:

USP General Chapter <1090>

 IV: Site of the study:

Pharmaceutical organization name

V: Responsibility:

• Analyst/Executive QC: To perform the dissolution test as per protocol and report the results.
• Assistant Manager QC: To check & verify the analysis performed for Dissolution test.
• Head Quality Control: To ensure the activities are executed as per protocol.
• Head Quality Assurance: To ensure the results obtained are within the predefined acceptance criteria.

VI: Materials and Instrument:

• Product details:

Sr. No	Name of product	Batch Number	Mfg. Date	Exp. Date	Type of sample
1					Reference Sample (Innovator sample)
2					Test sample

• Instruments:

Sr. No	Instruments	Make
1	Analytical  Balance	Mettler Toledo
2	Analytical  Balance	Mettler Toledo
3	pH Meter	LABINDIA
4	Dissolution Test Apparatus	LABINDIA
5	UV Spectrophotometer	SHIMADZU

• Reagent / Chemicals:

Sr. No	Reagents/Chemicals	Grade
1	Sodium Hydroxide	AR Grade
2	Monobasic Potassium Phosphate	AR Grade
3	Diethylamine	AR Grade
4	Phosphoric Acid	AR Grade
5	Acetonitrile	HPLC Grade
6	Potassium Chloride	AR  Grade
7	Hydrochloric Acid	AR  Grade
8	Sodium Acetate Trihydrate	AR  Grade
9	Glacial Acetic Acid	AR  Grade

•  Standard:

Sildenafil Citrate USP

VII: Dissolution profiling media & Time points:

Perform the Dissolution profiling in the following corresponding medium :

• Medium:

1. Dissolution Medium : Purified Water
2. Dissolution Medium : Phosphate Buffer pH 6.8
3. Dissolution Medium : Acetate  Buffer pH 4.5
4. Dissolution Medium : Hydrochloric Acid Buffer pH 1.2

• Time points:

5, 10, 15, 20, 30 & 45 minutes

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 VIII. Method of Analysis:

•  Dissolution Medium: Purified Water  

•   Dissolution parameters:

Dissolution media	Purified Water
RPM	50
Apparatus	Paddle  (USP Type II)
Volume	900 ml
Time point	45 minutes
Temperature	37.0°C ± 0.5ºC

• Chromatographic Condition:

Column	As per product Requirement
Flow Rate	1.0 ml/min
Injection Volume	20 µL
Wavelength	230 nm
Column Oven Temperature	250C
Auto Sampler Temperature	Ambient
Run Time	About 10 minutes
Retention Time for Principle Peak	About 5 minutes

•  Preparation of Buffer:

Prepare a solution of 0.5 M monobasic potassium phosphate and 0.01 M Diethyl amine in purified

Water in the ratio (1: 1). Adjust with phosphoric acid to a pH 4.5. Filter through 0.45 µ membrane filter.

• Preparation of Mobile Phase:

Prepare a degassed mixture of purified water, Acetonitrile and Buffer in the ratio 130:70:8

• Standard Solution:

Weigh accurately and transfer 30 mg of API working standard into a 100 ml volumetric

Flask. Dissolve and Dilute to volume with Purified Water. Further dilute 5 ml to 50 ml with the purified

Water. (Prepare the standard solution in duplicate for similarity factor)

• Sample Solution:

Transfer 900 ml of dissolution medium in the vessel carefully and allow the medium to equilibrate to a

Temperature of 37 + 0.5^oC. Place one tablet in each of the vessel and operate the apparatus at 50 rpm for 45 Minutes. Withdraw l0 ml of the sample from each Dissolution Vessel and filter through 0.45 pm membrane Filter. Further dilute 5 ml to 20 ml with dissolution medium.

• Procedure:

Separately inject 20 µL of Blank, standard solution preparation -1 (five injection) and

Standard solution preparation -2 (single injection) and test preparation into the chromatographic system

and record the peak area count of Sildenafil . Calculate the content of the Sildenafil

• System Suitability

1) The similarity factor should be between 0.98 and 1.02

2) The % RSD of Sildenafil in standard preparation for retention times should not be more than

l % and for peak area response should not be more than 2.0 %.

3)  The tailing factor for Sildenafil peak in standard preparation should not be more than 2.0

4)  The theoretical plates for Sildenafil peak in standard preparation should not be more than 2000

•     Calculation:

% drug release

Sample Area x Std. Wt. Mg x 5 x 900 x 20 x Std. Potency x 100 x 474.58

——————————————————————————————-         

Standard Area x 100 x 50 x1 x 5 x100 x L.C x 666.70

Where,

Std.Potency	Standard Potency
LC	Labelled Claim
447.58	Molecular Weight of Sildenafil
666.70	Molecular Weight of Sildenafil Citrate

•  Specification:

Not less than 85.0 % of the labelled amount release in 45 minutes

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 IX) Acceptance criteria:

F1 value should be in between 1 to 15

F2 value should be in between 50 to 100

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X) Results:

1) Observation and results to be recorded in individual data sheet

2)  Summarize the finding of the method study to draw Inference.

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 XI) Conclusion:

Based on the interpretation of the results in method Summary and Comparative dissolution profile protocol draw the conclusion.

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XII) Attachment:   

1) Protocol.

2) Report.

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Note : All testing shall be done as per Comparative dissolution profile protocol