[0001]The present invention generally relates to a pharmaceutical composition of diabetic drug. Specifically, the present invention relates to a sustained release pharmaceutical composition of glimepiride comprising of nanocomposite of glimepiride in soluplus®. The sustained release composition of the present invention possesses excellent release properties.
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] Glimepiride is an orally available medium to-long-acting sulfonylurea anti diabetic drug which lowers the blood glucose level in the healthy subjects as well as in patients with type 2 diabetes. Glimepiride belongs to BCS class II drug i.e. it has low aqueous solubility and high permeability with drug pKa: 6.2 showing small intestine as the major absorption site. Due to its shorter biological half-life (5hr), it requires frequent administration. To reduce the dosing frequency and to improve patient compliance prolonged release dosage forms are required.
[0004] Nagpal et al, Current Nanomedicine, 7(2), 2017, 142-57discloses solid dispersions (SD) of acelofenac by solvent evaporation technique and in the form of co-grinding mixture (CGM). Four batches of neem gum based solid dispersions of acelofenac were prepared by varying the drug polymer ratio (1:1,1:2,1:3,1:4).Prepared solid dispersions were evaluated for solubility, FTIR, DSC, XRD, SEM and in vitro release and optimized batch was utilized to develop solid dosage form in the tablet form. The final dosage form was evaluated for physiochemical characterziartion, in vivo and in v/Yropharmacodynmaic studies. Solubility studies indicated 1:3 drugs to neem gum ratio for the formulation of solid dispersion of drug. CGM also indicated improved solubility of drug.
[0005] Opara et al, International Journal of Pharmaceutics, 496 (2), 2015, 741-750, evaluated a novel blend of polyvinyl caprolactam-polyvinyl acetate- polyethylene glycol 6000 grafted copolymer (Soluplus) and polyethylene glycol (PEG) 4000 for solubility enhancement, physicochemical stability and anti-diabetic efficacy of the produced solid dispersions containing glimepiride, a biopharmaceutics classification system (BCS) class II

sulphony- lurea. Different batches of glimepiride solid dispersions (SD) were prepared by the solvent evaporation method using the individual polymers and blends of the polymers at different ratios. The Soluplusl-PEG 4000 (sol-PEG) hybrid polymer based glimepiride solid dispersions were characterized by differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, micromeritics and dissolution studies. In vivo anti-diabetic activity was determined by measuring the changes in blood glucose concentrations in albino rats. The solid dispersions showed good flow properties and excellent practical yield. Drug content and release from the different formulations increased when Soluplusl was used as the main matrix polymer. The kinetics of drug release from all the solid dispersions followed first order. Solid state characterization confirmed the formation of amorphous glimepiride solid dispersions in the Sol-PEG hybrid polymer and no strong drug-polymer interaction was observed. The blood glucose reduction in albino rats by the Sol-PEG-Glim SDS was significantly (p < 0.05) higher and more sustained when compared with the plain drug sample and commercially available product. Optimized SD batches (SP1 and SP3) showed a reduction in blood glucose level from 100% to 9.81% and 8.97%, respectively, at Tmax of 3 h. The Sol-PEG-Glim SD was found to be stable over a period of 6 months (at 40 C, 70% RH) with no significant changes in the drug content.
[0006] Rafshanjani et al, International current pharmaceutical journal, 4(10), 2015, 436-41, conducted study to enhance the dissolution rate of glimepiride solid lipid nano particle dispersions using hot homogenization method and glimepiride solid dispersion by precipitation method. Solid lipid nanoparticles have been used as suitable carriers for delivery of drug with poor solubility. In this investigation glycerylmonostearate and stearic acid were used as solid lipid, Lutrol F- 68 as surfactant, Tween 80 as stabilizer and the used polymer were urea crystal and P-cyclodextrin. Three formulations were prepared in different ratios for two methods and were designated as GMLN1 to GMLN3 in case of hot homogenization method and GMP1 to GMP3 for precipitation method. The evaluation of all the dispersions were done by in vitro dissolution studies using US Pharmacopeia type II apparatus (paddle method) in 900ml distilled water at 50 rpm to a temperature of 37°C ±0.5°C for 45 minutes. In situ and externally sink method revealed the release pattern of drug was found to follow zero order, first order and Korsmeyer- Peppas equations. Improved dissolution profile was observed in all the solid lipid nano particle dispersions as compared to pure drug as well as market preparation. Thus, glycerylmonostearate and P-cyclodextrin can be successfully used as carrier for improvement of dissolution and bioavailability of Glimepiride.

[0007] Various compositions of the glimepirideare available in commercial market. However, due to the shorter half-life of the drug,it requires frequent administration. To reduce the dosing frequency and to improve patient compliance prolonged release dosage forms are required. There is, therefore, a need to develop a sustained release pharmaceutical composition of glimepiride. The present invention investigates the possibility of enhancing the solubility, and hence the bioavailability of poorly water soluble glimepiride via formation of nanocomposite and incorporating them into matrix tablets to produce sustain release dosage forms.
OBJECTS OF THE INVENTION
[0008] An object of the present invention is to provide a sustained release pharmaceutical
composition of glimepiride.
[0009] Another object of the present invention is to provide asustained release
pharmaceutical composition comprising of nanocomposite of glimepiride using soluplus® in
different ratios.
[0010] Another object of the present invention is to provide a matrix tablet of
nanocomposite formulation comprising of glimepiride and soluplus®.
SUMMARY OF THE INVENTION
[0011] The present invention generally relates to a pharmaceutical composition of
diabetic drug. Specifically, the present invention relates to a sustained release pharmaceutical
composition of glimepiride comprising of nanocomposite of glimepiride in soluplus®. The
sustained release composition of the present invention possesses excellent dissolution
properties.
[0012] In one aspect, the present invention relates to a sustained release pharmaceutical
composition comprising of:
(a) nanocomposite of glimepiride in soluplus®;
(b) binder selected from natural gum or synthetic gum; and
(c) one or more pharmaceutically acceptable excipients.
[0013] In another aspect, the nanocomposite of glimepiride in soluplus® of the present invention comprises nano-emulsions of glimepiride and soluplus® in a ratio ranges from 1:0.5 to 1:5.

[0014] In another aspect, the nanocomposite of glimepiride in soluplus® of the present
invention is present in an amount ranges from about 2% to about 10%> by weight of the
composition.
[0015] In another aspect, the binder in sustained release pharmaceutical composition of
the present invention is present in an amount ranges from about 3% to about 15% by weight
of the composition.
[0016] In another aspect, the one or more pharmaceutically acceptable excipients of the
present invention is present in an amount ranges from about 75% to about 95% by weight of
the composition.
[0017] In yet another aspect, the present invention relates to a sustained release
pharmaceutical composition comprising of:
(a) about 4% of nanocomposite comprising of nanoemulsion of glimepiride and soluplus®;
(b) about 5%> of binder selected from natural gum or synthetic gum; and
(c) about 9P/o of one or more pharmaceutically acceptable excipients.
[0018] In another aspect, the one or more pharmaceutically acceptable excipient(s) of the
sustained release composition is selected from diluents, lubricants and glidants.
[0019] In another aspect, the natural gum of the present invention is neem gum and the
synthetic gum of the present invention is acacia gum.
[0020] In another aspect, the diluents of the sustained release pharmaceutical composition
of the present invention is selected from the group consisting of sugars, dextrates, dextrin,
dextrose, fructose, lactitol, mannitol, sucrose, starch, lactose, xylitol, sorbitol, talc,
microcrystalline cellulose, calcium carbonate, calcium phosphate dibasic or tribasic and
calcium sulphate.
[0021] In another aspect, the lubricant of the sustained release pharmaceutical
composition of the present invention is selected from the group consisting of talc, magnesium
stearate, aluminium stearate,calcium aluminium stearate,zinc stearate, polyethylene glycol,
glyceryl behenate, mineral oil, sodium stearyl fumarate, stearic acid, and hydrogenated
vegetable oil.
[0022] In another aspect, the glidant of the sustained release pharmaceutical composition
of the present invention is selected from the group consisting of silicon dioxide; magnesium
trisilicate, powdered cellulose, starch, talc, tribasic calcium phosphate, calcium silicate,
magnesium silicate, colloidal silicon dioxide and silicon hydrogel.

[0023] In yet another aspect, the present invention relates to a process for preparation of a
sustained release pharmaceutical composition comprising of nanocomposite of glimepiride in soluplus®.
[0024] Various objects, features, aspects and advantages of the inventive subject matter
5 will become more apparent from the following detailed description of preferred
embodiments.
BRIEF DESCRIPTION OF THE FIGURES
[0025] Figure 1 depicts the solubility of nanocomposite of glimepiride and soluplus® in
different ratio.
[0026] Figure 2 depicts the FTIR spectral data for nanocomposite
[0027] Figure 3 depicts the DLS spectra of nanocomposite, NC2
[0028] Figure 4 depicts the DLS spectra of nanocomposite, NC3
[0029] Figure 5 illustrates the SEM images of pure drug, soluplus® and nanocomposite,
NC2
[0030] Figure 6 illustrates the XRD peaks of nanocomposite, NC2
[0031] Figure 7 depicts the percentage drug release of various nanocomposites of the
present invention
[0032] Figure 8 depicts the percentage drug release of various sustained release tablets of
the present invention
DETAILED DESCRIPTION OF THE INVENTION
[0033] 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
25 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 as defined by the appended claims.
[0034] Unless the context requires otherwise, throughout the specification which follow,
the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be
30 construed in an open, inclusive sense that is as “including, but not limited to.”
[0035] 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
6

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.
[0036] As used in this specification and the appended claims, the singular forms “a,”
5 “an,” and “the” include plural referents unless the content clearly dictates otherwise. It should
also be noted that the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise.
[0037] In some embodiments, the numbers expressing quantities of ingredients,
properties such as concentration, reaction conditions, and so forth, used to describe and claim
10 certain embodiments of the invention 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 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
15 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.
[0038] The recitation of ranges of values herein is merely intended to serve as a
20 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.
[0039] All processes described herein can be performed in any suitable order unless
otherwise indicated herein or otherwise clearly contradicted by context. The use of any and
25 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.
30 [0040] The headings and abstract of the invention provided herein are for convenience
only and do not interpret the scope or meaning of the embodiments.
[0041] 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
7

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.
5 [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.
10 [0043] 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
15 occurs, the specification is herein deemed to contain the group as modified thus fulfilling the
written description that follows, and the embodiments described herein, 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.
20 [0044] It should also be appreciated that the present invention 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.
25 [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] In a general embodiment, the present invention relates to a sustained release
30 pharmaceutical composition of glimepiride comprising of nanocomposite of glimepiride in
soluplus®. The sustained release composition of the present invention possesses excellent dissolution properties.
[0047] Glimepiride is an oral blood-glucose-lowering drug of the sulfonylurea class.
Chemically, glimepiride is identified as 3-ethyl-4-methyl-N-[2-(4-{[(trans-4-methylcyclo-
8

hexyl)carbamoyl]sulfamoyl}phenyl)ethyl]-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide and their pharmaceutically acceptable salts, polymorphs, solvates, hydrates, enantiomers and mixtures thereof.
[0048] Soluplus®,is a polyethylene glycol, polyvinyl acetate and polyvinylcaprolactame-
5 based graft copolymer (PVAc-PVCap- PEG). Soluplus® is marketed by BASF.
[0049] The term "sustained release" as used herein refers to the dosage form which is not
immediate release and is taken to encompass controlled release, prolonged release, timed release, retarded release, extended release and delayed release. Sustained release can be used interchangeably with prolonged release, programmed release, timed release, extended release,
10 controlled release and other such dosage forms.
[0050] The term, "dosage form" according to the present invention refers to tablets,
pellets, beads, granules, capsules, microcapsules and tablets in capsules.
[0051] The term, "therapeutically effective amount" as used herein refers to the amount
of active agent, which halts or reduces the progress of the condition being treated or which
15 otherwise completely or partly cures or acts palliatively on the condition. A person skilled in
the art can easily determine such an amount by routine experimentation and with an undue burden.
[0052] The term, "pharmaceutically acceptable" as used herein refers to a carrier
comprised of a material that is not biologically or otherwise undesirable.
20 [0053] In an embodiment, the present invention relates asustained release pharmaceutical
composition comprising of:
(a) nanocomposite of glimepiride in soluplus®;
(b) binder selected from natural gum or synthetic gum; and
(c) one or more pharmaceutically acceptable excipients.
25 [0054] In another embodiment, the present invention relates to a sustained release
pharmaceutical composition comprising of:
(a) about 4% of nanocomposite comprising of nanoemulsion of glimepiride and
soluplus®;
(b) about 5% of neem gum; and
30 (c) about 91% of one or more pharmaceutically acceptable excipients.
[0055] In another embodiment, the present invention relates to a sustained release
pharmaceutical composition comprising of:
(a) about 4% of nanocomposite comprising of nanoemulsion of glimepiride and
soluplus®;
9

(b) about 5% of acacia gum; and
(c) about 91% of one or more pharmaceutically acceptable excipients.
[0056] In another embodiment, the nanocomposite of glimepiride in soluplus® of the
present invention comprises nanoemulsions of glimepiride and soluplus® in a ratio ranges
5 from 1:0.5 to 1:5. Preferably, in the ratio selected from 1:1, 1:2, 1:3 and 1:4. More preferably
in the ratio of 1:2 and 1:3.
[0057] In another embodiment, the nanocomposite of glimepiride in soluplus® of the
present invention is present in an amount ranges from about 2% to about 10% by weight of the sustained release pharmaceutical composition. Preferably in an amount of 2%, 3%, 4%,
10 6% and 8% by weight of the composition.More preferably in an an amount of 3%, 4% and
6% by weight of the composition.
[0058] In another embodiment, the binder in sustained release pharmaceutical
composition of the present invention is present in an amount ranges from about 3% to about 15% by weight of the composition. Preferably, in an amount of 5%, 7%, 9%, 10%, 12% and
15 13% by weight of the composition. More preferably, in an amount of 5%, 7%, 9% and 10%
by weight of the composition.
[0059] In another embodiment, the pharmaceutically acceptable excipients selected from
the group consisting diluents, lubricants, disintegrants, glidants, surface-active agents, antioxidants, thickeners, suspending agents, flavoring agents, sweeteners, and colorants. The
20 amount of excipient employed will depend upon how much active agent is to be used. One
excipient can perform more than one function. In yet another embodiment of the present invention, the diluent of the sustained release pharmaceutical composition of the present invention is selected from the group consisting of sugars, dextrates, dextrin, dextrose, fructose, lactitol, mannitol, sucrose, starch, lactose, xylitol, sorbitol, talc, microcrystalline
25 cellulose, calcium carbonate, calcium phosphate dibasic or tribasic and calcium sulphate. In
another embodiment of the present invention, the lubricant of the sustained release pharmaceutical composition of the present invention is selected from the group consisting of talc, magnesium stearate, aluminium stearate, calcium aluminium stearate, zinc stearate, polyethylene glycol, glyceryl behenate, mineral oil, sodium stearyl fumarate, stearic acid, and
30 hydrogenated vegetable oil. In an embodiment of the present invention, the glidant of the
sustained release pharmaceutical composition of the present invention is selected from the group consisting of silicon dioxide; magnesium trisilicate, powdered cellulose, starch, talc, tribasic calcium phosphate, calcium silicate, magnesium silicate, colloidal silicon dioxide and silicon hydrogel.
10

[0060] In another embodiment, the present invention provides a simple and cost-effective
method for preparation of a sustained release pharmaceutical dosage form comprising a
therapeutically effective amount of nanocomposite of glimepiride. The pharmaceutical
composition of the invention can be formed by various methods known in the art such as by
5 dry granulation, wet granulation, melt granulation, direct compression, double compression,
extrusion spheronization, layering and the like.
[0061] In another embodiment, the present invention provides a simple and cost-effective
method for preparation of a sustained release pharmaceutical dosage form comprising a therapeutically effective amount of nanocomposite of glimepiride by direct compression.
10 [0062] While the foregoing describes various embodiments of the disclosure, other and
further embodiments of the disclosure may be devised without departing from the basic scope thereof. The scope of the invention is determined by the claims that follow. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with
15 information and knowledge available to the person having ordinary skill in the art.
EXAMPLES
[0063] The present invention is further explained in the form of following examples.
However, it is to be understood that the following examples are merely illustrative and are
20 not to be taken as limitations upon the scope of the invention.
Example 1: Preparation of Nano-composites
[0064] Nano-emulsions of glimepiride in soluplus were formulated using the single
emulsion technique. The drug and the soluplus in different ratios (1:1, 1:2 and 1:3) were dissolved in dicholoromethane (DCM) 40 ml to form the organic phase; 40 ml of distilled
25 water with 0.05% Tween 80 surfactant formed the aqueous phase. Using a syringe pump, the
organic phase was slowly dropped into the aqueous phase (flow rate; 0.3 mL per minute), while continuous probe ultrasonication in an ice bath was used for effective homogenization of the two phases. The mixture was then magnetically stirred continuously for 24 hours for the removal of DCM and successively lyophilised (Allied Frost) at -40˚C for about 12 hours
30 and gently ground to obtain free flowing powders. The powders were then sieved through
(#80) sieve size and preserved under desiccation. The samples were labeled as NC 1, NC 2, NC3 and NC 4 to denote the nanoparticles of drug: polymer 1:1, 1:2, 1:3 and 1:4 respectively.
11

Example 2: Evaluation of Nanocomposites
[0065] Equilibrium solubility was determined by dissolving 50mg of various
formulations equivalent to 10mg drug in 50ml distilled water in volumetric flask for 24h with
intermittent stirring in orbital shaker and then filtered. Absorbance of various solutions was
5 taken by double beam UV spectrophotometer at 230 nm.
[0066] Four NC batches with different drug to polymer ratios (1:1, 1:2, 1:3 and 1:4) were
prepared and evaluated for equilibrium solubility studies in distilled water. The aqueous solubility of pure drug glimepiride was calculated to be 32.67µg/ml. Addition of polymer, soluplus leads to significant improvement in drug solubility i.e. 78.604 µg/ml with NC1,
10 275.581µg/ml with NC2, 226.744µg/ml with NC3 and 170.93(µg/ml) with NC4. The drug
solubility results are given in Figure 1. The data clearly shows that the nanocomposite of the present invention showssignificant enhancement of solubility. The significant solubility enhancement may be due to reduction in drug particle size (which can be further confirmed by particle size analysis) and change in nature of drug particles from crystalline to
15 amorphous.
Example 3: Fourier Transform Infrared Spectroscopy Analysis
[0067] About 10 mg of pure drug sample was mixed with potassium bromide of equal
weight. The mixture was properly grinded using pestle and mortar. Pellets are formed by
compressing the mixture by using hydraulic press. Transparent pellets formed in this way are
20 scanned. The IR spectrum was recorded using KBr pellet over the range of 400 –4000 cm-1
using (Perkin Elmer Spectrum 400) FTIR spectrophotometer. An FTIR spectrum obtained is given in Figure 2.
Example 4: Particle size analysis
[0068] Droplet size analysis and PDI measurement were carried out by dynamic light
25 scattering with a Zetasizer HAS 3000. All samples were subjected to sonication prior to
droplet size and PDI determination. NC2 and NC3 nanocomposite formulation was evaluated for droplet size analysis. Average droplet size for NC2 formulation was found to be 127.6 nm. Polydispersity Index (PDI) value of 0.284 indicated the uniform droplet size distribution of nano composites NC2. The droplet size for NC3 was found to be 588.1 nm and PDI value
30 was to 0.332 indicating wide distribution of particles in NC3. The increased concentration of
polymer soluplus may lead to increased size of droplets. DLS spectra obtained for NC2 and NC3 are given in figure 3 and figure 4 respectively.
12

Example 5: Scanning Electron Microscopy (SEM)
[0069] Samples of pure drug (glimepiride), soluplus and NC2 were mounted onto the stubs using double sided adhesive tape and then coated with gold palladium alloy (150-200 A°) using fine coat ion sputter (Joel, fine coat ion sputter, JFC-1100). The samples were 5 subsequently analyzed under the scanning electron microscope for external morphology. The crystalline nature of drug was clearly seen in SEM image where drug appeared as clear, smooth surfaced rectangular particles. SEM of NC2 showed flat Irregular flakes with no clear shape with different surface appearance. SEM of soluplus showed porous surfaced irregular particles. Images of SEM are given in figure 5.
10 Example 6: X-Ray Diffraction
[0070] Powder X-Ray Diffraction patterns were traced employing X-ray diffractometer for the samples using Ni filtered Cu (K-α) radiations, a voltage of 45 kV, a current of 40 mA. The samples were analyzed over 2θrange of 0-50o with scan step size of 0.0170o (2θ) and scan step time 25 s.
15 [0071] Glimepiride showed sharp peaks of the diffraction angle of 2θat 6.619, 13.6647, 18.384, 19.3712, 21.3616 , 23.2021, 25.004, 26.5223 with the peak intensities of 80.48, 100.00, 61.28, 72.57, 48.50, 18.25, 23.15, 27.79, 19.87and the area of 1154.29, 1912.43, 878.96, 1272.26, 618.37, 290.82, 221.34, 265.74, respectively. Slight shift in characteristic peaks and a significant decrease in intensity of these peaks are seen in X-RD of NC2. This
20 suggests conversion of crystalline form of drug to amorphous form which is also confirmed in DSC studies. The overlay diagram of X-RD is shown in Figure 6. Example 7: In vitro Dissolution Studies:
[0072] In vitro dissolution studies of various formulations were carried out in 900ml of phosphate buffer (pH 7.4) at 37±0.5oC with the stirrer rotation speed of 100 rpm using USP
25 dissolution apparatus II (paddle stirrer). Aliquot of 5 ml were withdrawn at specified time intervals (5, 15, 30, 45, 60, 90, and 120 min). The samples were suitably diluted and assayed spectrophotometrically at 230 nm. The dissolution data is given in figure 7.
Example 8: Sustained Release formulation of matrix tablets of nanocomposites [0073] Nanocomposities (NC2) were further converted into unit solid dosage form, tablet. 30 Direct compression technique was used to compress the tablets using single punch tablet compression machine. Various ingredients (Avicel 102, talc, and magnesium stearate) were first sieved and then mixed sequentially. Tablet of 100 mg weight were compressed and evaluated.
13

Composition of tablet batches

INGREDIENTS (mg) T1 T2 T3 T4
Pure Drug 2 2 - -
NC Powder (equivalent to 2 mg drug) - - 4 4
Acacia 5 - 5 -
Neem Gum - 5 - 5
MCC (Avicel) 102 90 90 88 88
Talc 1 1 1 1
Mg Stearate 2 2 2 2
Total weight (mg) 100 100 100 100
Formulation of Tablets:
[0074] NC2 batch was used for conversion into tablets. The four tablet batches of 100 mg
5 each (T1, T2, T3 and T4) were formulated as per the formulation given in (Table 4.4) using
single punch tablet compression machine. The effect of addition of neem gum was compared with acacia gum. The active blends were directly compressed.
[0075] Physicochemical characterization of tablet: The tablets were evaluated for
weight variation, hardness, friability, disintegration test. The tablets weight were uniform
10 (with in variation limits) and disintegration time was less. The results are depicted in the table
below.

Parameter Tablet (T1) Tablet (T2) Tablet (T3) Tablet (T4)
Weight variation Pass Pass Pass Pass
Hardness (kg/cm2) 3.75±0.31 2.95±0.3 3.2±0.51 2.8±0.45
Friability (%) 0.54±0.15 0.66±0.25 0.56±0.34 0.73±0.13
DisintegrationTime (min) 52±5 30±4 41 ±4 20±3
Tablet Thickness 3.1±0.02 3.4±0.01 3.1±0.19 3.3±0.15
Tablet Diameter 8.14±0.03 8.12±0.15 8.04±0.06 8.15±0.09
14

In vitro release studies of tablets
[0076] The presence of purified neem gum in the tablet may lead to fast disintegration of tablet thereby releasing more than 60% drug in 3h and after that the release was slow and sustained till 12 h. Better dissolution characteristics was seen in tablets containing nanocomposite drug and purified neem gum. The in-vitro drug release data is shown in the Figure 8.
[0077] The drug release was compared between T4 and T3; and T2 and Tl batch by applying student t-test to evaluate the effect of neem gum on in vitro dissolution of nanocomposites and pure drug respectively. The p value (0.017 which is less than 0.05) for T4 and T3, indicated significant difference of neem gum on dissolution of NC2. Whereas p value (0.08 which is more than 0.05) for T2 and Tl, indicated insignificant difference of neem gum on dissolution of pure drug. The presence of soluplus along with binder leads to significant change in dissolution behavior of pure drug.
[0078] A skilled artisan will appreciate that the quantity and type of each ingredient including the medicinal plant can be used in different combinations or singly. All such variations and combinations would be falling within the scope of present disclosure [0079] 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.

We Claim:

A sustained release pharmaceutical composition comprising of:
(a) nanocomposite of glimepiride in soluplus®;
(b) binder selected from natural gum or synthetic gum; and
(c) one or more pharmaceutically acceptable excipients.

2. The sustained release pharmaceutical composition as claimed in claim 1, wherein the nanocomposite of glimepiride in soluplus® comprises nano-emulsions of glimepiride and soluplus® in a ratio ranges from 1:0.5 to 1:5.
3. The sustained release pharmaceutical composition as claimed in claim 1, wherein the nanocomposite of glimepiride in soluplus®is present in an amount ranges from about 2% to about 10% by weight of the composition.
4. The sustained release pharmaceutical composition as claimed in claim 1, wherein the binder is present in an amount ranges from about 3% to about 15% by weight of the composition.
5. The sustained release pharmaceutical composition as claimed in claim 1, wherein the one or more pharmaceutically acceptable excipients is present in an amount ranges from about 75%) to about 95% by weight of the composition.
6. The sustained release pharmaceutical composition as claimed in claim 1, wherein the composition comprises:

(a) about 4% of nanocomposite comprising of nanoemulsion of glimerpiride and soluplus®;
(b) about 5%> of binder;
(c) about 9P/o of one or more pharmaceutically acceptable excipients.
7. The sustained release pharmaceutical composition as claimed in any one of the claims 1 to
6, wherein the natural gum is neem gum and the synthetic gum is acacia gum.
8. The sustained release pharmaceutical composition as claimed in any one of the claims 1 to
7, wherein the one or more pharmaceutically acceptable excipients is selected from diluents,
lubricants andglidants.
9. The sustained release pharmaceutical composition as claimed in claim 1, wherein the
composition comprises:
(a) about 4% of nanocomposite comprising of nanoemulsion of glimerpiride and soluplus®;
(b) about 5%> of neem gum;

(c) about 91% of one or more pharmaceutical^ acceptable excipients.
10. The sustained release pharmaceutical composition as claimed in claim 1, wherein the nanocomposite comprises nanoemulsion of glimerpiride and soluplus® in the ration of 1:2.
11. The sustained release pharmaceutical composition as claimed in any one of the claims 1 to 10, wherein the composition is in the form of tablets, pellets, beads, granules, capsules, microcapsules and tablets in capsules.