FORM 2
THE PATENTS ACT 1970
(39 of 1970)
&
The Patents [Amendment] Rules, 2006
PROVISIONAL SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION Pharmaceutical Formulations Of Telmisartan And Process For Preparing The Same
2. APPLICANT NAME
NATIONALITY ADDRESS : : Troikaa Pharmaceuticals Ltd.
: India
. Commerce House 1, Satyamarg, Ahmedabad 380 054, India Gujarat,
3. PREAMBLE TO THE DESCRIPTION
PROVISIONAL
The following specification describes the nature of this invention

Field of the Invention
i
The present invention provides pharmaceutical formulationsof telmisartan and process for
preparing the same.
r Background of the Invention
Telmisartan is a white to off-white, odorless crystalline powder. It is practically insoluble in
water or an aqueous solution in the pH range of 3 to 9, and sparingly soluble in a strong acid,
with the exception of hydrochloric acid in which it is insoluble. Telmisartan is soluble in
i
strong base. Its chemical name is 4,-[2-n-propyl-4-methyl-6- (1 -methylbenzimidazol-2-yl)benzimidazol- 1 -ylmethyl]biphenyl-2-carboxyliciacid.
U.S. patent publication 2004/0110813 Al, describes that the solubility of Telmisartan can be increased several hundred folds in a pharmaceutical composition comprising 3 to 50% of Telmisartan dispersed in a dissolving matrix comprising a) a basic agent wherein the molar ratio of basic agent: Telmisartan equals 1:1 to 10:1, b) a surfactant or emulsifier in an amount of about 2 to 3% of the final composition, c) 25 jto 70% of a water soluble diluent, and optionally 0 to 20% of further excipients and/or adjuvants.
WO/2003/059327 discloses a process of manufacturing bi-layered tablet of Telmisartan and
a diureticin which the telmisartan layer is manufactured as per the following steps: providing
a first tablet layer composition by a) preparing anaqueous solution of telmisartan, at least one
basic agent and, optionally, a solubilizer and/or a crystallization retarder; b) spray-drying said
aqueous solution to obtain a spray-dried granulate; c) mixing said spray-dried granulate with
a water-soluble diluent to obtain a premix; d) mixing said premix with a lubricant to obtain a
final blend. ;
WO/2006/136916 discloses a pharmaceutical composition comprising substantially pure telmisartan or a pharmaceutically acceptable salt, j ester or derivative thereof, having an effective average particle size of less than about 30p/l 00/60/15 microns. To formulate this
i
composition micronized particles of the substantially pure telmisartan or pharmaceutical ly acceptable salt, ester or derivative thereof are formulated into a pharmaceutical composition or dosage form. It is therefore a pre-reqiiisite 'of, this;, disclosure, to use micronized

Telmisartan for the purpose of manufacturing dosage forms in accordance with this disclosure.
WO/2007/144175 discloses compositions of Telmisartan with Hydrochlorothiazide, wherein telmisartan tablet cores prepared by compression of a blend containing telmisartan, NaOH, meglumine), polyvinylpyrrolidone, ludipress and other excipients. The hydrochlorothiazide layer is coated onto these tablet cores.
WO/2007/061415provides a pharmaceutical composition comprising a) a telmisartan compound, b) a surfactant, c) a basic agent, and d)' at least one diluent selected from water soluble and water insoluble diluents, wherein the pharmaceutical composition comprises less than 25% by total weight of the composition of water soluble diluents. Preferably the pharmaceutical composition comprises at least one diluent which is water insoluble, preferably microcrystalline cellulose. Telmisartan dissolves from the pharmaceutical composition of the present invention at a suitable rate. Preferably, at least 80% of the telmisartan in the pharmaceutical composition dissolves in a neutral aqueous environment within 45 minutes. More preferably, at least 80% of the telmisartan in the pharmaceutical composition dissolves in a neutral aqueous environment within 30 minutes, and most preferably at least 80%o of the Telmisartan is dissolved from the pharmaceutical composition in such aqueous solution within 20 minutes.
According to WO/2007/061415, the preferred' method of preparing a telmisartan pharmaceutical composition comprises the steps of 1) mixing a disintegrant, preferably sodium starch glycolate, and one or more diluents; preferably at least one water insoluble diluent, more preferably wherein at least one diluent is microcrystalline cellulose, in a high shear mixer to form a homogeneous mixture; 2) preparing a granulation suspension of purified water, alcohol, a basic agent, a surfactant, and telmisartan; 3) combining the homogeneous mixture and the granulation suspension to form a combined mixture; 4) preparing a granulation solution of water and a binder, preferably Povidone (e.g. PVP K-30); 5) adding the granulation solution to the combined mixture to form a granulate; 6) drying the formed granules; 7) sizing the dried granules; 8) mixing the dried granulate with a filler,
preferably sorbitol, and a disintegrant, preferably; sodium starch glycolate; 9) adding a
i
lubricant, preferably magnesium stearate to form a! final mixture; and 10) compressing the

final mixture into tablets, wherein the prepared pharmaceutical composition comprises less than 25% by weight of water soluble diluents.
As can be concluded by examination of the prior art, oral dosage forms of Telmisartan are focussed on ensuring that solubility of telmisartan is increased by incorporating an alkali in the formulation, along with incorporation of water soluble diluents 25-70 % (as per WO/2003/059327) and less than 25% by weight (as per Wo/2007/061415) and additionally incorporation of a surfactant to facilitate dissolution of telmisartan
The present invention discloses a composition of'telmisartan manufactured by a unique process, wherein excellent dissolution of telmisartan; is achived
Description of the Invention
According to one aspect of the present invention is to.proviq^pbarmaceutical formulations of
telmisartan such as tablets/capsules formulation with high dissolution profile without the use
of any surfactants. !
i i i
Another aspect of the present invention is to avoid the c0mpiex Sprav drying process to
manufacture the pharmaceutical formulation of telmisartan.
i
i The present invention enables one to prepare Telmisartarj tablets /capsules employing a novel process, wherein more than 85 % of telmisartan dissolves in a neutral aqueous environment, preferably within 10 minutes and more than 50% the telmisartan dissolves
in a neutral aqueous environment in 20 minute.
i
i These superior dissolution profiles are achieved without tht use 0f surfactants avoiding the spray drying process and instead, adopting the conventional granulation process.The superior dissolution profiles are displayed by the novel formulations in spite of the absence of surfactant.
The present invention provides pharmaceutical formulatk)ns comprising a) a telmisartan compound, b) one or more basic agent, c) Inter and .intra granular disintegrating agents d) at least one diluents selected from water soluble ancl water insoluble diluents wherein the

pharmaceutical composition comprises preferably ; less than 10% by total weight of the
i composition of water soluble diluents, e) a binder, fj a lubricants in addition to other suitable
pharmaceutical excipients.
According to the present invention, the pharmaceutical formulations preferably comprise a) a
i
telmisartan compound, b) one or more basic agent, jc) Inter and intra granular disintegrating agents d) a water insoluble diluent, e) a binder, f) a lubricants in addition to other suitable pharmaceutical excipients.
According to one embodiment the telmisartan pharmaceutical formulations are prepared by a
i process comprising of :• 1) mixing a disintegrant, preferably cross linked polyvinyl
pyrollidone (Crosspovidone), and one or more diluents, comprising(preferably) at least one
water insoluble diluent, more preferably wherein at least one diluent is compressible
i microcrystalline cellulose,' in a high shear mixer to form a homogeneous mixture, 2)
preparing a clear transparent granulation solution' of purified water, one or more basic
agent/s, telmisartan and polyvinyl pyrollidone (e.g; PVP K-30); 3) adding the granulation
solution to the mixture of step 1, to form a granulate; 4) drying the granulate; 5) sizing the
dried granules; 6) blending the dried granulate with disintegrant/s, lubricant/s, to obtain
granules ready for compression and compressing these granules into tablets. In preparing
capsules step 6) will typically be replaced by the step of filling capsule shells.
The bi-layered tablets of telmisartan can be prepared employing diuretic, such as
hydrochlorothiazide. The above described process can be used for manufacturing granules of
the telmisartan layer. Granules for the hydrochlorothiazide layer can be manufactured in the
conventional fashion. Compression of the two granules is done on a bi-layered tablet
compression machine. I
The following example demonstrates one embodiment of the present invention.
i Example 1,
Microcrystalline Cellulose (compressible grade) 151:50 gm, Crosspovidone 9.5 gm are mixed
in a rapid mixer granulator. Sodium Hydroxide, 3.67 gm is dissolved in suitable quantity of
purified water, followed by meglumine, 5.87gms. Continue stirring till a clear solution is
obtained. Telmisartan, 40 gms is added in small portions to this solution, with constant
i
stirring. Stirring is continued till all the telmisartan dissolves to give a clear transparent

solution. Polyvinyl pyrollidone K 30, 5.88 gm is added to the solution and stirring is continued till all the PVP K 30 dissolves. The resultant solution is used as a binder to bind the dry mix of compressible grade microcrystalline cellulose and Crosspovidone. The resultant
wet mass is granulated and dried. The dried granules are sifted through #20 sieve. The sifted
i
dried granules are blended with Crosspovidone, 7:5 gms, sodium starch glycolate 7.5gmss talc 2.3 gms and magnesium stearate 1.23 gms and compressed on a suitable tablet compression machine to produce tablets of telmisartan with the dissolution profile disclosed hereinabove.
While this provisional patent application contains the description of the principal inventive concepts, the complete patent application pursuant here to, will fully and particularly describe the preferred embodiments of the present invention.