Specification
FORM 2
THE PATENTS ACT 1970
(39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
"PHARMACEUTICAL LOZENGE COMPOSITION OF DESLORATADINE"
2. APPLICANT:
(a) NAME: CIPLA LTD.
(b)NATIONALITY: Indian Company incorporated under the Indian Companies Act, 1956
(c) ADDRESS: 289, Bellasis Road, Mumbai Central, Mumbai - 400 008, Maharashtra, India
3. PREAMBLE TO THE DESCRIPTION:
The following specification describes the invention and the manner in which it is to be performed.
Field of Invention:
The present invention relates to a pharmaceutical lozenge composition comprising desloratadine and a process for preparing such pharmaceutical lozenge composition and its use in preventing and/or treating the allergenic reactions or other histamine induced disorders.
Background and prior art:
Descarbonylethoxyloratadine, also called desloratadine is chemically known as 8-chloro-6,ll-dihydro-ll-(4-piperidylidene)-5H-benzo[5,6]-cyclohepta[l,2-b]pyridine. Desloratadine is a metabolic derivative of loratadine and is a long acting tricyclic histamine antagonist with selective H1-receptor antagonist activity. Desloratadine is used as a non-sedating antihistaminic drug. Desloratadine is a white to off-white powder that is slightly soluble in water, but very soluble in ethanol and propylene glycol. Desloratadine structure can be represented as-
Desloratadine is disclosed in U.S. Pat. No. 4,659,716 ('716 patent). It is currently marketed as Clarinex® in the United States. Clarinex® has been approved as an antihistaminic drug for prevention or treatment of allergenic reactions, which may result in symptoms such as sneezing, itchy eyes and hives. The '716 patent discloses methods for preparing and administering desloratadine and its pharmaceutically acceptable salts.
Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field.
U.S. Pat. No. 6,100,274 discloses a pharmaceutical composition for the treatment of urticaria or allergic rhinitis, which comprises a therapeutically effective amount of descarboethoxyloratadine (desloratadine-protective), or a pharmaceutically acceptable salt thereof. The pharmaceutical composition is suitable for oral administration and preferably in the form of tablet or capsules.
United States Patent Application Number 20020123504 Al discloses pharmaceutical compositions of desloratadine formulated to avoid the incompatibility between desloratadine" and reactive excipients such as lactose and other mono-and di-saccharides. Also disclosed is a method for preventing contact between desloratadine and reactive formulation components by applying an inert coating to desloratadine granules. Disclosed compositions include lactose-free, non-hygroscopic and anhydrous pharmaceutical compositions of desloratadine.
International" Patent Application Publication No. WO 2005/065047 discloses desloratadine compositions that include a stabilizer selected from an antioxidant, an organic compound providing an alkaline pH, and an alkali metal salt.
U.S. Pat. No. 6,514,520 discloses an antihistaminec syrup formulation comprising desloratadine and about 0.05 to about 5 mg/mL of an a.minopolycarboxylic acid or a salt thereof. However, when stored under dark conditions, a strong pink color has been observed to develop over time. Thus, a dye is used in the marketed formulation.
United States Patent Application Number 20020123504 Al discloses a syrup formulation of loratadine, desloratadine, or a pharmaceutically acceptable salt thereof, or a combination of two or more thereof, which contains only components recognized as being safe for human ingestion, that are sugar free, clear in color and that are storage-stable.
U.S. Patent Application Publication No. 2008/0262017 discloses a sugar-free antihistaminic syrup formulation containing lohtadine, desloratadine, or a pharmaceutically acceptable salt thereof, or a combination of two or more thereof and other pharmaceutical excipients.
Thus prior art discloses various dosage forms of desloratadine such as tablet (e.g. orally disintegrable tablets, bilayer tablets), capsule, and syrup. Amongst these dosage forms, the preferred drug delivery system for administering desloratadine is an oral tablet, however it is often difficult to swallow a tablet by large number of patients, particularly the elderly and the children. The tablet dosage form also further requires the use of a liquid for swallowing the said tablet.
It is also known in the art that desloratadine when administered orally, the time required to reach peak plasma level (tmax) is about > 3 hours and the study-state plasma levels are attained after about 6 days. Also the drug is extensively metabolized on oral administration which may decrease the amount of drug required to render its therapeutic effect. (Comparison of pharmacokinetics and metabolism of desloratadine, fexofenadine, levocetirizine and mizolastine in humans; Fundamental & clinical pharmacology, Molimard Metal, 2004, vol. 18 (4), pp. 399-4M). Hence the usefulness of currently available dosage forms of desloratadine may be limited for conditions where a rapid onset of drug action is desired.
Furthermore, desloratadine and its compositions are prone to oxidation and decomposition by acidic excipients to form impurities such as deschlorodesloratadine, dehydrodesloratadine and N-formyldesloratadine, more specifically N-formyldesloratadine. Also, being a secondary amine, there may be likelihood of desloratadine undergoing Maillard reaction in presence of excipients such as lactose (for example, Maillard reaction of lactose and fluoxetine hydrochloride, a secondary amine described in Journal of Pharmaceutical Sciences, 1998, 87(1): 31-39, by Wirth, et. al. The author identified N-formyl fluoxetine as a major product of the Maillard reaction between fluoxetine, a secondary amine, and lactose).
Hence there remains a need to formulate a suitable dosage form of desloratadine which may alleviate all the aforesaid problems associated with prior art dosage forms.
Object of the invention:
The object of the present invention is to provide a suitable oral pharmaceutical composition of desloratadine which remains stable during storage.
Another object of the present invention is to provide a suitable oral pharmaceutical composition of desloratadine which provides rapid onset of drug action.
Another object of the present invention is to provide a suitable oral pharmaceutical composition of desloratadine in which the quantity of desloratadine remains in the oral cavity over a prolonged time period to elicit a therapeutic effect.
Another object of the present invention is to provide oral pharmaceutical composition of desloratadine which possess good taste and also has a good feel in the mouth.
Another object of the present invention is to provide a simple process of manufacturing the oral pharmaceutical composition of desloratadine.
Summary of the Invention:
According to one aspect of the present invention there is provided a pharmaceutical lozenge composition comprising desloratadine and one or more pharmaceutically acceptable excipients.
According to another aspect of the present invention there is provided a process for manufacturing the said pharmaceutical lozenge composition comprising desloratadine.
According to a further aspect of the present invention is to provide a method of preventing or treating allergic reactions or other histamine induced disorders comprising administering the said pharmaceutical lozenge composition of desloratadine.
Detailed description:
The present inventors have formulated a pharmaceutical lozenge composition of desloratadine employing pharmaceutically acceptable excipients which may alleviate the aforesaid problems associated with prior art dosage forms.
The present inventors have surprisingly achieved above objectives by developing a simple composition of desloratadine which further is also cost effective. The subject composition can be administered to all patients, from children to elderly. The pharmaceutical lozenge compositions provided by the present invention are intended to be used in the treatment of allergic reactions or other histamine induced disorders by the administration to a patient in need of such treatment of the pharmaceutical lozenge composition containing a therapeutically effective amount of desloratadine which releases the desloratadine in the oral cavity which may reach the systemic circulation via absorption through oral mucosa.
The term "desloratadine" is used throughout the description in broad sense to include not only the desloratadine per se but also its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs and pharmaceutically acceptable prodrugs.
The solid dosage form is a lozenge which is not intended to be swallowed by the patient as in the case of solid dosage forms such as tablet and capsule. The term "lozenge" as used herein is intended to embrace all dosage forms where the product is formed by cooling a sugar-based or sugar alcohol based or sugar-free (e.g. isomalt) molten mass containing desloratadine.
The pharmaceutical lozenge composition of desloratadine according to the present invention, may possess good taste and good feel in the mouth.
In one embodiment, according to the present invention, the pharmaceutical lozenge composition comprises desloratadine and one or more pharmaceutically acceptable excipients comprising at least one sugar or sugar alcohol or their mixture.
According to the present invention, the pharmaceutical lozenge composition of desloratadine may be sugar based or sugar alcohol based optionally with one or more pharmaceutically acceptable excipients.
If the lozenge composition is sugar based, it may comprise a single sugar (e.g. sucrose, dextrose, maltose, glucose, arabinose, lactose, galactose etc) or mixture of sugars (e.g. mixture of sucrose & glucose, glucose and lactose, arabinose and maltose, glucose and fructose etc).
If the lozenge composition is sugar-alcohol based, it may comprise sorbitol, xylitol, maltitol, lactitol mannitol, a hydrogenated starch hydrosylate such as maltitol syrup or mixtures thereof, which may be in the form of the free sugar alcohols, derivatives thereof or mixtures thereof. Preferred sugar alcohol based lozenge-forming compositions comprise one or more of sorbitol, maltitol, and a hydrogenated starch hydrosylate or mixtures thereof. More preferred sugar alcohol based lozenge-forming compositions comprise one or more of sorbitol, maltitol and a hydrogenated glucose syrup, which is sold under the trade mark Lycasin (contains major component maltitol) and typically comprises a mixture of maltitol, sorbitol and hydrogenated oligo and poly-saccharides. Preferably, the sugar alcohol based lozenge-forming composition essentially does not consist of'any sugar.
One preferred lozenge-forming composition comprises an approximately equimolar mixture of alpha-D-gluco-pyranosyl-l,6-D-sorbitol and alpha-D-glucosopyranosyl-l,l-D-mannitol (isomalt) optionally in conjunction with a hydrogenated glucose syrup (contains major component as maltitol) such as lycasin, more preferably the sugar alcohol based pharmaceutical lozenge composition comprises a mixture of isomalt and Lycasin® (i.e. isomalt and maltitol syrup).
In one embodiment, the pharmaceutical lozenge composition of the present invention may be formulated using suitable non-sugar based artificial sweetening agents to develop sugar-free pharmaceutical composition of desloratadine which comprises sucralose, a fluorinated sucrose derivative, saccharin, nutritive dextrose, acesulfame potassium, saccharin, sodium cyclamate, aspartame, and naono-ammonium glycyrrhizinate (Magnasweet™).
In another embodiment, the pharmaceutical lozenge composition of the present invention may be formulated using suitable sugar alcohols and non-sugar based artificial sweetening agents optionally with one or more pharmacceuticall0.y acceptable excipients.
The sugar or sugar- alcohol may be present in the pharmaceutical lozenge composition of the present invention from about 10% to about 99.5% w'w of the composition.
The oral ijhacraaceuticaL ccm^cidtiaa
Documents
Application Documents
| # |
Name |
Date |
| 1 |
2895-MUM-2009- AFR.pdf |
2022-11-16 |
| 1 |
2895-MUM-2009-FORM 5(15-12-2010).pdf |
2010-12-15 |
| 2 |
2895-MUM-2009-FORM 2(TITLE PAGE)-(15-12-2010).pdf |
2010-12-15 |
| 2 |
2895-MUM-2009-AbandonedLetter.pdf |
2018-10-31 |
| 3 |
2895-mum-2009-form 2(15-12-2010).pdf |
2010-12-15 |
| 3 |
2895 MUM 2009 FORM 13 CIPLA LTD 214.pdf |
2018-08-10 |
| 4 |
2895 MUM 2009 FORM 26 CIPLA LTD 213.pdf |
2018-08-10 |
| 5 |
2895-MUM-2009-DESCRIPTION(COMPLETE)-(15-12-2010).pdf |
2010-12-15 |
| 5 |
2895-MUM-2009-CORRESPONDENCE(23-6-2010).pdf |
2018-08-10 |
| 6 |
2895-mum-2009-correspondence.pdf |
2018-08-10 |
| 6 |
2895-MUM-2009-CORRESPONDENCE(15-12-2010).pdf |
2010-12-15 |
| 7 |
2895-mum-2009-description(provisional).pdf |
2018-08-10 |
| 7 |
2895-MUM-2009-CLAIMS(15-12-2010).pdf |
2010-12-15 |
| 8 |
2895-MUM-2009-FER.pdf |
2018-08-10 |
| 9 |
2895-MUM-2009-FORM 1(23-6-2010).pdf |
2018-08-10 |
| 9 |
2895-MUM-2009-ABSTRACT(15-12-2010).pdf |
2010-12-15 |
| 10 |
2895-mum-2009-form 1.pdf |
2018-08-10 |
| 11 |
2895-MUM-2009- FORM 9 (22-07-2011).pdf |
2011-07-22 |
| 11 |
2895-mum-2009-form 2(title page).pdf |
2018-08-10 |
| 12 |
2895-MUM-2009- CORRESPONDENCE (22-07-2011).pdf |
2011-07-22 |
| 12 |
2895-mum-2009-form 2.pdf |
2018-08-10 |
| 13 |
2895-MUM-2009-FORM 18(13-12-2013).pdf |
2013-12-13 |
| 13 |
2895-mum-2009-form 26.pdf |
2018-08-10 |
| 14 |
2895-MUM-2009-CORRESPONDENCE(13-12-2013).pdf |
2013-12-13 |
| 14 |
2895-mum-2009-form 3.pdf |
2018-08-10 |
| 15 |
2895-MUM-2009-DUPLICATE-FER-2017-11-16-09-50-17.pdf |
2017-11-16 |
| 16 |
2895-MUM-2009-CORRESPONDENCE(13-12-2013).pdf |
2013-12-13 |
| 16 |
2895-mum-2009-form 3.pdf |
2018-08-10 |
| 17 |
2895-mum-2009-form 26.pdf |
2018-08-10 |
| 17 |
2895-MUM-2009-FORM 18(13-12-2013).pdf |
2013-12-13 |
| 18 |
2895-MUM-2009- CORRESPONDENCE (22-07-2011).pdf |
2011-07-22 |
| 18 |
2895-mum-2009-form 2.pdf |
2018-08-10 |
| 19 |
2895-MUM-2009- FORM 9 (22-07-2011).pdf |
2011-07-22 |
| 19 |
2895-mum-2009-form 2(title page).pdf |
2018-08-10 |
| 20 |
2895-mum-2009-form 1.pdf |
2018-08-10 |
| 21 |
2895-MUM-2009-ABSTRACT(15-12-2010).pdf |
2010-12-15 |
| 21 |
2895-MUM-2009-FORM 1(23-6-2010).pdf |
2018-08-10 |
| 22 |
2895-MUM-2009-FER.pdf |
2018-08-10 |
| 23 |
2895-MUM-2009-CLAIMS(15-12-2010).pdf |
2010-12-15 |
| 23 |
2895-mum-2009-description(provisional).pdf |
2018-08-10 |
| 24 |
2895-MUM-2009-CORRESPONDENCE(15-12-2010).pdf |
2010-12-15 |
| 24 |
2895-mum-2009-correspondence.pdf |
2018-08-10 |
| 25 |
2895-MUM-2009-DESCRIPTION(COMPLETE)-(15-12-2010).pdf |
2010-12-15 |
| 25 |
2895-MUM-2009-CORRESPONDENCE(23-6-2010).pdf |
2018-08-10 |
| 26 |
2895 MUM 2009 FORM 26 CIPLA LTD 213.pdf |
2018-08-10 |
| 27 |
2895-mum-2009-form 2(15-12-2010).pdf |
2010-12-15 |
| 27 |
2895 MUM 2009 FORM 13 CIPLA LTD 214.pdf |
2018-08-10 |
| 28 |
2895-MUM-2009-FORM 2(TITLE PAGE)-(15-12-2010).pdf |
2010-12-15 |
| 28 |
2895-MUM-2009-AbandonedLetter.pdf |
2018-10-31 |
| 29 |
2895-MUM-2009-FORM 5(15-12-2010).pdf |
2010-12-15 |
| 29 |
2895-MUM-2009- AFR.pdf |
2022-11-16 |
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