FORM 2
THE PATENTS ACT, 1970
(39 OF 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10; rule 13)
1. Title of the invention -: PROCESS FOR THE PREPARATION OF CRYSTALLINE
FORM I OF FINGOLIMOD HYDROCHLORIDE
2. Applicant(s)
(a) NAME : ALEMBIC PHARMACEUTICALS LIMITED
(b) NATIONALITY: An Indian Company.
(c) ADDRESS: Alembic Campus, Alembic Road,
Vadodara-390, 003, Gujarat, India
3. PREAMBLE TO THE DESCRIPTION
The following specification describes the invention :

Field of the invention
The present invention relates to an improved process for the preparation of crystalline form I of Fingolimod Hydrochloride.

Background of the invention
Fingolimod is a known immunosuppressant drug that causes lymphopenia by preventing egress of lymphocytes from lymph nodes. It is expected that fingolimod can be used as monotherapy for relap sing-remitting multiple sclerosis.
The chemical name of fingolimod is (2-amino-2-(2-(4-octy] phenyl)-ethyl-propane-l, 3-diol). It is illustrated by the chemical formula (I). The current pharmaceutical product containing this drug is being sold by Novartis using the trade name GILENYA in the form of Capsule.
A process for preparing fingolimod hydrochloride is disclosed in Example 29 of US 5952316. The process according to example 29 gives crystalline form I of fingolimod hydrochloride.
WO2010/055028 disclose XRD data of crystalline form I of fingolimod hydrochloride, description of this patent does not show any process for the preparation of crystalline form I of Fingolimod hydrochloride.
WO2011/009634 disclose polymorphic from A and form B of fingolimod hydrochloride.
Present inventors have focused on the problems associated with the prior art process and has developed an improved process for the preparation of crystalline form I of Fingolimod hydrochloride.
Further more, the process of present invention overcome disadvantages of prior process and gives high yield and purity of crystalline form I of Fingolimod hydrochloride.

Object of the invention:
It is an object of the present invention to provide an improved process for the preparation of crystalline form I of Fingolimod hydrochloride which gives Fingolimod hydrochloride salt with greater yield and purity comprising

A) Providing a solution of fingolimod in an alcoholic solvent.
B) Adding alcoholic HC1 to said reaction mixture
C) optionally charcoalizing and filtering the reaction mixture,
D) Cooling the reaction mixture and filtering the precipitated solid to get pure crystalline form I of fingolimod hydrochloride.
The alcoholic solvent used in step A) may preferably be a solvent or mixture of solvents selected from methanol, ethanol, and isopropyl alcohol. More preferable alcoholic solvent is isopropyl alcohol.
Description of drawing
Figure 1: XRD of crystalline form 1 of Fingolimod Hydrochloride. Figure 2: DSC of crystalline form 1 of Fingolimod Hydrochloride.
Detailed description of the invention:
Accordingly, present invention provides an improved process for the preparation of crystalline form I of Fingolimod Hydrochloride formula (I)


The present invention provides an improved process for the preparation of crystalline form I of Fingolimod hydrochloride which gives Fingolimod hydrochloride salt with greater yield and purity comprising
A) Providing a solution of Fingolimod in an alcoholic solvent.
B) Adding alcoholic HC1 to said reaction mixture
C) optionally charcoalizing and filtering the reaction mixture,
D) Cooling the reaction mixture and filtering the precipitated solid to get pure crystalline form I of Fingolimod hydrochloride
The alcoholic solvent used in step A) may preferably be a solvent or mixture of solvents selected from methanol, ethanol, and isopropyl alcohol. More preferable alcoholic solvent is isopropyl alcohol.


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 I
Charge Fingolimod (80g) in IPA (960 ml) at 20-25 °C. IPA. HC1(105.4 g) was added to the solution at 20-25°C. The reaction mixture was stirred for 1 hr at 40-50°C, then cooled at 25-30 C and stirred for two hrs. Further the reaction mixture cooled at 0-5 C and stirred for other two hrs. The crystalline solid thus obtained was filtered, washed with chilled IPA and dried under vacuum to obtained 73 g of crystalline form I of Fingolimod hydrochloride. XRD as provided in Fig. 1

1. A process for the preparation of form I of Fingolimod hydrochloride comprising steps of:
(i) Providing a solution of Fingolimod in an alcoholic solvent.
(ii) Adding alcoholic HCl to said reaction mixture
(iii) optionally charcoalizing and filtering the reaction mixture,
(iv) Facilitating crystallization of Fingolimod hydrochloride
(v) Isolating crystalline form I of Fingolimod hydrochloride
2. The process according to claim 2 where in alcohol is selected from the group comprising ethanol, methanol, IPA or mixture thereof.
3. The process according to claim 3 where in alcohol is IPA.