P r o u d t o b e P a k i s t a n i

Global Pharmaceutical (Pvt.) Ltd.

ANALYTICAL CONTROL Document # Revision Effective Date Next Review On
PROCEDURE GL/SAP/P/062 No.04 03-Oct-2018 02-Oct-2021
Page #
Protole Capsules 40mg Copy # 01
1 of 6

Author: Reviewed By: Approved By:

Asst. Manager Signature Dy. QC Manager Signature Quality Control Manager Signature
Naeem Qamar Shahbaz Daood Sohail Aslam

Registration No. 066482 Shelf Life: 02 Years

Reference: U.S.P. 39

Composition:

Each capsule contains:

Enteric coated pellets of

Omeprazole…….……….……40mg

(U.S.P. Specs.)

1. PRODUCT SPECIFICATIONS:

S# Parameters Filled Capsules

Off white to pale yellow spherical pellets filled in empty hard
01. Appearance
gelatin capsules.
02. Cap Color Dark green colored cap

03. Body color Light green colored body

04. Capsule size #0

Avg. Wt. ± 7.5%
05. Uniformity of Mass

06. Uniformity of dosage Units Meets the requirements

Dissolution (Acid Stage) NMT 10 % after 2 hr.

07.
NLT 80 % after 45 min.
Dissolution (Buffer Stage)
(Q+5%)
08. Identification Must Comply

09. Assay (Omeprazole) 90.0% to 110.0%

A. ANALYTICAL PROCEDURE: Filled Capsules

Copyright: This Document is the exclusive property of Global Pharmaceutical. And its contents must not be Communicated to
unauthorized persons, or persons outside the company without written consent of Management.
 P r o u d t o b e P a k i s t a n i
Global Pharmaceutical (Pvt.) Ltd.
ANALYTICAL CONTROL Document # Revision Effective Date Next Review On
PROCEDURE GL/SAP/P/062 No.04 03-Oct-2018 02-Oct-2021
Page #
Protole Capsules 40mg Copy # 01
2 of 6

A1.Appearance:
Off white to pale yellow spherical pellets filled in empty hard gelatin capsules.

A2.Cap Color:
Dark green colored Cap (As per Standard)

A3.Cap Color:
Light green colored Body (As per Standard)

A4.Capsule size:
#: 0

A5.Uniformity of Mass :( Weight variation)

Weigh 20 Capsules and calculate the average weight as:

Average weight = Weight of 20 Capsules
20
Weigh all these Capsules individually and mark among these weights maximum (W Max) & minimum (WMin) weight
Capsules. Calculate the maximum and minimum variation in percent as:

Maximum% age variation =(WMax) – (WAvg.) x 100

(WAvg.)
Minimum %age variation =(WMin) – (WAvg.) x 100
WAvg.)

Limit: ± 7.5%

A6.Uniformity of dosage Unit :

Select not fewer than 30 capsules. Accurately weigh 10 capsules individually. Calculate the active substance,
expressed as percentage of label claim of each capsule as described in assay. Calculate the Acceptance value
(AV).

Calculation of Acceptance Value

Calculate the Acceptance Value (AV) using the formula:

AV = [M – X] + ks

in which the terms are as defined in table

Variable Definition

Copyright: This Document is the exclusive property of Global Pharmaceutical. And its contents must not be Communicated to
unauthorized persons, or persons outside the company without written consent of Management.
 P r o u d t o b e P a k i s t a n i
Global Pharmaceutical (Pvt.) Ltd.
ANALYTICAL CONTROL Document # Revision Effective Date Next Review On
PROCEDURE GL/SAP/P/062 No.04 03-Oct-2018 02-Oct-2021
Page #
Protole Capsules 40mg Copy # 01
3 of 6

X Mean of individual contents (% label claim)

x1, x2,...,xi Individual estimated contents of the units tested. Where x1 = w 1 x A/W, here A is
contents of drug substance (5age of label claim), determined as described in
Assay and W is mean of individual weights of units used in the Assay.
W1, w2, ………wn Individual weights of the units tested for weight variations
n Sample size (number of units in a sample)
k Acceptability constant if n = 10, then k = 2.4 if n = 30, then k = 2.0
s Sample standard deviation
T Target test sample amount at time of manufacturer (T = 100.0% unless otherwise
specified in the individual monograph)
M Reference value; M (case 1), T < 101.5% or M (case 2), T > 101.5%
Case 1
If 98.5% < X < 101.5, then M = X , If X < 98.5%, then M = 98.5% If X > 101.5, then
M = 101.5%
Case 2
If 98.5% < X < T then M = X, If X < 98.5% then M = 98.5%, If X > T, then M = T%
AV Acceptance value; AV = | M-X |+ks
L1 Maximum allowed acceptance value (L1 = 15.0 unless otherwise specified in the
individual monograph)

L2 Maximum allowed range for deviation of each dosage unit tested from the
calculated value of M (L2 = 25.0 unless otherwise specified in the individual
monograph)

CRITERIA
Apply the following criteria, unless otherwise specified.
The requirements for dosage uniformity are met if the acceptance value of the first 10 dosage units is less than or
equal to L1. If the acceptance value is greater than L1, test the next 20 dosage units and calculate the
acceptance value. The requirements are met if the final acceptance value of the 30 dosage units is less than or
equal to L1 and no individual content of the dosage unit is less than (1 - L2 × 0.01) M nor more than (1 + L2 ×
0.01) M in calculation of acceptance value under content uniformity or under mass variation. Unless otherwise
specified, L1 is 15.0 and L2 is 25.0

A7. Dissolution:
Acid resistance Stage:
Medium : 0.1N Hydrochloric acid, 900ml
Apparatus1 :100rpm,
Time :02 hours.
Sample Solution : After 2 h, remove each sample from basket, and quantatively transfer into separate
volumetric flask to obtain solution having a final concentration of 0.2mg/ml. Proceed as directed for the sample
solution in assay, starting with “Add about 50ml of Diluent”
Analysis: standard solution and sample solution, calculate the quantity of labeled amount of omeprazole
dissolved in medium, in mg.
Results = T- Cs x D x (ru/rs)
T = labeled quantity of omeprazole in capsule (mg)
Cs= Concentration of Omeprazole (Standard) in standard solution.
D = dilution factor used in preparing the sample solution.
rs= peak response from the sample solution

Copyright: This Document is the exclusive property of Global Pharmaceutical. And its contents must not be Communicated to
unauthorized persons, or persons outside the company without written consent of Management.
 P r o u d t o b e P a k i s t a n i
Global Pharmaceutical (Pvt.) Ltd.
ANALYTICAL CONTROL Document # Revision Effective Date Next Review On
PROCEDURE GL/SAP/P/062 No.04 03-Oct-2018 02-Oct-2021
Page #
Protole Capsules 40mg Copy # 01
4 of 6
ru= peak response from the standard solution.
Tolerance: the average of the 6 units is NMT 10 % of omeprazole dissolved.
BufferStage:
Medium : 0.05M pH:6.8 phosphate buffer, 900ml
Apparatus1 :100rpm,
Time :45 min.
Buffer Preparation: Dissolve 6.8g of potassium dihydrogen phosphate and 0.89g of sodium hydroxide in
100ml of water, adjust pH: to 6.8 if necessary with sodium hydroxide or phosphoric acid.
Analysis:Proceed as directed for acid resistance stage with a new set of capsules from the same batch. After 2
hrs , replace the acid medium with buffer medium, and continue the test for 45min. determine the amount of
omeprazole dissolved from UV Absorbance at the wavelength of maximum absorbance at about 305nm on
portion of solutions under test passed through a nylon filter of 0.2-µm pore size, in comparison with standard
solution of Omeprazole in same medium.
Tolerance: NLT 80% (Q+5%) is dissolved.

A8.Identification (Omeprazole):
By HPLC
The principal peak in the chromatogram obtained with the test solution is similar in retention time and size to the
principal peak in the chromatogram obtained with reference solution.

A9.Assay(HPLC) :
Chromatographic system:

Column :4.0-mm × 15-cm, 5 µm, based-deactivated packing L7.

Lambda max. : 305nm

Flow Rate :1.2ml/min.

Temp. :Ambient

Injection :10µL

Procedure:

Solution A:

Dissolve 6.0g of glyceine in 1500ml of water, adjust with 50% sodium hydroxide solution to a pH: 9.0 and dilute

with water to 2000ml.

Solution B:

Acetonitrile and Methanol (85:15)

Diluent:
Dissolve 7.6g of sodium borate decahydrate in about 800ml of water. Add 1.0g of edentate disodium, and adjust
with 50% sodium hydroxide solution to a pH: 11.0± 0.1. Transfer the solution to a 2000ml volumetric flask, and
400ml of dehydrated alcohol and dilute with water to volume.

Copyright: This Document is the exclusive property of Global Pharmaceutical. And its contents must not be Communicated to
unauthorized persons, or persons outside the company without written consent of Management.
 P r o u d t o b e P a k i s t a n i
Global Pharmaceutical (Pvt.) Ltd.
ANALYTICAL CONTROL Document # Revision Effective Date Next Review On
PROCEDURE GL/SAP/P/062 No.04 03-Oct-2018 02-Oct-2021
Page #
Protole Capsules 40mg Copy # 01
5 of 6

Mobile phase:
See Table
Time (min.) Solution A (%) Solution B (%)
0 88 12
20 40 60
21 88 12
25 88 12

Standard Solution:
0.2mg /ml of Omeprazole (Standard) in diluent, using sonication if necessary.
Sample Solution:
Weigh and mix the contents of NLT 20 capsules. Transfer an accurately weighted portion of the capsule content,
equivalent to 20mg of Omeprazole, to a 100ml volumetric flask, and add about 50ml of diluent and sonicate for 15
min. cool and dilute with diluent to volume, mix and pass through a membrane filter 0.45µm or fine pore size.

Procedure: Separately inject equal volumes (about 10 µL) of the Standard solution, the sample solution into the
chromatograph, record the chromatograms, and measure the responses for the major peaks.

Calculations:
%age Assay: = Area of Sample X Concentration of Reference X Potency of Standard
Area of Reference X Concentration of Sample

(Limit: 90.0%- 110.0 %

2.0 AMENDMENT HISTORY

Copyright: This Document is the exclusive property of Global Pharmaceutical. And its contents must not be Communicated to
unauthorized persons, or persons outside the company without written consent of Management.
 P r o u d t o b e P a k i s t a n i
Global Pharmaceutical (Pvt.) Ltd.
ANALYTICAL CONTROL Document # Revision Effective Date Next Review On
PROCEDURE GL/SAP/P/062 No.04 03-Oct-2018 02-Oct-2021
Page #
Protole Capsules 40mg Copy # 01
6 of 6

Initiated Page
Rev.# Date Nature of Amendment Done By
by #
03 30.08.2016 D.Q.C.M. All Reviewed according to USP 39 M.R.
04 03.10.2018 D.Q.C.M. 1,4 Uniformity of mass, Prep. Of Buffer, Limit of Dissolution. M.R.

Copyright: This Document is the exclusive property of Global Pharmaceutical. And its contents must not be Communicated to
unauthorized persons, or persons outside the company without written consent of Management.