STIROLBIOFARM BALTIKUM LTD

3.2.P

Vitamin C Orange 500 mg chewable tablets

DRUG PRODUCT

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

3.2.P.1 Description and Composition of the Drug Product

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

3.2.P.1

Description and Composition of the Drug Product

3.2.P.1.1

Description

Finished product Vitamin Orange 500 mg chewable tablets is pink-orange biconvex tablets
with break line and inscription C and 500 on one side, having orange flavour and sweet and
sharp taste. On the surface white or bright orange inclusions are allowed; tablets may be with
powder-like blush or slightly cogged.

STIROLBIOFARM BALTIKUM LTD

3.2.P.1.2

Vitamin C Orange 500 mg chewable tablets

Composition

In the manufacturing process, per one tablet, the following materials are used:
Ingredient

Quantity
%
g

Function

Active substances:
Sodium ascorbate (Ph. Eur.1)
(with reference to ascorbic acid)

31.91

0.33800
0.30050

Active ingredient

Ascorbic acid, as granulate (95 %) (In-house)

(with reference to ascorbic acid)

22.30

0.21000
0.19950

Active ingredient

Mannitol (Ph. Eur.)

23.55

0.20351

Diluent

Compressible sugar (USP NF2)

16.99

0.14000

Sweetening agent

Sodium cyclamate (Ph. Eur.)

0.71

0.00671

Sweetening agent

0.03

0.00028

Flavouring agent

Aspartame (Ph. Eur.)

0.51

0.00580

Sweetening agent

Stearic acid (In-house / Ph. Eur.)

2.04

0.01920

Binder

Yellow colorant 6 (In-house)

0.41

0.00387

Colouring agent

Magnesium stearate (In-house / USP NF / Ph.

Eur.)

1.02

0.00940

Lubricant

Colloidal silicon dioxide

0.53

0.00493

Lubricant

100.0

0.94170

Excipients:

Orange flavour

Total:
_____________________________________

European Pharmacopoeia (Ph. Eur.) current edition

The United States Pharmacopeia National Formulary (USP NF) current edition
3
Orange flavouring agent contains the mixture of nature-identical flavouring substances,
maltodextrin and Arabic gum
2

STIROLBIOFARM BALTIKUM LTD

3.2.P.1.3

Vitamin C Orange 500 mg chewable tablets

Type of container used for dosage form

Finished product Vitamin C Orange 500 mg chewable tablets is packed as follows:

12 tablets are placed per polyvinylchloride (PVC) film / aluminium (Al) foil blister.
30 or 50 tablets are placed per plastic container.
1 blister or 1 plastic container together with Patient Information Leaflet is placed into cardboard
box.

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

3.2.P.4 Control of Excipients

STIROLBIOFARM BALTIKUM LTD

3.2.P.4

Vitamin C Orange 500 mg chewable tablets

Control of Excipients

For manufacturing of finished product Vitamin C Orange 500 mg chewable tablets the following
starting materials, described in pharmacopoeias are used:
Mannitol
Sucrose compressible
Sodium cyclamate
Flavouring agent orange
Aspartame
Strearic acid
Colouring agent
Magnesium stearate
Silica, colloidal anhydrous
Each

Ph. Eur.
USP NF
Ph. Eur.
In-house
Ph. Eur.
In-house / Ph. Eur.
In-house
In-house / Ph. Eur./ USP NF
In-house / Ph. Eur.

batch of above mentioned ingredients is tested in accordance with pharmacopoeial

requirements and corresponding Quality Specifications.

Company- manufacturer of magnesium stearate confirms that fatty acids, used for magnesium
stearate producing, have completely vegetable origin. According to EC directive 1999/82 EEC
the products, having vegetable origin, couldnt be the source of TSE risk.
In the manufacturing of product Vitamin C Orange 500 mg chewable tablets yellow colorant
Spectracol Dual FD&C Yellow No 6 LK (Sunset yellow FCF, CAS No. 2783-94-0) is used. It is
FDA certified colorant.
Also orange flavouring agent FD-9285-D-T, manufactured by company Givaudan Roure
Flavours Ltd (Switzerland) is used in the manufacturing process of Vitamin C 500 mg chewable
tablets. Company manufacturer of colouring agent declares that product complies with the
requirements of the EEC Directive 78/25/EC Colouring Matter in Medicines, the EC Directive
95/45/EC, and the FAO/WHO Food Drug and Nutrition paper 52/1 and 2 as well as that its
production facilities meet the requirements of the health Authorities of the country of origin of
the product. Certificate of origin is attached to the documentation.

The attached documentation includes:

1) company Stirolbiopharm Quality Specification for mannitol;

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

2) company Stirolbiopharm certificate of analysis for mannitol;

3) company-suppliers quality certificate for mannitol;
4) the copy of Ph. Eur. monograph Mannitol;
5) company Stirolbiopharm Quality Specification for sucrose compressible;
6) company Stirolbiopharm certificate of analysis for sucrose compressible;
7) company-suppliers quality certificate for sucrose compressible;
8) the copy of USP NF monograph Compressible Sugar;
9) company Stirolbiopharm Quality Specification for sodium cyclamate;
10) company Stirolbiopharm certificate of analysis for sodium cyclamate;
11) company-suppliers quality certificate for sodium cyclamate;
12) the copy of Ph. Eur. monograph Sodium cyclamate;
13) company Stirolbiopharm Quality Specification for flavouring agent;
14) company Stirolbiopharm certificate of analysis for flavouring agent;
15) company-suppliers quality certificate for flavouring agent;
16) company Stirolbiopharm Quality Specification for aspartame;
17) company Stirolbiopharm certificate of analysis for aspartame;
18) company-suppliers quality certificate for aspartame;
19) the copy of Ph. Eur. monograph Aspartame;
20) company Stirolbiopharm Quality Specification for stearic acid;
21) company Stirolbiopharm certificate of analysis for steariv acid;
22) company-suppliers quality certificate for stearic acid;
23) the copy of Ph. Eur. monograph Stearic acid;
24) company Stirolbiopharm Quality Specification for colouring agent;
25) company Stirolbiopharm certificate of analysis for colouring agent;
26) company-suppliers quality certificate for colouring agent;
27) company Stirolbiopharm Quality Specification and Analytical Procedures for magnesium
stearate;
28) company Stirolbiopharm certificate of analysis for magnesium stearate;
29) company-suppliers quality certificate for magnesium stearate;
30) the copy of ph. Eur. monograph Magnesium stearate;
31) the copy of USP NF monograph Magnesium stearate;

32) company Concern Stirol Quality Specification for silica colloidal;

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

33) company Concern Stirol certificate of analysis for silica colloidal;

34) company-suppliers quality certificate for colloidal silicon dioxide;
35) the copy of Ph. Eur. monograph Silica colloidal , anhydrous.

STIROLBIOFARM BALTIKUM LTD

3.2.P.4.1

Vitamin C Orange 500 mg chewable tablets

Specifications

All excipients, i.emannitol, sucrose compressible, sodium cyclamate, orange flavouring agent,
aspartame, stearic acid, yellow colouring agent, magnesium stearate and silica colloidal used in
the manufacture of Vitamin C Orange 500 mg chewable tablets are tested to conform to
corresponding Quality Specification requirements.

STIROLBIOFARM BALTIKUM LTD

3.2.P.4.2

Vitamin C Orange 500 mg chewable tablets

Analytical Procedures

All excipients are tested according to respective Quality Specification using pharmacopoeial
methods.

STIROLBIOFARM BALTIKUM LTD

3.2.P.4.3

Vitamin C Orange 500 mg chewable tablets

Validation of Analytical Procedures

Not applicable

STIROLBIOFARM BALTIKUM LTD

3.2.P.4.4

Vitamin C Orange 500 mg chewable tablets

Justification of Specifications

Specifications and established limits for all excipients are in accordance with manufacturers
Quality Specification or corresponding pharmacopoeial monograph. So, any justification is not
needed.

STIROLBIOFARM BALTIKUM LTD

3.2.P.4.5

Vitamin C Orange 500 mg chewable tablets

Excipients of Human or Animal Origin

Not applicable

STIROLBIOFARM BALTIKUM LTD

3.2.P.4.6

Novel Excipients
Not applicable

Vitamin C Orange 500 mg chewable tablets

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

3.2.P.5 Control of Drug Product

STIROLBIOFARM BALTIKUM LTD

3.2.P.5.1

Vitamin C Orange 500 mg chewable tablets

Specification(s)

All batches of the finished product Vitamin C Orange 500 mg chewable tablets are checked to
conform to the requirements of Quality Specification developed according to general
requirements of Ph. Eur. for solid dosage forms (tablets).

Specifications

Requirements

Methods of analyses

Description

Pink-orange biconvex tablets with

break line and inscription C and
500 on one side, having orange
flavour and sweet and sharp taste.
On the surface white or bright
orange inclusions are allowed;
Tablets may be with powder-like
blush or slightly cogged.

Determine visually

Identification

Passes tests A, B, C and D

In-house methods

Uniformity of mass

0.9417 g 5.0 %

Ph. Eur., 2.9.5

pH

From 4.0 to 5.0

Ph. Eur., 2.2.3

Friability

Not more than 3.0 %

Ph. Eur., 2.9.7

Aerosil

Not more than 0.5 %

In-house method

Loss on drying

Not more than 0.5 %

Ph. Eur., 2.2.32,

method d

Microbial contamination:

Ph. Eur., 2.6.12, 2.6.13

and 5.1.4

- bacteria
- fungi
- Enterobacteriaceae
- Pseudomonas aeruginosa
- Staphylococcus aureus

Not more than 1000/g

Not more than 100/g
Absence
Absence
Absence

Assay of ascorbic acid and

sodium ascorbate, calculated to
ascorbic acid

From 0.475 g to 0.525 g

In-house method

Ascorbic acid tablets are described in BP and USP. Corresponding monographs are presented on
the following pages.

STIROLBIOFARM BALTIKUM LTD

3.2.P.5.2

Vitamin C Orange 500 mg chewable tablets

Analytical Procedures

Generally the methods employed for finished product quality control are pharmacopoeial.
DESCRIPTION
Description of the tablets should comply with QS requirements. Determine visually.
IDENTIFICATION
A. Dissolve 0.2 g of powdered tablets to be examined in 5 ml of water R, add 1 ml of silver
nitrate solution R2 (17 g/l); a grey precipitate is formed (ascorbate).
B. Dissolve 0.02 g of powdered tablets to be examined in 10 ml of water R, drop sodium 2,6dichlorophenolindophanolate solution: the blue colour of the last reagent immediately disappears
(ascorbate).
Preparation of sodium 2,6-dichlorophenolindophenolate solution: dissolve 0.25 g of sodium 2,6dichlorophenolindophenolate in 500 ml of carbon dioxide-free water vigorously mixing and
filter into 1000 ml volumetric flask through paper filter. Make to volume with carbon dioxidefree water and mix. The solution prepared is available for 7 days when stored in cold, dark place.
C. Dissolve 0.2 g of powdered tablets to be examined in 5 ml of water; the solution obtained
shows characteristic reaction of sodium (colourless flame upon introduction of the solution
becomes yellow).
D. UV spectrophotometry. UV absorption spectrum of the test solution prepared under Assay
test within the range 220 nm to 320 nm should have maximum of absorbance at 244 nm
(ascorbic acid).
DEVIATION FROM AVERAGE MASS
Is determined according to Ph. Eur., 2.9.5. Not more than 2 individual masses deviate from the
average mass by more than 5 % and none deviates by more than 10 %.
FRIABILITY
Is determined according to Ph. Eur., 2.9.7. Examine 10 tablets.
Requirements: NMT 3.0 %.
pH
Is determined according to Ph. Eur., 2.2.3. Dissolve one tablet in 50 ml of water and measure pH
of the solution obtained
Requirements: from 4.0 to 5.0.

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

AEROSIL
Transfer accurately weighed about 1 g of powdered tablets to vessel and treat them with 200 ml
of warm water; filtrate through ash-less paper filter; wash vessel with water. Wash the residue on
filter with warm water (by 10 ml portions) until absence of visible residue on watch glass after
evaporation. Dry the filter with residue and ignite it. Treat residue after ignition under heating
with 30 ml of diluted hydrochloric acid, filtrate and wash residue on filter with warm water until
absence of chlorides in washing water. Dry the filter and residue, ignite it and then weigh with
precision 0.0001 g.
Requirements: NMT 0.5 %.
LOSS ON DRYING
Is determined according to Ph. Eur., 2.2.32, method d.
Requirements: NMT 0.5 %.
MICROBIAL CONTAMINATION
The test is carried out according to Ph. Eur., 2.6.12 and 2.6.13 requirements.
Transfer 10 g of the powdered tablets to be examined to sterile 100 ml volumetric vessel,
dissolve in sterile buffered sodium chloride-peptone solution pH 7.0, make to volume with the
same solvent and mix well (sample A).
Transfer 10 g of the powdered tablets to be examined to sterile 100 ml volumetric vessel,
dissolve in sterile buffered sodium chloride-peptone solution pH 7.0 containing polysorbate-80
(30 g/l), make to volume with the same solvent and mix well (sample B).
To determine total bacterial count add by pour-plate method 1 ml of the sample B to each of two
Petri dishes containing agar medium No 1.
To determine total count of fungi add by pour-plate method 1 ml of the sample A to each of two
Petri dishes containing dense agar medium No 2.
To detect bacteria belonging to the family of Enterobacteriaceae transfer 10 ml of the sample A
to 100 ml of the broth medium No 3.
To determine Staphylococus aureus and Pseudomonas aeruginosa transfer 10 ml of sample B to
100 ml of nutrition medium No 8.
Specifications for microbial contamination for the preparation to be examined are stated
according to Ph. Eur., 5.1.4, as for preparations of category 3 A.

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

Requirements:
Total viable aerobic count: not more than 1000 bacteria and not more than 100 fungi per 1 g of
the preparation to be examined.
Absence of bacteria belonging to family of Enterobacteriaceae per 1 g.
Absence of Staphylococus aureus per 1 g.
Absence of Pseudomona aeruginosa per 1 g.
ASSAY
Assay of ascorbic acid is determined by UV spectrometric method (Ph. Eur., 2.2.25).
Requirements: from 0.475 g to 0.525 g.
Accurately weighed about 0.08 g of powdered tablets into to 100 ml volumetric flask, add 70 ml
of water R, 1 ml of 0.1 M hydrochloric acid and shake vigorously for 10 min. Make to volume
with water R, mix and filter rejecting the first 10 ml of the filtrate.
Transfer 2 ml of the filtrate obtained to 100 ml volumetric flask; add 1 ml of 0.1 M hydrochloric
acid, make to volume with water R and mix well.
Measure the absorbance of the solution prepared at the wavelength 244 nm in 10 mm cell, using
0.001 M hydrochloric acid as the compensation liquid.
Measure the absorbance of the ascorbic acid CRS standard solution in parallel.
The content of ascorbic acid (X), per one tablet, in g is calculated as follows:

X=

A1 x m0 x 100 x 100 x 2 x b x C
A0 x 200 x 100 x 10 x m1 x 2 x 100

A1 x m0 x b x C
= A0 x m1 x 200

Where:
A1 absorbance of the test solution;
A0 absorbance of ascorbic acid CRS standard solution;
m0 mass of ascorbic acid CRS, g;
m1 mass of tablets powdered sample, g;
C assay of ascorbic acid in CRS, %;
b average mass of one tablet, g.
The content of C6H8O6 (ascorbic acid) and of C6H7NaO6 (sodium ascorbate) in one tablet should
be from 0.475 g to 0.525 g, calculating with reference to average tablet mass.

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

Preparation of the solutions

Ascorbic acid CRS standard solution. Accurately weighed about 0.08 g of ascorbic acid R
transfer to 200 ml volumetric flask, add 150 ml of water R, 2 ml of 0.1 M hydrochloric acid
solution, make to volume with water R and mix well.
The solution is available for 6 h.
Transfer 2 ml of the solution prepared to 100 ml volumetric flask, add 70 ml of water R, 1 ml of
0.1 M hydrochloric acid solution, make to volume with water R and mix well.
The solution is available for 4 h.
0.001 M hydrochloric acid solution. Transfer 1 ml of 0.1 M hydrochloric acid solution to
100 ml volumetric flask, make to volume with water R and mix well.
The solution is available for 1 month.
Note. All reagents, volumetric solutions and indicators are described in Ph. Eur. corresponding
chapters.

STIROLBIOFARM BALTIKUM LTD

3.2.P.5.3

Vitamin C Orange 500 mg chewable tablets

Validation of Analytical Procedures

Generally all methods of analyses are pharmacopoeial.

Description of the tablets is checked according to Ph. Eur. requirements.
Pink-orange biconvex tablets with break line and inscription C and 500 on one side, having
orange flavour and sweet and sharp taste. On the surface white or bright orange inclusions are
allowed; tablets may be with powder-like blush or slightly cogged.
For identification of active substances four specific methods are used:
A. It reduces silver nitrate solution R2 (17 g/l); producing a grey precipitate (ascorbate).
B. Dissolve 0.02 g of powdered tablets to be examined in 10 ml of water R, drop sodium 2,6dichlorophenolindophenolate solution: the blue colour of the last reagent immediately disappears
(ascorbate).
C. Dissolve 0.2 g of powdered tablets to be examined in 5 ml of water; the solution obtained
shows characteristic reaction of sodium (colourless flame upon introduction of the solution
becomes yellow).
D. UV spectrophotometry. UV absorption spectrum of the test solution prepared under Assay
test within the range 220 nm to 320 nm should have maximum of absorbance at 244 nm
(ascorbic acid).
pH, friability, loss on drying are determined according to Ph. Eur. requirements.
Average mass is determined according to Ph. Eur. requirements. 20 tablets are weighed with
precision 0.0001 g. Average mass should be within 5 % from nominal value.
Aerosil is performed according to In-house method.
Microbial contamination is determined according to Ph. Eur. requirements. The requirements
are as follows: total bacteria NMT 10 3/g and fungi NMT 102/g, absence of Enterobacteriaceae,
Pseudomonas aeruginosa and Staphylococcus aureus.
Assay of C6H8O6 (ascorbic acid) and of C6H7NaO6 (sodium ascorbate), calculated with reference
to ascorbic acid, is determined by UV spectrophotometric method developed.
Appropriate validation of UV spectrophotometric method, used for identification and for assay
determination was performed. Method was shown to be specific, linear (r = 0.9981) within used
interval (80 120 %), precise and accurate.
Validation Report, including validation plane and results, is presented on the following pages.

STIROLBIOFARM BALTIKUM LTD

3.2.P.5.4

Vitamin C Orange 500 mg chewable tablets

Batch Analyses

The analytical analysis results for 3 batches of Vitamin C Orange 500 mg chewable tablets are
tabulated below.
Quality certificates for corresponding batches No 840708, 850708 and 890708 are presented on
the following pages.
Tests

Requirements

Batch
No 840708

Batch
No 850708

Batch
No 890708

Description

Pink-orange biconvex tablets

with break line and
inscription C and 500 on
one side, having orange
flavour and sweet and sharp
taste. On the surface white or
bright orange inclusions are
allowed; Tablets may be with
powder-like blush or slightly
cogged.

Complies

Complies

Complies

Identification

Passes tests A, B, C and D

Uniformity of mass

0.9417 g 5.0 %

Passes tests
0.9264 g
3.2 %

Passes tests
0.9267 g
3.6 %

Passes tests
0.9322 g
1.8 %

pH

From 4.0 to 5.0

4.39

4.31

4.32

Friability

Not more than 3.0 %

1.50 %

1.94 %

1.76 %

Aerosil

Not more than 0.5 %

0.24 %

0.24 %

0.35 %

Loss on drying

Not more than 0.5 %

0.32 %

0.33 %

0.22 %

- bacteria

Not more than 1000/g

Less than 10

Less than 10

Less than 10

- fungi

Not more than 100/g

Less than 10

Less than 10

Less than 10

- Enterobacteriaceae

Absence

Not detected

Not detected

Not detected

- Pseudomonas
aeruginosa

Absence

Not detected

Not detected

Not detected

- Staphylococcus aureus

Absence

Not detected

Not detected

Not detected

Assay of ascorbic acid and

sodium ascorbate,
calculated to ascorbic acid

From 0.475 g to 0.525 g

0.504 g

0.514 g

0.487 g

Microbial contamination:

STIROLBIOFARM BALTIKUM LTD

3.2.P.5.5

Characterisation of Impurities

Not applicable

Vitamin C Orange 500 mg chewable tablets

STIROLBIOFARM BALTIKUM LTD

3.2.P.5.6

Vitamin C Orange 500 mg chewable tablets

Justification of Specification

All specifications and established limits for Vitamin C Orange 500 mg chewable tablets are in
accordance with the Ph. Eur. general requirements for tablets.
Description
The external appearance of the tablets remains unchanged during the whole products life.
Determine visually.
This test is performed in every batch.
Identification
The identification is carried out by four specific methods:
a) reducing of silver nitrate solution (prove of ascorbate ion);
b) discoloration of 2,6-dichlorophenolindophenolate solution (prove of ascorbate ion);
c) characteristic reaction of sodium;
d) comparison of the test solution absorption maxima versus the standard.
All above mentioned methods are specific methods and, therefore, appropriate for a selective
identification.
These tests are performed in every batch.
Average mass and uniformity of mass
The test is performed according to the established by ph. Eur. specification and acceptance
criterion. This test is performed in every batch.
Friability
The test is performed according to the established by Ph. Eur. specification and acceptance
criterion. This test is performed in every batch.
pH
The test is performed according to the established by manufacturer specification and acceptance
criterion. This test is performed in every batch.
Aerosil
The test is performed according to the established by manufacturer specification and acceptance
criterion. This test is performed in every batch.

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

Loss on drying
The test is performed according to the established by manufacturer specification and acceptance
criterion. This test is performed in every batch.
Microbial contamination
The test is carried out according to the required criteria of Ph. Eur. for preparations for oral
administration.
Assay
According to ICH Guidelines the content deviation for ascorbic acid in tablet is 5.0 %. Assay
requirements: from 0.475 to 0.525 g.
For this reason there is not necessary further justification.
This test will be performed in every batch.

In conclusion, the specification, analytical methods and limits set for quality control of the
finished product Vitamin C Orange 500 mg chewable tablets are found to be acceptable.

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

3.2.P.6 Reference Standards or Materials

STIROLBIOFARM BALTIKUM LTD

3.2.P.6

Vitamin C Orange 500 mg chewable tablets

Reference Standards or Materials

Ascorbic acid CRS In-house standard is used as reference substance assay determination by UV
spectrophotometric method. No other reference standards are needed in the routine analysis.

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

3.2.P.7 Container Closure System

STIROLBIOFARM BALTIKUM LTD

3.2.P.7

Container Closure System

3.2.P.7.1

Primary Packaging

Vitamin C Orange 500 mg chewable tablets

Finished product Vitamin C Orange 500 mg chewable tablets are packed in blisters, formed
according to internal standard OCT 64-074-91, from aluminium foil, manufactured by company
Alupak (Slovenia), and polyvinylchloride film, manufactured by company TBP (Slovenia).
Also the finished product Vitamin C 500 mg chewable tablets is packed in plastic containers.
The quality of the packaging materials is tested according to the corresponding internal
normative documentation.
To the documentation attached:
1) quality specification for aluminium foil used in Klckner blistering equipment and its
translation in English;
2) quality specification for aluminium foil used in NOACK blistering equipment and its
translation in English;
3) method 1 for analysis of aluminium foil and its translation in English;
4) quality specification for polyvinylchloride film used in Klckner blistering equipment and
its translation in English;
5) quality specification for polyvinylchloride film used in NOACK blistering equipment and
its translation in English;
6) method 2 for analysis of polyvinylchloride film and its translation in English;
7) quality specification for plastic container 75 ml;
8) quality specification for plastic container 90 ml;
9)

quality certificate for plastic containers.

STIROLBIOFARM BALTIKUM LTD

3.2.P.7.2

Vitamin C Orange 500 mg chewable tablets

Secondary Packaging

One blister or plastic container together with Patient Information Leaflet is packed in cardboard
box.
Cardboard boxes for blisters are tested according to internal standard 12301-81 or 1230380.

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

3.2.P.8 Stability

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

3.2.P.8

Stability

3.2.P.8.1

Stability Summary and Conclusion

3.2.P.8.1.1

Long-term stability studies

Long-term stability studies are carried out to identify characteristics of a product that may
change under defined conditions. This type of study is for the stability assessment of a product
under normal conditions.
Studies are designed to establish appropriate expiration periods and product storage
requirements.
Summary
Long- term stability studies for Vitamin C Orange 500 mg chewable tablets were carried out for
batches, packed in blisters as well as in plastic containers. The packaging is the same as that of
the marketed product.
The product was manufactured according to the proposed formulation on equipment that is
entirely representative of full-scale production.
Batches tested
010197, 020197, 0300197, 040197 and 050197 packed in PVC/Al blisters.
060197, 070197, 0800197, 090197 and 100197 packed in plastic containers.
210304, 220304 and 230304 - packed in PVC/Al blisters (according to current Quality
Specification for the finished product).
Tests performed
Tests checked were description, identification, uniformity of tablet mass, pH, aerosol, friability,
loss on drying, microbial contamination and assay.
Test methods
The validated analytical methods employed in the stability tests for Vitamin C Orange 500 mg
chewable tablets are the same as for freshly prepared product.
Storage conditions
All stability batches were stored protected from light at (25 2) C/ (60 5)% RH under
controlled conditions.
Frequency of analysis
0; 6; 12, 18; 24; 30 and 33 months

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

Results
Stability test results obtained after 33 months storage at (25 2) C/ (605)% RH demonstrate
conformance of the product Vitamin C Orange 500 mg chewable tablets to the quality
specification requirements.

3.2.P.8.1.2

Accelerated stability studies

Not applicable

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

Conclusion
Finished product Vitamin C Orange 500 mg chewable tablets when properly stored is a stable
product. On the basis of stability testing results, the 3 years shelf life for Vitamin C Orange
500 mg chewable tablets is established.

STIROLBIOFARM BALTIKUM LTD

3.2.P.8.2

Vitamin C Orange 500 mg chewable tablets

Post-approval Stability Protocol and Stability Commitment

Stability studies are ongoing and will be continued. Upon approval, at least one batch of
manufactured finished product Vitamin C Orange 500 mg chewable tablets will be incorporated
annually into a programme of ongoing stability trials. All batches included in the stability
program will be tested according to the protocol (long-term).

STIROLBIOFARM BALTIKUM LTD

3.2.P.8.3

Vitamin C Orange 500 mg chewable tablets

Stability Data

The analytical methods employed in the stability tests for Vitamin C Orange 500 mg chewable
tablets are those used for the freshly prepared finished product analyses.
The results of stability tests are summarized in the table format and presented on the following
pages.

STIROLBIOFARM BALTIKUM LTD

3.2.A

Vitamin C Orange 500 mg chewable tablets

APPENDICES

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

3.2.A

Appendices

3.2.A.1
3.2.A.2
3.2.A.3

Facilities and Equipment

Adventitious Agents Safety Evaluation
Excipients
Not applicable

STIROLBIOFARM BALTIKUM LTD

3.2.R

Vitamin C Orange 500 mg chewable tablets

REGIONAL INFORMATION

STIROLBIOFARM BALTIKUM LTD

3.2.R

Vitamin C Orange 500 mg chewable tablets

Regional information

Company DSM Nutritional Products Ltd. has been granted Certificate of Suitability of
monographs of European Pharmacopoeia No R1-CEP 1996-078-Rev 01 for the active substance
Ascorbic Acid. Certificate of Suitability is presented on the following pages.

Company DSM Nutritional Products Ltd. has been granted Certificate of Suitability of
monographs of European Pharmacopoeia No R0-CEP 2002-254-Rev 00 for the active substance
Sodium Ascorbate. Certificate of Suitability is presented on the following pages.

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

3.3. LITERATURE REFERENCES

STIROLBIOFARM BALTIKUM LTD

Vitamin C Orange 500 mg chewable tablets

Literature

1. J.E.F. Reynolds. Martindale. The Extra Pharmacopoeia. London: The Pharmaceutical Press,
1989.
2. Rote Liste 2003.
3. Remingtons Pharmaceutical Sciences. Easton, Pennsylvania 18042: Mack Publishing
Company, 1990.
4. Raymond C. Rowe, Paul J. Sheskey, Paul J. Weller. Handbook of Pharmaceutical Excipients,
Fourth Edition. London, Chicago: Pharmaceutical Press, 2003.
5. Russian Pharmacopoeia XI edition ( XI).
6. Ukrainian State Pharmacopoeia ().
7. European Pharmacopoeia current edition.
8. The United States Pharmacopeia current edition.
9. The British Pharmacopoeia current edition.