Title of Invention

A PROCESS OF PREPARING LORATADINE NASAL SPRAY SOLUTION

Abstract The process of preparing loratadine nasal spray solution comprises the following steps: i) adding loratadine 0.4% to 0.5% w/v in sufficient quantity of purified water under stirring to make a slurry and adding Hydrochloric acid 1M solution for dissolving and forming a clear solution of loratadine; ii) adding Glycerin 0.5% to 10% w/v, Propylene glycol 0.1% to 50% w/v and Polyoxyl-35 castor oil 0.1% to 50% w/v to the clear solution of loratadine and stirring to form a homogenous solution; iii) dissolving Disodium edetate 0.025% to 0.3% w/v in purified water and adding Phenyl ehtyf alcohol 0.1% to 0.3% w/v and 50% Benzaffconium chloride solution 0.001% to 0.04% w/v and stirring to form solution and mixing the said solution to the homogenous solution of the above step (ii); iv) preparing a 5% w/v solution of Sodium Hydroxide in purified water; v) adjusting the pH of homogenous solution of the above step (iii) in the range of 4 to 7 by using Sodium Hydroxide solution of the above step (iv); vi) making up the desired volume by adding desired quantity of purified water and stirring; vii) filtering the solution of the above step (vi) and filtering it in the containers as per requirement. Dated this 19th Day of December, 2002
Full Text HE PATENTS ACT, 1970 (39 of 1970)
COMPLETE SPECIFICATION (See Section 10)
A PROCESS OF PREPARING LORATADINE NASAL SPRAY SOLUTION
M/S. ALEMBIC LIMITED, ALEMBIC ROAD, VADODARA- 390 003, GUJARAT, an Indian Company incorporated under the Companies Act, 1956.
The following specification particularly describes and ascertains the nature of this invention, and the manner in which it is to be performed.





This invention relates to a process of preparing loratadine nasal spray solution-More particularly this invention relates to a process of preparing loratadine nasal spray solution for the treatment of allegic rhinitis by making the drug loratadine available at the site of action in the form of nasal spray to provide relief from symptoms with a reduced dosage as compared to oral therapy thereby lesser quantity of drug is required to elicit a pharmaceutical response without any side effects.
Allergic Rhinitis, affects a number of people and the cause of the same are many.
Oral therapy with antihistamine drugs is well known and Loratadine belongs to the class of new antihistaminic drugs which is currently used in oral therapy and is available in the form of Syrup and Tablets but in the oral therapy the relief from the symptoms is slow and the side effects like headache and eye pain is also associated and the quantity of drug required to elicit a pharmaceutical response is high.
Treatment of allergic rhinitis is symptomatic and therefore a rapid relief from symptoms is desirable.
The present invention consists of a pharmaceutical composition where by the drug Loratadine also known as ethyl 4-18-chloro-5,6-dihydro-l 1 H benzo [5,6] cyclohepta [1,2-b]pyridin-l1-ylidene)-l-piperidinecarboxylate can be made available at the site of action in the form of a Nasal Spray which provides rapid relief from symptoms with lesser quantity of drug is required to elicit a pharmaceutical response and thus reduced dosage as compared to oral therapy and freedom from side effects like headache and eye pain associated with oral therapy and return to normalcy from the time symptoms appear is very fast thus increases work efficiency and reduces days away from work.
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Accordingly this invention provides the following steps:
i) adding loratadine 0.4% to 0.5% w/v jn sufficient quantity of purified water under
stirring to make a slurry and adding Hydrochloric acid 1M solution for dissolving
and forming a clear solution of loratadine, ii) adding Propylene glycol 0.1% to 50% w/v and PoIyoxyl-35 castor oil 0.1% to
50% w/v to the clear solution of loratadine and stirring to form a homogenous
solution, Hi) dissolving Disodium edetate 0.025% to 0.3% w/v in purified water and adding
Phenyl ehtyl alcohol 0.1% to 0.3% w/v and 50% Benzalkonium chloride solution
0.001% to 0.04% w/v and stirring to form solution and mixing the said solution to
the homogenous solution of the above step (ii), iv) preparing a 5% w/v solution of Sodium Hydroxide in purified water, v) adjusting the pH of homogenous solution of the above step (iii) in the range of 4
to 7 by using Sodium Hydroxide solution 5% w/v of the above step (iv), vi) making up the desired volume by adding desired quantity of purified water and
stirring, vii) filtering the solution of the above step (vi) and filtering it in the containers as per
requirement.
The process of preparing loratadine nasal spray solution wil! be clear from the following examples.
Example: 1
1. Transfer 20 kg of Polyoxyl-35-castor oil and 25 kg of Propylene Glycol to a s.s. vessel filter with a mechanical stirrer.
2. Heat the mixture of step (1) to 65°C and under stiring add 0.5 kg Loratadine and stir till a clear solution is formed.
3. Dissolve 0.1 kg of Disodium edetate in 25 litres Purified water and transfer the solution to the solution of step (2).
4. Transfer 0.25 kg of Phenyl ethyl alcohol and Benzalkonium chloride solution (50%) to a s.s. vessel. Add 10 litres Purified water under stirring and stir till a homogenous mixture is formed.
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5. Transfer the mixture of step 4 to the solution of step 3 and stir till a clear solution is formed.
6. Prepare a 5% w/v solution of Sodium hydroxide in purified water.
7. Check the pH of the solution of step 5 and adjust the pH in the range of 4 to 7 using the 5% w/v solution of Sodium hydroxide solution.
8. Make up the volume to 100-L with Purified Water and stir.
9. Filter the solution and fill it in containers.
Example 2 :
1. Transfer 20 kg of Polyoxyl-35-castor oil and 35 kg of Propylene Glycol to a s.s. vessel filter with a mechanical stirrer.
2. Heat the mixture of step (1) to 65°C and under stiring add 0.5 kg Loratadine and stir till a clear solution is formed.
3. Under stirring allow the solution of step 2 to cool to ambient temperature.
4. Transfer 10 kg of Glycerin to the solution of step 3 and stir.
5. Transfer Phenyl ethyl alcohol 0.25 kg and Benzalkonium chloride solution (50%) 0.04 kg to a s.s. vessel. Add 10 Uteres of purified water and mix.
6. Transfer a solution of step 5 to the solution of step 4 and stir.
7. Prepare a 5% w/v solution of Sodium hydroxide in purified water.
8. Check the pH of the solution of step 5 and adjust the pH in the range of 4 to 7 using the 5% w/v solution of Sodium hydroxide solution.
9. Make up the volume to 100-L with Purified Water and stir.
10. Filter the solution and fill it in containers.
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Example 3
1. Transfer 20 litres of Purified water to a s.s. vessel filter with a mechanical stirrer.
2. Add 0.4 kg of Loratadine to the water to step (3) and stri to make a slurry.
3. Under stirring slowly add Hydrochloric acid 1M solution to dissolve Loratadine
4. Transfer 15 kg of Propylene glycol and 15 kg of Poiyoxyl-35-castor oil to the Loratadine solution and stir.
5. Dissolve Disodium edetate in 20-L of Purified water and add 0.25 kg Phenyl ethyl alcohol and 0.04 litres of Benzalkonium chloride solution (50%) and transfer the solution to the solution of step 4.
6. Prepare a 5% solution of Sodium Hydroxide in Purified water.
7. Check the pH of the solution of step 5 and adjust the pH in the range of 4 to 7 using the 20% w/v solution of Tromethamine of step 6.
8. Make up the volume to 100-L with Purified Water and stir.
9. Filter the solution and fill it in containers.
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Example : 4
1. Transfer 20-L of Purified water to a s.s. vessel filter with a mechanical stirrer.
2. Add Loratadine to the water to step (1) and stri to make a slurry.
3. Under stirring slowly add Hydrochloric acid 1M solution to dissolve Loratadine
4. Transfer Propylene glycol, PoIyoxyl-35-castor oil and Glycerin to the Loratadine solution and stir.
5. Dissolve Disodium edetate in 40-L of Purified water and add Phenyl ethyl alcohol and Benzalkonium chloride solution (50%) and transfer the solution to the solution of step 4.
6. Prepare a 20% w/v solution of Tromethamine in Purified water.
7. Check the pH of the solution of step 5 and adjust the pH in the range of 4 to 7 using the 20%o w/v solution of Tromethamine of step 6.
8. Make up the volume to 100-L with Purified Water and stir.
9. Filter the solution and fill it in containers.
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The above description by way of examples is given to illustrate the invention rather then to limit its scope.
We claim:
1. The process of preparing loratadine nasal spray solution comprises the following
steps:
i) adding loratadine 0.4% to 0.5% w/v in sufficient quantity of purified water under
stirring to make a slurry and adding Hydrochloric acid 1M solution for dissolving
and forming a clear solution of loratadine, ii) adding Propylene glycol 0.1% to 50% w/v and Polyoxyl-35 castor oil 0.1% to
50% w/v to the clear solution of loratadine and stirring to form a homogenous
solution, iii) dissolving Disodium edetate 0.025% to 0.3% w/v in purified water and adding
Phenyl ehtyl alcohol 0.1% to 0.3% w/v and 50% Benzalkonium chloride solution
0.001% to 0.04% w/v and stirring to form solution and mixing the said solution to
the homogenous solution of the above step (ii), iv) preparing a 5% w/v solution of Sodium Hydroxide in purified water, v) adjusting the pH of homogenous solution of the above step (iii) in the range of 4
to 7 by using Sodium Hydroxide solution 5% w/v of the above step (iv), vi) making up the desired volume by adding desired quantity of purified water and
stirring, vii) filtering the solution of the above step (vi) and filtering it in the containers as per
requirement.
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2. A process of preparing loratadine nasal spray solution as claimed in claim 1 wherein
in place of 5% solution of Sodium Hydroxide a 20% w/v solution of Tromethamine
in purified water is prepared and used for adjusting the pH in the range of 4 to 7 of
the solution prepared in step (iii) of claim I.
3. A process of preparing loratadine nasal spray solution as claimed in claim 1 or 2
wherein Glycerin 0.5% to 10% w/v is added with the Propylene Glycol 0.1% to 50%
and Polyoxyl-35 castor oil 0.1% to 50% w/v and then mixed to the loratadine
solution of step (iO to form a homogenous solution of step (ii) of claim 1.
4. A process as claimed in claim 1, 2 or 3 wherein in step (iii) of claim 1 Phenyl ethyl
alcohol 0.1% to 0.3% w/v and 50% Benzalkonium chloride solution 0.001% to
0.04% w/v is added in desired quantity of purified water and stirred to mix and form
a homogenous solution for adding in the homogeneous solution of loratadine of step
(ii) of claim 1.
5. A process as claimed in any of the preceding claims wherein Polyoxyl-35 castor oil
0.1% to 50% w/v and Propylene Glycol 01% to 50% w/v is mixed and heated from
60 to 70 C and loratadine 0.4% to 0.5% w/v is added under stirring to form a clear
solution and allowed to cool to the ambian temperature to form a homogeneous
solution of loratadine.
6. A process as claimed in claim 5 wherein Glycerin 0.5% to 10% w/v is added to the
said homogenous solution of loratadine.
7. A process as claimed in claim 5 wherein Disodium edetate 0.025% to 0.3% w/v is dissolved in desired quantity of purified water and added to the said homogenous solution of loratadine.
8. A process of preparing loratadine nasal spray solution substantially as herein described and illustrated in example 1 to 4 of the complete specification.
Dated this 19lh Day of December, 2002
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This invention relates to a process of preparing loratadine nasal spray solution. More particularly this invention relates to a process of preparing loratadine nasal spray solution for the treatment of allergic rhinitis by making the drug loratadine available at the site of action in the form of nasal spray to provide relief from symptoms with a reduced dosage as compared to oral therapy thereby lesser quantity of drug is required to elicit a pharmaceutical response without any side effects Allergic Rhinitis, affects a number of people and the cause of the same are many. Oral therapy with antihistaminic drugs is well known and Loratadine belongs to the class of new antihistaminic drugs which is currently used in oral therapy and is available in the form of Syrup and Tablets but in the oral therapy the relief from the symptoms is slow and the side effects like headache and eye pain is also associated and the quantity of drug required to elicit a pharmaceutical response is high.
Treatment of allergic rhinitis is symptomatic and therefore a rapid relief from symptoms is desirable.
The present invention consists of a pharmaceutical composition where by the drug Loratadine also known as ethyl 4-18-chloro-5,6-dihydro-ll H benzo [5,6] cyclohepta [l,2-b]pyridin-ll-ylidene)-l-piperidinecarboxylate can be made available at the site of action in the form of a Nasal Spray which provides rapid relief from symptoms with lesser quantity of drug is required to elicit a pharmaceutical response and thus reduced dosage as compared to oral therapy and freedom from side effects like headache and eye pain associated with oral therapy and return to normalcy from the time symptoms appear is very fast thus increases work efficiency and reduces days away from work.
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Example 3
1. Transfer 20 litres of Purified water to a s. s. vessel filter with a mechanical stirrer.
2. Add 0.4 kg of Loratadine to the water to step (1) and stri to make a slurry.
3. Under stirring slowly add Hydrochloric acid 1M solution to dissolve Loratadine
4. Transfer 15 kg of Propylene glycol and 15 kg of Polyoxyl-35-castor oil to the Loratadine solution and stir.
5. Dissolve Disodium edetate in 20-L of Purified water and add 0.25 kg Phenyl ethyl alcohol and 0.04 litres of Benzaikonium chloride solution (50%) and transfer the solution to the solution of step 4.
6. Prepare a 5% solution of Sodium Hydroxide in Purified water.
7. Check the pH of the solution of step 5 and adjust the pH in the range of 4 to 7 using the 20% w/v solution of Tromethamine of step 6.
8. Make up the volume to 100-L with Purified Water and stir.
9. Filter the solution and fill it in containers.
Example: 4
1. Transfer 20-L of Purified water to a s.s. vessel filter with a mechanical stirrer.
2. Add Loratadine to the water to step (1) and stri to make a slurry.
3. Under stirring slowly add Hydrochloric acid 1M solution to dissolve Loratadine
4. Transfer Propylene glycol, Polyoxyl-35-castor oil and Glycerin to the Loratadine solution and stir.
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5. Dissolve Disodium edetate in 40-L of Purified water and add Phenyl ethyl alcohol and Benzalkonium chloride solution (50%) and transfer the solution to the solution of step 4.
6. Prepare a 20% w/v solution of Tromethamine in Purified water.
1. Check the pH of the solution of step 5 and adjust the pH in the range of 4 to 7 using the 20% w/v solution of Tromethamine of step 6.
8. Make up the volume to 100-L with Purified Water and stir.
9. Filter the solution and fill it in containers.
Test reports

Sr, No. Parameters Test Results
Ex.1 Ex.2 Ex 3 Ex.4
1 Appearance Pale yellow coloured solution Pale yellow coloured solution Pale yellow coloured solution Pale yellow
coloured
solution
2 PH 4.57
5.30 6.00 6.60
3 'Clarity Clear Clear Clear Clear
4 Assay 98.2% 99.0% 100.0% 99.70%
The above description by way of examples is given to illustrate the invention rather then to limit its scope.
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We claim:
1. The process of preparing loratadine nasal spray solution comprises the following
steps:
i) adding loratadine 0.4% to 0.5% w/v in sufficient quantity of purified water under
stirring to make a slurry and adding Hydrochloric acid 1M solution for dissolving
and forming a clear solution of loratadine; ii) adding Glycerin 0.5% to 10% w/v, Propylene glycol 0.1% to 50% w/v and
Polyoxyl-35 castor oil 0.1% to 50% w/v to the clear solution of loratadine and
stirring to form a homogenous solution, iii) dissolving Disodium edetate 0.025% to 0.3% w/v in purified water and adding
Phenyl ehtyl alcohol 0.1% to 0.3% w/v and 50% Benzalkonium chloride solution
0.001% to 0.04% w/v and stirring to form solution and mixing the said solution to
the homogenous solution of the above step (ii); iv) preparing a 5% w/v solution of Sodium Hydroxide in purified water; v) adjusting the pH of homogenous solution of the above step (iii) in the range of 4
to 7 by using Sodium Hydroxide solution of the above step (iv); vi) making up the desired volume by adding desired quantity of purified water and
stirring; and vii) filtering the solution of the above step (vi) and filling it in the containers as per
requirement.
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2. A process as claimed in claim 1 wherein optionally in place of 5% solution of
Sodium Hydroxide 20% w/v solution of Tromethamine in purified water can be used
for adjusting the pH in the range of 4 to 7 of the solution prepared in step (iii) of
claim 1.
3. A process as claimed in any one of the preceding claims wherein Polyoxyl-35 castor
oil 0.1% to 50% w/v and Propylene Glycol 01% to 50% w/v is mixed and heated
from 60 to 70°C and loratadine 0.4% to 0.5% w/v is added under stirring to form a
clear solution and allowed to cool to the ambian temperature to form a homogeneous
solution of loratadine,
4. A process of preparing loratadine nasal spray solution substantially as herein
described and illustrated in example 1 to 4 of the complete specification.
Dated this 19th Day of December, 2002

(Anuradha Ramu) Agent for the Applicant
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Documents:

1202-mum-2001 abstract.pdf

1202-mum-2001 claims(cancelled).pdf

1202-mum-2001 claims.pdf

1202-mum-2001 correspondence.pdf

1202-mum-2001 corresponence(ipo).pdf

1202-mum-2001 description(granted).pdf

1202-mum-2001 form 1(20-07-2004).pdf

1202-mum-2001 form 1(21-12-2001).pdf

1202-mum-2001 form 13.pdf

1202-mum-2001 form 19(3-6-2003).pdf

1202-mum-2001 form 2(granted).pdf

1202-mum-2001 form 2(provisional specification).pdf

1202-mum-2001 form 2(title page).pdf

1202-mum-2001 form 3(16-07-2004).pdf

1202-mum-2001 form 3(supersided).pdf

1202-mum-2001 form 5.pdf

1202-mum-2001 others.pdf

1202-mum-2001 petition rule 138.pdf

1202-mum-2001 power of attorney.pdf

1202-mum-2001-abstract.doc

1202-mum-2001-claims.doc

1202-mum-2001-description(granted).doc

1202-mum-2001-form 2(granted).doc


Patent Number 205011
Indian Patent Application Number 1202/MUM/2001
PG Journal Number 31/2008
Publication Date 01-Aug-2008
Grant Date 13-Mar-2007
Date of Filing 21-Dec-2001
Name of Patentee M/S. ALEMBIC LIMITED
Applicant Address ALEMBIC ROAD, VADODARA - 390 003, GUJARAT, INDIA
Inventors:
# Inventor's Name Inventor's Address
1 BHATTACHARYA SAMPAD C/O ALEMBIC LIMITED, ALEMBIC ROAD, VADODARA - 390 003, GUJARAT, INDIA
PCT International Classification Number A 61 K 9/72
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA