Ranbaxy Laboratories Limited is an Indian multinational pharmaceutical company that was incorporated in India in 1961. The company went public in 1973 and Japanese pharmaceutical company Daiichi Sankyo acquired a controlling share in 2008. In 2014, Sun Pharma acquired the entire 63.4% share of Ranbaxy making the conglomerate the world’s fifth largest specialty generic pharma company.

Recent patent filed by the company
1. Patent no. US 20160287583 “ORAL DISPERSIBLE COMPOSTION OF DPP-IN INHIBITION
The present invention provides oral dispersible compositions of a DPP-IV inhibitor that will rapidly disintegrate within three minutes. These compositions have an acceptable taste, offer a pleasant mouth feel, and leave minimal residue in the mouth after administration. The present invention further provides processes for preparing said oral dispersible compositions. It also provides a method of treating diabetes by administering said oral dispersible compositions.
A first aspect of the present invention provides an oral dispersible composition comprising a DPP-IV inhibitor and one or more pharmaceutically acceptable excipients, wherein the composition disintegrates within three minutes.
According to one embodiment of this aspect, there is provided an oral dispersible composition comprising a DPP-IV inhibitor and one or more pharmaceutically acceptable excipients, wherein the DPP-IV inhibitor is coated with a polymer selected from pH-independent polymers or pH-dependent polymers.
According to another embodiment of this aspect, there is provided an oral dispersible composition comprising a DPP-IV inhibitor and one or more pharmaceutically acceptable excipients, wherein the DPP-IV inhibitor is complexed with a complexing agent selected from a cyclodextrin or an ion-exchange resin.
According to another embodiment of this aspect, there is provided an oral dispersible composition comprising a DPP-IV inhibitor and one or more pharmaceutically acceptable excipients, wherein the pharmaceutically acceptable excipients are selected from the group comprising sweeteners, disintegrants, fillers, suspending agents, lubricants, binders, wetting agents, coloring agents, flavoring agents, and combinations thereof.

2. Patent no.US 20160185760 “PROCESS FOR THE PREPARATION OF MALIC ACID SALT OF SUNITINIB”.

The present inventors have developed a simple and efficient process for the preparation of malic acid salt of sunitinib. The present process does not require the isolation of sunitinib base from the reaction mixture and it can be directly converted into malic acid salt of sunitinib. The present process also avoids the preparation and isolation of malic acid salt of N-[2-(diethylamino)ethyl]-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide of Formula II. The malic acid salt of sunitinib can be obtained by the present process with a yield of about 80% or above directly from the reaction mixture. Thus, the present process minimizes the steps involved in the preparation of sunitinib while it is efficient to obtain malic acid salt of sunitinib with higher yield.
The term “malic acid salt of sunitinib” includes a combination of sunitinib and L-malic acid in any ratio between about 1:0.5 and about 1:1.5.

In one aspect of the present invention is provided a process for the preparation of malic acid salt of sunitinib, wherein the process comprises: a) reacting N-[2-(diethylamino)ethyl]-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide of Formula II with 5-fluoro-1,3-dihydro-2H-indol-2-one of Formula III in the presence of a solvent to obtain sunitinib base; and b) treating the reaction mixture obtained in step a) with malic acid to obtain malic acid salt of sunitinib.
The solvent may be water, an organic solvent or a mixture thereof. The organic solvent may be an alkanol, for example, n-propanol, methanol, ethanol, isopropanol or n-butanol, an ester, for example, n-butyl acetate, isopropyl acetate, methyl acetate or ethyl acetate, a nitrile, for example, acetonitrile, an aromatic hydrocarbon, for example, toluene, a cyclic ether, for example, tetrahydrofuran, or a ketone, for example, acetone, or a mixture thereof. The reaction mixture may also contain a base. The base may be an organic amine, for example, pyrrolidine. The reaction may be carried out at a temperature of about the boiling point of the solvent. For example, the reaction may be carried out at about 75° C. to about 80° C. when ethanol is used as a solvent. The reaction may be carried out for about 10 minutes to about 10 hours, for example, about 1 hour to about 5 hours. Sunitinib base so obtained need not be isolated from the reaction mixture in any form, solid or oil. The reaction mixture comprising sunitinib base is treated with malic acid to form the malic acid salt of sunitinib. The malic acid may be L-malic acid, D-malic acid, or a mixture thereof. The formation of malic acid salt of sunitinib may be carried out in the same reaction mixture—for example, at substantially the same reaction conditions in which sunitinib base is formed. The malic acid salt of sunitinib may be isolated by filtration, solvent removal, evaporation, solvent precipitation, layer separation, decantation, centrifugation, or a combination thereof.
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.

3. Patent no.US 20160143923 “LOW DOSE PHARMACEUTICAL COMPOSTION OF DOXYCYCLINE”.

The present invention provides a low dose pharmaceutical composition of doxycycline comprising 32 mg or 34 mg of doxycycline and one or more pharmaceutically acceptable excipients for the treatment of acne, and processes for its preparation. A first aspect of the present invention provides a low dose pharmaceutical composition comprising 32 mg or 34 mg of doxycycline and one or more pharmaceutically acceptable excipients.
According to one embodiment of this aspect, the low dose pharmaceutical composition is intended for once daily administration. According to another embodiment of this aspect, the low dose pharmaceutical composition is an immediate release composition. A second aspect of the present invention provides a method of treating acne by administering a low dose pharmaceutical composition comprising 32 mg or 34 mg of doxycycline and one or more pharmaceutically acceptable excipients.

The pharmaceutical composition may be in the form of capsules or tablets. Preferably, the pharmaceutical composition is in the form of tablets. The term “doxycycline,” as used herein, includes doxycycline base and its pharmaceutically acceptable salts, hydrates, solvates, esters, or prodrugs. Preferably, doxycycline is used as its hyclate salt, which is doxycycline hydrochloride hemiethanolate hemihydrate.
The term “low dose,” as used herein, refers to a dose of 32 mg or 34 mg doxycycline base, which is less than the conventional dose of 40 mg which is required to produce the therapeutic effect.

The term “pharmaceutically acceptable excipients,” as used herein, includes any physiologically inert additives that are routinely used in pharmaceutical compositions. Pharmaceutically acceptable excipients are selected from the group comprising binders, diluents, disintegrants, lubricants/glidants/antiadherants, and mixtures thereof. The pharmaceutically acceptable excipients may be added intragranularly as well as extragranularly.
Examples of binders include povidone, copovidone, polyvinylpyrrolidone, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose, ethyl cellulose, xanthan gum, gum acacia, gum arabic, tragacanth, sorbitol, dextrose, sucrose, mannitol, gelatin, pullulan, sodium alginate, calcium alginate, ammonium calcium alginate, propylene glycol, polyvinyl alcohol, corn syrup, methacrylates, carboxyvinyl polymers like carbomers, and mixtures thereof.
Examples of diluents include microcrystalline cellulose, powdered cellulose, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, calcium carbonate, lactose monohydrate, lactose anhydrous, sucrose, sorbitol, xylitol, erythritol, kaolin, calcium silicate, maltodextrin, starch, modified starch, e.g., pregelatinized starch, maize starch, corn starch, and mixtures thereof.
Examples of disintegrants include hydroxypropyl cellulose (L-HPC), crospovidone, croscarmellose sodium, carboxymethyl cellulose sodium, carboxymethyl cellulose calcium, sodium starch glycolate, gums, alginic acid or alginates, starch, corn starch, modified starch, carboxymethyl starch, polyacrylates, and mixtures thereof.
Examples of lubricants/glidants/antiadherents include magnesium stearate, hydrogenated vegetable oil, glyceryl behenate, glyceryl monostearate, stearic acid, sodium stearyl fumarate, calcium stearate, zinc stearate, aluminum silicate, talc, colloidal silicon dioxide, sucrose esters of fatty acids, waxes, silica gel, and mixtures thereof.
Various solvents that may be employed during the preparation of the pharmaceutical composition of the present invention are selected from the group comprising methyl alcohol, ethyl alcohol, isopropyl alcohol, n-butyl alcohol, acetone, acetonitrile, chloroform, methylene chloride, water, and mixtures thereof.
The pharmaceutical composition of the present invention may be prepared by any of the well-known processes including wet granulation, dry granulation, direct compression, top spray granulation and drug layering.
The pharmaceutical composition of the present invention may be in the form of a tablet or a capsule. The tablet or capsule may be further coated with a film coating prepared by using a film-forming polymer and one or more pharmaceutically acceptable excipients. The pharmaceutically acceptable excipients may be plasticizers, opacifiers, coloring agents, and mixtures thereof.

4. Patent no. US 20160015708 “STABLE DOSAGE FROM OF IMATINIB MESYLATE.

In one general aspect, the present invention relates to a stable oral pharmaceutical dosage form comprising imatinib mesylate and one or more pharmaceutically acceptable excipients, wherein the amount of imatinib calculated as free base is more than 80% by weight based on the total weight of the oral pharmaceutical dosage form, and wherein the oral pharmaceutical dosage form does not show polymorphic conversion after storage at 40° C. and 75% relative humidity for three months.
In an embodiment of the above aspect, the pharmaceutically acceptable excipients are selected from diluents, binders, disintegrants, lubricants, glidants, granulating solvents, and coloring agents.In another embodiment, imatinib mesylate is present in alpha crystalline form.In yet another embodiment, the alpha crystalline form does not convert to the beta crystalline form when the oral pharmaceutical dosage form is stored at 40° C. and 75% relative humidity for three months.
In another embodiment, the stable oral pharmaceutical dosage form is a tablet.In another embodiment, the stable oral pharmaceutical dosage form is a capsule.In a further embodiment, the stable oral pharmaceutical dosage form is dispensed in a package comprising blister packs or high-density polyethylene (HDPE) bottles.
In a further embodiment, the package may additionally contain a desiccant.In another general aspect, the present invention relates to a process for preparing a stable oral pharmaceutical dosage form comprising imatinib mesylate and one or more pharmaceutically acceptable excipients, wherein the amount of imatinib calculated as free base is more than 80% by weight based on the total weight of the oral pharmaceutical dosage form, and wherein the oral dosage form does not show polymorphic conversion after storage at 40° C. and 75% relative humidity for three months, and wherein the process comprises the conventional processes of dry granulation or wet granulation.

The present invention provides stable oral pharmaceutical dosage forms comprising imatinib mesylate in a polymorphic form, for example, alpha crystalline form, and one or more pharmaceutically acceptable excipients such that the amount of imatinib calculated as free base is more than 80% by weight based on the total tablet weight.The stable oral pharmaceutical dosage forms can be tablets or capsules.
As used herein, the term “pharmaceutically acceptable excipient” includes conventional pharmaceutical additives known in the art such as diluents, binders, disintegrants, lubricants, glidants, granulating solvents, coloring agents, or combinations thereof.

5. Patent no. US 20150336913 “PROCESS FOR THE PREPARATION OF DASATINIB AND ITS INTERMEDIATES”.

The present invention relates to processes for the preparation of dasatinib and its intermediates. Dasatinib monohydrate of Formula A, chemically, N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide monohydrate, is a cyclic protein tyrosine kinase inhibitor. Dasatinib monohydrate is marketed under the brand name SPRYCEL® and is indicated for the treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) with resistance or intolerance to prior therapy including imatinib. SPRYCEL® is also indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. The compound of Formula 1a, wherein R1 and R2 can be independently selected from the group consisting of hydrogen, amino protecting group, and 6-chloro-2-methyl-pyrimidin-4-yl, 6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl, encompasses dasatinib of Formula B, and key intermediates of dasatinib of Formula 1b, Formula 1c, and Formula 1d, or salts thereof .U.S. Pat. No. 6,596,746 provides a process for the preparation of tert-butyl {5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl}carbamate (Formula 1b), 2-amino-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide (Formula 1c), and N-(2-chloro-6-methylphenyl)-2-[(6-chloro-2-methylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide (Formula 1d) which are the intermediates for the preparation of dasatinib.

The second step involves treating a stirred solution of ethyl 2-[(tert-butoxycarbonyl)amino]-1,3-thiazole-5-carboxylate in tetrahydrofuran-methanol with 6N aqueous sodium hydroxide solution at room temperature for 24 hours. Most of the tetrahydrofuran-methanol were removed by distillation under reduced pressure and the aqueous solution was acidified with 6N hydrochloric acid to obtain a solid which was filtered, washed with water and ether, then air dried, followed by drying in vacuo to obtain 2-[(tert-butoxycarbonyl)amino]-1,3-thiazole-5-carboxylic acid.
The third step involves adding a 2M solution of oxalyl chloride in dichloromethane to a stirred solution of 2-[(tert-butoxycarbonyl)amino]-1,3-thiazole-5-carboxylic acid in tetrahydrofuran and N,N-dimethylformamide, and then stirring the solution at room temperature for 4 hours. The solvent was evaporated under reduced pressure and in vacuo to obtain tert-butyl[5-(chlorocarbonyl)-1,3-thiazol-2-yl]carbamate.

The fourth step involves adding 2-chloro-6-methylaniline to a stirred solution of tert-butyl[5-(chlorocarbonyl)-1,3-thiazol-2-yl]carbamate in dichloromethane at 0° C. Diisopropylamine was added to the reaction mixture, warmed to room temperature, stirred for 24 hours, diluted with dichloromethane, and washed with 2N hydrochloric acid. The organic extract thus obtained was dried, filtered, and concentrated to obtain a residue. The residue was diluted with ethyl acetate-ether, filtered, washed with ether, and dried in vacuo to obtain tert-butyl{5-[(2-chloro-6-methylphenyl) carbamoyl]-1,3-thiazol-2-yl}carbamate (Formula 1b) in an overall yield of 48%.

The fifth step involves treating tert-butyl{5-[(2-chloro-6-methylphenyl) carbamoyl]-1,3-thiazol-2-yl}carbamate (Formula 1b) obtained in the fourth step with trifluoroacetic acid at room temperature to obtain 2-amino-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide (Formula 1c).
The sixth step involves reacting 2-amino-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide (Formula 1c) with 4,6-dichloro-2-methylpyrimidine in the presence of sodium hydride in tetrahydrofuran to obtain N-(2-chloro-6-methylphenyl)-2-[(6-chloro-2-methylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide (Formula 1d).
The seventh step of the process involves reacting N-(2-chloro-6-methylphenyl)-2-[(6-chloro-2-methylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide (Formula 1d) obtained in the sixth step with 1-(2-hydroxyethyl)piperazine to obtain dasatinib of Formula B.

6. Patent no. US 20150329489 “SAXAGLIPTIN SALTS”.

A first aspect of the present invention provides saxagliptin bisulphate. A second aspect of the present invention provides a crystalline form of saxagliptin bisulphate. A third aspect of the present invention provides saxagliptin acetate. A fourth aspect of the present invention provides a crystalline form of saxagliptin acetate. A fifth aspect of the present invention provides saxagliptin oxalate. A sixth aspect of the present invention provides a crystalline form of saxagliptin oxalate. A seventh aspect of the present invention provides a process for the preparation of a compound of Formula I which comprises treating saxagliptin or its salt with HA, wherein HA is selected from sulphuric acid, acetic acid, and oxalic acid. An eighth aspect of the present invention provides saxagliptin bicarbonate of Formula II. A ninth aspect of the present invention provides a crystalline form of saxagliptin bicarbonate.

7. Patent no. US 20150329526 “PROCESS FOR THE PREPARATION OF PAZOPANIB OR SALTS THEREOF”.
A first aspect of the present invention provides a process for the preparation of pazopanib of Formula Ia or its salts.

8. Patent no. US 20150313848 “PHARMACEUTICAL COMPOSTION OF RIFAXIMIN”

The present invention provides stable pharmaceutical compositions of rifaximin comprising a specific mixture of polymorphic forms of rifaximin, i.e., a mixture of Form α and Form β of rifaximin in a particular relative polymorphic distribution ratio. It is expected that the particular relative polymorphic distribution ratio of these polymorphic forms would remain stable throughout the shelf-life of the compositions, and thus would provide end users with a uniform therapeutic effect. It further provides processes for the preparation of these stable pharmaceutical compositions.

Detail description
A first aspect of the present invention provides a stable pharmaceutical composition of rifaximin comprising: (i) a mixture of Form α and Form β of rifaximin; and (ii) one or more pharmaceutically acceptable excipients,
wherein the relative polymorphic distribution ratio of Form α to Form β is from about 15:85 to about 85:15, and wherein said ratio remains substantially unchanged in the pharmaceutical composition after exposure to a relative humidity of 75% and a temperature of 40° C. for at least three months.
According to one embodiment of the above aspect, there is provided a stable pharmaceutical composition of rifaximin comprising: (i) a mixture of Form α and Form β of rifaximin; and (ii) one or more pharmaceutically acceptable excipients, wherein the relative polymorphic distribution ratio of Form α to Form β is from about 30:70 to about 70:30, and wherein said ratio remains substantially unchanged in the pharmaceutical composition after exposure to a relative humidity of 75% and a temperature of 40° C. for at least three months.
9. Patent no.US20150299160 “PROCESS FOR THE PREPARATION OF RIVAROABAN AND INTERMEDIATES THEREOF”
The present invention provides processes for the preparation of rivaroxaban and its intermediates. A first aspect of the present invention provides a process for the preparation of 5-chloro-N-[(2S)-3-chloro-2-hydroxypropyl]thiophene-2-carboxamide of Formula II wherein the process comprises treating a compound of Formula III or a salt thereof with a reactive derivative of a compound of Formula IV.

10. Patent no.US20150291591 “PROCESS FOR THE PREPARATION OF POLYMORPHS OF DORIPENEM”.

The present inventors have developed a simple and advantageous process for the preparation of the Type I crystal and the Type IV crystal of doripenem. By employing the present method, Type I and Type IV crystals of doripenem can be prepared in a reproducible and stable manner. The Type I and Type IV crystals obtained by the present invention are suitable for the development of pharmaceutical dosage forms.

A first aspect of the present invention provides a process for the preparation of Type I crystalline form of doripenem having interplanar spacing (d) values measured by XRPD substantially at 11.97, 5.99, 5.33, 4.42, 4.34, 4.21, 3.2, 2.99 and 2.71±0.02, wherein the process comprises:
a) Providing an aqueous solution of doripenem;
b) Treating the solution obtained in step a) with methanol;
c) Seeding the mixture obtained from step b) with Type I or Type IV crystals; and
d) Isolating the Type I crystal of doripenem.
The starting doripenem may be prepared according to the methods described in the prior art, for example, U.S. Pat. Nos. 6,111,098 and 5,317,016 and PCT Publication Nos. WO 2009/118680, WO 2007/029084 or WO 2006/117763. The aqueous solution of doripenem may be prepared by dissolving doripenem in water, or directly obtained, for example, by layer separation from the reaction mixture in which doripenem is formed. The temperature of the aqueous solution of doripenem may be maintained at about −20° C. to about 10° C., for example, about 0° C. to about 5° C. The aqueous solution of doripenem is treated with methanol. The treatment with methanol may be carried out by adding methanol to the aqueous solution of doripenem or by adding the aqueous solution of doripenem to methanol. The treatment with methanol may be carried out over a period of about 1 minute to about 10 hours, for example, about 4 minutes to about 15 minutes. The mixture so obtained is seeded with Type I or Type IV crystals of doripenem. The mixture may be stirred at a temperature of about 10° C. to about −30° C., for example, about −3° C. to about −15° C. The mixture may be stirred for about 0.5 hours to about 24 hours, for example, for about 2 hours to about 4 hours. The mixture so obtained may optionally be further treated with methanol. The further treatment with methanol may be carried out over a period of about 5 minutes to about 10 hours, for example, about 15 minutes to about 1 hour. The mixture may be stirred further at a temperature of about 10° C. to about −30° C., for example, −3° C. to about −15° C., for about 0.5 hours to about 24 hours, for example, about 2 hours to about 4 hours. The Type I crystal of doripenem is isolated from the mixture so obtained. The isolation may be carried out, for example, by filtration and/or decantation. The Type I crystal of doripenem so obtained may be further dried under vacuum at a temperature of about 40° C. to about 55° C., for example, about 45° C. to about 50° C. The Type I crystal of doripenem, so obtained, has interplanar spacing (d) values in XRPD substantially at 11.97, 5.99, 5.33, 4.42, 4.34, 4.21, 3.2, 2.99 and 2.71±0.02.

11. Patent no.US20150246899 “PROCESS FOR THE PREPARTATION OF DABIGATRAN ETEXILATE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF”.

The present invention relates to a process for the preparation of dabigatran etexilate. The present invention also relates to trifluoroacetate salt of dabigatran etexilate and a process for its preparation. The present invention further relates to crystalline Form I and crystalline Form II of trifluoroacetate salt of dabigatran etexilate and processes for their preparation. The present invention further relates to a process for the preparation of pharmaceutically acceptable salts, including methanesulfonate salt, of dabigatran etexilate.

12. Patent no.US 20150231084 “OSMOTIC FLOATING TABLETS”

The present invention relates to an osmotic floating tablet comprising: (i) an inner core comprising a drug, one or more low density polymers, and one or more pharmaceutically acceptable excipients; and (ii) an outer osmotic coating surrounding the inner core that is substantially permeable to the surrounding fluids and substantially impermeable to the drug. The present invention also includes processes for the preparation of said osmotic floating tablet.

13. Patent no.US20150232426 “PROCESS FOR THE PREPARATION OF OXCARBAZEPINE AND ITS USE AS INTERMEDIATE IN THE PREPARATION OF ESLICARBAZEPINE ACETAE”.

The present invention provides a process for the preparation of oxcarbazepine of Formula (1), which is an Active Pharmaceutical Ingredient (API) and a useful intermediate in the preparation of eslicarbazepine acetate of Formula (A). The present invention further provides a process for the preparation of eslicarbazepine acetate. The Patent Description & Claims data below is from USPTO Patent Application 20150232426, Process for the preparation of oxcarbazepine and its use as intermediate in the preparation of eslicarbazepine aceta