FIELD OF THE INVENTION

[0001] The present invention relates to pharmaceutical formulations.
Specifically, the present invention relates to sustained release formulation for oral delivery of Remogliflozin or its pharmaceutically acceptable salts. The present invention further relates to the process of preparing a sustained release formulation of Remogliflozin or its pharmaceutically acceptable salts. The present invention also relates to the use of sustained release formulation of Remogliflozin or its pharmaceutically acceptable salts for the treatment of diabetes mellitus.
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] Type 2 diabetes mellitus (T2DM) is an emerging epidemic in Asian countries, especially in India. With the advent of the SGLT-2 inhibitor class of drugs demonstrating benefits beyond glycemic control, namely weight loss, blood pressure reduction, and cardiovascular and renal protection, the management of T2DM has taken a quantum leap. Remogliflozin is the latest addition to the SGLT-2 inhibitor class of drugs for the management of T2DM. [0004] Remogliflozin works by inhibiting the sodium-glucose transport (SGLT) proteins which are responsible for glucose reabsorption in the kidney (Fujimori et al., Journal of Pharmacology and Experimental Therapeutics 2008, 327, 268-276). Blocking this transporter causes blood glucose to be eliminated through the urine. Remogliflozin is selective for SGLT2 and is used as Remogliflozin etabonate, which is a prodrug of remogliflozin and is chemically represented as shown below:
~^y XT
HO V*-*^^0-^^^^ N—PI

[0005] Remoghflozin etabonate is a potent and selective inhibitor of SGLT-2
with the unique distinction of being administered as a prodrug and exhibits short
half-life necessitating twice-daily dosing. After administration, Remoghflozin
etabonate is de-esterified by non-specific esterases present in mucosal cells of the
gastrointestinal tract to get converted into its active form remoghflozin.
[0006] Several studies have demonstrated that oral administration of
Remoghflozin etabonate increases urinary glucose excretion in a dose-dependent
manner in both rodents and humans (Fujimori et al., Journal of Pharmacology and
Experimental Therapeutics 2008, 327, 268-276). PCT application
WO2001016147 relates to remoghflozin base, WO02053573 relates to remoghflozin etabonate, WO2012006398A2 relates to biphasic formulation comprising remoghflozin etabonate in immediate and controlled release phases, and WO2010092125 relates to composition comprising (a) an SGLT2 inhibitor, and (b) a DPPIV inhibitor, and (c) a third anti-diabetic agent. [0007] Improvements in the therapeutic regimes employing remoghflozin etabonate may be achieved by a dosage form that allows a reduction in dosing frequency, i.e., once daily versus twice daily, providing patient convenience that would probably improve compliance. Although several approaches have been reported in the art with respect to formulations comprising remoghflozin, there remains a substantial need in the art for new and improved pharmaceutical formulations of remoghflozin which can reduce dosing frequency and extend effective plasma levels exhibit advantageous effect on the treatment of diabetes mellitus and can overcome deficiencies associated with the known arts.
OBJECTS OF THE INVENTION
[0008] An object of the present invention is to provide new and improved
formulation of Remoghflozin.
[0009] Another object of the present invention is to provide new and
improved formulation of Remoghflozin that allows a reduction in dosing frequency and improves patient compliance.

[0010] Still another object of the present invention is to provide new and
improved formulation of Remogliflozin that exhibit advantageous effect on the
treatment of diabetes mellitus.
[0011] Yet another object of the present invention is to provide sustained
release formulations of Remogliflozin as oral dosage forms.
[0012] The other objects and preferred embodiments and advantages of the
present invention will become more apparent from the following description of
the present invention when read in conjunction with the accompanying examples
and figures, which are not intended to limit scope of the present invention in any
manner.
SUMMARY OF THE INVENTION
[0013] This summary is provided to introduce a selection of concepts in a
simplified form that are further described below in 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.
[0014] The present invention relates to pharmaceutical formulations.
Specifically, the present invention relates to pharmaceutical formulations for oral
delivery of Remogliflozin or its pharmaceutically acceptable salts.
[0015] In one aspect, the present invention relates to new and improved
formulation of Remogliflozin.
[0016] In another aspect, the present invention relates to new and improved
formulation of Remogliflozin that allows a reduction in dosing frequency and
exhibit advantageous effect on the treatment of diabetes mellitus.
[0017] In another aspect, the present invention relates to sustained release
formulation of Remogliflozin or its pharmaceutically acceptable salts.
[0018] In yet another aspect, the present invention relates to sustained
release formulation for oral delivery of Remogliflozin or its pharmaceutically
acceptable salts.

[0019] In another aspect, the present invention relates to sustained release
formulation of Remogliflozin or its pharmaceutically acceptable salts comprising
one or more pharmaceutically acceptable excipients.
[0020] In a preferred embodiment, the pharmaceutically acceptable salt of
Remogliflozin is preferably Remogliflozin etabonate.
[0021] In another aspect, the present invention relates to sustained release
formulation of Remogliflozin or its pharmaceutically acceptable salts comprising
one or more pharmaceutically acceptable excipients, wherein the pharmaceutically
acceptable excipients are selected from but not limited to polymer, diluent, binder,
glidant, lubricant and solvent.
[0022] In still another aspect, the present invention relates to sustained
release formulation of Remogliflozin or its pharmaceutically acceptable salts,
wherein the formulation is formulated in the oral dosage form selected from but
not limited to tablets or capsules, preferably the oral dosage form is tablets.
[0023] In yet another aspect, the present invention relates to sustained
release formulation of Remogliflozin, wherein the formulation contains
Remogliflozin or its pharmaceutically acceptable salts in an amount of about 50
mg to 1000 mg.
[0024] In another aspect, the present invention relates to sustained release
formulation of Remogliflozin or its pharmaceutically acceptable salts, wherein the
formulation provides sustained drug release profile at a specified rate to achieve
desired drug concentration.
[0025] In another aspect, the present invention relates to sustained release
formulation of Remogliflozin, wherein the formulation comprises remogliflozin
etabonate along with polymer, diluent, glidant, binder, lubricant and solvent.
[0026] According to embodiments of the present invention, the sustained
release formulation of remogliflozin or its pharmaceutically acceptable salts can
further include a coating, preferably film coating.
[0027] The present invention further relates to the process of preparing a
sustained release formulation of Remogliflozin or its pharmaceutically acceptable
salts.

[0028] In another aspect, the present invention relates to sustained release
formulation of Remoglifiozin, wherein the formulation is useful for the treatment
of diabetes mellitus, impaired glucose tolerance, insulin resistance, and diabetic
complications such as hyperglycemia, hyperinsulinemia, and obesity.
[0029] In another aspect, the present invention relates to a method of
treating diabetes mellitus by administering a fixed oral dosage form comprising Remoglifiozin etabonate in a sustained release form, to a subject in need thereof. [0030] Other aspects of the invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learnt by the practice of the invention.
DETAILED DESCRIPTION
[0031] 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 scope of the present disclosure as defined by the appended claims.
[0032] 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.
[0033] 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.
[0034] In some embodiments, the numbers expressing quantities of
ingredients, properties such as concentration, reaction conditions, and so forth,
used to describe and claim 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 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.
[0035] 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.
[0036] 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."
[0037] 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. 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.
[0038] 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.
[0039] 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.
[0040] 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.
[0041] The headings and abstract of the invention provided herein are for
convenience only and do not interpret the scope or meaning of the embodiments.
[0042] 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.
[0043] 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.
[0044] The term "Pharmaceutical formulation" refers to the combination of
one or more active pharmaceutical ingredients and one or more pharmaceutically
acceptable excipients.
[0045] The term "pharmaceutically acceptable excipient" according to the
present invention means, but not limited to, any inactive ingredient which is
required for the formulation of Remogliflozin in a suitable dosage form.
Particularly the excipient includes, but are not limited to polymers, diluents,
binders, glidant, lubricant, carriers, fillers, bulking agents, disintegrants, surface
active agents, stabilizers, absorption accelerators, flavoring agents, preservatives,
antioxidants, buffering agents, and any other excipient commonly used in the
pharmaceutical industry.
[0046] The term "Remogliflozin" refers to remogliflozin, its salts,
hydroxylated forms, hydrates, solvates, polymorphic forms, analogs, derivatives,
esters, complex, co-crystals, and prodrugs thereof.
[0047] The term "Sustained release" dosage form is defined as well
characterized and reproducible dosage form, which is designed to control the drug
release profile at a specified rate to achieve desired drug concentration either in
blood plasma or at target site.
[0048] "Subject" includes humans, non-human mammals (e.g., dogs, cats,
rabbits, cattle, horses, sheep and the like) or non-mammals (e.g., birds and the
like).
[0049] The present invention relates to pharmaceutical formulations.
Specifically, the present invention relates to pharmaceutical formulations for oral
delivery of Remogliflozin or its pharmaceutically acceptable salts.

[0050] In one embodiment, the present invention relates to new and
improved formulation of Remogliflozin.
[0051] In another embodiment, the present invention relates to new and
improved formulation of Remogliflozin that allows a reduction in dosing
frequency and exhibit advantageous effect on the treatment of diabetes mellitus.
[0052] In one embodiment, the present invention relates to sustained release
formulation of Remogliflozin or its pharmaceutically acceptable salts.
[0053] In yet another embodiment, the present invention relates to sustained
release formulation for oral delivery of Remogliflozin or its pharmaceutically
acceptable salts.
[0054] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin or its pharmaceutically acceptable salts
comprising one or more pharmaceutically acceptable excipients.
[0055] In a preferred embodiment, the pharmaceutically acceptable salt of
Remogliflozin can be selected from but not limited to Remogliflozin etabonate or
Remogliflozin hydrochloride, preferably Remogliflozin etabonate.
[0056] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin or its pharmaceutically acceptable salts
comprising one or more pharmaceutically acceptable excipients, wherein the
pharmaceutically acceptable excipients are selected from but not limited to
polymer, diluent, binder, glidant, lubricant and solvent.
[0057] In still another embodiment, the present invention relates to
sustained release formulation of Remogliflozin or its pharmaceutically acceptable
salts, wherein the formulation is formulated in the oral dosage form selected from
but not limited to tablets or capsules, preferably the oral dosage form is tablets.
[0058] In yet another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the formulation contains
Remogliflozin or its pharmaceutically acceptable salts in an amount of about 50
mg to 1000 mg.

[0059] In a preferred embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the formulation contains
Remogliflozin etabonate in an amount of about 50 mg to 1000 mg.
[0060] In a preferred embodiment, sustained release tablets of
Remogliflozin contain remogliflozin etabonate in an amount of 100 mg, 200 mg,
300 mg or 500 mg, along with one or more pharmaceutically acceptable
excipients.
[0061] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin or its pharmaceutically acceptable salts,
wherein the formulation provides sustained drug release profile at a specified rate
to achieve desired drug concentration.
[0062] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the formulation comprises
remogliflozin etabonate along with polymer, diluent, glidant, binder, lubricant and
solvent.
[0063] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the polymer can be selected from
but not limited to acrypol 912G, methocel K100M, methocel K4M , methocel
K100LV and the like.
[0064] In a preferred embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the polymer is acrypol 912G.
[0065] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the amount of polymer in the
formulation is in the range of 10-30% w/w by total weight of the formulation,
preferable 20% w/w by total weight of the formulation.
[0066] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the diluent can be selected from
but not limited to Microcrystalline Cellulose (including microcrystalhne cellulose
pH102), starch, Lactose Monohydrate, dicalcium phosphate and the like, or
combinations thereof.

[0067] In a preferred embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the diluent is Microcrystalline
Cellulose, starch or combinations thereof.
[0068] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the amount of diluent in the
formulation is in the range of 5-40% w/w by total weight of the formulation.
[0069] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the glidant can be selected from
but not limited to talcum, colloidal silicon dioxide and the like, or a combination
thereof.
[0070] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the amount of glidant in the
formulation is in the range of 0.1 to 5% w/w by total weight of the formulation.
[0071] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the binder can be selected from but
not limited to Polyvinylpyrrolidone (PVPK -30), PVPK90, hydroxy propyl
cellulose and the like, or a combination thereof.
[0072] In a preferred embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the binder is Polyvinylpyrrolidone
(PVPK -30).
[0073] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the amount of binder in the
formulation is in the range of 0.5-5% w/w by total weight of the formulation.
[0074] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the lubricant can be selected from
but not limited to magnesium stearate, sodium stearyl fumarate the like, or a
combination thereof.
[0075] In a preferred embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the lubricant is magnesium
stearate.

[0076] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the amount of lubricant in the
formulation is in the range of 0.25-2.5% w/w by total weight of the formulation.
[0077] According to embodiments of the present invention, the sustained
release formulation of Remogliflozin or its pharmaceutically acceptable salts can further include a coating, preferably film coating.
[0078] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the solvent can be selected from but not limited to isopropyl alcohol and the like, present in quantity sufficient to make the total weight of the formulation as 100%.
[0079] In one embodiment, the present invention relates to sustained release
formulation of Remogliflozin comprising:
a) Remogliflozin etabonate;
b) Microcrystalline Cellulose;
c) Starch;
d) Acrypol912G;
e) Polyvinylpyrrolidone;
f) Talcum;
g) Colloidal silicon dioxide; h) Magnesium stearate; and i) Isopropyl alcohol.
[0080] In one embodiment, the present invention relates to sustained release
formulation of Remogliflozin comprising:
a) Remogliflozin etabonate 50%;
b) Microcrystalline Cellulose 19.25%;
c) Starch 5%;
d) Acrypol912G 20%;
e) Polyvinylpyrrolidone 2.5%;
f) Talcum 1%;
g) Colloidal silicon dioxide 1%;
h) Magnesium stearate 1.25%; and

i) Isopropyl alcohol quantity sufficient to make 100%;
wherein the components are present in w/w% with respect to the total
weight of the formulation.
[0081] In one embodiment, the present invention relates to sustained release
formulation of Remogliflozin comprising:
a) Remogliflozin etabonate 50%;
b) Microcrystalline Cellulose 19.75%;
c) Starch 5%;
d) Acrypol912G 20%;
e) Polyvinylpyrrolidone 2.5%;
f) Talcum 0.5%;
g) Colloidal silicon dioxide 1%;
h) Magnesium stearate 1.25%; and
i) Isopropyl alcohol quantity sufficient to make 100%;
wherein the components are present in w/w% with respect to the total weight
of the formulation.
[0082] In one embodiment, the present invention relates to sustained release
formulation of Remogliflozin comprising:
a) Remogliflozin etabonate 66.67%;
b) Microcrystalline Cellulose 7.0%;
c) Starch 2.44%;
d) Acrypol912G 20%;
e) Polyvinylpyrrolidone 2.67%;
f) Talcum 0.44%;
g) Colloidal silicon dioxide 0.89%;
h) Magnesium stearate 0.89%; and
i) Isopropyl alcohol quantity sufficient to make 100%;
wherein the components are present in w/w% with respect to the total weight of the formulation.

[0083] In one embodiment, the present invention relates to sustained release
formulation of Remogliflozin comprising:
a) Remogliflozin etabonate 55.56%;
b) Microcrystalline Cellulose 14.0%;
c) Starch 5.56%;
d) Acrypol912G 20%;
e) Polyvinylpyrrolidone 2.67%;
f) Talcum 0.22%;
g) Colloidal silicon dioxide 0.89%;
h) Magnesium stearate 1.11%; and
i) Isopropyl alcohol quantity sufficient to make 100%;
wherein the components are present in w/w% with respect to the total weight
of the formulation.
[0084] In another embodiment, the present invention relates to sustained
release formulation of Remogliflozin, wherein the formulation is useful for the
treatment of diabetes mellitus, impaired glucose tolerance, insulin resistance, and
diabetic complications such as hyperglycemia, hyperinsulinemia, and obesity.
[0085] In another embodiment, the present invention relates to a method of
treating diabetes mellitus by administering a fixed oral dosage form comprising
Remogliflozin etabonate in a sustained release form, to a subject in need thereof.
[0086] In one embodiment, the present invention relates to a process of
preparing the sustained release formulation of Remogliflozin or its pharmaceutically acceptable salts.
[0087] In another embodiment, the present invention relates to a process of
preparing the sustained release formulation of Remogliflozin or its pharmaceutically acceptable salts, process comprising the steps of:
a) Shifting & dry mixing;
b) Binder Preparation;
c) Wet Mixing & Wet Milling;
d) Semi-drying and full drying;
e) Sizing; and

f) Sieving the lubricants & lubrication.
[0088] The present invention is further explained in the form of the following
examples. However, it is to be understood that the following examples are merely
illustrative and are not to be taken as limitations upon the scope of the invention.
[0089] Example 1: Compositions of the sustained release formulation of
Remogliflozin, in tablet form. Table 1: Composition of the 200 mg tablet for sustained release formulation
of Remogliflozin.

S.No Ingredients Mg / tablet w/w%
1 Remogliflozin etabonate 100.00 50
2 Microcrystalline Cellulose 38.50 19.25
3 Starch 10.00 5
4 Acrypol 912 G 40.00 20
5 Polyvinylpyrrolidone (PVPK -30) 5.00 2.5
6 Talcum 2.00 1
7 Colloidal silicon dioxide 2.00 1
8 Magnesium stearate 2.50 1.25
9 Isopropyl alcohol q.s. q.s.
Total weight of the tablet 200.00 100
Table 2: Composition of the 400 mg tablet for sustained release formulation
of Remogliflozin

S.No Ingredients Mg / tablet w/w%
1 Remogliflozin etabonate 200.00 50
2 Microcrystalline Cellulose 79.00 9.75
3 Starch 20.00 5
4 Acrypol 912 G 80.00 20
5 Polyvinylpyrrolidone (PVPK -30) 10.00 2.5
6 Talcum 2.00 0.5
7 Colloidal silicon dioxide 4.00 1
8 Magnesium stearate 5.00 1.25
9 Isopropyl alcohol q.s. q.s.
Total weight of the tablet 400.000 100

Table 3: Composition of the 450 mg tablet for sustained release formulation
of Remogliflozin.

S.No Ingredients Mg / tablet w/w%
1 Remogliflozin etabonate 300.00 66.67
2 Microcrystalline Cellulose 27.00 7
3 Starch 11.00 2.44
4 Acrypol 912 G 90.00 20.00
5 Polyvinylpyrrolidone (PVPK -30) 12.00 2.67
6 Talcum 2.00 0.44
7 Colloidal silicon dioxide 4.00 0.89
8 Magnesium stearate 4.00 0.89
9 Isopropyl alcohol q.s. q.s.
Total weight of the tablet 450.00 100
Table 4: Composition of the 900 mg tablet for sustained release formulation
of Remogliflozin.

S.No Ingredients Mg / tablet w/w%
1 Remogliflozin etabonate 500.00 55.56
2 Microcrystalline Cellulose 126.00 14
3 Starch 50.00 5.56
4 Acrypol 912 G 180.00 20
5 Polyvinylpyrrolidone (PVPK -30) 24.00 2.67
6 Talcum 2.00 0.22
7 Colloidal silicon dioxide 8.00 0.89
8 Magnesium stearate 10.00 1.11
9 Isopropyl alcohol q.s. q.s.
Total weight of the tablet 900.000 100
[0090] Example 2: Preparation of the sustained release formulation of
Remogliflozin.
[0091] Step 1: SIFTING & DRY MIXING
[0092] Remolgliflozin etabonate was sifted through vibratory mechanical
sifter and dry mixed with starch, microcrystalline cellulose and acrypol 912G, in
required amounts, as per the embodiments of the present invention. The dry mix

material was then transferred into Rapid Mixer Granulator and mixing was done
at slow impeller speed in the range of 70 - 100 rpm.
[0093] Step 2: BINDER PREPARATION
[0094] Isopropyl alcohol in quantity sufficient to make 100% w/w of the
formulation was taken in a clean container and Polyvinyl Pyrolidone K-30 was
added with continuous stirring till a homogeneous solution was obtained.
[0095] Step 3: WET MIXING & WET MILLING
[0096] The binder solution obtained in step 2 was added into the dry mix
material in rapid mixer granulator, obtained in step 1 followed by milling the wet
mass.
[0097] Step 4: SEMI DRYING & FULL DRYING
[0098] The integrity of Fluid Bed Dryer bag was checked before the start of
drying process. The wet material obtained in Step-3 was placed in the Fluid Bed
Dryer bag and air dried for 10 min. The air dried material was then heated in Fluid
Bed Dryer by keeping inlet temperature at 60±5°C and outlet temperature at
30±5°C, for 15 minutes or till the desired moisture content is obtained. The
integrity of FBD bags and FBD bowl sieve was checked after drying. The dried
granules were unloaded into clean and labeled HDPE drums lined with poly bags.
[0099] Step 5: SIZING
[00100] The dried granules were sized by vibro sifter.
[00101] Step 6: SIEVING THE LUBRICANTS & LUBRICATION
[00102] Microcrystalline cellulose, colloidal silicon dioxide IP, talcum and
magnesium stearate IP were sifted through Vibro Sifter equipped with 40# sieve
and collected in cleaned and labeled HDPE drum lined with poly bags.
Microcrystalline cellulose, colloidal silicon dioxide IP and talcum were
transferred into the octagonal blender and mixed for 12 minutes, followed by
addition of magnesium stearate and mixing for 03 minutes. The granules thus
obtained were the final SR formulation which is collected in cleaned and labeled
HDPE drum lined with poly bags.
[00103] 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 information and knowledge available to the person having ordinary skill in the art.
ADVANTAGES OF THE PRESENT INVENTION
[00104] The present invention provides a new and improved formulation of
Remogliflozin.
[00105] The present invention provides a new and improved formulation of
Remogliflozin that allows a reduction in dosing frequency and improves patient
compliance.
[00106] The present invention provides a new and improved formulation of
Remogliflozin that exhibit advantageous effect on the treatment of diabetes
mellitus.
[00107] The present invention provides a sustained release formulation of
Remogliflozin as oral dosage forms.

We Claim:

1. A sustained release formulation of Remogliflozin or its pharmaceutical^ acceptable salts comprising polymer, diluent, binder, glidant, lubricant and solvent, wherein the pharmaceutically acceptable salt of Remogliflozin is selected from Remogliflozin etabonate and Remogliflozin hydrochloride; and the formulation is formulated in the oral dosage form selected from tablets or capsules, in an amount of about 50 mg to 1000 mg.
2. The formulation as claimed in claim 1, wherein the formulation comprises Remogliflozin etabonate along with polymer, diluent, glidant, binder, lubricant and solvent and can further include a coating, preferably film coating.
3. The formulation as claimed in claim 1, wherein the polymer is selected from acrypol 912G, methocel K100M, methocel K4M and methocel K100LV, present in an amount in the range of 10-30% w/w by total weight of the formulation; diluent is selected from Microcrystalline Cellulose, starch, Lactose Monohydrate, dicalcium phosphate or a combination thereof, present in an amount in the range of 5-40% w/w by total weight of the formulation; glidant is selected from talcum, colloidal silicon dioxide and combinations thereof, present in an amount in the range of 0.1 to 5% w/w by total weight of the formulation; binder is selected from Polyvinylpyrrolidone (PVPK-30), PVPK90, hydroxy propyl cellulose and combinations thereof, present in an amount in the range of 0.5-5%) w/w by total weight of the formulation; and lubricant is selected from magnesium stearate, sodium stearyl fumarate and combinations thereof, present in an amount in the range of 0.25-2.5%) w/w by total weight of the formulation.
4. The formulation as claimed in claim 1, wherein the solvent is isopropyl alcohol, present in quantity sufficient to make the total weight of the formulation as 100%>.
5. A sustained release formulation of Remogliflozin comprising:

a) Remogliflozin etabonate;
b) Microcrystalline Cellulose;
c) Starch;
d) Acrypol 912 G;
e) Polyvinylpyrrolidone;
f) Talcum;
g) Colloidal silicon dioxide; h) Magnesium stearate; and i) Isopropyl alcohol.
A sustained release formulation of Remogliflozin comprising:
a) Remogliflozin etabonate 50%;
b) Microcrystalline Cellulose 19.25%;
c) Starch 5%;
d) Acrypol 912 G 20%;
e) Polyvinylpyrrolidone 2.5%;
f) Talcum 1%;
g) Colloidal silicon dioxide 1%;
h) Magnesium stearate 1.25%; and
i) Isopropyl alcohol quantity sufficient to make 100%;
wherein the components are present in w/w% with respect to the total weight of the formulation. A sustained release formulation of Remogliflozin comprising:
a) Remogliflozin etabonate 50%;
b) Microcrystalline Cellulose 19.75%;
c) Starch 5%;
d) Acrypol 912 G 20%;
e) Polyvinylpyrrolidone 2.5%;
f) Talcum 0.5%;
g) Colloidal silicon dioxide 1%;
h) Magnesium stearate 1.25%; and
i) Isopropyl alcohol quantity sufficient to make 100%;

wherein the components are present in w/w% with respect to the total weight of the formulation.
8. A sustained release formulation of Remogliflozin comprising:
a) Remogliflozin etabonate 66.67%;
b) Microcrystalline Cellulose 3.56%;
c) Starch 7.0%;
d) Acrypol 912 G 20%;
e) Polyvinylpyrrolidone 2.67%;
f) Talcum 0.44%;
g) Colloidal silicon dioxide 0.89%;
h) Magnesium stearate 0.89%; and
i) Isopropyl alcohol quantity sufficient to make 100%;
wherein the components are present in w/w% with respect to the total weight of the formulation.
9. A sustained release formulation of Remogliflozin comprising:
a) Remogliflozin etabonate 55.56%;
b) Microcrystalline Cellulose 14.0%;
c) Starch 5.56%;
d) Acrypol 912 G 20%;
e) Polyvinylpyrrolidone 2.67%;
f) Talcum 0.22%;
g) Colloidal silicon dioxide 0.89%;
h) Magnesium stearate 1.11%; and
i) Isopropyl alcohol quantity sufficient to make 100%;
wherein the components are present in w/w% with respect to the total weight of the formulation.
10. A process of preparing the sustained release formulation of Remogliflozin
or its pharmaceutically acceptable salts, process comprising the steps of:
a) Shifting & dry mixing;
b) Binder Preparation;
c) Wet Mixing & Wet Milling;

d) Semi-drying and full drying;
e) Sizing; and
f) Sieving the lubricants & lubrication.