Field of the invention:

The present invention describes novel crystalline form AL of Azilsartan medoxomil potassium (II)  process for their preparation and pharmaceutical compositions containing them.

Background of the invention:
Azilsartan medoxomil i.e. (5-methyl-2-oxo-l 3-dioxol-4-yl)methyl-2-ethoxy- 1 - ([2""-(5-oxo-4 5-dihydro-l 2 4-oxadiazol-3-yl)biphenyl-4-yl]methyl)-lH-benzimidazole-7-carboxylate (I) has the uses such as a strong and long lasting angiotensin II antagonistic activity and hypotensive action  and an insulin sensitizing activity  and which is useful as an agent for the prophylaxis or treatment of circulatory diseases such as hypertension  cardiac diseases (cardiac hypertrophy  cardiac failure  cardiac infarction and the like)  nephritis  stroke and the like and metabolic diseases such as diabetes and the like (US7  157 584). Azilsartan medoxomil is the prodrug of 2- ethoxy-l-([2""-(5-oxo-4 5-dihydro-l 2 4-oxadiazol-3-yl)biphenyl-4-yl]methyl)-lH-benzimidazole-7-carboxylic acid.

(I) (II)

It is disclosed in US7  157 584 that azilsartan medoxomil and salt thereof such as monopotassium salt (II) are benzimidazole derivative useful as an angiotensin II receptor antagonist.
Pharmaceutical Research  (2008) 25  530  explains that the ability to deliver the drug to the patient in a safe  efficacious and cost effective way depends largely upon the physicochemical properties of the APIs in the solid state and accordingly one of the challenging tasks in the pharmaceutical industry is to design pharmaceutical materials with specific physiochemical properties. It is known that different solid forms of the same drug may exhibit different properties  including characteristics that have functional implications with respect to their use as drug may have substantial differences in such pharmaceutically important properties as dissolution rates and bioavailability. Likewise  different polymorphs may have different processing properties  such as hygroscopisity  flow ability and the like  which could affect their suitability as active pharmaceuticals for commercial production. Also  it is known in the art that the amorphous forms of APIs generally exhibit the better solubility profile over the corresponding crystalline forms. This is because the lattice energy does not have to be overcome in order to dissolve the solid state structure as in the case for crystalline forms.
Thus  there is a need to develop the novel crystalline form of Azilsartan medoxomil Potassium  having better physicochemical properties. Especially  for the enhancement of the solubility. Also there is a constant need to have the cost effective and industrial friendly process for the preparation of crystalline form of Azilsartan medoxomil Potassium.
Description of the drawings
FIG. l depicts a powder X-ray diffractogram (PXRD) of novel crystalline Form AL of azilsartan medoxomil potassium.

Object of the invention:

Accordingly  the present invention provides novel crystalline form AL of Azilsartan Medoxomil potassium having X-ray powder diffraction pattern comprising peaks at about 6.2  13.3  14.7  16.0  18.7  22.8+0.2 degrees 2?.

Another object of the present invention is to provide a process for the preparation of form AL of Azilsartan medoxomil potassium comprising the step of:

(i) Dissolving azilsartan medoxomil in ester solvent by heating;
(ii) Adding a solution of potassium ethyl hexanoate in ester solvent to the reaction mixture;
(iii) Facilitating crystallization of azilsartan medoxomil potassium;
(iv) Isolating crystals of form AL of azilsartan medoxomil potassium.

Yet another object of the present invention is to provide a process for the preparation pharmaceutical composition comprising the said form AL of Azilsartan medoxomil potassium.

Description of invention:
An embodiment of present invention provides novel crystalline form AL of Azilsartan Medoxomil potassium.

Further embodiment of present invention provides novel crystalline form AL of Azilsartan Medoxomil potassium having X-ray powder diffraction pattern comprising peaks at about 6.2  13.3  14.7  16.0  18.7  22.8+0.2 degrees 2?.

Another embodiment of present invention provides crystalline form AL of Azilsartan Medoxomil potassium  which is characterized by X-ray powder diffraction pattern as depicted in Fig 1.

Further embodiment of the present invention is to provide novel process for the preparation of form AL of Azilsartan medoxomil potassium comprising the step of:

(i) Dissolving azilsartan medoxomil in ester solvent by heating
(ii) Adding a solution of potassium ethyl hexanoate in ester solvent to the reaction mixture
(iii) Facilitating crystallization of azilsartan medoxomil potassium
(iv) Isolating crystals of form AL of azilsartan medoxomil potassium

Yet another embodiment of the present invention is to provide process for the preparation pharmaceutical composition comprising the said form AL of Azilsartan medoxomil potassium.

Ester solvents as used here in above include but not limited to ethyl acetate  isopropyl acetate  butyl acetate  methyl acetate or mixture thereof.

Facilitating crystallization used here in above includes intermolecular contacts which facilitates the assembly of the molecules in to a crystalline lattice.

The following example illustrates the invention further. It should be understood however  that the invention is not confined to the specific limitations set forth in the individual example but rather to the scope of the appended claims.

Example: Preparation of Crystalline form AL
Azilsartan medoxomil (100g) was dissolved in ethyl acetate (3200 ml) at 75-800C. The resulting solution was stirred over a period of 1 hr at 75-800C and charcoal (2.5 g) was added to the solution at 75-800C. The reaction mixture was stirred for another 1 hr at 75-800C and then reaction mixture cooled and filter through hyflo bed. A solution of Potassium ethyl hexanoate (31. 4 g in 300 ml ethyl acetate) was added at 10-15 0C to the reaction mixture and stirred for 3 hrs at 10-15°C. Raised the temperature up to75-80oC and stirred the reaction mixture for another 1 hr and then cooled to 25-30 oC. The crystalline solid thus obtained was filtered in dehumidified area and dried under vacuum to obtained 85 g of crystalline form AL of azilsartan medoxomil potassium. XRD as provided in Fig. 1.

Claims

1. Novel crystalline form AL of Azilsartan Medoxomil potassium having X-ray powder diffraction pattern comprising peaks at about 6.2  13.3  14.7  16.0  18.7  22.8+0.2 degrees 2?.

2. A novel process for the preparation of form AL of Azilsartan medoxomil potassium comprising steps of:

(i) Dissolving azilsartan medoxomil in ester solvent by heating
(ii) Adding a solution of potassium ethyl hexanoate in ester solvent to the reaction mixture
(iii) Facilitating crystallization of azilsartan medoxomil potassium
(iv) Isolating crystals of form AL of azilsartan medoxomil potassium.

3. The process according to claim 2 where in ester is selected from the group comprising ethyl acetate  isopropyl acetate  butyl acetate  methyl acetate or mixture thereof.

4. The process according to claim 3 where in ester is ethyl acetate.

Dated this 10th day of July  2012.

Dr. Alpesh Pathak
Applicant’s Agent

Fig. 1 crystalline form AL of Azilsartan medoxomil Potassium

Dr.Alpesh Pathak
Applicant’s Agent