FIELD OF INVENTION
There is provided a dosages form comprising silodosin and one or more
pharmaceutically acceptable excipients. The present invention also provides a
stable capsule dosages form comprising silodosin and one or more
pharmaceutically acceptable excipients, wherein the dosages form is devoid of
sugar alcohol. The invention also relates to process of preparation of such
compositions.
BACKGROUND OF INVENTION
Silodosin is a-adrenergic antagonist that has high selectivity for the alA receptor
relative to alB and a lD receptors. Chemically, silodosin is l-(3-Hydroxypropyl)-
5-[(2R)-2-({2-[2 (2, 2, 2-trifluoroethoxy) phenoxy] ethyl} - amino) propyl]-2, 3-
dihydro-lH-indole-7-carboxamide. Its empirical formula is C25H32F3N3O4,
corresponding to a molecular weight of 495.53 having the following structural
formula:
Silodosin is marketed under the trade name Rapaflo® in United States in the form
of 4 mg and 8 mg capsules for the treatment of signs and symptoms of benign
prostatic hyperplasia (BPH).
BPH is a common disorder in elderly men, occurring in approximately 50% of men
aged 60 years and in 90% of those aged 85 years. BPH is a specific
histopathological entity characterized by stromal and epithelial cell hyperplasia.
I Q 6 - 0 7 - 2 0 1 7 1 7 : 21
For over a century, the two known etiologic factors for the pathogenesis of BPH
have been aging and the presence of functional testes. However, as the science of
prostate biology advances, this concept becomes inadequate as it does not cover all
aspects of BPH pathogenesis. Additional etiologic factors play a significant role in
regulating prostatic growth. In particular, evidence has emerged that prostatic
growth is under the immediate control of specific growth factors produced by
prostatic cells, acting locally on adjacent cells in a paracrine mechanism or to the
same cells in an autocrine mechanism. Therefore much effort is currently being put
into identifying therapeutic strategies aimed at inhibiting intraprostatic growth
factors.
BPH is a common cause of chronic lower urinary tract symptoms which may affect
both the filling (irritative symptoms) and voiding (obstructive symptoms) phases of
the micturition cycle. These symptoms affect the social, psychological, domestic,
occupational, physical and sexual lives of the patients leading to a profound,
negative impact on their quality of life. In addition to this, BPH can cause more
acute urological complications, particularly acute urinary retention (AUR), often
considered the most serious complication of BPH and less frequently recurrent
urinary tract infections, upper urinary tract dilatation, bladder stone formation and
recurrent hematuria.
There are several patent and non- patent literature known in the art which disclose
the formulation/ pharmaceutical composition/ dosages form of silodosin with one
or more pharmaceutically acceptable excipients.
U.S. Pat. No. 5,387,603 discloses silodosin as a product.
U.S. Pat. No. 5,403,847, U.S. Pat No. 5,780,485 and U.S. Pat. No. 6,015,819
disclose silodosin for treating benign prostatic hyperplasia.
I O S - 0 7 - 2 0 1 7 1 7 : 21
U.S. Patent Publication No. U.S. 2011/0319464 discloses a method for treating a
patient having symptoms associated with benign prostatic hyperplasia by
administering once daily a pharmaceutical composition of silodosin or a
pharmaceutical^ acceptable salt thereof.
PCT Patent Publication No. WO 2012/010669 and WO 2012/00926 disclose a
pharmaceutical composition comprising a mixture of silodosin with acrylate or
methacrylate copolymer; and an inclusion compound of silodosin with cyclodextrin
respectively.
U.S. Patent Publication No. US 2012/0064154 disclose a capsule composition
comprising silodosin, D-mannitol, a binder, lubricant selected from magnesium
stearate, calcium stearate or talc, and sodium lauryl sulfate.
U.S. Patent Publication No. US 2014/0243383 Al disclose a pharmaceutical
composition of silodosin which is free of partially pregelatinized starch. It suggests
the use of various polymers and disintegrants to achieve the desired dissolution
profile.
U.S. Patent Publication No. US 2015/0140101 Al disclose the use of sodium stearyl
fumarate and avoid the use of sodium lauryl sulphate to improve the dissolution
properties.
U.S. Patent Publication No. US 2016/0045446 Al disclose the granulation or
coating the silodosin drug particle with a coating agent comprising a non-enteric
polymer to improve the dissolution properties and masking the taste of silodosin.
PCT Patent Publication No. WO 2015/152680 Al disclose a granule composition
comprising silodosin and alkaline inorganic salt.
D E L H I 0 ^ 6 - 8 7 - 2 0 1 7 Ji 7 : 2 14
Indian Patent Publication No. 2867/MUM/2011 disclose the use of silodosin having
a particle size D90 less than about 10 microns to improve the dissolution profile.
Despite of the suggested methods in the art, it is extremely difficult to prepare
practically a stable and usable pharmaceutical composition comprising, as an active
ingredient, silodosin or salt thereof by conventional formulation methods which can
achieve precise content uniformity.
Silodosin is known to possess incompatibilities with several pharmaceutical
excipients and that yields degradation products of silodosin. For example, a most
popularly used filler is lactose when used as in formulating the tablets of silodosin;
the resulting tablets exhibits undesirable dissolution properties and unsatisfactory
hardness. Moreover, silodosin has a potent adhesive property, and in the case of
preparing a tablet or capsule, use of a lubricant such as magnesium stearate, calcium
stearate, sodium stearyl fiimarate and/or talc is inevitable. On the contrary, the
addition of such lubricants causes the problem of delaying in dissolution time.
Furthermore, silodosin is relatively unstable against a light exposure, and requires
a careful handling. In such cases, formulations are generally stored under a lightresistant
packaging. However, opaque light-resistant packages are difficult to detect
contaminations of foreign materials. Moreover, when patients are actually taking
formulations wrapped with light-resistant packages, the formulations are
occasionally stored with pulled out of light-resistant packages. Accordingly,
formulations, which can be stored without a light-resistant packaging and are highly
photostable, are desired.
Silodosin has also potent adhesive and electrostatic properties. Particularly, in cases
where formulations are prepared by a dry process, electrostatic charges are
generated by physical irritations caused through processes such as pulverization,
agitation, blending, granulation and the like, which in turn cause a decrease in
I P O D E L H I 0 6 - 0 7 - 2 8 1 7 1 7 : 2 1.
fluidity of pulverized, blended or granulated materials, worsen handling properties,
and decrease precision for content uniformity of an active ingredient.
The prior art references emphasize on using mannitol to improve the dissolution
profile of silodosin in water and there is no disclosure or teaching/suggestion in the
art about how to develop stable formulations of silodosin without employing
mannitol and which composition also ought to exhibit dissolution profile suitable
for once daily administration of said formulation.
Thus, there exists need to have dosages form of silodosin with better dissolution
properties without use of mannitol as filler. Further, there still remains a need for a
pharmaceutical formulations of silodosin with excellent storage stability and
bioavailability.
SUMMARY OF INVENTION
The present invention provides a dosages form of silodosin and one or more
pharmaceutically acceptable excipients and process of preparation thereof.
One embodiment of the present invention provides a stable capsule dosages form
comprising silodosin and one or more pharmaceutically acceptable excipients,
wherein the dosages form is devoid of sugar alcohol.
Another embodiment of the present invention provides a stable capsule dosages
form comprising silodosin and one or more pharmaceutically acceptable excipients,
wherein the dosages form is devoid of sugar alcohol, wherein silodosin is having
particle size of d90 in the range of 35 to 100 microns.
Another embodiment of the present invention provides a stable capsule dosages
form comprising silodosin and one or more pharmaceutically acceptable excipients,
G DELHI 0 6 - 0 7 - 2 0 1 7 - 1 7 : 2 I 6
wherein the dosages form is devoid of sugar alcohol, wherein the capsule shell
contains less than 2.5% of titanium dioxide.
Another embodiment of the present invention provides a stable capsule dosages
form comprising about 1% w/w to about 5% w/w of silodosin, about 75% w/w to
about 99% w/w of filler/diluent, about 75% w/w to about 99% w/w of binder, about
0.01% w/w to about 2% w/w of lubricant, about 0.1% w/w to about 5% w/w of
surfactant, wherein the capsule shell contains less than 2.5% of titanium dioxide,
wherein the dosages form is devoid of mannitol, magnesium stearate, calcium
stearate, sodium stearyl fumarate and/or talc.
Another embodiment of the present invention provides a method of treatment of
urination difficulties, signs and symptoms of benign prostatic hyperplasia and
prostatic hypertrophy by administering a stable capsule dosages form comprising
silodosin and one or more pharmaceutically acceptable excipients, wherein the
dosages form is devoid of sugar alcohol.
Another embodiment of the present invention provides a process of preparation of
a dosages form of silodosin and one or more pharmaceutically acceptable
excipients, wherein the process comprises: (i) sifting and blending silodosin with
one or more pharmaceutically acceptable excipients to form a uniform blend; (ii)
addition of lubricant/ glidants to mixture obtained in step (i); (iii) dry granulating
the mixture obtained in step (ii) to form granules; (iv) Addition of lubricant in
granules obtained in step (iii); (v) formulating the lubricated granules of step (iv)
to form final dosages form.
Embodiments of the stable dosages form may include one or more of the following
features. For example, the dosages form may further include one or more
pharmaceutically acceptable excipients. The pharmaceutically acceptable
excipients may include one or more diluent, binder, lubricant, glidant, surfactant
and disintegrant and the like.
I © 6 - 0 7 - 2 0 1 7 1? ' 2 i ?
The details of one or more embodiments of the inventions are set forth in the
description below. Other features, objects and advantages of the inventions will be
apparent from the description and claims.
DESCRIPTION OF INVENTION
The present invention relates to dosages forms comprising silodosin or a
pharmaceutical^ acceptable salt thereof and process for their preparation.
Applicants have surprisingly found that a stable dosages form can be achieved by
combining silodosin with one or more other pharmaceutical^ acceptable
excipients. Applicants have found that absorptions of silodosin from the digestive
tract are highly variable. The effect of a food was variable and decreased silodosin
Cmax by approximately 18 - 43% and AUC by 4 - 49%. It is very challenging to
harmonize the absorptions of silodosin. Applicants have found that the method for
preparing the composition has a significant effect on the bioavailability of silodosin.
The concentration of titanium dioxide in the capsule shell played an important role
in the stability of silodosin formulation. Applicants have surprisingly found that
capsule dosages form can be stabilized even when the concentration of titanium
dioxide in capsule shell is less than 2.5%, then the obtained dosages form is stable
and bioavailable. The present inventors have studied a variety of processes for
preparing formulations, and have found out that formulations, which has
satisfactory content uniformity without influenced by electrostatic charges has good
stability excellent dissolution properties and are prepared through dry granulation
process. The present inventors have also found that the capsules dosages form with
excellent dissolution profiles are prepared by admixing a lubricant in a specific ratio
with another pharmaceutically acceptable excipients having hydrophilic or surfaceactive
properties.
HI 06-07-2017 17:21
While working on the present invention, applicant has surprisingly found that when
silodosin was mixed with pregelatinized starch, zinc stearate and sodium lauryl
sulfate; dry granulated to form granules and filled in a capsule containing capsule
shell having less than 2.5% of titanium dioxide, the capsule dosages form is not
only stable over longer time but also exhibits better dissolution profile.
The term "silodosin" as used herein according to the present invention includes
silodosin in the form of free base, a pharmaceutically acceptable salt thereof,
amorphous silodosin, crystalline silodosin, any isomer, derivative, hydrate, solvate
or prodrug or a combination thereof.
The term "active ingredient" herein refers to a pharmaceutically active molecule as
well as its pharmaceutically acceptable and therapeutically active salts, esters,
amides, prodrugs, metabolites, enantiomers, polymorphs, analogues, etc. that
induce a desired pharmacological or physiological effect. Terms like "active",
"active agent", "active substance" may be used synonymously for "active
ingredient".
The term "therapeutically effective amount" or "effective amount" used
interchangeably, is defined to mean the amount or quantity of the active drug (e.g.
silodosin), which is sufficient to elicit an appreciable biological response when
administered to the patient. It will be appreciated that the precise therapeutic dose
will depend on the age and condition of the patient, nature of the condition to be
treated and will be at the ultimate discretion of the attendant physician.
The term "excipient" or "pharmaceutically acceptable excipients" means a
pharmacologically inactive component such as a diluent, disintegrant, carrier, and
the like, of a pharmaceutical product. The excipients that are useful in preparing a
dosages form are generally safe, non-toxic and are acceptable for veterinary as well
as human pharmaceutical use. Reference to an excipient includes both one excipient
and more than one excipient.
H I 0 6 - Q 7 - 2 0 1 7 1 7 : 2 1 9
The term "stable or stability or stabilized" means the dosages form comprising hard
gelatin capsules are stable under accelerated conditions (40°C/75% RH) for at least
six (06) months and are also stable under normal conditions (25°C/60% RH) for at
least twelve (12) months.
The term "composition" or "solid oral composition" or "dosage form" or
"pharmaceutical composition" as used herein synonymously include monolayered
tablets, bilayered tablets, caplets, minitablets, capsules, tablets in a capsule,
granules in a capsule, pellets, pellets in a capsule, powder, suspension or any other
suitable dosage form meant for oral administration. Capsule is in the form of soft
gelatin or hard gelatin.
Generally the dosages forms of the present invention prepared in unit dosage forms
are meant for immediate release.
As used in this specification and the appended claims, the singular forms "a", "an",
and "the" include plural references unless the context clearly dictates otherwise.
Thus for example, a reference to "a method" or "a process" includes one or more
methods, one or more processes and/or steps of the type described herein and/or
which will become apparent to those persons skilled in the art upon reading this
disclosure and so forth.
Particle size plays an important role in establishing solubility and dissolution of
silodosin. However, for proper mixing and avoiding the segregation of drug
particles during blending the drug should be of comparable particle size as that of
the excipients. This helps in providing the uniformity of content during the
formulation.
L H I 0 6 - 8 7 - 2 8 1 7 1 7 : 2^
Silodosin having a particle size of d90 in the range of 1-150 microns is used in
preparing dosages form, preferably d90in the range of 35 to 120 microns and more
preferably d90 in the range of 35 to 100 microns.
Desired particle size of silodosin was obtained by any suitable micronisation
technique known in the art such as dry milling, wet milling, air jet milling, sieving
etc. The desired particle size can be achieved using the controlled micronisation
process.
In one aspect of the present invention provides a stable capsule dosages form
comprising silodosin and one or more pharmaceutically acceptable excipients,
wherein the dosages form is devoid of sugar alcohol.
Sugar alcohols may include one or more of mannitol, maltitol, maltol, sorbitol,
lactitol, xylitol, and the like.
In another aspect of the present invention provides a stable capsule dosages form
comprising silodosin and one or more pharmaceutically acceptable excipients,
wherein the dosages form is devoid of sugar alcohol, wherein the one or more
pharmaceutically acceptable excipients are selected form the group comprising
diluent or fillers, binder, lubricant, glidant, surfactant, disintegrant or mixture
thereof. Some of the excipients may have two or more functions at the same time,
e.g. act as a filler and a binder.
The lubricants/glidants, improve the flow of a powder blend can be used for the
preparation of composition. Useful lubricants/glidants include but are not limited
to, stearic acid and its derivatives like zinc stearate, glyceryl monostearate; colloidal
silicon dioxide, magnesium silicate, magnesium trisilicate, and other forms of
silicon dioxide, such as aggregated silicates, hydrated silica or combination thereof.
Further, the amount of lubricant/glidant is preferably in the range of 0.01% to 2%
by weight of the composition.
- I 0 6 - 0 7 - 2 9 1 7 1 7 : 21
In another aspects of the present invention provides a dosages form, wherein the
dosages form comprise lubricants, wherein the lubricant is selected from zinc
stearate, glyceryl monostearate or combination thereof.
In another aspects of the present invention provides a dosages form comprising
silodosin, wherein lubricant is not magnesium stearate, calcium stearate, sodium
stearyl fumarate and/or talc.
The diluents/fillers include but are not limited to pregelatinized starch, maize starch,
potato starch, rice starch, wheat starch, powdered celluloses, dibasic calcium
phosphate, calcium phosphate, calcium carbonate, magnesium carbonate,
microcrystalline cellulose and the like and combination thereof; more preferably
selected from pregelatinized starch and microcrystalline cellulose.
Further, the amount of the diluents or bulking agent is in the range of 75-99% by
weight of the composition, preferably in the range of 90-98% by weight of the
composition, more preferably in the range of 95-97% by weight of the composition.
The surfactants include but are not limited to anionic, cationic, non-ionic or
amphoteric surfactants or those known to the person skilled in the art. Further, the
amount of surfactant present in the dosages form of silodosin, or salt thereof ranges
from about 0.1% to about 5% by total weight of the composition.
The binders include but are not limited to pregelatinized starch, hydroxypropyl
cellulose, hydroxypropyl methylcellulose, polyvinyl pyrrolidone, powdered acacia,
gelatin, guar gum, carbomers, acacia mucilage, alginic acid, carbomer,
carboxymethylcellulose calcium, carboxymethylcellulose sodium, microcrystalline
cellulose, powdered cellulose, ethyl cellulose, liquid glucose, xanthan gum,
hydroxyethyl cellulose, maltodextrin, methylcellulose, polydextrose, polyethylene
oxide, sodium alginate, corn starch, starch paste, sucrose or combination thereof
HI 8 6 . - 0 - 7 - 2 0 1 7 17 : 2 1
The disintegrants include but are not limited to pregelatinized starch,
croscarmellose sodium, crospovidone, sodium starch glycolate and the like or
combination thereof. Further, the amount of disintegrant is preferably in the range
of 5% to 35% by weight of the composition.
The dosages form of silodosin or salts thereof can be prepared by any suitable
method known in the art such as direct compression, dry or wet granulation,
fluidized bed granulation, melt extrusion, melt granulation, spray coating, freeze
drying, spray drying and solution evaporation.
In another aspect of the present invention provides the process of formulating a
silodosin composition, wherein the process comprises: (i) sifting and blending
silodosin with one or more pharmaceutical^ acceptable excipients to form a
uniform blend; (ii) addition of lubricant/ glidants to mixture obtained in step (i);
(iii) dry.granulating the mixture obtained in step (ii) to form granules; (iv) Addition
of lubricant in granules obtained in step (iii); (v) formulating the lubricated
granules of step (iv) to form final dosages form.
Dosage forms prepared by the above process can be subjected to in-vitro dissolution
test to determine the extent and rate at which the active substance is released from
the dosage forms and the content of the active substance can be determined in
solutions by using techniques such as high performance liquid chromatography.
It is known in the art that silodosin and its compositions are light sensitive, they are
generally stored in a light-resistant packaging. Accordingly suitable packaging
materials include amber colour high-density polyethylene (HDPE) containers,
white opaque high-density polyethylene (HDPE) containers, aluminum/aluminum
foil blisters and white opaque polyvinyl chloride/polyvinylidene chloride
(PVC/PVdC) blisters.
LUX - 8 6 - 0 7 - 2 0 2 7 1 7 - 2 \3
Furthermore, the stability of the pharmaceutical of the present invention against a
light exposure can be improved by careful handling, storing under a light-resistant
packaging.
In another aspect of the present invention provides a stable capsule dosages form
comprising silodosin and one or more pharmaceutically acceptable excipients,
wherein the dosages form is devoid of sugar alcohol, wherein the silodosin is having
particle size of d90 in the range 1-150 microns.
In another aspect of the present invention provides a stable capsule dosages form
comprising silodosin and one or more pharmaceutically acceptable excipients,
wherein the dosages form is devoid of sugar alcohol, wherein the silodosin is having
particle size of d90 in the range of 35 to 100 microns.
In another aspect of the present invention provides a stable capsule dosages form
comprising about 1% w/w to about 5% w/w of silodosin, about 75% w/w to about
99% w/w of filler/diluent, about 75% w/w to about 99% w/w of binder, about 0.01 %
w/w to about 2% w/w of lubricant, about 0.1% w/w to about 5% w/w of surfactant,
wherein the capsule shell contains less than 2.5% of titanium dioxide, wherein the
dosages form is devoid of mannitol, magnesium stearate, calcium stearate, sodium
stearyl fiimarate and/or talc.
In another aspect of the present invention provides a stable capsule dosages form
comprising silodosin and one or more pharmaceutically acceptable excipients,
wherein the dosages form is devoid of sugar alcohol, wherein the silodosin is having
particle size of d90 in the range 1-150 microns, wherein the dosages form is prepared
by using dry granulation process.
In another aspect of the present invention provides a stable capsule dosages form
comprising silodosin and one or more pharmaceutically acceptable excipients,
wherein the dosages form is devoid of sugar alcohol, wherein the silodosin is having
DELHI 86-07-2017 17:21
I
particle size of d9oin the range 1-150 microns, wherein the capsule shell contains
less than 2.5% of titanium dioxide.
In another aspect of the present invention provides a dosages form, wherein said
composition comprises lubricants and binder/ diluents, wherein the ratio of said
lubricant to said binder/ diluents is between 1:100 and 1:400 (weight / weight).
In another aspect of the present invention provides a dosages form, wherein said
composition comprises lubricants and surfactant, wherein the ratio of said lubricant
to said surfactant is between 1:1 and 1:5 (weight/ weight).
In another aspect of the present invention provides a dosages form, wherein said
composition comprises surfactant and binder/ diluents, wherein the ratio of said
surfactant to said binder/ diluents is between 1:100 and 1:200 (weight / weight).
Solid oral compositions of the present invention comprising therapeutically
effective amount of silodosin is useful in treating the urination difficulties, signs
and symptoms of benign prostatic hyperplasia and prostatic hypertrophy.
The invention is further illustrated by the following examples which are provided
to be exemplary of the invention and do not limit the scope of the invention. While
the present invention has been described in terms of its specific embodiments,
certain modifications and equivalents will be apparent to those skilled in the art and
are intended to be included within the scope of the present invention.
Example 1: Dosages form of silodosin
S.No Ingredient
Dry Mix
1 Silodosin
Qty. / Cap. (mg)
4.000
H I 0 : 6 - 0 7 - 2 0 1 7 17 : 2 I
2
3
4
Pregelatinized Starch (Low Moisture)
Sodium Lauryl Sulphate
Zinc stearate
164.525
1.050
0.255
Lubrication
5 Zinc stearate 0.170
Procedure: Silodosin, sodium lauryl sulphate and pregelatinized starch were mixed
in blender of form uniform mixture. To this mixture first portion of zinc stearate
was added and mixed uniformly. The mixture was dry granulated using roller
compactor and ribbons were milled and sifted. The granules thus obtained were
blended with second portion of zinc stearate and the resulting blend was then filled
into capsule. The composition of capsule shell is given below.
Composition of Capsule Shell:
Composition
Titanium dioxide
Gelatin
Water
Cap
2.0%
83.50%
14.50%
Body
2.0%
83.50%
14.50%
The stability study of this formulation was conducted at 40°C. 115 % R.H. over the
period of 6 months. The amount of the impurities measured in the formulation after
the storage period indicates that the formulation of the invention is stable under
accelerated conditions.
Table 1- Results of stability study of Example 1
Tests
Dehydro impurity
Initial
0.04
1 Month
0.10
2 Month
0.15
3 Month
0.22
6 Month
0.38
PO DELHI © 6 - 8 7 - 2 8 1 7 1 7 : 2 2^
Highest individual
unspecified impurity
Total impurities
S-isomer content (%)
By Chiral HPLC
(Process related
impurity)
0.07
0.24
0.04
0.08
0.36
0.04
0.04
0.36
0.05
0.03
0.38
0.05
0.08
0.65
0.04
From the above stability study, it was found that the capsule formulations of the
present invention which comprise silodosin with other pharmaceutically acceptable
excipients had significantly superior storage stability.
The dosages form of Example 1 is subject to dissolution study and results are
compared to the marketed formulation of Silodosin i.e. Rapaflo®. The dissolution
test was carried out using 6 capsules at a paddle speed of 50 revolutions per minute
(rpm) according to Method 2 of Dissolution Test (USP), using a sinker and 900 mL
of different test medium. 5 mL of the dissolved solution was taken at 5, 10, 15 and
30 minutes after starting the test, and the same volume of test medium was filled
immediately. The solutions taken at each point of time were filtered through a
membrane filter with a pore size of not more than 0.45 )^m. The first 4 mL of the
filtrates was discarded, and the subsequent filtrate was used as a test solution. The
results are reproduced below in Table 2.
Table 2- Comparison of release profile of dosages form of Example 1 with
marketed formulation of silodosin i.e. Rapaflo®
Time
(Min)
Rapaflo
Capsule
Example 1
(Average)
0.1NHC1 medium
Rapaflo
Capsule
Example 1
(Average)
pH 4.5 Acetate buffer
Rapaflo
Capsule
Example 1
(Average)
pH6.8 Phosphate
Buffer
I 0 6 - 0 7 - 2 0 1 7 17 : 21
05
10
15
30
79
92
95
97
62
99
98
98
64
86
87
90
24
97
100
100
70
89
90
92
40
92
96
98
From the results of dissolution study as represented in Table 2, it was found that the
dosages form as illustrated in Example 1 shows better stability and release profile
when compared to the marketed formulation of silodosin.
Example 2: Dosages form of silodosin
S. No Ingredient Qty. / Cap. (mg)
Dry Mix
1
2
3
4
Silodosin
Pregelatinized Starch
Sodium Lauryl Sulphate
Zinc stearate
4.000
163.775
1.800
0.255
Lubrication
5 Zinc stearate 0.170
Procedure: The capsule dosages form was prepared by the process as described in
Example 1.
Example 3: Dosages form of silodosin
S.No Ingredient Qty. / Cap. (mg)
Dry Mix
1
2
Silodosin
Pregelatinized Starch
4.000
164.525
I PO DELHI 8 6 . - 8 7 - 2 8 1 7 I 7 : 2 J
3
4
Sodium Lauryl Sulphate
Zinc stearate
1.050
0.255
Lubrication
5 Zinc stearate 0.170
Procedure: The capsule dosages form was prepared by the process as described in
Example 1.
Example 4: Dosages form of silodosin
S. No Ingredient Qty. / Cap. (mg)
Dry Mix
1
2
3
4
Silodosin
Pregelatinized Starch
Sodium Lauryl Sulphate
Zinc stearate
4.000
184.525
1.050
0.255
Lubrication
5 Zinc stearate 0.170
Procedure: The capsule dosages form was prepared by the process as described in
Example 1.
Example 5: Dosages form of silodosin
S.No Ingredient Qty. / Cap. (% w/w)
Dry Mix
1
2
3
Silodosin
Pregelatinized Starch
Sodium Lauryl Sulphate
1-5
75-99
0.1-5
HI B 6 - 0 7 - 2 Q 1 7 - IT '-21^
4 Zinc stearate
Lubrication
5 Zinc stearate
0.01-2
0.01-2
Procedure: The capsule dosages form was prepared by the process as described in
Example 1.
While the invention has been described in terms of its specific embodiments, certain
modifications and equivalents will be apparent to those skilled in the art and are
intended to be included within the scope of the invention.

WE CLAIM:
1. A stable capsule dosages form comprising silodosin and one or more
pharmaceutical^ acceptable excipients, wherein the dosages form is devoid
of sugar alcohol.
2. The dosages form as claimed in claim 1, wherein the capsule shell contains
less than 2.5% of titanium dioxide.
3. The dosages form as claimed in claim 1, wherein the one or more
pharmaceutical^ acceptable excipients are selected form the group
comprising diluent, binder, lubricant, glidant, surfactant and disintegrant.
4. The dosages form as claimed in claim 2, wherein the lubricant is selected
from zinc stearate and/or glyceryl monostearate.
5. The dosages form as claimed in claim 1, wherein silodosin is having particle
size of d9o in the range 1-150 microns.
6. The dosages form as claimed in claims 1, wherein the dosages form is
prepared by a dry granulation process.
7. The dosages form as claimed in claim 1, wherein the dosages form is used
in the treatment of urination difficulties, signs and symptoms of benign
prostatic hyperplasia and prostatic hypertrophy.
8. The process of preparation of dosages form of claim 1, wherein the process
comprises: (i) sifting and blending silodosin with one or more
pharmaceutical^ acceptable excipients to form a uniform blend; (ii)
addition of lubricant/ glidants to mixture obtained in step (i); (iii) dry
granulating the mixture obtained in step (ii) to form granules; (iv) Addition
of lubricant in granules obtained in step (iii); (v) formulating the lubricated
granules of step (iv) to form final dosages form.
9. A stable capsule dosages form comprising silodosin and one or more
pharmaceutically acceptable excipients, wherein the dosages form is devoid
of sugar alcohol, wherein the silodosin is having particle size of d9o in the
range 35 to 100 microns.
10. A stable capsule dosages form comprising about 1% w/w to about 5% w/w
of silodosin, about 75% w/w to about 99% w/w of filler/diluent, about 75%
w/w to about 99% w/w of binder, about 0.01% w/w to about 2% w/w of
lubricant, about 0.1% w/w to about 5% w/w of surfactant, wherein the
capsule shell contains less than 2.5% of titanium dioxide, wherein the
dosages form is devoid of mannitol, magnesium stearate, calcium stearate,
sodium stearyl fumarate and/or talc.