WO2011089584A1

WO2011089584A1 - Process for the preparation of a granular oral composition

Info

Publication number: WO2011089584A1
Application number: PCT/IB2011/050315
Authority: WO
Inventors: Rakesh Kumar Khattar; Rajesh Agrawal; Awdhesh Omray
Original assignee: Modi-Mundipharma Pvt. Ltd
Priority date: 2010-01-25
Filing date: 2011-01-25
Publication date: 2011-07-28

Abstract

A process for the preparation of a granular oral complex comprising the steps of mixing 5 to 10% polyvinylpyrrolidone iodine powder, a soluble diluent with 20 to 25% effervescent agent and 17 to 25% acidifying agent having moisture content less then 0.2% w/w and particle size less then 250 micron; granulating the above mixture with 80% isopropyl alcohol; granulating with 1:1 hydro alcoholic solution; drying the granules obtained at a temperature not exceeding 40°C; and micronizing the granules to size less than 175 micron.

Description

"PROCESS FOR THE PREPARATION OF A GRANULAR ORAL COMPOSITION"

TECHNICAL FIELD

The present invention relates to a process for the preparation of a granular oral composition having a low dissolution time.

BACKGROUND

Iodine has long been used in various pharmaceutical forms (solution, tincture) for disinfection of small wounds. Despite this efficacy, it has number of side effects.

Povidone-iodine (Merck Index 13th edition, 2001) is a complex of polyvinylpyrrolidone as a polymer of l-vinyl-2-pyrrolidone and iodine, and has been widely used all over the world as a safe medicament having a bactericidal action for an agent for treating bedsore, sterilization of fingers and hands, disinfection of oral cavity, pharynx and the like. A gargle which is diluted with water before use has been generally used as a povidone-iodine agent for disinfection of the oral cavity and pharynx.

Owing to its complexation with Polyvinylpyrrolidone, iodine is released slowly and gradually thus reducing its side effects. It has long been used in the prophylactic and therapeutic field during the management of various infections. Free iodine, slowly liberated from the povidone-iodine (PVPI) complex in solution, kills eukaryotic or prokaryotic cells through iodination of lipids and oxidation of cytoplasm and membrane compounds. This compound is a broad spectrum antiseptic and exhibits a broad range of microbicidal activity against bacteria, fungi, protozoa, and viruses.

US 5846564 discloses an effervescent composition for the extemporaneous preparation of iodinated polyvinylpyrrolidone solutions, employs at-least one disintegrant, apart from iodinated polyvinylpyrrolidone and at- least one effervescent agent. It claims to have dissolution time of around 3 to 10 minutes.

Thus there is a rising need for the development of an iodinated polyvinylpyrrolidone composition having a low dissolution time. The inventors of the present invention have tried to overcome this problem by providing a process for the preparation of a granular oral composition having a low dissolution time.

SUMMARY

The present invention relates to a process for the preparation of a granular oral composition comprising polyvinylpyrrolidone-iodine complex in granular form and involves the following steps: i. mixing 5 to 10% polyvinylpyrrolidone iodine powder, a soluble diluent with 20 to 25% effervescent agent and 17 to 25% acidifying agent having moisture content less then 0.2% w/w and particle size less then 250 micron; ii. granulating the above mixture with 80% isopropyl alcohol;

iii. granulating with 1 : 1 hydro alcoholic solution;

iv. drying the granules obtained at a temperature not exceeding 40°C; and v. Micronizing the granules to size less than 175 micron.

The invention will now be discussed with reference to the accompanying examples. DESCRIPTION

The present disclosure provides a process for the preparation of a granular oral composition comprising polyvinylpyrrolidone-iodine complex in granular form.

The process comprises the following steps: i. mixing 5 to 10%> polyvinylpyrrolidone iodine powder, a soluble diluent with 20 to 25% effervescent agent and 17 to 25% acidifying agent having moisture content less then 0.2% w/w and particle size less then 250 micron; ii. granulating the above mixture with 80% isopropyl alcohol; iii. granulating with 1 : 1 hydro alcoholic solution;

The entire manufacturing process is to be carried out at relative humidity less then 30% and a temperature below 25 °C. The controlled granulation process employed, results in characteristic granules which have faster solubilization. Further, the composition prepared by the process of the present invention has a dissolution time of less than 3 minutes and does not employ any disintegrant. This results in a faster and complete solubilization of Polyvinylpyrrolidone-Iodine (PVP-I), when the granules are dissolved in water. In one of the embodiments the effervescent agent is selected from sodium and potassium carbonate, sodium and potassium bicarbonate, sodium glycine carbonate and calcium carbonate.

In another embodiment the acidifying agent is selected from anhydrous citric acid, carbonic acids, monohydrated or anhydrous malic acid, fumaric acid or tartaric acid.

The sweetener is selected from sodium saccharine, sucralose, aspartame, acesulfame - K and tagatose The composition of the present invention, is useful in oral care, providing extemporaneous production of Iodinated - Polyvinylpyrrolidone (PVP-I) in solution form. It is very handy, economical and reproducible drug delivery system, having less storage and handling space requirement. EXAMPLE

The process of instant invention can be performed using API quantity between 5 - 50% w/w and using 5 -95% w/w of other excipient listed. More preferably the process of the instant invention was performed using the following specific quantity of ingredients: S.No. Quantitative Category Examples w/w% of

ingredients

1 > 5% to 10% Active Povidone iodine

2 20% - 25% Effervescent agent; Sodium bicarbonate;

alkalizing agent carbonates and bicarbonates of sodium and potassium, sodium glycine carbonate or calcium carbonate

3 17% - 25% Acidic component; Citric acid anhydrous, acidifying agent carbonic acids or their derivatives, monohydrated or anhydrous malic acid, fumaric acid or tartaric acids

4 35% - 40% Soluble alcoholic Mannitol, sorbitol, xylitol, sugar maltitol, lactitol

5 < 1% Soluble artificial Sodium saccharine, sweetener sucralose, aspartame, acesulfame-K and tagatose

6 < 1% Flavor, cooling Menthol; methyl salicylate, agent peppermint, spearmint or mint

7 < 1% Flavor Eucalyptus oil, clove oil, eugenol oil, cardamom oil

8 < 1% Flavor and Glycyrrhizic acid, sodium sweetener salt of glycyrrhizic acid or related salts

9 7% - 10% Moistening agent Isopropyl alcohol, aliphatic alkyl alcohols-ethyl alcohol, n-propyl alcohol

10 1.2% - 2.5% Binding agent Purified water The present invention is not intended to be restricted to any particular form or arrangement, or any specific embodiment, or any specific use, disclosed herein, since the same may be modified in various particulars or relations without departing from the spirit of the invention.

The various embodiments described above can be combined to provide further embodiments. All of the U.S. patents, referred to in this specification are incorporated herein by reference, in their entirety. Aspects of the embodiments can be modified, if necessary to employ concepts of the various patents to provide yet further embodiments.

Although the disclosure of the method has been described in connection with the embodiment of the present disclosure illustrated in the accompanying examples, it is not limited thereto. It will be apparent to those skilled in the art that various substitutions, modifications and changes may be made thereto without departing from the scope and spirit of the disclosure.

Claims

We Claim:

1. A process for the preparation of a granular oral complex comprising the steps of : i. mixing 5 to 10% polyvinylpyrrolidone iodine powder, a soluble diluent with 20 to 25% effervescent agent and 17 to 25% acidifying agent having moisture content less then 0.2% w/w and particle size less then 250 micron; ii. granulating the above mixture with 80% isopropyl alcohol;

iii. granulating with 1 : 1 hydro alcoholic solution;

2. The process as claimed in claim 1, wherein said diluent is selected from the group consisting of soluble alcoholic sugars like mannitol, sorbitol, xylitol, maltitol, lactitol or combinations thereof

3. The process as claimed in claim 1, wherein said effervescent agent is selected from the group consisting of sodium and potassium carbonate, sodium and potassium bicarbonate, sodium glycine carbonate and calcium carbonate.

4. The process as claimed in claim 1, wherein said acidifying agent is selected from the group consisting of anhydrous citric acid, carbonic acids, monohydrated or anhydrous malic acid, fumaric acid or tartaric acid.

5. The process as claimed in claim 1, further comprising excipients, flavours and sweeteners.

6. The process as claimed in claim 5, wherein said sweetener is selected from the group consisting of sodium saccharine, sucralose, aspartame, acesulfame - K and tagatose.

7. The process as claimed in claim 5, wherein said flavouring agent is selected from the group consisting of menthol, methyl salicylate, peppermint, spearmint or mint, eucalyptus oil, clove oil, eugenol oil, cardamom oil, glycyrrhizic acid.

8. The composition prepared by the process of claim 1, wherein the dissolution time is less than 3 minutes.

9. The process as claimed in claim 1 , wherein the relative humidity at which the process is to be carried out is preferably less than 30%.

10. The process as claimed in claim 1, wherein the temperature at which the process is to be carried out is preferably less than 25°C.