FIELD OF THE INVENTION
[0001] The present invention relates to natural mucoadhesive polymers. Specifically, the present invention relates to a process for thiolation of gum ghatti, a polymer having excellent mucoadhesive and drug delivery benefits for developing mucoadhesive pharmaceutical, cosmetic and nutraceutical compositions.
BACKGROUND OF THE INVENTION
[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art. [0003] Mucoadhesion is the phenomenon involving interactions between polymer and mucosal surface or mucin. Mucoadhesive interactions lead to the development of strong mucoadhesive bond due to electrostatic, mechanical/ physical crosslinking, chemical bonding, wetting or adsorption interactions. Mucoadhesive drug delivery systems could be designed for active targeting of different biological locations like nasal, buccal, gastro intestinal, rectal, vaginal etc. Mucoadhesive polymers could be used alone or in combination for providing sufficient mucoadhesive property to the drug delivery system. Mucoadhesive polymers are polymeric compounds exhibiting comparatively high adhesive properties on mucosa. Polymer composites and chemical modification of polymers could enhance mucoadhesive capacity of the polymers. [0004] Use of natural mucoadhesive polymers such as karaya gum, moringa gum, xanthan gum, gellan gum, tamarind gum, and psyllium husk are gaining popularity these days.
[0005] While, gum ghatti is a high molecular weight, anionic polysaccharide obtained from Anogeissus latifolia family Combretaceae. Primary structure of gum ghatti is composed of D-glucuronic acid, D-xylose, D-mannose, D-galactose, and L-arabinose. Gum ghatti is widely used in paper production, pharmaceutical and food industries due to its thickening and emulsification properties. It is

employed as sustained release, matrix forming, film forming and mucoadhesive
polymer for developing pharmaceutical formulations.
[0006] Thiomers or thiolated polymers are important for mucoadhesive
polymers, exhibiting capability to form inter and intra chain disulfide bonds
within the polymeric network and strongly improve cohesive properties.
Thiol/disulfide chemical reactions with cysteine rich mucin lead to the formation
of strong covalent bonds in thiomers. Thiomers when compared with the
unmodified polymers show strong adhesive strength which is sufficient to localize
dosage form at a given specific site for a prolonged period of time. Apart from
improvement in mucoadhesive properties thiolated polymers have also been
reported to exhibit permeation enhancing, enzyme inhibition, controlled release,
and thermal stability effects. Thiolation procedure have been successfully
implemented for enhancing the mucoadhesive potential of various gums viz.
karaya gum, moringa gum, xanthan gum, gellan gum, tamarind gum, and psyllium
husk.
[0007] To the best of our knowledge; thiolation of gum ghatti and its
mucoadhesive potential has not been reported in the literature.
[0008] Contemplated herein is a process for the preparation of thiolated gum
ghatti for developing mucoadhesive pharmaceutical, nutraceutical and edible
compositions.
[0009] The present invention satisfies the existing needs, as well as others,
and generally overcomes the deficiencies found in the prior art.
OBJECTS OF THE INVENTION
[0010] An object of the present invention is to provide a natural
mucoadhesive polymer for developing mucoadhesive pharmaceutical, cosmetic
and nutraceutical compositions.
[0011] An object of the present invention is to provide a modified natural
mucoadhesive polymer.
[0012] An object of the present invention is to provide a modified natural
mucoadhesive carbohydrate polymer.

[0013] An object of the present invention is to provide a thiolated gum ghatti
having excellent mucoadhesive and drug delivery benefits.
[0014] An object of the present invention is to provide a process for thiolation
of natural mucoadhesive polymer.
[0015] An object of the present invention is to provide a process for thiolation
of gum ghatti.
[0016] Another object of the present invention is to provide a process for
thiolation of gum ghatti using l-Ethyl-3-(3-Dimethylaminopropyl) carbodiimide
Hydrochloride (EDAC) and thioglycolic acid.
[0017] Another object of the present invention is to provide a process for
thiolation of gum ghatti, wherein the said thiolation is achieved by the ester
formation (esterification) between hydroxyl group and carboxyl group of gum
ghatti and thioglycolic acid.
[0018] Another object of the present invention is to provide a process for
thiolation of gum ghatti comprising (a) dissolving Pure gum ghatti in deionized
water, followed by the (b) addition of ED AC and thioglycolic acid and kept
undisturbed for 3 hr at room temperature; (c) adding the reaction mixture in
dialysis membrane; (d)dialyzing against hydrochloric acid (HO) at 10 ± 1 °C for
lhr;(e) dialyzing against HC1 containing sodium chloride for 2 hr at room
temperature;(f) lyophilizing the reaction mixture at -30 ± 1 °C under 10.01 mbar
pressure; and (e) keeping the mixture at +4 °C.
[0019] Yet another object of the present invention is to provide a thiolated
gum ghatti having excellent mucoadhesive and drug delivery benefits for oral
delivery.
[0020] Yet another object of the present invention is to provide a
mucoadhesive coated compressed oral pharmaceutical composition.
[0021] Yet another object of the present invention is to provide a method for
mucoadhesive coating of oral pharmaceutical composition.
[0022] Yet another object of the present invention is to provide a method for
mucoadhesive coating of tablets by industrially viable compression techniques.

[0023] Yet another object of the present invention is to provide a method for preparing compressed tablet comprising thiolated gum ghatti, comprising acts of dissolution of thiolated gum ghatti, lyophilisation and compressing, to obtain the mucoadhesive preparation
[0024] Yet another object of the present invention is to provide a compressed tablet comprises domperidone as active agent.
SUMMARY OF THE INVENTION
[0025] This summary is provided to introduce a selection of concepts in a
simplified form that is further described below in the detailed description section.
This summary is not intended to identify key features or essential features of the
claimed subject matter, nor is it intended to be used as an aid in determining the
scope of the claimed subject matter.
[0026] The present invention relates to a natural mucoadhesive polymer.
Specifically, the present invention relates to a process of thiolation of natural
mucoadhesive polymer having excellent mucoadhesive and drug delivery benefits
for developing mucoadhesive pharmaceutical, cosmetic and nutraceutical
compositions.
[0027] In an aspect, the present invention relates to a natural mucoadhesive
polymer, wherein the polymer is a carbohydrate polymer.
[0028] In an aspect, the present invention relates to a natural mucoadhesive
polymer, wherein the polymer is gum ghatti.
[0029] In an aspect, the present invention relates to a natural mucoadhesive
polymer, wherein the polymer is modified gum ghatti.
[0030] In an aspect, the present invention relates to a natural mucoadhesive
polymer, wherein the polymer is modified gum ghatti.
[0031] In an aspect, the present invention relates to modified gum ghatti,
wherein the modified gum ghatti is thiolated gum ghatti.
[0032] In another aspect, the present invention relates to a process for
preparing thiolated gum ghatti, wherein the process comprises thiolation.

[0033] In another aspect, the present invention relates to thiolation process
for preparing thiolated gum ghatti, wherein the process comprises binding of at
least one carboxyl group of said mucoadhesive polymer to the hydroxyl group of
thioglycolic acid via an ester bond.
[0034] In an aspect, the present invention relates to thiolation process for
preparing thiolated gum ghatti, wherein the process comprises (a) dissolving Pure
gum ghatti in deionized water; (b) addition of ED AC and thioglycolic acid and
kept undisturbed at room temperature; (c) adding the reaction mixture in dialysis
membrane; (d) primary dialysis against hydrochloric acid (HC1); (e) secondary
dialysis against HC1 containing sodium chloride at room temperature; (f)
lyophilizing the dialyzed reaction mixture; and (e) storing said mixture at low
temperature.
[0035] In yet another aspect, the present invention relates to thiolated gum
ghatti, wherein the thiolated gum ghatti is formulated as a drug carrier matrix in a
tablet, a gelling excipient in a semisolid or liquid formulation, an adhesive wound
dressing, a scaffold in tissue engineering, a microparticulate drug delivery system,
or a nanoparticulate drug delivery system.
[0036] In yet another aspect, the present invention relates to a formulation
comprising thiolated gum ghatti, wherein the thiolated gum ghatti is formulated as
a drug carrier matrix in a compressed tablet.
[0037] In yet another aspect, the present invention relates to a formulation
comprising thiolated gum ghatti, wherein the formulation is pharmaceutical,
cosmetic or nutraceutical formulation.
[0038] In yet another aspect, the present invention relates to a compressed
tablet comprises domperidone as active agent.
[0039] In further aspect, the present invention relates to a method for
preparing compressed tablet comprising thiolated gum ghatti, comprising acts of
dissolution of thiolated gum ghatti, lyophilization and compressing, to obtain the
mucoadhesive preparation.

[0040] Various objects, features, aspects and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiments.
DETAILED DESCRIPTION OF THE INVENTION
[0041] The following is a detailed description of embodiments of the disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure.
[0042] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply. [0043] Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.
[0044] In some embodiments, numbers have been used for quantifying weight percentages, ratios, and so forth, to describe and claim certain embodiments of the invention and are to be understood as being modified in some instances by the term "about." Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be

obtained by a particular embodiment. In some embodiments, the numerical
parameters should be construed in light of the number of reported significant
digits and by applying ordinary rounding techniques. Notwithstanding that the
numerical ranges and parameters setting forth the broad scope of some
embodiments of the invention are approximations, the numerical values set forth
in the specific examples are reported as precisely as practicable. The numerical
values presented in some embodiments of the invention may contain certain errors
necessarily resulting from the standard deviation found in their respective testing
measurements.
[0045] Various terms as used herein are shown below. To the extent a term
used in a claim is not defined below, it should be given the broadest definition
persons in the pertinent art have given that term as reflected in printed
publications and issued patents at the time of filing.
[0046] As used in the description herein and throughout the claims that
follow, the meaning of "a," "an," and "the" includes plural reference unless the
context clearly dictates otherwise. Also, as used in the description herein, the
meaning of "in" includes "in" and "on" unless the context clearly dictates
otherwise.
[0047] Unless the context requires otherwise, throughout the specification
which follow, the word "comprise" and variations thereof, such as, "comprises"
and "comprising" are to be construed in an open, inclusive sense that is as
"including, but not limited to."
[0048] The recitation of ranges of values herein is merely intended to serve as
a shorthand method of referring individually to each separate value falling within
the range. Unless otherwise indicated herein, each individual value is incorporated
into the specification as if it were individually recited herein.
[0049] All methods described herein can be performed in any suitable order
unless otherwise indicated herein or otherwise clearly contradicted by context.
The use of any and all examples, or exemplary language (e.g. "such as") provided
with respect to certain embodiments herein is intended merely to better illuminate
the invention and does not pose a limitation on the scope of the invention

otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention. [0050] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member can be referred to and claimed individually or in any combination with other members of the group or other elements found herein. One or more members of a group can be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is herein deemed to contain the group as modified.
[0051] The description that follows, and the embodiments described therein, is provided by way of illustration of an example, or examples, of particular embodiments of the principles and aspects of the present disclosure. These examples are provided for the purposes of explanation, and not of limitation, of those principles and of the disclosure.
[0052] It should also be appreciated that the present disclosure can be implemented in numerous ways, including as a system, a method or a device. In this specification, these implementations, or any other form that the invention may take, may be referred to as processes. In general, the order of the steps of the disclosed processes may be altered within the scope of the invention. [0053] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments. [0054] The following discussion provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus if one embodiment comprises elements a, b, and c, and a second embodiment comprises elements b and d, then the inventive subject matter is also considered to include other remaining combinations of a, b, c, or d, even if not explicitly disclosed. [0055] While a particular form of the invention has been illustrated and described, it will be apparent that various modifications can be made without departing from the spirit and scope of the invention.

[0056] The present invention provides a natural mucoadhesive polymer for
developing mucoadhesive pharmaceutical, cosmetic and nutraceutical
compositions.
[0057] In an embodiment of the present invention, the natural mucoadhesive
polymer is a carbohydrate polymer.
[0058] In an embodiment of the present invention, the natural mucoadhesive
polymer be obtained from the whole plant / tree or from parts.
[0059] In an embodiment of the present invention, the natural mucoadhesive
polymer be obtained from the whole plant / tree or from parts of Anogeissus
latifolia (Axlewood), such as, for example, the leaves, the stem, the bark, the
fruits, the nuts, the seeds, the flowers, the roots or any other parts of the plant /
tree thereof.
[0060] In an embodiment of the present invention, the natural mucoadhesive
polymer is a modified natural mucoadhesive polymer.
[0061] In an embodiment of the present invention, the modified
mucoadhesive polymer is a thiolated mucoadhesive polymer.
[0062] In an embodiment of the present invention, the thiolated
mucoadhesive polymer is a thiolated mucoadhesive carbohydrate polymer.
[0063] In an embodiment of the present invention, the thiolated
mucoadhesive polymer is thiolated gum ghatti.
[0064] In an embodiment, the present invention provides a process for
preparing thiolated mucoadhesive polymer.
[0065] In an embodiment, the present invention provides a process for
preparing thiolated gum ghatti.
[0066] In an embodiment, the present invention provides a method for
thiolation of gum ghatti, wherein the said thiolation is achieved by the ester
formation (esterification) between hydroxyl group and carboxyl group of gum
ghatti and thioglycolic acid.
[0067] In an embodiment of the present invention, the process for preparing
thiolated gum ghatti comprising (a) dissolving Pure gum ghatti in deionized water,
followed by the (b) addition of ED AC and thioglycolic acid and kept undisturbed

for 3 hr at room temperature; (c) adding the reaction mixture in dialysis membrane; (d) dialyzing against hydrochloric acid (HO) at 10 ± 1 °C for 1 hr; (e) dialyzing against HC1 containing sodium chloride for 2 hr at room temperature; (f) lyophilizing the reaction mixture at -30 ± 1 °C under 10.01 mbar pressure; and (e) keeping the mixture at +4 °C.
[0068] In an embodiment of the present invention, a method of obtaining mucoadhesive compressed tablet preparation comprising thiolated gum ghatti, comprising acts of dissolution of thiolated gum ghatti, lyophilization and compressing, to obtain the mucoadhesive preparation.
[0069] In an embodiment of the present invention, the mucoadhesive compressed tablet preparation comprise therapeutic agents which include any material suitable for use at the intended treatment site including analgesics, anti¬cholinergics, anti-fungal agents, antihistamines, steroidal or non-steroidal anti¬inflammatory agents, anti-parasitic agents, antiviral agents, biostatic compositions, chemotherapeutic/antineoplastic agents, cytokines, decongestants, hemostatic agents (e.g., thrombin), immunosuppressors, mucolytics, nucleic acids, peptides, proteins, steroids, vasoconstrictors, vitamins, mixtures thereof, and other therapeutic materials that will be known to those skilled in the art. [0070] In another embodiment of the present invention, the mucoadhesive preparations are intended for the local or systemic administration of a single or multiple pharmaceutical agent and may be applied to any mucosal surfaces selected from a group comprising buccal, sublingual, pharyngeal, esophageal, gastro-intestinal, nasal, ophthalmic, and vaginal mucosae or any combinations thereof.
[0071] In an embodiment of the present invention, the mucosal surface of the subject is selected from a non-limiting group comprising oral, nasal mucosae, throat, ocular, vaginal, or rectal cavities.
[0072] In an embodiment of the present invention, the mucoadhesive polymers polymers of this invention are useful in the pharmaceutical field as drug carrier matrix in tablets, as gelling excipients in semisolid and liquid formulations,

as adhesive wound dressings, as scaffold in the field of tissue engineering as well
as for the preparation of micro and nanoparticulate drug delivery systems.
[0073] In an embodiment of the present invention, the mucoadhesive
polymers of this invention are useful in the cosmetic field are in particular,
applications as hair care products such as hair styling gels, fixing agents,
colorants, cleaning agents, and coatings for hair, lashes, eyebrows of interest,
because of the protein structure of hair thiol partial structures present with which
polymers according to this invention can react. The use in nail varnish, make-ups
and antiperspirants is also advantageous.
[0074] In an embodiment of the present invention, the thiolated gum ghatti is
useful for preparing mucoadhesive compressed tablets of domperidone.
[0075] In an embodiment of the present invention, the thiolated gum ghatti is
bio-degradable and environment friendly.
[0076] In an embodiment, the herbal skin care composition of the present
invention maybe used on the body part in any manner known to a person skilled
in the art.
[0077] The present disclosure is further explained in the form of following
examples. However, it is to be understood that the foregoing examples are merely
illustrative and are not to be taken as limitations upon the scope of the invention.
Various changes and modifications to the disclosed embodiments will be apparent
to those skilled in the art. Such changes and modifications may be made without
departing from the scope of the invention.
[0078] Example 1: Synthesis of Thiolated Gum Ghatti
Pure gum ghatti (2 g) was firstly dissolved in 50 mL of deionized water, followed
by the addition of EDAC (50 mM) and thioglycolic acid (4 g). The
aforementioned reaction mixture was kept undisturbed for 3 hr at room
temperature. Further, the reaction mixture was added in dialysis membrane and
dialyzed against 5 mM hydrochloric acid (HO) at 10 ± 1 °C for 1 hr, against 5
mM HC1 containing sodium chloride (1%) for 2 hr at room temperature and
against 1 mM HC1 containing sodium chloride (1%) for 2 hr at room temperature.
Afterwards, the reaction mixture was collected and lyophilized (Allied frost,

Delhi, India) at -30 ± 1 °C under 10.01 mbar pressure and the mixture was kept at
+4°C.
Using Ellman's reagent, the degree of thiol group substitution was measured [24].
The amount of accurately weighed thiolated gum ghatti (50 mg) was dissolved in
water (25 ml). Aliquot (2.5 ml) was taken from the above prepared solution and
was diluted with 2.5 ml of 0.5 M phosphate buffer (pH 8.0) and was allowed to
react with 5 ml of Ellman's reagent for two hours. The absorbance of reaction
mixture was measured using UV spectrophotometer at 450 nm. The total number
of thiol groups was calculated using the standard curve of thioglycolic acid with
Ellman's reagent.
Thiolated gum ghatti was found to contain 4.5 mM of thiol groups/g of polymer
as determined by Ellman's method.
[0079] Example 2: Characterization of Thiolated Gum Ghatti: Fourier Transform
Infrared Spectroscopy (FTIR)
Powder samples of pure gum ghatti and thiolated gum ghatti were subjected to
FTIR analysis using FTIR spectrophotometer (Alpha, Bruker, Japan). Sample
pellets were prepared with KBr and FTIR spectra were recorded in the frequency
range of 4000- 400 cm"1. The possible interactions between the drug and different
components of the tablet formulation were also evaluated by FTIR analysis.
The FTIR spectra of gum ghatti shows stretching vibration of-OH at 3441.74 cm-
1,-OH at 3161.30 cm"1, -CH at 2932.40 cm"1, C=0 alkene at 1669.32 cm"1, C-H
alkane atl450.02 cm"1 and 1035.51 cm"1 attributed to C-0 primary alcohol. All
the characteristic peaks of gum ghatti were found in thiolated gum ghatti.
However, the presence of additional -SH stretch at 2571.48 cm^confirms the
thiolation of gum ghatti. Thiolation of gum ghatti was authorized by the formation
of ester bonds between carboxyl group of thioglycolic acid and hydroxyl group of
gum ghatti.
[0080] Example 3: Characterization of Thiolated Gum Ghatti: Differential
Scanning Calorimetry (DSC)
DSC thermograms of pure gum ghatti and thiolated gum ghatti were recorded
using differential scanning calorimeter (Mettler Toledo Star System, 305,

Switzerland). A required amount of sample was crimped in a standard aluminium
pan and heated over a temperature range of 40 °C to 300 °C at a heating rate 10
°C per minute in a nitrogen atmosphere.
The thermogramof pure gum ghatti shows endothermic peak at 64.42 °C (onset
53.97°C, endset 81.97 °C, enthalpy -39.36 mJ/g) and 183.73 °C (onset 182.93 °C,
endsetl85.38 °C, enthalpy 0.16 mJ/g). DSC thermogram of thiolated gum ghatti
depicts endothermic peaks at 199.73 C (onset 198.39 °C, endset 200.55 °C,
enthalpy -0.24mJ/g) and 206.39 °C (onset 204.43 °C, endset 207.62 °C, enthalpy -
1.41 mJ/g). The increase in endothermic transition temperature and heat of fusion
in thiolated gum ghatti indicated thiol modification of gum ghatti.
[0081] Example 4: Characterization of Thiolated Gum Ghatti: X-Ray Diffraction
Analysis (XRD)
X-ray diffraction patterns of pure gum ghatti and thiolated gum ghatti were
traced/recorded using X-ray diffractometer (Miniflex 2, Rigaku, Japan) with Ni
filtered Cu (K-a) radiations, with voltage rate of 45 kV, and a current of 40 raA.
The samples (gum ghatti and thiolated gum ghatti) were analyzed over 20 range of
0° to 80° with scan step size of 0.0170° (20), scan step time of 25 s and scan speed
0.05 min"1.
X-ray diffractogram of gum ghatti is typical amorphous material with a broad
characteristic peak at 19.97, while the diffractogram of thiolated gum ghatti
depicts sharp peaks at 27.41, 31.75, 45.52, 56.52, 66.26, 75.30 and 84.00 (20),
indicating significant crystalline behavior of the modified gum.
[0082] Example 5: Characterization of Thiolated Gum Ghatti: Scanning Electron
Microscopy (SEM)
The external morphology (shape and surface) of gum ghatti and thiolated gum
ghatti was determined by scanning electron microscope (Joel, fine coat ion
sputter, JFC-1100). Double sided adhesive tape is used to adhere the gold
palladium alloy (150-200 A°) coated samples onto the stubs of microscope.
[0083] Example 6: Characterization of Thiolated Gum Ghatti: Rheology
Rheological behavior of gum ghatti and thiolated gum ghatti was analyzed using
rheometer (MCR 92, Anton Paar, Austria).For temperature sweep analysis,

samples were analyzed in temperature range of 20 °C to 60 °C with 2 °C/min
constant shear rate of 10s"1. The samples were carried out under shear rate sweep
analysis ranging from 0.1 to 1000 s"1 to evaluate the flow behavior, with a data
acquisition duration varying from 30 sec on a logarithmic scale at a constant
temperature of 25°C.
SEM technique examined the surface morphology of gum ghatti and thiolated
gum ghatti. SEM of pure gum ghatti indicates the presence of polyhedral flakes
with rough surface morphology. However, thiolated gum ghatti shows sharp
lucent crystalline flakes with relatively smooth surface. Relative smooth surface
of thiolated gum ghatti may be helpful in providing larger surface area for
interaction with mucosal layer and hence responsible for enhanced mucoadhesive
interaction.
[0084] Example 7: Polymer Mucin Interaction Study
For polymer-mucin interaction study pure gum (gum ghatti) (1% w/v), thiolated
gum (gum ghatti) (1% w/v), and mucin (5% w/v) solutions were prepared in SGF
(simulated gastric fluid) medium without enzymes [26]. The experiments
(viscometric) were performed on pure gum, thiolated gum, mucin, pure gum
mucin mixture and thiolated gum mucin mixture solutions. All the mixture
solutions were allowed to stand for at least 1 hr at 37.0 ±0.1 °C (prior to
analysis). The rheological measurements were performed using Brookfield
viscometer (Model DV-III, Brookfield, USA). Each sample (mixture solutions)
was added to the viscometer and equilibrated for 2 min. The measurement was
made with the shear rate up to about 25 s"1.
For in-silico evaluation; gum ghatti and thiolated gum ghatti were interacted with
glycosylated mucin (Avogadro 1.2 platform) using molecular mechanics
simulations (MM+ force field; Polak- Ribere conjugate gradient; Chem- Lite3.0.,
FL, USA) [27].
Interaction of thiolated gum with mucin resulted in the formation of strong
mucoadhesive bond via disulfide exchange.

[0085] Example 8: In-vivo Toxicity Study
For in-vivo toxicity study, Wistar rats (150-200 g body weight) were obtained
from Lala Lajpat Rai University of Veterinary & Animal Sciences, India and were
kept under standard housing conditions following balanced diet and water ad
libitum. The study protocol was approved by the animal ethics committee of the
institute (Reg.No. 1181/PO/ReBi/S/08/CPCSEA; vide Protocol No.
IAEC/CCP/20/01/PR-004). The single dose in vivo acute oral toxicity study on pure gum ghatti and thiolated gum ghatti was performed as per Organization for Economic Co-operation and Development (OECD) 423 guidelines. The animals were divided into five different groups, Group-I (control group; n=3), Group-II (pure gum ghatti; Dose- 300 mg/kg; n= 3), Group-Ill (thiolated gum ghatti; Dose-300 mg/kg; n=3), Group-IV (pure gum ghatti; Dose- 2000 mg/kg; n= 3), Group-V (thiolated gum ghatti; Dose- 2000 mg/kg; n= 3) and the sample was administered per orally by feeding needles made of stainless steel. On the 14th day of the experimental procedure, animals were sacrificed by cervical dislocation for histological examination of stomach and intestine.
Histopathological images of stomach and intestine tissues of rats after oral administration of gum ghatti and thiolated gum ghatti are shown in Figure 6. In the histopathological images of stomach, the gastric glands surface epithelium was found normal with no ulcerative spots. No deformations were observed in lacteals and goblet cells of duodenum. Further, villi and microvilli (hair like projections) were in normal condition. It was affirmed that both stomach and intestine tissues did not show any evidence of toxicity after single oral dose (300 mg/ kg and 2000 mg/ kg body weight) oral administration of pure and thiolated gum ghatti in Wistar rats.
[0086] Example 9: Preparation of Core Tablet of Domperidone Core tablet (80 mg) of domperidone was formulated using domperidone (10 mg) as an active ingredient and Avicel 112 (63 mg), PVP K30 (5 mg), Talc (1 mg), magnesium stearate (1 mg) as tablet excipients. All ingredients were sieved (60#), and blended using double cone blender for 15-20 min. Tablets with 80 mg weight

were prepared using multiple station tablet punching machine equipped with 6 mm concave round die-punch tooling (A.K. Industries, Nakodar, India). Various evaluation parameters were resulted for core tablets. The inner core tablets of domperidone were found to be 80 ± 5 mg in weight. The thickness of the core tablets was found be 1.82 ± 0.10 mm, hardness and friability of core tablets were3.7 ± 0.50 kg/cm2 and 0.79 ± 0.15%.The evaluation indicated significant quality attributes in core tablets.
Table 1: Composition of core tablet of domperidone
Ingredients Quantity
Domperidone 10 mg
Avicelll2 63 mg
PVP K30 5 mg
Talc 1 mg
Magnesium Stearate 1 mg
Total Weight 80 mg

[0087] Example 10: Compression Coating of Core Tablets
An appropriate blend of coating polymer (pure gum ghatti (FIGG, F2GG, F3GG
& F4GG) and thiolated gum ghatti (F5TGG, F6TGG, F7TGG & F8TGG)) was
press coated over the formulated core tablet as per the composition given in Table
1. Avicel-112 was added quantity sufficient for making the total tablet weight
equal to 600 mg. The die cavity was first half filled with polymer (coating
material), then core tablet was placed in the die, and remaining coating material
was added over the core tablet. Compression coating was performed using
multipunch tableting machine having 8.5 mm concave punches at an applied force
of 5000 kg. Physicochemical characterization done for the tablets as per standard
procedures.
Table 2: Composition of compression coating mucoadhesive tablet batches of
gum ghatti ghatti and thiolated gum ghatti
Batches Gum Thiolated Avicel 112 PVP K30 Talc (mg)
Ghatti Gum (mg) (mg)
(mg) Ghatti (mg)
FIGG
350
5
145 20

F2GG 400 - 95 20 5
F3GG 450 - 45 20 5
F4GG 500 - - 20 5
F5TGG - 350 145 20 5
F6TGG - 400 95 20 5
F7TGG - 450 45 20 5
F8TGG - 500 - 20 5
Table 3: Physicochemical characterization of core tablet and compressed
coated tablets using pure gum ghatti

Parameter Core tablet F1GG F2GG F3GG F4GG
Weight variation Pass Pass Pass Pass Pass
Thickness (mm) 1.82±0.10 3.87±0.05 3.85±0.03 3.87±0.08 3.86±0.10
Hardness (kg/cm2) 3.7±0.50 4.2± 0.52 3.6±0.49 4.1±0.51 3.9±0.48
Friability (%) 0.79±0.15 0.78±0.13 0.76±0.11 0.78±0.15 0.77±0.14
Mucoadhesion strength (g) 4.67± 0.79 5.71±0.72 6.87±0.81 8.99± 0.75
5 Table 4: Physicochemical characterization of core tablet and compressed
coated tablets using thiolated gum ghatti

Parameter Core tablet F5TGG F6TGG F7TGG F8TGG
Weight variation Pass Pass Pass Pass Pass
Thickness (mm) 1.82±0.10 3.85± 0.15 3.87±0.08 3.86±0.18 3.88±0.09
Hardness (kg/cm2) 3.7±0.50 3.8±0.48 3.6±0.32 3.9±0.35 3.7±0.29
Friability (%) 0.79±0.15 0.79±0.11 0.77± 0.09 0.79±0.13 0.78±0.17
Mucoadhesion strength (g) 11.76±1.34 13.27±1.41 15.62±1.19 18.83±2.07
[0088] Example 11: Ex-Vivo Determination of Mucoadhesive Strength Mucoadhesion testing of compressed coated tablets of domperidone was done 10 using two different polymers (gum ghatti and thiolated gum ghatti) and was executed employing texture analyzer (TA.XT plus, Stable MicroSystems, UK).

Tablet was attached to cylindrical probe with the help of double side adhesive tape. The pig stomach (tissue) was equilibrated at 37.0 ± 0.5 °C for 15 min before placing onto the holder stage. The probe attached with tablet was dispersed into the medium for framed time proceeding to the test. Afterwards, the hydrated disc was shifted to downward direction to get in contact with rinsed tissue at a defined force and sus- tained until time specified. The probe was uplifted at predetermined test speed and maximum detaching force (Fmax) that required to separate the tablet equipped with probe from tissue which can be determined from software (Texture Exponent 32). The precursor settings of the instrument were tested with different parameters such as test speed (0.5 mm/s), contact time (60 s), contact force (1.0 N) and distance (15 mm). Probe without attached sample (tablet) was also assessed to examine the animal tissue uniformity [33]. The results depicted a notable increase in mucoadhesive property of thiolated gum compared to pure gum. Additionally, mucoadhesive strength was directly proportional to the concentration of thiolated gum which was used as coating material for developing mucoadhesive tablets of domperidone. [0089] Example 12: In-Vitro Drug Release
In-vitro dissolution study of compressed domperidone tablets was executed using USP-II Paddle type dissolution apparatus (DS 8000, Lab India, India) with a rotating speed (50 rpm at 37± 0.5 °C) using dissolution medium 0.1 N HC1 (pH 1.2). At fixed time intervals, samples (5ml) were taken out and filtered through membrane filter (0.45 urn). Further it was diluted and analyzed using UV double beam spectrophotometer (AU 2701, Systronics, Mumbai, India) at 287 nm. Drug release cumulative percentage was deliberated using an equation derived from calibration curve. Pharmacokinetic models such as Zero order, First order, Higuchi, Kosmeyer-Peppas and Hixon-Crowell were fitted with release data of prepared tablets to perceive kinetic drug release modeling.

Core tablet released 80.19%> and 94.63%> domperidone in 30 and 60 min respectively. Core tablets compression coated with gum ghatti (F4GG) depicted 51.85%o and 95.33%> drug release in 0.5 and 6 h respectively. However core tablets coated with thiolated gum ghatti (F4TGG) exhibited35.28% and 78.95% drug release after 0.5 and 6 h respectively.

We Claim:

1. A thiolated mucoadhesive polymer, wherein said thiolated polymer
prepared by a process of thiolation comprising
(a) dissolving Pure mucoadhesive polymer in deionized water;
(b) addition of ED AC and thioglycolic acid and kept undisturbed at room temperature;
(c) adding the reaction mixture in dialysis membrane;
(d) primary dialysis against hydrochloric acid (HC1);
(e) secondary dialysis against HC1 containing sodium chloride at room temperature;
(f) lyophilizing the dialyzed reaction mixture; and
(g) storing said mixture at low temperature.

2. The thiolated mucoadhesive polymer as claimed in claim 1, wherein said polymer is carbohydrate polymer.
3. The thiolated mucoadhesive polymer as claimed in claim 1, wherein said polymer is gum ghatti.
4. The thiolated mucoadhesive polymer as claimed in claim 1, wherein said thiolation comprises binding of at least one carboxyl group of said mucoadhesive polymer to the hydroxyl group of thioglycolic acid via an ester bond.
5. A thiolated gum ghatti prepared by a process of thiolation comprising

(a) dissolving Pure gum ghatti in deionized water;
(b) addition of ED AC and thioglycolic acid and kept undisturbed at room temperature;
(c) adding the reaction mixture in dialysis membrane;
(d) primary dialysis against hydrochloric acid (HC1);
(e) secondary dialysis against HC1 containing sodium chloride at room temperature;
(f) lyophilizing the dialyzed reaction mixture; and
(g) storing said mixture at low temperature.

6. The thiolated gum ghatti as claimed in claim 5, wherein said thiolated gum ghatti comprises at least 4.5 mM of covalently bound thiol groups per gram of gum ghatti.
7. The thiolated gum ghatti as claimed in claim 5, wherein said thiolated gum ghatti is formulated as a drug carrier matrix in a tablet, a gelling excipient in a semisolid or liquid formulation, an adhesive wound dressing, a scaffold in tissue engineering, a microparticulate drug delivery system, or a nanoparticulate drug delivery system.
8. The thiolated gum ghatti as claimed in claim 5, wherein said formulation is pharmaceutical, cosmetic or nutraceutical formulation.
9. The thiolated gum ghatti as claimed in claim 7, wherein said thiolated gum ghatti is formulated as a drug carrier matrix in a compressed tablet.
10. The compressed tablet as claimed in claim 9, wherein the method for preparing compressed tablet comprising thiolated gum ghatti, comprising acts of dissolution of thiolated gum ghatti, lyophilisation and compressing, to obtain the mucoadhesive preparation
11. The thiolated gum ghatti as claimed in claim 8, wherein said compressed tablet comprises domperidone as active agent.