Title of Invention

AN ANTITUSSIVE COMPOSITION AND METHOD OF MAKING THE SAME

Abstract A process for making film coated tablet of prenoxdiazine hydrochloride consisting of the following steps: (1) Milling dispensed quantity of diluents, sieving the milled diluents and transferring into the bowl of planetary mixer; (2)Sifting prenoxdiazine Hydrochloride through a vibrosifter using 40# and transferring into bowl of planetary mixer; (3)dry Mixing contents of planetary mixer for 10 to 20 minutes; (4) Preparing a binder slurry by dispersing / dissolving binder in a solvent. (5)Wet Mixing by adding a slurry to the contents of the planetary mixer, gradually with continuous stirring (6)Wet Milling the wet mass obtained from step 5 through a mill with 6 to 10 mm perforated sieve to obtain granules; (7)Drying the granules in a F.B.D/Tray drier at 50 °C with occasionally raking maintaining Loss on drying:(by I.R.moisture balance) 1.5 % +/- 0.5%; (8) Lubrication by sifting the dried granules through 16# sieve on vibrosifter transferring the dried granules to a planetary mixer and mix for 2 minutes sifting lubricants, disintegrants using 60# sieve and adding to the planetary mixer for blend to make lubricated granules; (9)Compressing the lubricated granules to form core tablets on single/ double rotary compression machine using suitable die and punch complying with the necessary environmental condition Temperature : Between 23 °C & 27 ° C Relative Humidity : Below 50% 23 (10)Film Coating the core tablets by preparing a film coating solution using coating polymers, colors, plasticizers and solvents such as Isopropyl Alcohol, Methylene Chloride. Transfer Methylene Chloride and Isopropyl Alcohol into s.s. containers and stir for five minutes using overhead stirrer; transferring coating materials into the same container under fast stirring till smooth and uniform slurry is formed; just prior to the actual coating passing the slurry through 80 # sieve transferring tablet (cores) after dedusting into a coating pan and heating the tablet bed by inching process using hot air blower and maintaining the initial temperature below 50°C spray coating the sieved slurry on the tablet cores intermittently avoiding overwetting, after the last coat of coating suspension is applied drying of the film coated tablet for 15 - 20 minutes and applying about 50 gms of talc (10 mX 5 times) onto the tablet bed to get the required gloss and rolling the tablets for 5 minutes and then transfer them onto the trays for cooling to form the synergistic antispasmodic, analgesic formulation.
Full Text FORM-2 THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE
Specification
(See section 10 and rule 13)
AN ANTITUSSIVE COMPOSITION AND METHOD OF MAKING THE SAME
SANJEEV KHANDELWAL,
an Indian National
of Prem Nivas, 13, Altamount Road, Mumbai 400 026, Maharashtra, India

23-2-2007
THE FOLLOWING SPECIFICATION PARTICULARLY DESCRIBES THE INVENTION AND THE MANNER IN WHICH IT IS TO BE PERFORMED:-

- 4 APR 2005

FIELD OF INVENTION
This invention relates to an antitussive composition and method of making the same.
In particular, this invention relates to a process for making an oral dosage composition in the tablet form containing Prenoxdiazine Hydrochloride
In particular this invention envisages a film coated tablet formulation for oral administration containing Prenoxdiazine Hydrochloride.
Therapeutic effective amount of Prenoxdiazine used in the formulation is preferably as Prenoxdiazine Hydrochloride or any pharmaceutically acceptable form of it.
Drugs used for treatment of cough can be classified as follows: Cough Suppressants, Expectorants and Mucolytics.
Cough is characterized by forced expiration against a closed glottis, which suddenly opens to expel air and any unwanted material from respiratory tract. The treatment on cough depends upon whether the cough is productive or non¬productive.
A productive cough is characterized by presence of sputum and may be associated with conditions such as chronic bronchitis, bronchiectasis, or cystic fibrosis. Expectorants are used for treatment of productive cough.
2

A non- productive cough may be considered as serving no useful purpose for the patient. For example the symptoms of common cold may often include a non¬productive cough and cough suppressants may provide some relief to the patients particularly if administered at night. It has a few side effects as compared to codeine.
Prenoxdiazine Hydrochloride is used as a peripherally acting cough suppressant for non-productive cough. Prenoxdiazine Hybenzate is also used for this purpose. It does not depress respiratory center and can be given safely to elderly patients.
The active material in the formulation can be formulated within a dosage form wherein it is mixed along with excipients to form an uniform blend and thereafter bound with suitable binder to form granules of the mixed active blend or at least one of the active drug can be coated with a suitable polymer for obtaining two different granular mass of each drug.
DETAILED DESCRIPTION OF THE INVENTION
The main feature of this invention is the use of the active ingredient for making the oral dosage form of the formulation prenoxdiazine hydrochloride in a single dosage form. The method for treating a patient comprises orally administering a pharmaceutical formulation comprising of (a) 50 mg to 200 mg of prenoxdiazine hydrochloride per tablet (b) pharmaceutical acceptable inert excipients (c) a pharmaceutical acceptable carrier.
According to this invention therefore there is provided a synergistic antispasmodic, analgesic formulation comprising a core consisting of (a) 50 mg to 200 mg of prenoxdiazine hydrochloride (b) pharmaceutical acceptable inert excipients
3

consisting of at least one diluent 10% to 80% of the total mass of the formulation, at least one binder being 0.1% to 4% of the total mass of the formulation, at least one glidant from 0.01% to 3% of the total mass of the formulation., at least one lubricant being from 0.6% to 5% of the total mass of the formulation, and at least one disintegrant being 0.6% to 8% of the total mass of the formulation and at least one film coat on the core consisting of at least one film forming polymer and a plasticizer 2 to 4 wt % based on the weight of the core composition.
The diluent may be any pharmaceutically acceptable inert material selected from the group consisting of micorcrystalline cellulose, starches, lactose, mannitol, calcium phosphate, dibasic calcium phosphate and mixtures of these.
The disintegrating agent in the formulation which will accelerate the dispersion of the active particles is at least one compound selected from a group of compounds consisting of cross-linked polyvinylpyrrolidone, carboxymethyl starch, natural starch, microcrystalline cellulose, polarcrin potassium resins, cellulose gum and mixtures of these.
The binders in the formulation increases the bulk density of the active particles and make it easier to formulate in a compressed form, It is at least one compound selected from a group of compounds consisting of pregelatinized starch, starches, gelatin, vinyl chloride, povidone, hydroxypropyl cellulose, ethyl cellulose, cellulose acetate phthalate, hydroxypropylmethuyl cellulose and mixture of these. The formulation optionally includes one surfactant selected from the group consisting of: sodium lauryl sulfate, sodium carboxy methylcellulose, calcium carboxy methylcellulose, polysorbates, and sorbitan esters.
4

The glidants in the formulation accelerate the flow of the granules at the time of tabletting or filling is at least one compound selected from a group of compounds consisting of corn starch, talcum, colloidal silicon dioxide, silicon dioxide and mixtures of these.
The formulation includes a lubricant, which reduces adhesion and ease release of the product, is at least one compound selected from a group of compounds includes magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, surfactants, talc, waxes and zinc stearate.
The coating layer of the formulation is preferably used to form a protective layer that will protect the formulation from moisture which includes film forming cellulose polymers such as Ethyl Cellulose and/ or hydroxypropylmethylcellulose, hydroxy propyl cellulose, plasticizers such as propylene glycol, surfactants, coloring agents that may comprises at least one of the approved food and drug colors such as yellow iron oxides, tetrazine, brillant blue etc, solvents such as purified water, isopropyl alcohol, acetone, methylene chloride and opacifier includes titanium dioxide. The weight of the film coating layer preferably 2 to 4 wt % based on the weight of the core composition may be employed.
According to one aspect of this invention there is provided a process for making a
formulation comprising the steps of
1.Milling:
Mill dispensed quantity of diluents through fitz mill (impact forward high speed)
fitted with 0. 5 mm screen. Transfer into bowl of planetary mixer.
5

2.Sifting:
Sift other adjuvant diluents prenoxdiazine Hydrochloride through vibrosifter using
40#
Transfer into bowl of planetary mixer.
3.Dry Mixing:
Mix contents of planetary mixer for 15 minutes.
4.Preparation of binder slurry by dispersing / dissolving the binder in solvent.
5.Wet Mixing:
Add slurry to the contents of the planetary mixer, gradually with continuous stirring, check consistency and binding .If necessary additional wetting can be imparted using solvent.
6.Wet Milling:
Mill the wet mass obtained from step 5 through fitz mill with 8 mm perforation
sieve (knives forward medium speed)
7.Drying:
Dry the granules in F.B.D/Tray drier at 50 °C. Rake the granules occasionally
while drying in tray drier. Record temp, time, loss on drying.
In-Process control:
Loss on drying:(by I.R.moisture balance) 1.5 % +/- 0.5%
6

8.Lubrication:
a) Sift the dried granules through 16# sieve on vibrosifter and oversize should be passed through fitz mill using 1.5mm sieve. Transfer granules to the planetary mixer and mix for 2 minutes.
b) Sift lubricants, disintegrants using 60# sieve and blend the above materials in a suitable blender.
9.Compression:
After receiving the clearance from Q.C Dept transfer the granules to compression area and tablet compression machine should have been given clearance by in-process Q.C Dept. to take the product for compression.
Compress the tablets on single/ double rotary compression machine using suitable
die and punch complying with the necessary environmental condition.
Environmental conditions of Compression cubicle:
Temperature : Between 23 °C & 27 ° C
Relative Humidity : Below 50%
lO.Film Coating Process
Prepare the film coating solution using coating polymers, colors, plastiziers and
solvents such as Isopropyl Alcohol, Methylene Chloride.Transfer Methylene
Chloride and Isopropyl Alcohol into s.s. Containers and stir for five minutes using
overhead stirrer.
Slowly transfer coating materials into the same container under fast stirring till
smooth and uniform slurry is formed. Stir them continuously for 25 minutes. Just
prior to the actual use, pass the suspension through 80 # sieve. Transfer the
dedusted tablet (cores) into the coating pan and heat the tablet bed by inching
process using hot air blower. The initial temperature should not exceed 45 - 50°C.
7

Once the tablet bed attains 45 C it is ready for spray coating. Start the exhaust. Start spraying the tablet bed with coating Suspension. Discontinue temporarily spraying of the suspension. If the tablet bed is found to be slightly over wet, allow the bed to dry completely and then continue with the spraying. After the last coat of coating suspension is applied continue drying of the tablet for 15 - 20 minutes. Thereafter apply about 50 gms of talc (10 m X 5 times) on to the tablet bed to get the required gloss. Continue to roll the tablets for 5 minutes and then transfer them onto the trays for Cooling. Pack the cool tablets in a double polybag and store them in tight container away from moisture and heat.
The following points are to be noted carefully during the entire coating process:
1. Compressor pressure should not fall below 3 kg/ cm.
2. Spraying should be stopped immediately if the air pressure falls below 3 kg.
3. Temperature of the tablet bed should be maintained between 40 ° -45 ° C.
4. Continuous spraying from start to end would be preferred.
5. Avoid even slight overwetting.
6. Avoid droping of coating solution directly into the coating pan.
7. Avoid spraying of solution on to the blower, exhaust or to the uncovered part of the coating pan since this will generate coating particles, which may stick to the tablet resulting in rough surfaces.
8. Powerful exhaust should be provided since it is dangerou s to inhale the vapour of methylene chloride and IPA over a longer period of time.
9. Avoid very close look of the tablet bed during the spraying of solutions to avoid inhalation of concentrated vapour of the solution.
lO.The increase in weight of coated tablet to the desire weight. 11. After the final coat dry the tablets for about 15-30 minutes to get rid of the residual solvent.
8

12.All the electrical appliances and switches inside the coating room should Preferably is flame proof.
Following are few examples sited in accordance to the said formulation. But it is not intended that the scope of this invention is limited to these.
EXAMPLE - 1 [Batch size : 1,00,000 tablets ] Each tablet contains
Prenoxdiazine Hydrochloride 200 mg
Excipients q.s
Manufacturing process:
The process of this invention involves the following steps:-
1.Milling:
Mill 10.6 kgs of Lactose through fitz mill (impact forward high speed) fitted with
0. 5 mm screen. Transfer into bowl of planetary mixer.
2.Sifting:
Sift 2.7 kg of Starch, 20 kg of Prenoxdiazine Hydochloride through vibrosifter
using 40#
Transfer into bowl of planetary mixer.
3.Dry Mixing:
Mix contents of planetary mixer for 15 minutes.
4.Preparation of PVP slurry using following materials: Preparation of PVP slurry using the following
9

1.20 kg of Polyvinyl Pyrrolidone K-30, 0.300 kg of Glycerine in sufficient quantity of D.M water.
5.Wet Mixing:
Add slurry to the contents of the planetary mixer, gradually with continuous stirring. Check consistency and binding .If necessary additional wetting can be imparted using D.M.water.
6.Wet Milling:
Mill the wet mass obtained from step 5 through fitz mill with 8 mm perforation
sieve (knives forward medium speed)
7.Drying:
Dry the granules in F.B.D at 50 ° C. Rake the granules occasionally while drying in
tray drier. Record temp, time, loss on drying.
In-Process control:
Loss on drying:(by I.R.moisture balance) 1.8 %w/w.
8.Lubrication:
a) Sift the dried granules through 16# sieve on vibrosifter and oversize should
be passed through fitz mill using 1.5mm sieve.
Transfer granules to the planetary mixer and mix for 2 minutes.
b) Sift 0.6 kg of Talcum, 0.6 kgs of Magnesium Stearate, 1.0 kg of Maize
Starch using 60# sieve.
10

c) Add all the lubricants except Magnesium stearate to the planetary mixer and mix for 10 minutes. Add Magnesium Stearate and mix for 5 minutes. Unload the lubricated granules in polybag placed in s.s containers.

9.Compression:
Transfer the granules to compression area and tablet compression machine.
Compress the tablets on single/ double rotary compression machine complying
with the following parameters.
Between 23 ° C & 27 ° C
Environmental conditions of Compression cubicle:
Temperature :
Relative Humidity : Below 50%

In-Process control tests: ( uncoated tablets )
Appearance
White , circular, biconvex, uncoated tablets with
Break line on one side and plain surface on the
Diameter Average weight Weight Variation Hardness Thickness
Disintegration Time Fraibility
other.
10.3 mm (10.15 to 10.45)
370 mg
Individual (+/ - 3 % of avg wt)
3.0 Kg/cm2
4.3 to 4.5 mm
Maximum 10 minutes.
0.12 %w/w
10.Film Coating Process
Prepare the film coating solution using 0.9 kgs of hydroxypropyl methylcellulose,
0.05 kg of titanium dioxide and 0.025 kg of glycerine. Transfer above ingredients
11

into s.s. containers containing 7.0 kg of Isopropyl Alcohol and stir for five minutes using overhead stirrer. Add slowly 14.0 kg of methylene chloride with stirring to get smooth slurry. Stir them continuously for 25 minutes. It is then pass through 80 # nylon cloth. Spray this solution to the tablet bed with complying necessary parameters as mentioned before.
COATED TABLET SPECIFICATIONS:
a. Appearance : White colored ,circular, biconvex coated tablets
b. Avg Wt.
c. Weight Variation
d. Diameter
e. Disintegration
with break line on one side. 378 mg
Individual: +/- 5% Of avg. wt. 10.30 - 10. 50 mm. N.M.T. 30 mins.
EXAMPLE - 2 [Batch size : 1,00,000 tablets ] Each tablet contains
Prenoxdiazine Hydrochloride 200 mg
Excipients q.s
Manufacturing process:
The process of this invention involves the following steps:-
1.Milling:
Mill 9.0 kgs of dibasic calcium phosphate through fitz mill (impact forward high
speed) fitted with 0. 5 mm screen. Transfer into bowl of planetary mixer.
2. Sifting:
12

Sift 4.8 kg of microcrystalline cellulose, 20 kg of Prenoxdiazine Hydochloride through vibrosifter using 40# Transfer into bowl of planetary mixer.
3.Dry Mixing:
Mix contents of planetary mixer for 15 minutes.
4.Preparation of PVP slurry using following materials:
Preparation of PVP slurry using the following
1.0 kg of Polyvinyl Pyrrolidone K-30, 0.200 kg of Glycerine in sufficient quantity
of D.M water.
5.Wet Mixing:
Add slurry to the contents of the planetary mixer, gradually with continuous stirring. Check consistency and binding .If necessary additional wetting can be imparted using D.M.water.
6.Wet Milling:
Mill the wet mass obtained from step 5 through fitz mill with 8 mm perforation
sieve (knives forward medium speed)
7.Drying:
Dry the granules in Tray drier at 50 ° C. Rake the granules occasionally while
drying in tray drier. Record temp, time, loss on drying.
In-Process control:
Loss on drying:(by I.R.moisture balance) 1.6 %w/w.
13

8.Lubrication:
a) Sift the dried granules through 16# sieve on vibrosifter and oversize should
be passed through fitz mill using 1.5mm sieve.
Transfer granules to the planetary mixer and mix for 2 minutes.
b) Mill 0.6 kg of Talcum and 0.4 kgs of Stearic acid. Sift 1.0 kg of sodium starch glycollate using 60# sieve.
c) Add sodium starch glycollate to the planetary mixer and mix for 10 minutes. Then add blend of talcum and stearic acid and mix for 5 minutes. Unload the lubricated granules in polybag placed in s.s containers.
9.Compression:
After receiving the clearance from Q.C Dept transfer the granules to compression area and tablet compression machine should have been given clearance by in-process Q.C Dept to take the product for compression.
Compress the tablets on single/ double rotary compression machine complying
with the following parameters.
Environmental conditions of Compression cubicle:
Temperature : Between 23 ° C & 27 ° C
Relative Humidity : Below 50%
In-Process control tests: (uncoated tablets )
Appearance : White , circular, biconvex, uncoated tablets with
Break line on one side and plain surface on the
other.
14

Diameter Average weight Weight Variation Hardness Thickness
Disintegration Time Fraibility

10.3 mm (10.15 to 10.45)
370 mg
Individual (+/ - 3 % of avg wt)
3.0 Kg/cm2
4.3 to 4.5 mm
Maximum 9 minutes.
0.14 %w/w

10.Film Coating Process
Prepare the film coating solution using 0.6 kgs of hydroxypropyl methylcellulose, 0.3 kg of hydroxy propyl cellulose, 0.05 kg of titanium dioxide and 0.025 kg of propylene glycol. Transfer above ingredients into s.s. containers containing 7.0 kg of Isopropyl Alcohol and stir for five minutes using overhead stirrer. Add slowly 14.0 kg of methylene chloride with stirring to get smooth slurry. Stir them continuously for 25 minutes. It is then pass through 80 # nylon cloth. Spray this solution to the tablet bed with complying necessary parameters as mentioned before.
COATED TABLET SPECIFICATIONS:

a. Appearance
b. Avg Wt.
c. Weight Variation
d. Diameter
e. Disintegration

: White colored ,circular, biconvex coated tablets with break line on one side. : 378 mg
: Individual: +/- 5% Of avg. wt. : 10.30-10. 50 mm. : N.M.T. 30 mins.

15

EXAMPLE - 3 [Batch size : 1,00,000 tablets ] Each tablet contains
Prenoxdiazine Hydrochloride 100 mg
Excipients q.s
Manufacturing process:
The process of this invention involves the following steps:-
1.Milling:
Mill 5.0 kgs of Lactose through fitz mill (impact forward high speed) fitted with 0.
5 mm screen. Transfer into bowl of planetary mixer.
2.Sifting:
Sift 1.4 kg of Starch, 10 kg of Prenoxdiazine Hydochloride through vibrosifter
using 40#
Transfer into bowl of planetary mixer.
3.Dry Mixing:
Mix contents of planetary mixer for 15 minutes.
4.Preparation of PVP slurry using following materials:
Preparation of PVP slurry using the following
0.6 kg of Polyvinyl Pyrrolidone K-30, 0.100 kg of Glycerine in sufficient quantity
of D.M water.
5.Wet Mixing:
16

Add slurry to the contents of the planetary mixer, gradually with continuous stirring. Check consistency and binding .If necessary additional wetting can be imparted using D.M.water.
6.Wet Milling:
Mill the wet mass obtained from step 5 through fitz mill with 8 mm perforation
sieve (knives forward medium speed)
7.Drying:
Dry the granules in F.B.D at 50 ° C. Rake the granules occasionally while drying in
tray drier. Record temp, time, loss on drying.
In-Process control:
Loss on drying:(by I.R.moisture balance) 1.3 %w/w.
8.Lubrication:
a) Sift the dried granules through 20# sieve on vibrosifter and oversize should
be passed through fitz mill using 1.5mm sieve.
Transfer granules to the planetary mixer and mix for 2 minutes.
b) Sift 0.3 kg of Talcum, 0.3 kgs of Magnesium Stearate, 0.5 kg of Maize Starch using 60# sieve.
c) Add all the lubricants except Magnesium stearate to the planetary mixer and mix
for 10 minutes. Add Magnesium Stearate and mix for 5 minutes. Unload the lubricated granules in polybag placed in s.s containers.
17

9.Compression:
After receiving the clearance from Q.C Dept transfer the granules to compression area and tablet compression machine should have been given clearance by in-process Q.C Dept to take the product for compression.
Between 23 °C & 27 ° C
Compress the tablets on single/ double rotary compression machine complying
with the following parameters.
Environmental conditions of Compression cubicle:
Temperature
Relative Humidity : Below 50%
In-Process control tests: ( uncoated tablets )

Appearance Diameter Average weight Weight Variation Hardness Thickness Disintegration Tim Fraibility

White , circular, biconvex, uncoated tablets.
8.0 mm (±0.1 mm)
181 mg
Individual (±3 % of avg wt)
2.5 Kg/cm2
1.8 to 2.5 mm
Maximum 10 minutes.
0.08%w/w

lO.Film Coating Process
Prepare the film coating solution using 0.5 kgs of hydroxypropyl methylcellulose, 0.025 kg of titanium dioxide and 0.015 kg of glycerine. Transfer above ingredients into s.s. containers containing 3.5 kg of Isopropyl Alcohol and stir for five minutes using overhead stirrer. Add slowly 7.0 kg of methylene chloride with stirring to get smooth slurry. Stir them continuously for 25 minutes. It is then pass through 80
18

# nylon cloth. Spray this solution to the tablet bed with complying necessary parameters as mentioned before.
COATED TABLET SPECIFICATIONS:
a. Appearance : White colored ,circular, biconvex coated tablets.
b. AvgWt. :186mg
c. Weight Variation : Individual: +/- 5% Of avg. wt.
d. Diameter : 8.1 ± 0.1 mm.
e. Disintegration : N.M.T. 30 mins.
EXAMPLE - 4 [Batch size : 1,00,000 tablets ] Each tablet contains
Prenoxdiazine Hydrochloride 100 mg
Excipients q.s
Manufacturing process:
The process of this invention involves the following steps:-
1 .Milling:
Mill 4.4 kgs of dibasic calcium phosphate through fitz mill (impact forward high
speed) fitted with 0. 5 mm screen. Transfer into bowl of planetary mixer.
2. Sitting:
Sift 2.5 kg of microcrystalline cellulose, 10 kg of Prenoxdiazine Hydochloride
through vibrosifter using 40#
Transfer into bowl of planetary mixer.
19

3.Dry Mixing:
Mix contents of planetary mixer for 15 minutes.
4.Preparation of PVP slurry using following materials:
Preparation of PVP slurry using the following
0.5 kg of Polyvinyl Pyrrolidone K-30, 0.100 kg of polysorbate 80 in sufficient
quantity of D.M water.
5. Wet Mixing:
Add slurry to the contents of the planetary mixer, gradually with continuous stirring. Check consistency and binding .If necessary additional wetting can be imparted using D.M.water.
6.Wet Milling:
Mill the wet mass obtained from step 5 through fitz mill with 8 mm perforation
sieve (knives forward medium speed)
7.Drying:
Dry the granules in Tray drier at 50 ° C. Rake the granules occasionally while
drying in tray drier. Record temp, time, loss on drying.
In-Process control:
Loss on drying:(by I.R.moisture balance) 1.8 %w/w.
8.Lubrication:
a) Sift the dried granules through 16# sieve on vibrosifter and oversize should be passed through fitz mill using 1.5mm sieve. Transfer granules to the planetary mixer and mix for 2 minutes.
20

b) Mill 0.3 kg of Talcum and 0.2 kgs of Stearic acid. Sift 0.5 kg of sodium starch glycoliate using 60# sieve.
c) Add sodium starch glycoliate to the planetary mixer and mix for 10 minutes. Then add blend of talcum and stearic acid and mix for 5 minutes. Unload the lubricated granules in polybag placed in s.s containers.
9.Compression:
After receiving the clearance from Q.C Dept transfer the granules to compression area and tablet compression machine should have been given clearance by in-process Q.C Dept to take the product for compression.
Compress the tablets on single/ double rotary compression machine complying
with the following parameters.
Environmental conditions of Compression cubicle:
Temperature : Between 23 ° C & 27 ° C
Relative Humidity : Below 50%
Appearance Diameter Average weight Weight Variation Hardness Thickness
In-Process control tests: ( uncoated tablets )
White , circular, biconvex, uncoated tablets.
8.0 mm (±0.1 mm)
185 mg
Individual (±3 % of avg wt)
2.5 Kg/cm2
1.8 to 2.5 mm
Disintegration Time : Maximum 9 minutes.
Fraibility : 0.14 %w/w
21

10.Film Coating Process
Prepare the film coating solution using 0.3 kgs of hydroxypropyl methylcellulose, 0.2 kg of hydroxy propyl cellulose, 0.025 kg of titanium dioxide and 0.015 kg of propylene glycol. Transfer above ingredients into s.s. containers containing 7.0 kg of Isopropyl Alcohol and stir for five minutes using overhead stirrer. Add slowly 14.0 kg of methylene chloride with stirring to get smooth slurry. Stir them continuously for 25 minutes. It is then pass through 80 # nylon cloth. Spray this solution to the tablet bed with complying necessary parameters as mentioned before.
COATED TABLET SPECIFICATIONS:
a. Appearance : White colored ,circular, biconvex coated tablets.
b. Avg Wt. : 190 mg
c. Weight Variation : Individual: ± 5% Of avg. wt.
d. Diameter : 8.1 ± 0.1 mm.
e. Disintegration : N.M.T. 30 mins. .
22

I Claim:
[1] A process for making film coated tablet of prenoxdiazine hydrochloride consisting of the following steps:
(1) Milling dispensed quantity of diluents, sieving the milled diluents and
transferring into the bowl of planetary mixer;
(2)Sifting prenoxdiazine Hydrochloride through a vibrosifter using 40# and
transferring into bowl of planetary mixer;
(3)dry Mixing contents of planetary mixer for 10 to 20 minutes;
(4) Preparing a binder slurry by dispersing / dissolving binder in a solvent.
(5)Wet Mixing by adding a slurry to the contents of the planetary mixer,
gradually with continuous stirring
(6)Wet Milling the wet mass obtained from step 5 through a mill with 6 to
10 mm perforated sieve to obtain granules;
(7)Drying the granules in a F.B.D/Tray drier at 50 °C with occasionally
raking maintaining Loss on drying:(by I.R.moisture balance) 1.5 % +/-
0.5%;
(8) Lubrication by sifting the dried granules through 16# sieve on vibrosifter
transferring the dried granules to a planetary mixer and mix for 2 minutes
sifting lubricants, disintegrants using 60# sieve and adding to the planetary
mixer for blend to make lubricated granules;
(9)Compressing the lubricated granules to form core tablets on single/
double rotary compression machine using suitable die and punch complying
with the necessary environmental condition
Temperature : Between 23 °C & 27 ° C
Relative Humidity : Below 50%
23

(10)Film Coating the core tablets by preparing a film coating solution using coating polymers, colors, plasticizers and solvents such as Isopropyl Alcohol, Methylene Chloride. Transfer Methylene Chloride and Isopropyl Alcohol into s.s. containers and stir for five minutes using overhead stirrer; transferring coating materials into the same container under fast stirring till smooth and uniform slurry is formed; just prior to the actual coating passing the slurry through 80 # sieve transferring tablet (cores) after dedusting into a coating pan and heating the tablet bed by inching process using hot air blower and maintaining the initial temperature below 50°C spray coating the sieved slurry on the tablet cores intermittently avoiding overwetting, after the last coat of coating suspension is applied drying of the film coated tablet for 15 - 20 minutes and applying about 50 gms of talc (10 mX 5 times) onto the tablet bed to get the required gloss and rolling the tablets for 5 minutes and then transfer them onto the trays for cooling to form the synergistic antispasmodic, analgesic formulation.
[2] A process as claimed in claim 1, in which the diluent is at least one compound selected from a group consisting of micorcrystalline cellulose, starches, lactose, / mannitol, calcium phosphate, dibasic calcium phosphate and mixtures of these.
[3] A process as claimed in claim 1, in which disintegrating agent is at least one compound selected from a group consisting of cross-linked polyvinylpyrrolidone, carboxymethyl starch, natural starch, microcrystalline cellulose, polarcrin potassium resins, cellulose gum and mixtures of these.
[4] A process as claimed in claim 1, in which binder is at least one compound selected from a group consisting of pregelatinized starch, starches, gelatin, vinyl
24

chloride, povidone, hydroxypropyl cellulose, ethyl cellulose, cellulose acetate phthalate, hydroxypropylmethyl cellulose and mixture of these.
[5] A process as claimed in claim 1, in which glidant is at least one compound selected from a group consisting of corn starch, talcum, colloidal silicon dioxide, silicon dioxide and mixtures of these.
[6] A process as claimed in claim 1, in which the lubricant is at least one compound selected from a group consisting of magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, surfactants, talc, waxes and zinc stearate.
[7] A process as claimed in claim 1, in which the coating layer consists of at least one compound selected from a group consisting of film forming cellulose polymers such as Ethyl Cellulose and/ or hydroxypropylmethylcellulose, hydroxy propyl cellulose, plasticizers such as propylene glycol with or without surfactants and/or coloring agents that may comprises at least one of the approved food and drug colors such as yellow iron oxides, tetrazine, brillant blue etc, solvents such as purified water, isopropyl alcohol, acetone, methylene chloride and opacifier includes titanium dioxide.
[8] A process as claimed in claim 1, in which the surfactant is at least one compound selected from a group consisting of sodium lauryl sulfate, sodium carboxy methylcellulose, calcium carboxy methylcellulose, polysorbates, and sorbitan esters.
25

[9] A process as claimed in claim 1, which consists of making a tablet having :
(a) 50 mg to 200 mg of prenoxdiazine hydrochloride (b) pharmaceutical acceptable inert excipients consisting of at least one diluent 10% to 80% of the total mass of the formulation, at least one binder being 0.1% to 4% of the total mass of the formulation, at least one glidant from 0.01% to 3% of the total mass of the formulation., at least one lubricant being from 0.6% to 5% of the total mass of the formulation, and at least one disintegrant being 0.6% to 8% of the total mass of the formulation and at least one film coat on the core consisting of at least one film forming polymer and a plasticizer 2 to 4 wt % based on the weight of the core composition and optionally a surfactant.
Dated this 4th day of April, 2005.
MOHAN DEWAN
OF R.K.DEWAN & COMPANY
APPLICANT'S PATENT ATTORNEY

Documents:

425-mum-2004-claims(granted)-(23-2-2007).doc

425-mum-2004-claims(granted)-(23-2-2007).pdf

425-mum-2004-correspondence(23-2-2007).pdf

425-mum-2004-correspondence(ipo)-(28-2-2006).pdf

425-mum-2004-form 1(8-4-2004).pdf

425-mum-2004-form 18(2-6-2005).pdf

425-mum-2004-form 2(granted)-(23-2-2007).doc

425-mum-2004-form 2(granted)-(23-2-2007).pdf

425-mum-2004-form 3(8-4-2004).pdf

425-mum-2004-form 5(4-4-2005).pdf

425-mum-2004-form 9(6-4-2005).pdf

425-mum-2004-power of attorney(8-4-2004).pdf


Patent Number 218463
Indian Patent Application Number 425/MUM/2004
PG Journal Number 19/2008
Publication Date 09-May-2008
Grant Date 02-Apr-2008
Date of Filing 08-Apr-2004
Name of Patentee SANJEEV KHANDELWAL
Applicant Address PREM NIVAS, 13, ALTAMOUNT ROAD, MUMBAI 400 026
Inventors:
# Inventor's Name Inventor's Address
1 SANJEEV KHANDELWAL PREM NIVAS, 13, ALTAMOUNT ROAD, MUMBAI 400 026
PCT International Classification Number A 61 K 31/44
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA