Specification

Lovex, 100 mg Tablets

Tests

Specifications

References

Appearance

White or off white tablets with

Visual inspection

facet and breakline on one side.

Identification
1) HPLC

1)

The retention time of the

Ph.Eur. 2.2.29.

standard solution main peak and

2) Reaction on citrates

the test solution main peak should

Ph.Eur. 2.3.1.

be essentially identical.
2)

Gives reactions of citrates

600.0 mg 5 %

Ph.Eur. 2.9.5.

Disintegration

NMT 15 minutes

Ph.Eur. 2.9.1.

Friability

NMT 0.1 %

Ph.Eur. 2.9.7.

Dissolution

NMT 75 % of labeled amount of

Ph.Eur. 2.9.3.

Average weight and

uniformity of weight (by
weight variation)

Sildenafil Citrate in 45 minutes

Related substance (HPLC)

Any impurity NMT 1.0 %

Ph.Eur. 2.2.29.

Total impurity NMT 2.0 %

Microbial contamination

Ph.Eur. 5.1.4.

Total aerobic count

NMT 1000 cfu/g

Fungi

NMT 00 cfu/g

E. Coli

Absent/g

Assay

From 90.0 % to 110 %

Ph.Eur. 2.2.29.

Analytical Methods
Appearance.
White or off white tablets with facet and breakline on one side.
Identification
1)
Using method given under Assay by HPLC, the retention time of the standard solution main
peak and the test solution main peak should be essentially identical.
2)
Crush 20 tablets to the powder. Dissolve 0.5 mg of this powder in 10 ml of water R, filter
through paper. Add 3 ml of 200 g/l calcium chloride solution to 1 ml of filtrate and boiled. The white
residue formed, which resolves after cooling (Ph. Eur. 2.3.1).
Average weight and uniformity of weight (Ph. Eur. 2.9.5.)
600 mg 5 %
Weigh individually 20 tablets taken at random and determine the average mass. Not more than 2 of
the individual masses deviate from the average mass by more than 5 % and none deviates by more
than twice that percentage.
Disintegration ( Ph. Eur. 2.9.1.)
Must comply with test for uncoated tablets. Use water R at 37 2 C temperature. Add a disc to each
tube. Operate the apparatus for 15 min and examine the state of the tablets. If the tablets fail to
comply because of adherence to the discs, the results are invalid. Repeat the test on a further 6 tablets
omitting the discs.
Friability ( Ph. Eur. 2.9.7.)
Take a sample of whole tablets corresponding as near as possible to 6.0 g. The tablets are carefully
dedusted prior to testing. Accurately weigh the tablet sample, and place the tablets in the drum.
Rotate the drum 100 times, and remove the tablets. Remove any loose dust from the tablets as before,
and accurately weigh.
Generally, the test is run once. If obviously cracked, cleaved, or broken tablets are present in the
tablet sample after tumbling, the sample fails the test. If the results are difficult to interpret or if the
weight loss is greater than the targeted value, the test is repeated twice and the mean of the 3 tests

determined. A maximum loss of mass (obtained from a single test or from the mean of 3 tests) not
greater than 1.0 per cent is considered acceptable for the tablet.
Dissolution
Dissolution conditions
Apparatus
Dissolution medium
Rate
Time

: Type II (Padle)
: 500 ml, 0.1 M HCl
: 100 rpm
: 45 minutes

Method: Spectrophotometric (Ph. Eur. 2.2.25.)

Test solution:
Place one tablet in each vessel and carry out the method according to Ph. Eur. 2.9.3. After 45
minutes, pipette 25 ml of the solution from each vessel. Filter the solution through a suitable
membane fiber filer (diameters of pores 0.45 m), disregarding the first 5 ml. Dilute 5.0 ml of this
solution to 50.0 ml with 0.1 M HCl.
Standard solution:
Transfer approximately 14 mg of Sildenafil citrate WS, accurately weighed into a 10 ml volumetric
flask. Dissolve with sufficient volume (app. 5 ml) of 0.1 M HCl and dilute to the volume with the
same solvent. Pipette 1 ml of this solution a 50 ml volumetric flask. Dilute to the volume with 0.1 M
HCl. Protect solution from light.
Procedure:
Measure the absorbance values of the solutions using 0.1 M HCl as a blank at 290 nm wavelight.
Calculation:
D 1 m 0 500 50 P100 0.7129
D 1 m 0 P 1.4258
= ----------------------------------------------------- = ---------------------------D0 a 50 50 5 100
D0 a
D0 The absorbance value of Test Solution
D1 The absorbance value of Standard solution;
m0 Weigh of Sildenafil citrate WS, in mg;

a labeling amount of Sildenafil, mg;

P Potency of Sildenafil citrate WS , %,
0.7129 Conversation coefficient of Sildenafil citrate to Sildenafil
Limit: Not less than 75 % of the labeled amount of Sildenafil is dissolved in 45 minutes.
Related substance (HPLC, Ph. Eur. 2.2.29.)
Proceed as described in Assay.
Test solution (a):
Powder 10 tablets finely. Transfer 300 mg of the tablet powder (equivalent to 50 mg of Sildenafil) to
a 100 ml volumetric flask, add 70 ml of mobile phase, shake with mechanical shaker. Dilute to
volume with the same solvent and mix. Pipette 5 ml of this solution into 10 ml volumetric flask.
Dilute to the volume with mobile phase.
Test solution (b):
Dilute 1.0 ml of the test solution (a) to 100 ml the mobile phase.
Evaluations:
In the chromatogram obtained with the test solution (a):
1. The area of any peak is not greater than the area of the principal peak in the chromatogram
obtained with the test solution (b) (1.0 per cent)
2. The sum of the areas of all the peaks, apart from the principal peak is not greater than 2 times
the area of the principal peak in the chromatogram obtained with the test solution (b) (2.0 per
cent).
Calculation:
r 1 100
-------------------------- = Individual impurity, %
rt
r1 The peak area of the individual impurity obtained from the test solution (a);
rt The total peak apart from the mobile phase obtained from the test solution (a).
Microbial contamination (Ph. Eur. 5.1.4.)

Total viable aerobic count. Not more than 103 aerobic bacteria and not more than 102 fungi per gram.
Absence of Escherichia coli (1 g).
Assay (HPLC, Ph. Eur. 2.2.29.)
Chromatographic conditions:
Apparatus

: High Pressure Liquid Chromatography

Column

: C18, 15 cm 4.0 mm, 5 m, temperature 30 C

Detector

: UV, 290 nm

Flow rate

: 1.0 ml/min

Injection volume

: 15 l

Mobile phase

: filtered and degassed phosphate buffer pH 3.0 methanol

acetonitrile (58:25:17)

Pump

: Isocratic

Test solution:
Powder 20 tablets finally. Transfer 510 mg of the tablet powder to a 100 ml volumetric flask. Add 10
ml of Acetonitrile : water mixture (9:1 v/v), sonicate for 10 minutes, add sufficient volume of mobile
phase and sonicate 10 minutes. Shake with a mechanical shaker for 30 minutes. Dilute to the volume
with the mobile phase, centrifuge at 8000 rpm during 5 minutes.
Test solution (a):
Transfer 0.1 g of Sildenafil citrate WS to a 100 ml volumetric flask, add 70 ml of mobile phase.
Dilute to volume with the mobile phase and mix.
Phosphate buffer pH 3.0:
Transfer 7 ml of Triethylamine into 1000 ml volumetric flask consisting 900 ml of water R. Mix and
adjust pH to 3.0 with phosphoric acid. Dilute to the volume with water.
Calculation:

S 1 m 0 100P1000
S 1 m 0 P10
(Sildenafil/Tablet)=----- ---------- ----------------- b = -------------------- b,
S0 m 1 100 100
S0 m 1
where
S1 The peak area of Sildenafil citrate obtained from the test solution;
S0 The peak area of Sildenafil citrate obtained from the standard solution;
m0 Weight of Sildenafil citrate WS, in mg;
m1 Weight of sample, in mg;
b Average weight of tablets, in mg;
P Potency of Sildenafil citrate WS, in %.
Limit: From 90.0 % to 110.0 % of Sildenafil (C22H30N6O4S) in tablet.
Presentation.
100 mg tablets. Blister of 1x4 tablets in a carton box with a leaflet.
Labeling.
On primary packaging name of manufacturer, manufacturing country, name of customer and its
requisites, name of pharmaceutical product, INN, dosage, batch N, expire date.
On secondary packaging - name of manufacturer, manufacturing country, name of customer and its
requisites, name of pharmaceutical product, INN, dosage, dosage form, storage, batch N, quantity in
packaging, +expire date, bar code.
Storage. Store at a dry place at temperature below 25 C. Protect from light.
Shelf-Life. 2 years. Do not use after the expiry date printed on the pack.
Pharmacotherapeutic Group. Drugs used in erectile dysfunction.

LOVEX
Diagram 1: Flow Diagram of Manufacturing Process for tablets batch

Sifting

#40 mesh

SS Screen ( SS Screen

Tumbler bin; 200 l

30 minutes; 20 rpm

Tumbler bin; 200 l

5 minutes; 20 rpm

Tablet press
Tablet weight: 600mg (570-630)
Hardness: 20-25 kgf

Blister packaging machine

Blister of 1x4 tablets, 100 mg/tab

Pre-Mix

Final Blend

Compression

Packaging

Quality control product

Finished Product

Colloidal Silicon Dioxide USP/NF

(Aerosil 200)
Microcrystalline Cellulose Ph. Eur.
Materials from sifting step
Mannitol ,
Sildenafil Citrate USP,
Zinc Citrate dihydrate

Sifting

#40 mesh
SS Screen

Magnesium Stearate USP/NF

Manufacturing
Master Manufacturing Formula:
BATCH SIZE: 80 000 Tablets

Name of the Ingredient

Specifications

Overages (%)

Qty. /Batch (%)

Active Ingredients
1.

Sildenafil Citrate

USP

NIL

21.6

In-Active Ingredients
2.

Microcrystalline cellulose

Ph. Eur.

NIL

16.7

3.

Zinc acetate dihydrate

Ph. Eur./USP

NIL

1.7

4.

Aerosil

USP/NF

NIL

1.0

5.

Mannitol

Ph. Eur./USP

NIL

58.0

6.

Magnesium stearate

Ph. Eur.

NIL

1.0

MANUFACTURING PROCESS
OF
LOVEX
Sildenafil Tablets 100 mg
Method of Manufacture
All the operations are carried out in a clean area following good manufacturing practices and
under controlled conditions of temperature and humidity.
Line clearance:
Before manufacturing operation is begun:
All machineries and equipment used for manufacturing process are cleaned as per respective
standard operating procedure for cleaning.
The manufacturing area to be used is cleaned and made suitable for operations.
All the process, products name are properly displayed in notified area.
Safety gadgets like hand gloves, mask and slippers provided to workmen.
List of Equipments:
SS Screen
Sifter
Sieves
Tumbler bin
Tablet press
Blister packaging machine
OPERATIONAL PROCEDURE

Issue intimation slip to Q. A. D. for Swab Test / Wash Water Analysis & D. M. water analysis.
After getting approval (Line Clearance) from Q. A. D. start the procedure as follows.
1. WEIGHING:
Weigh accurately all the active and inactive ingredients. Recheck the weight of dispensed
materials received from stores.
2. SIFTING:
Sift Sildenafil Citrate USP, Colloidal Silicon Dioxide (Aerosil) USP/NF, Microcrystalline
Cellulose Ph. Eur., Mannitol Ph.Eur./USP, Zinc Acetate Dihydrate Ph.Eur./USP, and Magnesium
Stearate Ph.Eur. through sifter using 40 # sieve in In process container (IPC).

3. PRE- MIXING:
Take Aerosil, Microcrystalline Cellulose sift together then put to the 200 l tumbler bin along
with Mannitol, Sildenafil Citrate and Zinc Citrate Dihydrate. Mix during 30 min at 20 rpm.
4. FINAL BLEND:
Put Magnesium Stearate to the ready mix in the 200 l tumbler bin and mix for 5 min at 20 rpm.
5. COMPRESSION
Carry the IPC Container to the compression cubicle using trolley.
Mount the IPC content on the hopper of 27 station double rotary compression machine.
Adjust parameters as given in In process check and test the parameters for individual punch.
Discard the tablets obtained during trial run and put in SS bin for rejected materials.
The parameters if within limits compress the tablets and collect in capacity IPCs with proper
labeling.
In-process control Tablet average weight 600 mg 5% (570 mg 630 mg); Hardness 20-25
kgf.
6. VISUAL INSPECTION:
Visual inspection of the tablets is done & good tablets are stored.
7. OVERPRINTING DETAILS:
Print the required details on the Cartons & Box Labels.
8. PACKING (BLISTER PACKING)
To be packed as per the Standard Packing Specification.
9. STORAGE
Store below 25 C in a dry place. Protect from light.

ACCELERATED TIME (SHORT TERM) STABILITY STUDY REPORT

FOR
3 BATCHES STORED AT ROOM TEMPERATURE
25C ( 2C) AND RELATIVE HUMIDITY 60% ( 5%)

Stability studies were carried out on the three following batches of Lovex (100 mg tablets #4)
Batch No.

LV010612

LV020612

LV030612

Mfg. Date

01/06/2012

02/06/2012

03/06/2012

Expiry Date

01/06/2014

02/06/2014

03/06/2014

The 3 batches are stored in the commercial packaging.

(Alu-PVC blister pack of 10 tablets. Blister of 1x4 tablets in a carton box with a leaflet.)

ACCELERATED TIME (SHORT TERM) STABILITY STUDY REPORT

Product Name

Lovex

Generic Name

:
:

Sildenafil
Each tablet contains:
Sildenafil (as citrate) 100 mg;
excipients: microcrystalline cellulose, zinc citrate
dihydrate, aerosol, mannitol, magnesium stearate.

Batch No.

LV010612

Batch size

1 000 Tablets

Manufacturing Date

01/06/2012

Expiry Date

Storage Conditions

01/06/2014
Store at temperature 40C ( 20C ) & Relative
Humidity 75% ( 5%)

Pack Size

Description

Identification

Average weight of tablet

Disintegration time

Contents

Grateness of tablets
Dissolution
Related substances
Microbial limit test

Assay
Analytical Method

:
:
:
:
:

:
:

Alu-PVC blister pack of 4 Tablets

White to off white colored, round-shaped, flat, bevelled
edge, uncoated tablets with score mark on one side.
A: TLC
B: The retention times of the major peaks in the
chromatogram of the Assay preparation correspond to
those in the chromatogram of the Standard preparation,
as obtained in the Assay.
600 mg 5%
NMT 15.0 min
NMT 1.0%
NLT 75% of Active Ingredient dissolved in 45 minutes
Individual NMT 0.5%
total NMT 1.0%
Not more than 1000 cfu/gm total aerobic microbial
count.
Not more than 100 cfu/gm for yeast & mold,
Escherichia coli absent.
90110 mg
As per USP, Ph. Eur., Inhouse

ACCELERATED TIME (SHORT TERM) STABILITY STUDY REPORT

Tests
Description

Identification
Average weight of tablet and
Uniformity of weight
Disintegration time
Grateness of tablets
Dissolution
Related substances
Microbial limit test

Assay

0
12.06.12
Complies

Results of Analysis
3
6
10.09.12
10.12.13
Complies
Complies

Positive

Positive

Positive

600.0 mg 5 % (570.0630.0) mg

615 mg

611 mg

602 mg

NMT 15.0 min

NMT 1.0%
NLT 75%
Individual NMT 0.5%
total NMT 1.0%
Not more than 1000 cfu/gm total aerobic
microbial count
Not more than 100 cfu/gm for yeast &
mold, Escherichia coli absent.
90110 mg

5.0 min
1.0%
95%
Complies

8 min
1.0%
81%
Complies

7 min
1.0%
79%
Complies

Complies

Complies

Complies

105 mg/tab

101 mg/tab

103 mg/tab

Limits
White to off white colored, round-shaped,
flat, bevelled edge, uncoated tablets with
score mark on one side.
Positive

Discussion: The results show that there are no significant physical or chemical changes when the product is kept at a temperature of 25C
2C and relative humidity 60% 5 % for 12 months.
Remarks: The above product is stable for a period of 24 months.

ACCELERATED TIME (SHORT TERM) STABILITY STUDY REPORT

Product Name

Lovex

Generic Name

:
:

Sildenafil
Each tablet contains:
Sildenafil (as citrate) 100 mg;
excipients: microcrystalline cellulose, zinc citrate
dihydrate, aerosol, mannitol, magnesium stearate.

Batch No.

LV020612

Batch size

1 000 Tablets

Manufacturing Date

02/06/2012

Expiry Date

Storage Conditions

02/06/2014
Store at temperature 40C ( 20C ) & Relative
Humidity 75% ( 5%)

Pack Size

Description

Identification

Average weight of tablet

Disintegration time

Contents

Grateness of tablets
Dissolution
Related substances
Microbial limit test

Assay
Analytical Method

:
:
:
:
:

:
:

Alu-PVC blister pack of 4 Tablets

White to off white colored, round-shaped, flat, bevelled
edge, uncoated tablets with score mark on one side.
A: TLC
B: The retention times of the major peaks in the
chromatogram of the Assay preparation correspond to
those in the chromatogram of the Standard preparation,
as obtained in the Assay.
600 mg 5%
NMT 15.0 min
NMT 1.0%
NLT 75% of Active Ingredient dissolved in 45 minutes
Individual NMT 0.5%
total NMT 1.0%
Not more than 1000 cfu/gm total aerobic microbial
count.
Not more than 100 cfu/gm for yeast & mold,
Escherichia coli absent.
90110 mg
As per USP, Ph. Eur., Inhouse

ACCELERATED TIME (SHORT TERM) STABILITY STUDY REPORT

Tests
Description

Identification
Average weight of tablet and
Uniformity of weight
Disintegration time
Grateness of tablets
Dissolution
Related substances
Microbial limit test

Assay

0
12.06.12
Complies

Results of Analysis
3
6
10.09.12
10.12.13
Complies
Complies

Positive

Positive

Positive

600.0 mg 5 % (570.0630.0) mg

598 mg

595 mg

601 mg

NMT 15.0 min

NMT 1.0%
NLT 75%
Individual NMT 0.5%
total NMT 1.0%
Not more than 1000 cfu/gm total aerobic
microbial count
Not more than 100 cfu/gm for yeast &
mold, Escherichia coli absent.
90110 mg

7.0 min
1.0%
90%
Complies

6.0 min
1.0%
88%
Complies

5.0 min
1.0%
85%
Complies

Complies

Complies

Complies

98 mg/tab

96 mg/tab

97 mg/tab

Limits
White to off white colored, round-shaped,
flat, bevelled edge, uncoated tablets with
score mark on one side.
Positive

Discussion: The results show that there are no significant physical or chemical changes when the product is kept at a temperature of 25C
2C and relative humidity 60% 5 % for 12 months.
Remarks: The above product is stable for a period of 24 months.

ACCELERATED TIME (SHORT TERM) STABILITY STUDY REPORT

Product Name

Lovex

Generic Name

:
:

Sildenafil
Each tablet contains:
Sildenafil (as citrate) 100 mg;
excipients: microcrystalline cellulose, zinc citrate
dihydrate, aerosol, mannitol, magnesium stearate.

Batch No.

LV020612

Batch size

1 000 Tablets

Manufacturing Date

03/06/2012

Expiry Date

Storage Conditions

03/06/2014
Store at temperature 40C ( 20C ) & Relative
Humidity 75% ( 5%)

Pack Size

Description

Identification

Average weight of tablet

Disintegration time

Contents

Grateness of tablets
Dissolution
Related substances
Microbial limit test

Assay
Analytical Method

:
:
:
:
:

:
:

Alu-PVC blister pack of 4 Tablets

White to off white colored, round-shaped, flat, bevelled
edge, uncoated tablets with score mark on one side.
A: TLC
B: The retention times of the major peaks in the
chromatogram of the Assay preparation correspond to
those in the chromatogram of the Standard preparation,
as obtained in the Assay.
600 mg 5%
NMT 15.0 min
NMT 1.0%
NLT 75% of Active Ingredient dissolved in 45 minutes
Individual NMT 0.5%
total NMT 1.0%
Not more than 1000 cfu/gm total aerobic microbial
count.
Not more than 100 cfu/gm for yeast & mold,
Escherichia coli absent.
90110 mg
As per USP, Ph. Eur., Inhouse

ACCELERATED TIME (SHORT TERM) STABILITY STUDY REPORT

Tests
Description

Identification
Average weight of tablet and
Uniformity of weight
Disintegration time
Grateness of tablets
Dissolution
Related substances
Microbial limit test

Assay

0
12.06.12
Complies

Results of Analysis
3
6
10.09.12
10.12.13
Complies
Complies

Positive

Positive

Positive

600.0 mg 5 % (570.0630.0) mg

615 mg

611 mg

602 mg

NMT 15.0 min

NMT 1.0%
NLT 75%
Individual NMT 0.5%
total NMT 1.0%
Not more than 1000 cfu/gm total aerobic
microbial count
Not more than 100 cfu/gm for yeast &
mold, Escherichia coli absent.
90110 mg

8.0 wT
1.0%
90%
Complies

5.0 wT
1.0%
87%
Complies

6.0 wT
1.0%
84%
Complies

Complies

Complies

Complies

103 mg/tab

95 mg/tab

98 mg/tab

Limits
White to off white colored, round-shaped,
flat, bevelled edge, uncoated tablets with
score mark on one side.
Positive

Discussion: The results show that there is no significant physical or chemical changes when the product is kept at a temperature of 400C (
20C ) and Relative Humidity 75% ( 5%) for 6 months.
Remarks: The 24 months expiration period is supported by the available stability study performed under accelerated conditions (40C
2C/75% RH 5%RH) for 6 months.

LOVEX
Diagram 1: Flow Diagram of Manufacturing Process for tablets batch

Sifting

Tumbler bin; 200L

Pre-Mix

30 minutes; 20 rpm

Tumbler bin; 200L

5 minutes; 20 rpm

Tablet press
Tablet weight: 600 mg (570-630)
Hardness: 20-25 kgf

Blister packaging machine

Blister of 1x4 tablets, 100mg/tab

Final Blend

Compression

Packaging

Quality control product

Finished Product

#40 mesh
SS Screen

Colloidal Silicon Dioxide NF

(Aerosil 200)
microcrystalline cellulose
Materials from sifting step
Mannitol,
Sildenafil Citrate,
zinc citrate dihydrate

Sifting

#40 mesh
SS Screen

Magnesium stearate, NF

Specification
Lovex, 100 mg Tablets
Tests

Specifications

References

Appearance

White or off white tablets with

Visual inspection

facet and breakline on one side.

Identification
1) HPLC

1)

The retention time of the

Ph.Eur. 2.2.29.

standard solution main peak and

2) Reaction on citrates

the test solution main peak should

Ph.Eur. 2.3.1.

be essentially identical.
2)

Gives reactions of citrates

600.0 mg 5 %

Ph.Eur. 2.9.5.

Disintegration

NMT 15 minutes

Ph.Eur. 2.9.1.

Friability

NMT 0.1 %

Ph.Eur. 2.9.7.

Dissolution

NMT 75 % of labeled amount of

Ph.Eur. 2.9.3.

Average weight and

uniformity of weight (by
weight variation)

Sildenafil Citrate in 45 minutes

Related substance (HPLC)

Any impurity NMT 1.0 %

Ph.Eur. 2.2.29.

Total impurity NMT 2.0 %

Microbial contamination

Ph.Eur. 5.1.4.

Total aerobic count

NMT 1000 cfu/g

Fungi

NMT 00 cfu/g

E. Coli

Absent/g

Assay

From 90.0 % to 110 %

Ph.Eur. 2.2.29.

Analytical Methods
Appearance.
White or off white tablets with facet and breakline on one side.
Identification
1)
Using method given under Assay by HPLC, the retention time of the standard solution main
peak and the test solution main peak should be essentially identical.
2)
Crush 20 tablets to the powder. Dissolve 0.5 mg of this powder in 10 ml of water R, filter
through paper. Add 3 ml of 200 g/l calcium chloride solution to 1 ml of filtrate and boiled. The white
residue formed, which resolves after cooling (Ph. Eur. 2.3.1).
Average weight and uniformity of weight (Ph. Eur. 2.9.5.)
600 mg 5 %
Weigh individually 20 tablets taken at random and determine the average mass. Not more than 2 of
the individual masses deviate from the average mass by more than 5 % and none deviates by more
than twice that percentage.
Disintegration ( Ph. Eur. 2.9.1.)
Must comply with test for uncoated tablets. Use water R at 37 2 C temperature. Add a disc to each
tube. Operate the apparatus for 15 min and examine the state of the tablets. If the tablets fail to
comply because of adherence to the discs, the results are invalid. Repeat the test on a further 6 tablets
omitting the discs.
Friability ( Ph. Eur. 2.9.7.)
Take a sample of whole tablets corresponding as near as possible to 6.0 g. The tablets are carefully
dedusted prior to testing. Accurately weigh the tablet sample, and place the tablets in the drum.
Rotate the drum 100 times, and remove the tablets. Remove any loose dust from the tablets as before,
and accurately weigh.
Generally, the test is run once. If obviously cracked, cleaved, or broken tablets are present in the
tablet sample after tumbling, the sample fails the test. If the results are difficult to interpret or if the
weight loss is greater than the targeted value, the test is repeated twice and the mean of the 3 tests

determined. A maximum loss of mass (obtained from a single test or from the mean of 3 tests) not
greater than 1.0 per cent is considered acceptable for the tablet.
Dissolution
Dissolution conditions
Apparatus
Dissolution medium
Rate
Time

: Type II (Padle)
: 500 ml, 0.1 M HCl
: 100 rpm
: 45 minutes

Method: Spectrophotometric (Ph. Eur. 2.2.25.)

Test solution:
Place one tablet in each vessel and carry out the method according to Ph. Eur. 2.9.3. After 45
minutes, pipette 25 ml of the solution from each vessel. Filter the solution through a suitable
membane fiber filer (diameters of pores 0.45 m), disregarding the first 5 ml. Dilute 5.0 ml of this
solution to 50.0 ml with 0.1 M HCl.
Standard solution:
Transfer approximately 14 mg of Sildenafil citrate WS, accurately weighed into a 10 ml volumetric
flask. Dissolve with sufficient volume (app. 5 ml) of 0.1 M HCl and dilute to the volume with the
same solvent. Pipette 1 ml of this solution a 50 ml volumetric flask. Dilute to the volume with 0.1 M
HCl. Protect solution from light.
Procedure:
Measure the absorbance values of the solutions using 0.1 M HCl as a blank at 290 nm wavelight.
Calculation:
D 1 m 0 500 50 P100 0.7129
D 1 m 0 P 1.4258
= ----------------------------------------------------- = ---------------------------D0 a 50 50 5 100
D0 a
D0 The absorbance value of Test Solution
D1 The absorbance value of Standard solution;
m0 Weigh of Sildenafil citrate WS, in mg;

a labeling amount of Sildenafil, mg;

P Potency of Sildenafil citrate WS , %,
0.7129 Conversation coefficient of Sildenafil citrate to Sildenafil
Limit: Not less than 75 % of the labeled amount of Sildenafil is dissolved in 45 minutes.
Related substance (HPLC, Ph. Eur. 2.2.29.)
Proceed as described in Assay.
Test solution (a):
Powder 10 tablets finely. Transfer 300 mg of the tablet powder (equivalent to 50 mg of Sildenafil) to
a 100 ml volumetric flask, add 70 ml of mobile phase, shake with mechanical shaker. Dilute to
volume with the same solvent and mix. Pipette 5 ml of this solution into 10 ml volumetric flask.
Dilute to the volume with mobile phase.
Test solution (b):
Dilute 1.0 ml of the test solution (a) to 100 ml the mobile phase.
Evaluations:
In the chromatogram obtained with the test solution (a):
1. The area of any peak is not greater than the area of the principal peak in the chromatogram
obtained with the test solution (b) (1.0 per cent)
2. The sum of the areas of all the peaks, apart from the principal peak is not greater than 2 times
the area of the principal peak in the chromatogram obtained with the test solution (b) (2.0 per
cent).
Calculation:
r 1 100
-------------------------- = Individual impurity, %
rt
r1 The peak area of the individual impurity obtained from the test solution (a);
rt The total peak apart from the mobile phase obtained from the test solution (a).
Microbial contamination (Ph. Eur. 5.1.4.)

Total viable aerobic count. Not more than 103 aerobic bacteria and not more than 102 fungi per gram.
Absence of Escherichia coli (1 g).
Assay (HPLC, Ph. Eur. 2.2.29.)
Chromatographic conditions:
Apparatus

: High Pressure Liquid Chromatography

Column

: C18, 15 cm 4.0 mm, 5 m, temperature 30 C

Detector

: UV, 290 nm

Flow rate

: 1.0 ml/min

Injection volume

: 15 l

Mobile phase

: filtered and degassed phosphate buffer pH 3.0 methanol

acetonitrile (58:25:17)

Pump

: Isocratic

Test solution:
Powder 20 tablets finally. Transfer 510 mg of the tablet powder to a 100 ml volumetric flask. Add 10
ml of Acetonitrile : water mixture (9:1 v/v), sonicate for 10 minutes, add sufficient volume of mobile
phase and sonicate 10 minutes. Shake with a mechanical shaker for 30 minutes. Dilute to the volume
with the mobile phase, centrifuge at 8000 rpm during 5 minutes.
Test solution (a):
Transfer 0.1 g of Sildenafil citrate WS to a 100 ml volumetric flask, add 70 ml of mobile phase.
Dilute to volume with the mobile phase and mix.
Phosphate buffer pH 3.0:
Transfer 7 ml of Triethylamine into 1000 ml volumetric flask consisting 900 ml of water R. Mix and
adjust pH to 3.0 with phosphoric acid. Dilute to the volume with water.
Calculation:

S 1 m 0 100P1000
S 1 m 0 P10
(Sildenafil/Tablet)=----- ---------- ----------------- b = -------------------- b,
S0 m 1 100 100
S0 m 1
where
S1 The peak area of Sildenafil citrate obtained from the test solution;
S0 The peak area of Sildenafil citrate obtained from the standard solution;
m0 Weight of Sildenafil citrate WS, in mg;
m1 Weight of sample, in mg;
b Average weight of tablets, in mg;
P Potency of Sildenafil citrate WS, in %.
Limit: From 90.0 % to 110.0 % of Sildenafil (C22H30N6O4S) in tablet.
Presentation.
100 mg tablets. Blister of 1x4 tablets in a carton box with a leaflet.
Labeling.
On primary packaging name of manufacturer, manufacturing country, name of customer and its
requisites, name of pharmaceutical product, INN, dosage, batch N, expire date.
On secondary packaging - name of manufacturer, manufacturing country, name of customer and its
requisites, name of pharmaceutical product, INN, dosage, dosage form, storage, batch N, quantity in
packaging, +expire date, bar code.
Storage. Store at a dry place at temperature below 25 C. Protect from light.
Shelf-Life. 2 years. Do not use after the expiry date printed on the pack.
Pharmacotherapeutic Group. Drugs used in erectile dysfunction.

In Vitro Bioequvalence Study for Lovex (Sildenafil 100 mg tablets)

manufactured by PharmImpEx (Georgia) vs Viagra (Sildenafil 100 mg
tablets) manufactured by Pfizer PMG (France)

Sponsor - SKR, georgia

Introduction

Lovex (Sildenafil 100 mg tablet) is a generic medicinal product containing sildenafil as an

active substance.
Lovex contains the same active substance as the reference medicinal product (Viagra) sildenafil in form of the citrate salt.
Sildenafil is potent inhibitor of cyclic guanosine monophosphate (cGMP) specific
phosphodiesterase (PDE5). During natural erection, nitric oxide (NO) is released and this triggers the
synthesis of cGMP which, in turn, relaxes the corpora cavernosa (a key point in the erection process).
PDE5 present in the corpus cavernosum breaks down cGMP, sildenafil prevents the breakdown of
cGMP and, thus enhances the induced erectile response. Sildenafil has a high potency and selectivity
for PDE5 and via smooth muscle relaxation can induce a rise in intracavernosal pressure during
stimulation.
The safety and efficacy profile of sildenafil has been demonstrated in several clinical trials
details of which can be found in the EPAR for Viagra. In addition, there is a long-term post-marketing
experience contributing to the knowledge of the use of this product. Since this application is a generic
application referring to the reference medicinal product Viagra, summary of the clinical data of
sildenafil citrate is available and no new clinical studies regarding pharmacology, pharmacokinetics
and efficacy and safety have been conducted.
The indication for Lovex is the same as for reference medicinal product. Lovex is indicated for
the treatment of men with erectile dysfunction, which is the inability to achieve or maintain a penile
erection sufficient for satisfactory sexual performance. In order for sildenafil to be effective, sexual
stimulation is required.
Lovex is presented as uncoated tablets containing 100 mg of sildenafil (active substance). The
active substance is in form of citrate salt. Excipients used in the preparation of Lovex are well known
excipients used in tablets preparations such as microcrystalline cellulose, zinc citrate dihydrate, aerosol,
mannitol, magnesium stearate.
Active Substance
The active substance, sildenafil citrate, is chemically designated as 5-[2-Ethoxy-5-(4methylpiperazin-1-ylsulfonyl)phenyl]-1,6-dihydro-1-methyl-3-propylpyrazolo[4,3-d]pyrimidin-7-one
citrate;

1-{[3-6,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-

ethoxyphenyl]sulfonyl}-4-methylpiperazone citrate. It does not show polymorphism or enantiomerism.

Sildenafil citrate was originally approved in 1998 as an oral formulation for the treatment of
erectile dysfunction. It is a potent and specific inhibitor of phosphodiesterase type 5 which enhances
vasodilation by inhibiting the catabolism of cyclic guanosine monophosphate (GMP).

The solubility of sildenafil citrate in water has been determinate as being 3.5 mg/ml. Solubility
determinations in various buffers showed a maximum solubility of approximately 24 mg/ml at pH 2.0.
Sildenafil citrate is designated as a class 1 drug substance according to BCS classification:
highly soluble and highly permeable.
Biowaiver is a regulatory drug approval process when generic drug interchangeability is
established based on biopharmaceutical properties an in vitro equivalence test instead of in vivo
bioequivalence studies.
In vitro equivalence test is a dissolution test that includes comparison of the dissolution profile
between the test and reference product (or different doses of the same drug product) in three media: pH
1.2, pH 4.5 and pH 6.8.
In vitro equivalence report for generic drugs according biowaiver procedure includes:
1. Aims of study
The main aim of study is to establish generic drugs interchangeability that can be proved by in
vitro dissolution kinetics study, which is performed instead of in vivo bioequivalence studies.
2. Information about reference and test product
Reference product: Viagra, 100 mg tablets
Test product: Lovex, 100 mg tablets
3. Dissolution kinetics study conditions, assay procedure conditions and results of study
This is a test intended for evaluation of dissolution profiles similarity when the quantity of API
released is assayed in three or more previously chosen time points and in three different media: pH 1.2,
pH 4.5, pH 6.2. and pH 6.8.
Bioequivalence study was performed on the 100 mg strength in accordance with the Note for
Guidance on the Investigation of Bioavailability and Bioequivalence - World Health Organization
(WHO) Proposal to waive in vivo bioequivalence requirements for the WHO model list of essential
medicines immediate release, solid oral dosage forms. Working document QAS/04.109/Rev.1.
Methods of dissolution kinetics study
Presentation
Dissolution test was conducted on 12 dosage units of the test product Lovex, 100 mg tablets,
PharmImpEx (Georgia), versus 12 dosage units of the reference product, Viagra, 100 mg, tablets,
Pfizer PGM, France.
The current official USP dissolution test conditions and acceptance criterion were applied. The
following method and tolerances were applied: the dissolution of sildenafil citrate from its tablets was
performed according to the rotating basket method using a USP dissolution tester, apparatus II

(Erweka) in 500 ml of three (3) different buffers (pH 1.2 (HCl buffer) pH 4.5 (acetate buffer) and pH
6.8 (phosphate buffer). All buffers are prepared as per USP requirement. The stirring speed was 100
rpm and the temperature was maintained at 37 0.5 C. Aliquots each of 25 ml from the dissolution
medium were withdrawn at 10, 15, 20, 30 and 45 minutes time intervals. The samples withdrawn were
then filtered, adequately diluted and analyzed spectrophotometrically for sildenafil citrate content by
measuring the absorbance at max - 290 nm (UV-1601 PC, Shimadzu, Japan). A similar volume of
buffers respectively was added to the dissolution medium in order to maintain the volume in the vessel
constant. Each experiment was carried out in triplicate.
Test product - Lovex, 100 mg tablets, manufactured by PharmImpEx, Georgia.
Referense product Viagra, 100 mg tabletebi (Batch N 0752702), manufacturer Pfizer PGM,
France.
12-12 tablets were used in study.
Test solution:
Place one tablet in each vessel and carry out the method according to USP method After , 15, 20,
30 and 45 minutes time intervals, pipette 25 ml of the solution from each vessel. Filter the solution
through a suitable membane fiber filer (diameters of pores 0.45 m), disregarding the first 5 ml. Dilute
5.0 ml of this solution to 50.0 ml with 0.1 M HCl.
Standard solution:
Transfer approximately 14 mg of Sildenafil citrate WS, accurately weighed into a 10 ml
volumetric flask. Dissolve with sufficient volume (app. 5 ml) of 0.1 M HCl and dilute to the volume
with the same solvent. Pipette 1 ml of this solution a 50 ml volumetric flask. Dilute to the volume with
0.1 M HCl. Protect solution from light.
Procedure:
Measure the absorbance values of the solutions using appropriate buffer as a blank at 290 nm
wavelight.
Calculation:
D 1 m 0 500 50 P100 0.7129
D 1 m 0 P 1.4258
= -------------- -------------------------------------- = ---------------------------- (1)
D0 a 50 50 5 100
D0 a
D0 The absorbance value of Test Solution
D1 The absorbance value of Standard solution;
m0 Weigh of Sildenafil citrate WS, in mg;
a labeling amount of Sildenafil, mg;
P Potency of Sildenafil citrate WS, %,

0.7129 Conversation coefficient of Sildenafil citrate to Sildenafil

Statistical analysis
All statistical analyses were made using ANOVA, followed by Fishers PLSD (pair- wise least
significant difference) for multiple comparisons at p 0.05 using the StatView statistical software
program.
Results of In vitro dissolution studies
In vitro dissolution studies of test tablets containing 100 mg of Sildenafil together with the
conventional market product Viagra 100 mg oral tablets (Pfizer, France).
Dissolution profiles of the prepared 12-12 tablets were compared with the commercial product using
the similarity factor (2) defined by the following equation (2):

f2 = 50log [

(2)

where n is the number of sampling time points, R(t) and T(t) are the mean percent dissolved of the
reference (commercial product) and the test (prepared tablets), respectively, up to each time point t. 2
represents a logarithmic transformation of the sum squared error of differences between the reference
and the test products over all time points. In order to consider similar dissolution profiles, 2 values
should be higher than 50. According to literature studies, similarity factor f2 value is 50 to 100.
Concerning, the experimental values for the simi1arity factor f2 obtained are grater that 50 and lower
than 100 and that indicates that the drugs achieve similar dissolution profiles.
Table 1. Dissolution rate (%) of Lovex (100 mg Tablets, manufacturer PharmImpEx, Georgia)
(T) and Viagra (100 mg Tablets, manufacturer Pfizer PGM, France) (R) in different buffers
during 45 min.
10 min

15 min

20 min

25 min

30 min

45 min

pH 1.2
T

38

51

68

76

89

99

40

58

73

82

93

100

pH 4.5
T

31

50

66

76

83

90

39

55

71

81

89

98

pH 6.8
T

30

42

61

75

83

89

37

49

69

80

87

97

f2 (pH 1.2) = 64.22; f2 (pH 4.5) = 61.09; f2 (pH 6.8) = 59.52.

Fig. 1. Dissolution profiles in Buffer pH 1.2.
120.00%

% Dissolution rate

100.00%
80.00%
60.00%
40.00%
20.00%
0.00%

10

15

20

25

30

45

30

45

Time, min

Pink line - Lovex, blue line - Viagra.

Fig. 2. Dissolution profiles in Buffer pH 6.8
120.00%

% Dissolution rate

100.00%
80.00%
60.00%

40.00%
20.00%
0.00%

10

15

20
25
Time, min

Pink line - Lovex, blue line - Viagra.

Fig. 3. Dissolution profiles in Buffer pH 4.5

120.00%

%Dissolution rate

100.00%
80.00%
60.00%
40.00%
20.00%

0.00%

10

15

20
25
Time, min

30

45

Pink line - Lovex, blue line - Viagra.

Results of the in vitro dissolution study illustrated in Table 1 that Lovex shows dissolution profiles
similar to commercial product in 3 different buffers, with f2 values of 64.22, 61.09 and 59.52 in buffers
with pH 1.2, pH 4.5 and pH 6.8, respectively. Dissolution profiles illustrated in Fig. 1-3 shows
similarity between test (Lovex) and reference (Viagra) products.
Conclusion
About 75% of Sildenafil citrate was released in 25 min for and. The pilot batch of Lovex
showed hydration ratio of 4.1 indicating the rapid water uptake and hence faster drug release. Good
elasticity can be assured from the folding endurance. The release of both products is in required limits
for immediate release products.
According to test results, the reference and test products achieve different release profiles at
different time in three media, but these discrepancies dont influence the absorption profile and
bioavailability with consequences on the clinical use as shown by the in vivo results.
References
1.

USP 30/NF 25

2.

Bird, A.E. (1994) Analytical Profiles of Drug Substances and Excipients 23: 1-52.

3.

A. H. Elshafeey, E. R. Bendasand O. H. Mohamed, Intranasal microemulsion of sildenafil citrate:

in vitro evaluation and in vivo pharmacokinetic study in rabbits, AAPSPharmSciTech. 10 (2009)
361367; DOI: 10.1208/s12249-009-9213-6.

4.

World Health Organization (WHO) Proposal to waive in vivo bioequivalence requirements for the
WHO model list of essential medicines immediate release, solid oral dosage forms. Working
document QAS/04.109/Rev.1.

5.

J. W. Moore and H. H. Flanner, Mathematical comparison of dissolution profiles, Pharmaceutical

Technology, 20 (1996) 6474.

6.

Declaration of Helsinki. As amended by the 59th World Medical Assembly (WMA). World
Medical

Association,

Seoul,

South

http://www.wma.net/e/ethicsunit/helsinki.htm.

Korea,

October

2008.

Available

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Brand name
LOVEX
Generic Name
Sildenafil
Pharmaceutical Form
Tablets
Composition
Each tablet contains:
Sildenafil (as citrate) 100 mg;
excipients: microcrystalline cellulose, zinc citrate dihydrate, aerosol, mannitol, magnesium
stearate.
ATC Code
G04BE03
Pharmacotherapeutic Group
Drugs used in erectile dysfunction.
Pharmacological Properties
Pharmacodynamic
Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5).
The physiological mechanism responsible for erection of the penis involves the release of nitric oxide
(NO) in the corpus cavernosum during sexual stimulation. Nitric oxide then activates the enzyme
guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP),
producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.
Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the
relaxant effect of NO on this tissue. When the NO/cGMP pathway is activated, as occurs with sexual
stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP.
Studies in vitro have shown that sildenafil is selective for PDE5.
Sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological
effects.
Pharmacokinetic
Sildenafil is rapidly absorbed. Maximum observed plasma concentrations (Cmax) are reached within 30
to 120 minutes (median 60 minutes) of oral dosing in the fasted state. The mean absolute oral
bioavailability is 41% (range 25-63%). When sildenafil is taken with food, the rate of absorption is
reduced. The mean steady state volume of distribution (Vd) for sildenafil is 105 l. Sildenafil and its
major circulating N-desmethyl metabolite is 96% bound to plasma proteins.
Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic
microsomal isoenzymes. The major circulating metabolite results from N-demethylation of sildenafil.
This metabolite has a phosphodiesterase selectivity profile similar to sildenafil and potency for PDE5
approximately 50% that of the parent drug. Plasma concentrations of this metabolite are approximately

40% of those seen for sildenafil. The N-desmethyl metabolite is further metabolised, with a terminal
half life of approximately (T1/2) 4 h.
The total body clearance of sildenafil is 41 l/h with a resultant terminal phase half-life of 3-5 h. After
oral administration sildenafil is excreted as metabolites predominantly in the faeces (approximately
80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of administered
oral dose).
In volunteers with mild (creatinine clearance 50-80 mL/min) to moderate (creatinine clearance 30-49
mL/min) renal impairment the pharmacokinetics of sildenafil were not altered after receiving a 50 mg
single oral dose. In volunteers with severe renal impairment (creatinine clearance < 30 mL/min)
sildenafil clearance was reduced.
In volunteers with mild to moderate hepatic cirrhosis (Child-Pugh A and B) sildenafil clearance was
reduced.
Indications
Treatment of men with erectile dysfunction, which is the inability to achieve or maintain a penile
erection sufficient for satisfactory sexual performance.
Dosage and Administration
For oral use. The recommended dose is 50 mg taken as needed approximately one hour before sexual
activity. Based on efficacy and toleration, the dose may be increased to 100 mg or decreased to 25 mg.
The maximum recommended dose is 100 mg. The maximum recommended dosing frequency is once
per day.
Adverse Reactions
Nervous system disorders: headache, migraine, dizziness, insomnia, depression.
Eye disorders: visual disorders, mydriasis, conjunctivitis, eye pain, cataract, scleral redness.
Gastrointestinal disorders: dyspepsia, colitis, dry mouth, diarrhea, rectal hemorrhage.
Cardiovascular disorders: angina pectoris, AV block, tachycardia, hypotension, heart failure, cardiac
arrest, cardiomyopathy, cerebrovascular thrombosis.
Respiratory system disorders: nasal congestion, asthma, laryngitis, pharyngitis, sinusitis, dyspnea,
bronchitis, cough.
Musculoskeletal disorders: arthritis, bone pain.
Hypersensitivity reactions: urticaria, pruritus, exfoliative dermatitis.
Urinary disorders: urinary tract infection.
Hematologic disorders: anemia, leukopenia.
Other: flushing, herpes simplex.
Contraindications
Known hypersensitivity to sildenafil or any ingredient in the formulation.
Concomitant use of nitric oxide donors or nitrates.
Sildenafil is not indicated for individuals below 18 years of age.
Overdose
In single dose volunteer studies of doses up to 800 mg, adverse reactions were similar to those seen at
lower doses, but the incidence rates and severities were increased.

Treatment: In cases of overdose, standard supportive measures should be adopted as required. Renal
dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and it is
not eliminated in the urine.
Pregnancy and Lactation
Lovex is not indicated for use by women.
Interaction with Other Medicinal Products
Lovex metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 and 2C9.
Therefore, inhibitors of these isoenzymes (such as ketoconazole, erythromycin, cimetidine) may reduce
sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance.
Single doses of antacid did not affect the bioavailability of sildenafil.
No effect on Lovex pharmacokinetics of CYP2C9 inhibitors (such as tolbutamide, warfarin), CYP2D6
inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and
related diuretics, loop and potassium sparing diuretics, ACE inhibitors, calcium channel blockers, betaadrenoreceptor antagonists or inducers of CYP450 metabolism (such as rifampicin, barbiturates).
Lovex did not affect the steady state pharmacokinetics of saquinavir and ritonavir.
Lovex did not potentiate the increase in bleeding time caused by acetyl salicylic acid.
Sildenafil did not potentiate the hypotensive effects of alcohol in healthy volunteers with mean
maximum blood alcohol levels of 80 mg/dl.
Consistent with its known effects on the nitric oxide/cyclic guanosine monophosphate (cGMP)
pathway, Lovex was shown to potentiate the hypotensive effects of nitrates, and its co-administration
with nitric oxide donors or nitrates in any form is therefore contraindicated.
Special Warnings and Precautions
There is a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular
disease. Therefore, treatments for erectile dysfunction should not be generally used in men for whom
sexual activity is inadvisable because of their underlying cardiovascular status.
Lovex should be used with caution in patients with anatomical deformation of the penis (such as
angulation, cavernosal fibrosis or Peyronies disease), or in patients who have conditions which may
predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia).
In vitro studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of
sodium nitroprusside (a nitric oxide donor).
There is no safety information on the administration of sildenafil to patients with bleeding disorders or
active peptic ulceration. Therefore sildenafil should be administered to these patients only after careful
benefit-risk assessment.
Effects on Ability to Drive and Use Machines
As dizziness and altered vision were reported in clinical trials with sildenafil, patients should be aware
of how they react to Lovex, before driving or operating machinery.
Presentation
100 mg tablets. Blister of 1x4 tablets in a carton box with a leaflet.
Storage
Store in a dry place at a temperature not exceeding 25 .

Protect form light.

Keep out of reach of children.
Shelf-Life
2 years.
Do not use after the expiry date printed on the pack.
Availability
Rx only.
Manufacturer
Manufactured by PharmImpEx Ltd. for SKR Ltd
Address of Manufacturer
Georgia 0159,
Tbilisi, Chiaureli St. 2
Tel. (+995) 599443856
www.lovex.ge

(LOVEX)

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LOVEX
Comprims 100 mg
Mode d'emploi

Veuillez lire attentivement les instructions avec utilisation!

Conservez ces instructions car vous serez peut-tre amens les lire nouveau. Si vous avez quelques questions, veuillez consulter
votre mdecin. Ceci est votre mdicament. Ne le recommandez personne d'autre, il peut nuire la sant.

No. d'enregistrement R.2004.352.8323

Groupe pharmaco-thrapeutique et code ATC: Aphrodisiaque (mdicament pour disfonctionnement rectile) G04BE

INN: Citrate de Sildnafil

Composition: Le Citrate de Sildnafil, de la cellulose microcristalline, le zinc dihydrate de citrate, d'un arosol, le mannitol, le
starate de magnsium.

Description: Lovex est prsent en comprim blanc, gris-blanc, ou blanc-jaune, surface plate, avec des divisions diamtrales sur une
face et des marges bien structures.

INDICATIONS THERAPEUTIQUES
Lovex est prescrit pour les disfonctionnements rectiles, y compris pour les patients atteints de diabte, de surpoids, ayant subit une
prostatectomie ou un traumatisme de l'pine dorsale. Une stimulation sexuelle est ncessaire afin de rendre Lovex efficace.
CONTRE-INDICATION
Lovex est contre-indiqu pour les patients allergiques l'un des composants du comprim. Lovex est contre-indiqu pour les patients
utilisant des nitrates organiques de faon rgulire et/ou par intermittence, sous toute forme. Aucune donne clinique contrle
concernant la scurit ou l'efficacit du citrate de sildnafil n'a t effectue concernant les groupes suivants: les patients ayant une
tension artrielle basse, les patients atteints d'une rtinite pigmentaire, les patients souffrant d'infarctus du myocarde, attaque, ou
arythmie dans les six derniers mois, affaiblissment hpatique, maladie hrditaire dgnrative.
POSOLOGIE ET ADMINISTRATION
Lovex se prend par voie orale. La dose recommande est de 50mg, pris une heure avant les rapports sexuels. Selon l'efficacit du
traitement et de la tolrance, la dose peut tre augmente 100mg ou rduite 25mg. La dose maximale recommande est 100mg. La
frquence maximale recommande est d'une fois par jour. A partir d'un certain ge, la dose initiale recommande est de 25 mg. Selon
l'efficacit du traitement et de la tolrance, la dose peut tre augmente 50mg ou 100mg. Pour les patients avec des insuffisances
rnales ou hpatiques, la dose initiale recommande est de 25mg. Selon l'efficacit du traitement et de la tolrance, la dose peut tre
augmente 50mg ou 100mg. Lovex est contre-indiqu aux personnes en dessous de l'ge de 18 ans.
EFFETS SECONDAIRES
Les plus frquents sont: des maux de tte, des rougissements, des dyspepsies, des congestions nasales, des infections du systme
urinaire, des troubles de la vision, de la diarrhe, des vertiges, des ruptions cutanes.

PRECAUTIONS

Il existe un potentiel de risque cardiaque de l'activit sexuel chez les patients ayant des maladies cardiovasculaires prexistantes.
Avant de prescrire le citrate de sildnafil, le pharmacien devra prvenir avec attention les patients dj soumis une multiple
mdication contre l'hypertension. Le citrate de sildnafil possde des proprits systmiques de dilatation des veines rsultant d'une
baisse provisoire de la tension artrielle. De cette faon, Lovex augmente les effets d'hypotension dus aux nitrates organiques.

Le citrate de sildnafil doit tre utilis avec prcaution dans le cas de patients avec des dformations anatomiques du pnis (tels que
angulation, fibroses caverneuses ou maladie de la Peyronie) ou dans le cas d'un patient prdispos un priapisme (tels que l'anmie,
des mylomes multiples ou une leucmie).
La scurit du citrate de sildnafil est connue chez les patients souffrant d'hmorragies et chez les patients ayant une ulcration
peptique active. Avant de prescrire le citrate de sildnafil, de tels patients, une valuation des risques et de l'efficacit doit tre
effectue.
EFFETS SUR L'APTITUDE A EFFECTUER LES TACHES QUOTIDIENNES
Prendre en considration le fait que durant les tudes cliniques certains cas de maladies et de troubles de la vision ont t rapports. Il
est recommand aux patients de faire attention aux diffrentes ractions lors de leurs tches quotidiennes.
INTERACTIONS
Si vous tes sous traitement d'un autre mdicament, veuillez en rfrer votre pharmacien.
EMBALLAGE
Des comprims de 70mg N.4 sous emballage
STOCKAGE
Un endroit sec, non-expos la lumire, une temprature infrieure 25 degrs C
VALIDITE
2 ans

STATUT
Uniquement sous prescription
FABRICANT
Gorgie 0159,
Tbilissi, Chiaureli 2
Tel. (+995) 599443856
www.lovex.md

Nous vous prions de prsenter toute rclamation avec la mention du numro de srie indiqu sur la bote ou l'tiquette


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loveqsi
(Lovex)
samkurnalo saSualebis dasaxeleba
loveqsi (Lovex)
generikuli (saerTaSoriso arapatentirebuli) dasaxeleba
sildenafili
samkurnalo forma
tabletebi
Semadgenloba
1 tableti Seicavs:
sildenafils (citratis saxiT) 100 mg-s;
damxmare nivTierebebi: mikrokristaluri celuloza, TuTiis citratis dihidrati, aerosili, manitoli,
magniumis stearati.
aTq-kodi
G04BE03
klinikur-farmakologiuri jgufi
ereqtiuli disfunqciis samkurnalo saSualeba
farmakologiuri Tvisebebi
farmakodinamika. sildenafili aris cgmf-specifikuri me-5 tipis fosfodiesTerazas (fde 5) Zlieri
seleqtiuri inhibitori.
ereqciis fiziologiuri meqanizmis realizacia dakavSirebulia seqsualuri stimulaciis dros
mRvimovan sxeulSi azotis oqsidis (NO) gamoTavisuflebasTan. azotis oqsidi aaqtivebs
gianilatciklazas, rac iwvevs
cgmf-is donis momatebas, mRvimovani sxeulis gluvkunTovani qsovilis modunebas da masSi sisxlis
midinebis gazrdas.
sildenafili uSualod mRvimovani sxeulis gluv kunTebze ar moqmedebs, magram fde 5-s
blokadisa da cgmf-is stabilizaciis gziT igi aZlierebs azotis oqsidis momadunebel efeqts.
in vitro kvlevebma aCvena, rom sildenafili seleqtiurad moqmedebs fde 5-ze. sildenafilis
efeqturobis aucilebeli pirobaa seqsualuri stimulacia.
farmakokinetika. sildenafili kargad Seiwoveba kuW-nawlavis traqtidan. uzmoze peroraluri
miRebis Semdeg maqsimaluri koncentracia plazmaSi (Cmax) 30_120 wT-Si (saSualod 60 wT-Si)
miiRweva. saSualo absoluturi bioSeRwevadobaa 41% (25_63%). Wamis dros preparatis miRebisas
Sewovis siCqare mcirdeba. ganawilebis moculobaa 105 l. sildenafili da misi ZiriTadi N-demeTilis
metaboliti 96% ukavSirdebian plazmis cilebs.
sildenafili ZiriTadad RviZlSi metabolizdeba, CYP3A4 (ZiriTadi gza) da CYP2C9
(meorexarisxovani gza) izofermentebis monawileobiT. ZiriTadi metaboliti warmoiqmneba sildenafilis
N-demeTilirebis Sedegad. es metaboliti seleqtiurad moqmedebs fde 5-ze, magram misi aqtiuroba
sildenafilis aqtiurobis 50%-s Seadgens. am metabolitis koncentracia plazmaSi sildenafilis koncentraciis

40%-s Seadgens. N-demeTilis metaboliti ganicdis Semdgom metabolizms. misi naxevargamoyofis

periodi (T1/2) aris 4 sT.
sildenafilis saerTo klirensia 41 l/sT, naxevarganoyofis periodi _ 3_5 sT. igi gamoiyofa
metabolitebis saxiT, ZiriTadad nawlavebiT (miRebuli dozis daaxloebiT 80%) da naklebad _ SardiT
(daaxloebiT 13%).
Tirkmlis funqciis msubuqi da zomiri ukmarisobis mqone pirebSi sildenafilis farmakokinetika ar
icvleba. Tirkmlis funqciis mZime ukmarisobis dros klirensi Semcirebulia.
RviZlis cirozis mqone pirebSi sildenafilis klirensi mcirdema.
Cvenebebi
ereqciis darRveva, romelic ganisazRvreba sasqeso aqtis gansaxorcieleblad ereqciis miRwevisa da
SenarCunebis SeuZleblobiT.
miRebis wesi da dozebi
preparati miiReba peroralurad, sasqeso aqtamde 1 sT-iT adre. rekomendebuli erTjeradi dozaa 50
mg. efeqturobisa da amtanobis gaTvaliswinebiT SesaZlebelia dozis 100 mg-mde gazrda an 25 mg-mde
Semcireba. maqsimaluri sadReRamiso dozaa 100 mg.
preparati miiReba erTxel dReSi.
gverdiTi movlenebi
nervuli sistemis mxriv: Tavis tkivili, Sakiki, Tavbruxveva, uZiloba, depresia.
mxedvelobis mxriv: mxedvelobis darRveva, midriazi, koniunqtiviti, Tvalis tkivili, kataraqta,
sklerebis siwiTle.
saWmlis momnelebeli sistemis mxriv: dispepsia, koliti, qserostomia, diarea, reqtaluri sisxldena.
gul-sisxlZarRvTa sistemis mxriv: stenokardia, atrio-ventrikuluri blokada, taqikardia, hipotenzia,
gulis ukmarisoba, gulis gaCereba, kardiomiopaTia, Tavis tvinis sisxlZarRvebis Trombozi.
sasunTqi sistemis mxriv: asTma, laringiti, faringiti, sinusiti, qoSini, bronqiti, xvela, cxviris
lorwovani garsis SeSupeba.
sayrden-mamoZravebeli sistemis mxriv: arTritebi, Zvlebis tkivili.
alergiuli reaqciebi: WinWris cieba, qavili, eqsfoliaciuri dermatiti,
Sard-sasqeso sistemis mxriv: saSarde gzebis infeqciebi.
sisxlmbadi organoebis mriv: anemia, leikopenia.
sxva: saxis kanis hiperemia, martivi herpesi.
ukuCvenebebi
momatebuli mgrZnobeloba sildenafilis an preparatis romelime komponentis mimarT.
azotis oqsidis donatorebis an nitratebis erTdrouli miReba.
preparati ar iniSneba 18 wlamde asakis pirebSi.
Warbi dozireba
erT miRebaze 800 mg preparatis gamoyenebisas aRiniSneba gverdiTi efeqtebis gaZliereba.
mkurnaloba: simtomuri Terapia. dializi araefeqturia.
orsuloba da laqtacia
qalebSi preparati ar gamoiyeneba.

urTierTqmedeba sxva samkurnalo saSualebebTan

loveqsi metabolizdeba CYP3A4 da CYP2C9 izofermentebis monawileobiT, ris gamoc am
izofermentebis inhibitorebi (mag., CYP3A4 izofermentebis inhibitorebi ketokonazoli, eriTromicini,
cimetidini) amcireben, xolo induqtorebi _ zrdian sildenafilis klirens.
antacidebis erTjeradi miReba ar moqmedebs sildenafilis bioSeRwevadobaze.
CYP2C9 izofermentebis inhibitorebi (mag., tolbutamidi, varfarini), CYP2D6 inhibitorebi (mag.,
serotoninis ukuSTanqvis seleqciuri blokatorebi, tricikluri antidepresantebi), Tiaziduri da Tiazidis
msgavsi diurezuli saSualebebi, maryuJovani da kaliumis Semnaxveli diurezuli saSualebebi, agf
inhibitorebi, kalciumis arxebis blokatorebi, -adrenoreceptorebis antagonistebi, CYP450 metabolizmis
induqtorebi (rifampicini, barbituratebi) ar moqmedeben loveqsis farmakokinetikaze.
loveqsi ar moqmedebs ritonavirisa da sakvinaviris farmakokinetikaze.
loveqsi damatebiT ar axangrZlivebs sisxldenis dros acetilsalicilis mJavas miRebisas.
sildenafili ar aZlierebs alkoholis hipotenziur moqmedebas janmrTel pirebSi, Tu alkoholis
maqsimaluri koncentracia sisxlSi Seadgens 80 mg/dl-s.
NO/cgmf-is cvlis procesze moqmedebis gamo loveqsi zrdis nitratebis hipotenzur efeqts. loveqsisa
da nitratebis an NO-s sxva donorebis erTdrouli gamoyeneba ukunaCvenebia.
gansakuTrebuli miTiTebebi
seqsualuri aqtivobiT ganpirobebuli gul-sisxlZarRvTa sistemis mxriv garkveuli uaryofiTi
efeqtebis ganviTarebis garkveuli riskis gamo, preparatis daniSvnamde saWiroa pacientis saTanado
gamokvleva.
preparati sifrTxiliT gamoiyeneba sasqeso organos anatomiuri defeqtis dros (mag., angulacia,
kavernozuli fibrozi an peironis daavadeba) an iseTi daavadebebis dros, romlebmac SeiZleba priapizmis
ganviTareba gamoiwvios (namgliseburi anemia, mravlobiTi mieloma, leikozi).
trombocitebze Catarebulma in vitro kvlevebma aCvena, rom sildenafili aZlierebs natriumis
nitroprusidis antiagregantul Tvisebebs.
informacia preparatis gamoyenebis usafrTxoebis Sesaxeb kuWisa da Tormetgoja nawlavis
peptikuri wylulis mqone pacientebSi, aseve sisxldeniT mimdinare daavadebebis dros ar moipovba, ris
gamoc aseT pacientebSi preparati iniSneba mxolod riskisa da sargebelis Sefasebis Semdeg.
preparatis zemoqmedeba avtotransportisa da meqanizmebis marTvis unarze: loveqsis klinikuri
kvlevebis dros aRiniSneboda Tavbruxveva da mxedvelobis darRveva, ris gamoc satransporto
saSualebebis marTvis an potenciurad saSiSi meqanizmebis gamoyenebis dros saWiroa ganisazRvros
preparatis miRebaze pacientis individualuri reaqcia.
SefuTva
100 mg tabletebi. 4 tableti konturul ujredovan SefuTvaSi (blisteri), 1 blisteri muyaos kolofSi.
Senaxvis pirobebi
inaxeba mSral, sinaTlisagan dacul adgilas, ara umetes 25C temperaturaze.
inaxeba bavSvebisaTvis miuwvdomel adgilas.
vargisobis vada
2 weli.
SefuTvaze aRniSnuli vadis gasvlis Semdeg preparatis gamoyeneba dauSvebelia.

gacemis wesi
gaicema receptiT.
mwarmoebeli
Sps `farmimpeqsi~ Sps `SKR~-is dakveTiT
mwarmoeblis misamarTi
saqarTvelo 0159,
Tbilisi, Wiaurelis q. #2