WO2017013682A1

WO2017013682A1 - Process of preparation of co-processed polymer and it's pharmaceutical application

Info

Publication number: WO2017013682A1
Application number: PCT/IN2016/050244
Authority: WO
Inventors: Harshal Ashok PAWAR; Swati Ramesh KAMAT; Pritam Dinesh CHOUDHARY; Amit Jagannath GAVASANE; Paraag GIDE
Original assignee: Pawar Harshal Ashok; Kamat Swati Ramesh; Choudhary Pritam Dinesh; Gavasane Amit Jagannath; Gide Paraag
Priority date: 2015-07-20
Filing date: 2016-07-19
Publication date: 2017-01-26

Abstract

The present invention discloses co-processed polymer of one or more polysacharides useful for preparing the pharmaceutical dosage forms. The present invention also disclosed the process to prepare the co-processed polymer.

Description

Field of invention

The present invention relates to co-processed polymer of two or more natural polysaccharides. The present invention also relates to a process of preparation thereof and applications in making various dosage forms.

Background of the invention

Most formulations contain excipients at a higher concentration than the active pharmaceutical ingredient (API) and as a consequence excipients contribute critically towards processing, stability, safety and performance of solid dosage forms. The majority of the excipients that are currently available fail to meet the desired set of functionalities, therefore, creating urgency for the development of high functionality excipients. High functionality excipients can be obtained by developing new chemical excipients, improved grades of existing excipients, and new combinations of existing excipients. Developing a new chemical excipient is uneconomical and laborious from the stand point of safety and regulatory clearances. The primary reason for this lack of new chemical excipients is the relatively high cost involved in discovery and development of excipient. To categorize the newly developed excipient in "Generally recognized as safe" (GRAS) category, the manufacturer has to perform all necessary research, including the formation of an expert panel to review safety concerns, and may have to prepare to use these findings to defend its product's GRAS status. Approval procedures are simplified if the new excipient is obtained from two known and safe excipients and without any chemical change. Also if particularly, one excipient has multifunctional role to play, it is more advantageous to develop such excipient.

Object of the invention

An object of the present invention is to provide a co-processed polymer prepared from two or more natural polysaccharides.

Another object of the present invention is to provide various applications of such co-processed polymer prepared from two or more natural polysaccharides.

Yet another object of the present invention is to provide processes for preparation of co-processed polymer. Summary of the invention

According to an aspect of the present invention there is provided a co-processed polymer prepared from two or more natural polysaccharides.

In another aspect the present invention provides the co-processed polymer of two or more natural polysaccharides which exhibits excellent physical properties as compared to individual gums and their physical mixtures. The co-processed polymer has excellent physical properties as compared to individual polysaccharide or gum or mucilage and their physical mixtures. The Carr's Index and angle of repose for the co-processed polymer is about 50% of that of its physical mixture implying excellent flow properties over their physical mixture. Hausner ratio is below 1.25 and preferably below 1.2 and most preferably about 1.15 again implying excellent flow properties.

The co-processed polymer of the present invention has double the viscosity than the viscosity exhibited by physical mixture and swelling index is more than 500 %. This makes the co-processed polymer ideal binder and release retarding agent and it can be used in much lesser amounts than the amounts in which the gums are used for the said functions.

Thus, co-processed polymer of the present invention has good physical properties and can play multiple roles in various dosage forms. Another aspect of the present invention is to provide applications of the co- processed polymer of xanthan gum and guar gum. The co-processed polymer of the present invention improves the tablet hardness and friability. The co-processed polymer provides an alternative to conventional binders. The tablets have improved friability and thus resistant to normal wear and tear that takes place during transporting, handling, coating and packing. The co-processed polymer also used to prepare sustained and extended release dosage forms, particularly tablets. Thus, it provides alternative to conventional release retard agents. Yet another aspect of the present invention provides a process to prepare the co- processed polymer comprising two or more polysaccharides. The process comprises the steps of a) dispersing or dissolving two or more natural polysaccharides (gums or mucilages) in water b) mixing the dispersion or solution till to get a homogenous solution c) precipitating the co-processed polymer using organic solvent selected from iso-propyl alcohol (IPA), ethanol or acetone d) collecting and drying the precipitate and e) optionally pulverizing the dried precipitate to get the co-processed polymer. Brief description of the drawings

Fig. 1: Overlapping of IR spectra of co-processed polymer of 1: 1 xanthan gum and guar gum and their physical mixture.

Fig. 2: Overlapping of DSC of co-processed polymer of 1: 1 xanthan gum and guar gum and their physical mixture.

Description of the invention

The present invention relates to various co-processed polymers of two or more natural polysaccharides.

The polysaccharide is gum or mucilages which is selected from the group comprising Guar gum, Xanthan gum, Acacia gum, Karaya gum, Gum Ghatti, Locust bean gum, Okra gum, Albizia gum, Tara gum, Cassiatora, Cordia, Taro, Konjac, Isabgol mucilage, Phoenix mucilage, Jackfruit gum, Tamarind seed polysaccharide, Fenugreek mucilage, Honey locust gum, Mimosa scrabella, Mimosa pudica, Ocimum mucilage, Gum rosin, Black gram, Gulmohar mucilage, Almond gum, Cashew gum, Moringaoleifera gum, Gum damar, Gum Copal, Kondagogu Gum, Bhara gum, Hakea gum, Grewia gum, Olibanum gum, Terminalia gum, Cocculus mucilage, Aloe mucilage, Hibiscus mucilage, Neem gum, Moi gum, Konjacglucomannan, Curdlan gum, Gellan gum, Colanic acid or K30 antigen.

The two or more natural polysaccharides or gums are taken in any proportion from 1: 10 to 10: 1, preferably from 1:5 to 5: 1. The most suitable proportion is 1: 1. Application of the co-processed polymer is described as follows.

The co-processing of the two or more polysaccharides or gums according to the present invention leads to a co-processed polymer that has improved flow property and compressibility. Hence, it is beneficial in compression of tablets. The co- processed gum has enhanced swelling property compared to individual component gums and hence is beneficial as release retard agent. Interestingly it is noted that such co-processed polymer enhances disintegration properties including reduction of disintegration time and improving disintegration pattern. Hence it is beneficial as a disintegrant for conventional oral solid dosage forms particularly tablets.

The co-processed polymers according to the present invention exhibit significantly enhanced physical properties over its individual components. The significantly enhanced physical property is one or more of flow properties, disintegration property, compressibility, binding property, property to enhance hardness, viscosity, swelling property, gelling property, emulsifying property, suspending property, film forming property and sustained release property.

The flow properties of gums are usually undesirable. However, the co-processing has dramatically improved the flow properties when compared with physical mixture of two or more gums.

In one embodiment, the co-processed polymer prepared from 1 : 1 Xanthan gum and Guar gum according to the present invention is not only exhibited improved properties over mere physical mixture of the two or more gums, but also exhibited significant change in the physical properties as shown in Table 1 below. The co- processed polymer has excellent flow properties, compressibility, hardness, viscosity, and swelling capacity as seen from data reported under i) Carr's Index ii) Hausner's ratio and iii) Angle of repose.

Table 1 Properties Physical mixture CPG

Bulk density 0.568 0.576

Tapped density 0.78 0.6625

Carr' s index 27.179% 13%

Hausner's ratio 0.73 1.15

Angle of repose 20.89° 11°

Swelling index 375% 675%

Due to significant change in properties of the co-processed polymer, it is effective in very low amounts to produce the same or enhanced effect while in other cases, it produces an effect which cannot be produced by a mere physical mixture of two or more polysaccharides in any concentration.

The co-processed polymer of the present invention imparts enhanced binding properties to the compositions. Enhanced binding is indicated by enhanced hardness and increase in disintegration time.

In an embodiment of the present invention the binding capacity of the co-processed polymer is evaluated using high dose drug Venlafaxine HCl (around 37.5% of formulation) as exemplified under example 1. This drug has poor compressibility and poor binding capacity. The task was to produce tablets that have disintegration time of 8 to 10 min. As seen from example 1, 4 % of xanthan gum or 4 % of guar gum could not achieve the target disintegration time. Physical mixture of xanthan gum and guar gum produced tablets with better disintegration time however the co- processed polymer of two gums in the same concentration lowers the disintegration time many folds. This experiment also reflects that if a disintegration time of 1 to 3 minute is desired, even 1 % concentration of co -processed polymer is sufficient. This will reduce the tablet weight or in other words, it can act as a binder in as low as 1% concentration for making tablet.

Gums impart quite variable disintegration times to their preparations. Usually, guar gum does not increase disintegration time but xanthan gum does. The present inventors have tested the capacity of co-processed polymer to act as a super disintegrating agent and whether it was able to produce an oral disintegrating tablet.

In one embodiment as exemplified under example 2, the oral disintegrating tablets of Ondansetron hydrochloride are prepared using up to 10 % of each of i) xanthan gum ii) guar gum iii) physical mixture (1: 1) and iv) co-processed polymer (1: 1). The co-processed polymer could produce oral disintegrating tablet that disintegrated within 1 minute preferably within 30 seconds when it is used in dry form up to 10 % concentration. The hardness of these tablets was better than the hardness of tablets produced from individual gums and their physical mixtures. Many a times hardness of oral disintegrating tablets poses a problem in that such tablet is brittle and difficult to handle while packing. Example 2 shows that tablets containing CPG are compressed at hardness of 2 - 2.5 kg/cm² and they can disintegrate much faster.

Thus, the co-processed polymer of the present invention has dual action and is used as binder as well as disintegrants in pharmaceuticals. In wet granulation, it preferably acts as a binder whereas in direct compression it acts as a disintegrant. This provides flexibility to use same excipient in different ways.

The co-processed polymer according to the present invention exhibits significantly higher swelling index as compared to the physical mixture of the counterpart polysaccharides or gums or mucilages. In an embodiment, the co-processed polymer of xanthan gum and guar gum has 675 % swelling index (refer Table 1) as against 375 % swelling index of their physical mixture. This is an indication that it has capacity to act as a sustained release agent. In another embodiment as exemplified under example 3, diclofenac tablets of 200 mg weight having diclofenac sodium (75 mg) are formulated using direct compression process with i) co-processed polymer (75 mg) and also ii) physical mixture of xanthan gum and guar gum. As noted in example 3, the physical mixture having the same concentrations of xanthan gum and guar gum could not sustain the release of the drug diclofenac sodium while the co-processed polymer in the same amounts produced sustained action over 8 to 10 hrs. Surprisingly the direct compression process has produced this action. This may eliminate the need of granulation and save processing time and cost of production.

The gums are used in oral films along with other film forming polymers. The film forming capacity of the co-processed polymer alone is tested. In another embodiment the film forming capacity of the co-processed polymer test as exemplified under example 4, oral films of Ondansetron hydrochloride were prepared. The co-processed polymer produced excellent oral films without use of any other polymer which dissolve in mouth instantly. These films released more than 85 % drug within 15 minutes and are stable.

The co-processed polymer also exhibits a gel forming capacity. The co-processed polymer in amounts from 0.5 to 5 % can be soaked in water for 2 to 8 hrs to produce gels. The soaked gel solution can be stirred to get desired homogeneity. Drug can be dissolved in alcohol or hydroalcoholic solution or water and added to such gel while stirring and the co-processed polymer (2 %) soaked for 4 to 5 hours produced excellent gel upon little stirring. In one embodiment as exemplified under example 5, a translucent gel of diclofenac sodium was produced having sufficient viscosity and spreadability.

The co-processed polymer has capacity of emulsification. The resultant emulsions prepared using the co-processed polymer of the present invention are stable and free of odour of oil. In an embodiment, the example 6 wherein an oil/water emulsion is prepared in which arachis oil is emulsified using co-processed polymer and such emulsion is found stable for four hours. Similarly stable water/oil emulsions using the co-processed polymer of the present invention can be prepared.

Thus, multifunctional polymer is successfully produced by co-processing two or more natural gums such as xanthan and guar gums preferably in a ratio of 1 : 1. This co-processed polymer differs significantly in properties from the two natural gums. It can act as binder, disintegrant, sustained release agent, film forming agent, gel forming agent, suspending agent, emulsifier and can have more roles to play. The co-processed polymers of the present invention serve as ideal excipients for use in excipient nutraceutical, pharmaceutical, biopharmaceutical, food, cosmetic, cosmeceutical, agrochemical compositions.

The co-processed polymers of the present invention can be used as such in variety of preparations or they can be admixed with other excipients such as cellulose, starch, lactose, mannitol and likes to prepare excipient mixtures which are further employed in variety of preparations. According to an embodiment, the process to prepare the co-processed polymer comprises 1) dispersing or dissolving two or more natural polysaccharides (gums or mucilages) in water 2) mixing the dispersion or solution till one gets a homogenous solution 3) precipitating the co-processed polymer using organic solvent selected from iso-propyl alcohol (IP A), ethanol and acetone 4) collecting and drying the precipitate and 5) optionally pulverizing the dried precipitate to get the desired co-processed polymer.

The process of preparation of the co-processed polymers is simple and economical. The process incorporates precipitation of the co-processed polymers by using solvent /anti-solvent method which imparts unique properties to the co-processed polymers. The process to prepare the co-processed polymers of two or more polysaccharides is performed at room temperature and thus has advantage over the hot melt method. Further, it is evident from the figures, fig. 1 and fig. 2 that there is no change in the chemical properties of the polysaccharides which confirms that there is no chemical interaction between the two polysaccharides. Thus, the process to prepare co-processed polymer according to the present invention merely changes the physical properties of individual gums in such a way that the resultant co- processed polymers exhibit beneficial physical properties and can be used as multifunctional excipient. The natural polysaccharide comprises gum or mucilage. The terms co-processed polymer or CPPor co-processed gum or CPG, as used herein, are interchangeably used and have the same meaning in the description. According to the present invention, the combination of gums used for making the co-processed polymer or co-processed gum is selected from the group comprising Xanthan gum and Guar gum (CPG XG), Xanthan gum and Acacia (CPG XA), Acacia and gum Karaya (CPG AK), Xanthan gum and gum Karaya (CPG XGKG), Guar gum and gum Karaya (CPG GK), Xanthan gum and gum Ghati (CPG XGh), Guar gum and gum Ghati (CPG GGh), Guar gum and Acacia (CPG GA) or gum Karaya and gum Ghati (CPG KGh).

According to another embodiment the co-processed polymer is selected from the group comprising co-processed polymer of Xanthan gum and Guar gum (CPG XG), co-processed polymer of Xanthan gum and Acacia (CPG XA), co-processed polymer of Acacia and gum Karaya (CPG AK), co-processed polymer of Xanthan gum and gum Karaya (CPG XGKG), co-processed polymer of Guar gum and gum Karaya (CPG GK), co-processed polymer of Xanthan gum and gum Ghati (CPG XGh), co-processed polymer of Guar gum and gum Ghati (CPG GGh), co- processed polymer of Guar gum and Acacia (CPG GA) or co-processed polymer of gum Karaya and gum Ghati (CPG KGh).

Various applications of the co-processed polymers of present invention and the approximate amount/range in which they can be used are as described in table 2.

Table 2

The drug which can be used for making oral disintegrating tablet is selected from the group comprising ondansetron hydrochloride, ibuprofen, lamotrigine, paracetamol, oxycodone, diclofenac, amlodipine, clonazepam, cetirizine, donepezil, risperidone, tramadol, alprazolam, carbidopa-levodopa, dipheniramine, prednisolone, zolmitriptan, selegiline, sildenafil citrate, vardenafil hydrochloride, tadalafil, mirtazapine, fexofenadine, imodium, famotidine, olanzapine, mirtazapine, loratadine, piroxicam, rizatriptan and likes. The drug which can be used for making sustained release tablet is selected from the group comprising aceclofenac, chlorpheniramine maleate, metoprolol succinate, lornoxicam, nifedipine, metformin hydrochloride, diclofenac, glipizide, venlaflaxine hydrochloride, divalproex sodium, tramadol hydrochloride, lithium carbonate, quetiapine fumarate, clarithromycin, tamsulosine hydrochloride, amitriptyline hydrochloride, oxcarbazepine, amisulpriden, pregabalin, ranolazine, progesterone, etodolac, lamotrigine, valsartan and likes.

The drug which can be used for making film is selected from the group comprising curcumin, phenylephrine, levocetrizine, elitriptan, nifedipine, pilocarpine, propranolol, losartan potassium, venlafaxine, lamotrigine, tramadol, hydrochlorthiazide, famotidine, ondansetran hydrochloride, isosorbide dinitrated omperidone, ropinirole, granisetron, amlodipine, Zolpidem or ivabradine hydrochloride and likes. Examples

Example 1:

Evaluation of co-processed polymer as binder

Formulation: Tablet prepared using XG, GG and the co-processed polymer (CPG).

Table 3 Formulation

Ingredients (mg) Fl F2 F3 F4 F5 F6

Venlafaxine 37.5 37.5 37.5 37.5 37.5 37.5

Microcrystalline cellulose (MCC) 56.5 56.5 56.5 56.5 56.5 56.5

PVP K30 4 — — — — —

Starch — 12 — — — —

XG (Xanthan Gum) — — 4 — — —

GG (Guar Gum) — — — 4 — —

XG+GG (PHY MIX) — — — — 4 —

CPG (Co-processed polymer of XG 4 and GG)

IPA (Isopropyl alcohol) q.s. q.s. q.s. q.s. q.s. q.s.

Magnesium stearate 1 1 1 1 1 1

Talc 1 1 1 1 1 1 q.s.: quantity sufficient Procedure:

Batches Fl, F3, F4, F5 and F6 were prepared by following method:

The drug, MCC and binder powder were weighed and thoroughly mixed. This mixture was then granulated by using IPA (q.s.) and granules were sieved through mesh size #10. Granules were dried in hot air oven at 50°C and then sieved through mesh size #20 and retained on mesh size #40. Magnesium stearate and talc were added. Tablets were punched on single press compression machine with 8 mm round, flat faced punch. Hardness was set around 4.

Preparation of Batch F2:

Drug and MCC weighed and thoroughly mixed. Starch paste (10%w/w) was added to bind the mixture and granules were sieved through mesh size #10. Quantity of starch powder in used starch paste was calculated. Granules were dried in hot air oven at 50° C and then sieved through mesh size #20 and retained on mesh size #40. Magnesium stearate and talc were added. Tablets were punched on single press compression machine with 8 mm round, flat faced punch. Hardness was set around 4.

Binding property:

Table 4

Conclusion: From this study it is noted that the individual counterparts viz. xanthan and guar gums lack good binding properties but their co-processed polymer in the same concentration enhanced disintegration time 4 folds indicating strong binding properties. CPG provides binding very similar to PVP-K30, a conventional binder. CPG can be used in much lesser amounts as compared to starch used in paste form.

Example 2

Evaluation of theco-processed polymer of XG and GG as disintegrating agent Formulation: Oral disintegrating tablet (ODT)

Table 5

Xanthan Gum (XG) — 20 — —

PHY MIX (XG+GG) — — 20 —

CPG XG and GG) — — — 20

Sodium saccharine 3 3 3 3

Flavour 2 2 2 2

Talc 2 2 2 2

Magnesium stearate 2 2 2 2

Procedure:

All the ingredients were weighed, mixed thoroughly and sieved through mesh size #40 to get a homogenous mixture. This mixture was directly compressed using single press compression machine with 9 mm flat faced punch. Hardness was set around 3.

Post compression evaluation:

Table 6

Conclusion: The formulation F10 prepared employing CPG showed good disintegrating property at 10% concentration.

The prepared formulation disintegrated completely in just 28 seconds indicating applicability of CPG as a disintegrant. It has been noted that the disintegration time of tablets prepared using CPG is comparable to that of PHY MIX with improved hardness which is essential for storage, handling and transportation.

Example 3 Evaluation of the co-processed polymer of xanthan gum and guar gum as sustained release agent

Formulation: Directly compressible sustained release (SR) tablet

Table 7

Procedure: All the ingredients were weighed, mixed thoroughly and sieved through mesh size #40 to get a homogenous mixture. This mixture was directly compressed using single press compression machine with 9 mm flat faced punch. Hardness was set around 5.

Dissolution was performed in paddle type apparatus, RPM 50, bath temperature 37 degrees, dissolution medium- 900 ml phosphate buffer pH 7.5.

Dissolution study of tablets:

Table 8

4 52.00 -

5 58.57 -

6 66.44 -

7 70.13 -

8 74.80 -

9 80.93 -

10 95.39 -

11 96.16 -

12 101.55 -

Conclusion: The CPG XG improves flow property thus ideal for direct compression of tablet. The tablets thus formed had good hardness and showed release upto 12 hours. Thus, using CPG wet granulation step can be avoided which is common for SR (sustained release) formulations. It can be concluded that physical mixture (PHY MIX ) of XG and GG is not suitable for direct compression SR tablets.

Example 4

Evaluation of the co-processed polymerof as film forming agent

Formulation: Film

Table 9

Properties of CPG:

Table 10

Dissolution study:

Dissolution was performed in paddle type apparatus, RPM 50, bath temperature 37 degrees, dissolution medium- 900 ml 0.1 N HCl.

Table 11A

Stability Data on Films

Conclusion: This study suggests that the co-processed polymer forms stable film as compared to the physical mixture of its counterparts. Also the film shows excellent dissolution properties. Example 5:

Evaluation of the co-processed polymer as gel forming agent

Procedure: CPG (2% w/w) solution in purified water was prepared by soaking the gum in water for 5 hours. This was then stirred a little to get homogenous consistency. Diclofenac sodium (l%w/w) was dissolved in ethanol (1 ml) and added to the gel base. Viscosity was measured using Brookfield viscometer, using spindle no. 7 at 20 RPM.

Table 12

Conclusion: This study suggests that the co-processed polymer has good gel forming capacity.

Example 6

Evaluation of the co-processed polymer as emulsifying agent

Formulation: Oil/water emulsion (O/W)

Table 13

Procedure: Arachis oil and CPG XG were triturated together in a ceramic mortar. Water was then added at once and pestle was moved vigorously in one direction till clicking sound was heard. Formed emulsion was kept for around 4 hours

Properties of Emulsion prepared using CPG:

Table 14

Conclusion: This study suggests that the co-processed polymer exhibits good emulsifying property.

Example 7

Evaluation of viscosity of the co-processed gum

The co-processed polymer is selected from the group comprising a co-processed polymer of Xanthan gum and Guar gum (CPG XG), co-processed polymer of Xanthan gum and Acacia (CPG XA), co-processed polymer of Acacia and gum Karaya (CPG AK), co-processed polymer of Xanthan gum and gum Karaya (CPG XK), co-processed polymer of Guar gum and gum Karaya (CPG GK), co-processed polymer of Xanthan gum and gum Ghati (CPG XGh), co-processed polymer of Guar gum and gum Ghati (CPG GGh), co-processed polymer of Guar gum and Acacia (CPG GA), co-processed polymer of gum Karaya and gum Ghati (CPG KGh) or co-processed polymer of Xanthan gum, Guar gum and Acacia (XGA). Viscosity studies of the co-processed polymers are performed on 0.05% w/w solution using Ostwald viscometer and the data is as in table 15 below.

Table 15 Sr.No. Viscosity (cps)

Co-processed Co-processed Physical mixture polymer polymer (CPG) (PHY MIX)

1 CPG AK 0.933859 0.782423

2 CPG XA 2.016 0.9081

3 CPG XK 0.984338 0.896000

4 CPG GK 1.123155 0.990316

5 CPG XGh 0.974596 0.785965

6 CPG GGh 1.226105 0.990316

7 CPG GA 1.839158 1.163228

8 CPG KGh 0.958877 0.911719

9 CPG XGA 1.116070 0.943158

From the above study it can be concluded that co-processed gum (CPG) gives more viscous solution than the physical mixture of two or more individual counterpart (PHY MIX). In other words lesser co-processed gum (CPG) will be required to impart same viscosity if compared with the quantity required by the counterparts.

Example 8

Evaluation of the co-processed polymer of Xanthan gum and Acacia (CPG XA) as emulsifying agent

Formulation: Emulsion

Table 16

Procedure: Arachis oil and CPG XA were triturated together in a ceramic mortar. Water was then added at once and pestle was moved vigorously in one direction till clicking sound was heard. Formed emulsion was kept for around 4 hours.

Emulsifying property:

Table 17

Conclusion: The co-processed polymer of CPG XA has good emulsifying property.

Example 9

Evaluation of the co-processed polymer of Acacia and gum Karaya (CPG AK) emulsifying agent

Formulation: Emulsion (O/W)

Table 18

Procedure: Arachis oil and CPG AK were triturated together in a ceramic mortar. Water was then added at once and pestle was moved vigorously in one direction till clicking sound was heard. Formed emulsion was kept for around 4 hours.

Emulsifying property

Table 19 Parameters Observation

Colour Buff coloured

Odour Characteristic

Texture Smooth

Consistency Creamy

Observation on standing No separation of oil observed

Conclusion: The co-processed polymer of CPG AK has good emulsifying property. Example 10

Evaluation of the co-processed polymer of Xanthan gum and gum Karaya (CPG XK) as emulsifying agent

Formulation: Emulsion (O/W)

Table 20

Procedure: Arachis oil and CPG XK were triturated together in a ceramic mortar. Water was then added at once and pestle was moved vigorously in one direction till clicking sound was heard. Formed emulsion was kept for around 4 hours.

Emulsifying Property

Table 21

Conclusion: The co-processed polymer of Xanthan gum and gum Karaya (CPG XK) has good emulsifying property.

Example 11

Evaluation of the co-processed polymer of Guar gum and gum Karaya (CPG GK) as gel forming agent

Formulation: Gel

Preparation: 2% w/w CPG GK gum solution in purified water was prepared by soaking the gum in water for 5 hours. This was then stirred a little to get homogenous consistency. Diclofenac sodium (1% w/w of the gel base) was dissolved in ethanol (1 ml) and added to the gel base. Viscosity was measured using Brookfield viscometer, using spindle no. 7 at 20 RPM.

Gel forming property:

Table 22

Conclusion: This study suggests that the co-processed polymer of Guar gum and gum Karaya (CPG GK) exhibits good gel forming capacity.

Example 12

Evaluation of the co-processed polymer of Xanthan gum and gum Ghati (CPG XGh) as disintegranting agent

Formulation: ODT of Lamotrigine prepared employing the co-processed polymer

Table 23 Formulation

Ingredients (mg) Fl F2 F3 F4

Lamotrigine 25 125 25 125

Mannitol 156 780 156 780

CPG 10 50 — —

PHY MIX — — 10 50

Sodium saccharine 3 15 3 15

Flavour 2 10 2 10

Talc 2 10 2 10

Mg stearate 2 10 2 10

Procedure: All the ingredients were weighed, mixed thoroughly and sieved through mesh size #40 to get a homogenous mixture. This mixture was directly compressed using single press compression machine with 9 mm flat faced punch. Hardness was set around 3.5.

Post compression evaluation:

Table 24

Conclusion: The co-processed polymer CPG XGh showed good disintegrating property at 5 % concentration. The prepared formulation disintegrated completely in just 25 seconds indicating applicability of CPG XGh as a disintegrant. It has been noted that the disintegration time of tablets prepared using CPG XGh is better than that of PHY XGh. Example 13

Evaluation of the co-processed polymer of Guar gum and gum Ghati (CPG GGh) as gel forming agent Formulation: Gel

Preparation: 2% w/w CPG GGh gum solution in purified water was prepared by soaking the gum in water for 5 hours. This was then stirred a little to get homogenous consistency. Diclofenac sodium (l%w/w of the gel base) was dissolved in 1 ml ethanol and added to the gel base. Viscosity was measured using Brookfield viscometer, using spindle no. 7 at 20 RPM.

Gel forming property:

Table 25

Conclusion: This study suggests that the co-processed polymer of Guar gum and gum Ghati (CPG GGh) exhibits good gel forming capacity.

Example 14

Evaluation of the co-processed polymer of Guar gum and Acacia (CPG GA)as gel forming agent

Formulation: Gel

Preparation: 2% w/w CPG GA gum solution in purified water was prepared by soaking the gum in water for 5 hours. This was then stirred a little to get homogenous consistency. Diclofenac sodium (l%w/w of the gel base) was dissolved in 1 ml ethanol and added to the gel base. Viscosity was measured using Brookfield viscometer, using spindle no. 7 at 20 RPM.

Gel forming property:

Table 26 Parameters CPG GA PHY MIX GA

PH 7 7

Consistency Viscous , gel like Viscous , gel like

Colour Translucent Translucent

Odour Odourless Odourless

Viscosity 7500 cps 2500 cps

Spreadability 3.58 2.76

% Assay 98.46 % 99.58 %

Conclusion: This study suggests that the co-processed polymer of Guar gum and gum Acacia (CPG GA) exhibits good gel forming capacity.

Example 15

Evaluation of the co-processed polymer of gum Karaya and gum Ghati (CPG KGh) as emulsifying agent

Formulation: Emulsion (O/W)

Table 27

Procedure: Arachis oil and CPG KGh were triturated together in a ceramic mortar. Water was then added at once and pestle was moved vigorously in one direction till clicking sound was heard. Formed emulsion was kept for around 4 hours.

Emulsifying property:

Table 28 Parameters Observation

Colour Brown coloured

Odour Characteristic

Texture Smooth

Consistency Creamy

Observation on standing No separation of oil observed

Conclusion: The co-processed polymer of gum Karaya and gum Ghati (CPG KGh) has good emulsifying property. Example 16

Evaluation of the co-processed polymer of Xanthan gum, Guar gum and Acacia (CPG XGA) as disintegranting agent

Formulation: ODT of Lamotrigine prepared employing the co-processed polymer

Table 29

Post compression evaluation: Table 30

Conclusion: The co-processed polymer of Xanthan gum, Guar gum and Acacia (CPG XGA) showed good disintegrating property at 5 % concentration. The prepared formulation disintegrated completely in just 19 seconds indicating applicability of CPG XGA as a disintegrant. It has been noted that the disintegration time of tablets prepared using CPG XGA is better than that of PHY MIX XGA.

Claims

We claim,

1. Co-processed polymer comprising two or more natural polysaccharides possessing at least one significantly enhanced physical property from its counterpart components.

2. The co-processed polymer as claimed in claim 1 wherein said physical property is one or more of flow properties, disintegration property, compressibility, binding property, property to enhance hardness, viscosity, swelling property, gelling property, emulsifying property, film forming property, sustained release property.

3. The co-processed polymer as claimed in claim 1 wherein said polysaccharide is gum or mucilage selected from the group comprising Guar gum, Xanthan gum, Acacia gum, Karaya gum, Gum Ghatti, Locust bean gum, Okra gum, Albizia gum, Tara gum, Cassiatora,Cordia, Taro, Konjac, Isabgol mucilage, Phoenix mucilage, Jackfruit gum, Tamarind seed polysaccharide, Fenugreek mucilage, Honey locust gum, Mimosa scrabella, Mimosa pudica, Ocimum mucilage, Gum rosin, Black gram, Gulmohar mucilage, Almond gum, Cashew gum, Moringaoleifera gum, Gum damar, Gum Copal, Kondagogu Gum, Bhara gum, Hakea gum, Grewia gum, Olibanum gum, Terminalia gum, Cocculus mucilage, Aloe mucilage, Hibiscus mucilage, Neem gum, Moi gum, Konjacglucomannan, Curdlan gum, Gellan gum, Colanic acid or K30 antigen.

4. The co-processed polymer as claimed in claim 1 wherein said polysaccharides are used in the ratio from 1: 10 to 10: 1.

5. The co-processed polymer as claimed in claim 1 is used as bulking agent, binder, disintegrating agent, emulsifying agent, film forming agent, gel forming agent, sustained release agent, viscosity enhancer and swelling agent.

6. The co-processed polymer as claimed in claim 1 to 5 wherein said copolymer with enhanced properties is suitable for use in preparing excipient, nutraceutical, pharmaceutical, biopharmaceutical, food, cosmetic, cosmeceutical, agrochemical compositions.

7. The co-processed polymer as claimed in claim 6 wherein said preparation is selected from pill, lozenge, tablet, capsule, oral disintegrating table, sustained release tablet or capsule, dispersible tablets, sachet preparations, films, gel, emulsion, cream, powder for suspension or solutions.

8. Composition comprising co-processed polymer of two or more natural polysaccharides.

9. A process to prepare the co-processed polymer of two or more polysaccharides comprising the steps of a) dispersing or dissolving two or more polysaccharides in first solvent b) mixing the dispersion or solution to get a homogenous solution c) precipitating the co-processed polymer using second solvent d) collecting and drying the precipitate and e) optionally pulverizing the dried precipitate to get the co-processed polymer.

10. The process as claimed in claim 8 wherein said first solvent is water and said second solvent is organic solvent selected from iso-propyl alcohol, ethanol or acetone.