Process for isolation of solid ferric derisomaltose

Abstract

A novel process for isolation of ferric derisomaltose in solid form includes the steps of reacting a reduced dextran with at least one iron salt in presence of at least one base and isolating the solid ferric derisomaltose by treatment with at least one organic solvent. The disclosed process is simple, cost effective and provides industrially viable isolation process of solid ferric derisomaltose by using a suitable organic solvent and avoiding use of membrane filtration and spray drying techniques.

Description

TITLE OF THE INVENTION PROCESS FOR ISOLATION OF SOLID FERRIC DERISOMALTOSE FIELD OF THE INVENTION

[0001] The present invention relates to a novel process for isolation of solid ferric derisomaltose. Particularly, the present invention relates to a commercially feasible, facile and robust process to prepare a pharmaceutically acceptable ferric derisomaltose. More particularly, the present invention relates to a novel process for isolation of solid ferric derisomaltose by using a suitable organic solvent and avoiding membrane filtration and spray drying techniques. BACKGROUND OF THE INVENTION

[0002] Ferric derisomaltose (Brand Name: MONOFERRIC®) was first approved by USFDA in 2020 for intravenous use as an iron replacement product indicated for treatment of iron deficiency anemia in adult patients, who have intolerance to oral iron or have had unsatisfactory response to oral iron, or who have non-hemodialysis dependent chronic kidney disease.

[0003] The approved product MONOFERRIC®contains the active ingredient ferric derisomaltose. Ferric derisomaltose is an iron carbohydrate complex with a matrix structure composed of interchanging layers of ferric hydroxide and the carbohydrate derisomaltose. Derisomaltose consists of linear, hydrogenated isomaltooligosaccarides with an average molecular weight of 1000 Daltons and a narrow molecular weight of distribution that is almost devoid of mono and disaccharides.

[0004] Ferric derisomaltose has the following empirical formula: {FeO(1-3X) (OH)(1+3X) (C6H5O73-)x}, (H2O)T,-(C6H10O6)R(-C6H10O5-)Z R, (NaCl)Y X = 0.0311; T = 0.25; R = 0.14; Z = 0.49; Y=0.14

[0005] A schematic representation of ferric derisomaltose is presented below:

[0006] non-transparent aqueous solution with pH 5.0-7.0, containing ferric derisomaltose dissolved in water for injections and filled into Type I glass vials. Each 1 mL of solution contains 100mg of elemental iron as ferric derisomaltose in water for injection.

[0007] Ferric derisomaltose was first disclosed in US Patent No. 8,815,301 as an iron oligosaccharide compound comprising a hydrogenated oligosaccharide in stable association with ferric oxyhydroxide. The hydrogenated dextran used was purified by a membrane filtration process and the solution was directly used for preparation of ferric derisomaltose without isolating the intermediate dextran. According to process described in US8815301, the obtained ferric derisomaltose was purified by membrane filtration process followed by spray drying to isolate the solid. However, this process has several drawbacks. It was found that material produced by this process requires use of membrane filtration process twice and spray drying technique, which increases both cost and time.

[0008] Indian Patent discloses a process for synthesis of solvent free water soluble ferric derisomaltose that is free of toxic impurities. The process includes use of in-situ preparation of modified dextran, which is free of low molecular weight carbohydrate, and it is used for preparation of ferric derisomaltose. The obtained ferric derisomaltose according to the process described in this patent is isolated by spray drying technique. The process described in this patent has several drawbacks. For example, it was found that the process involves use of spray drying technique for the isolation of ferric derisomaltose, which is costly.

[0009] Chinese Patent Application No. 115983126A discloses another method for preparation of iron isomaltose anhydride including use of a deep neural network model to determine the time sequence incidence relation between a stirring speed and a reaction temperature. The use of a video acquisition module involves controlling and mapping of a synergistic parameter of the stirring speed and the reaction temperature to the state change of a reaction liquid. The drawbacks of the disclosed process are that the process is not industrially viable and is costly as involves the use of a video acquisition module.

[0010] Indian Patent No. 381772 discloses a process for preparation of stable iron isomaltoside with reduced toxicity. The process involves use of in- situ reduced dextran for the preparation of iron isomaltoside and isolation through spray dryer technique. The drawbacks associated with this process include the use of spray drying technique, which is costly and does not involve isolation of reduced dextran, hence there is possibility of poor control of product quality.

[0011] Chinese Patent Application No. 109646454A discloses a method for preparing isomaltose acid anhydride iron including ultrafiltration membrane purification techniques for the purification of complex and isolation of isomaltose acid anhydride iron by spray drier techniques. The drawbacks of the disclosed process are that material produced by the process requires useof ultrafiltration membrane and techniques, which increases both cost and time.

[0012] Hence, there is need to develop an alternative process for preparation of ferric derisomaltose, which is simple, viable on a commercial scale, cost effective and provides ferric derisomaltose product as solid powder.

[0013] The present inventors have found a novel process for the isolation of solid ferric derisomaltose, which fulfills the aforesaid objectives. SUMMARY OF THE INVENTION

[0014] A novel method for isolation of solid ferric derisomaltose includes the steps of: a) reacting the reduced dextran with an iron salt in presence of at least one base; and b) isolating ferric derisomaltose obtained in step (a) by using at least one organic solvent.

[0015] In some embodiments, the present invention provides a novel process for isolating the reduced dextran, which includes the steps of: i) preparing a reduced dextran from a reaction between dextran and at least one reducing agent under basic conditions; and ii) isolating reduced dextran obtained in step (i) by at least one organic solvent.

[0016] In certain embodiments, a suitable organic solvent used for the isolation of reduced dextran is selected from methanol, ethanol, isopropanol, acetone, acetonitrile or mixture thereof. In some preferred embodiments, the suitable organic solvent is methanol, ethanol and mixtures thereof. In some preferred embodiments, the suitable organic solvent is methanol.

[0017] In certain suitable organic solvent used for the isolation of ferric derisomaltose is selected from methanol, ethanol, isopropanol, acetone, acetonitrile, tetrahydrofuran, dioxane, dimethyl formamide, dimethylacetamide, N-methyl pyrrolidinone and mixtures thereof. In some preferred embodiments, the suitable organic solvent is acetone, methanol, ethanol or mixtures thereof. In some more preferred embodiments, the suitable organic solvent is acetone.

[0018] In certain embodiments, a suitable iron salt used in step (a) is selected from ferric chloride, ferrous chloride, ferric nitrate, ferrous nitrate, ferric sulfate, ferrous sulfate, ferric bromide, ferrous bromide or mixtures thereof. In some embodiments, the iron salt is selected from ferric chloride hexahydrate, ferric chloride tetrahydrate or mixtures thereof. In some preferred embodiments, the iron salt is ferric chloride hexahydrate.

[0019] The novel process for isolation of solid ferric derisomaltose yields a product having desired molecular weight in a range from about 50,000 to about 150,000 Daltons, and in some embodiments, from about 50,000 Daltons to about 90,000 Daltons. The novel process for isolation of solid ferric derisomaltose also yields a product having polydispersity of less than about 2.1, and in some embodiments, less than about 1.7.

[0020] The inventive process disclosed herein provides an improved process for preparation of reduced dextran that avoids use of membrane filtration techniques.

[0021] The novel process for isolation of solid ferric derisomaltose disclosed herein avoids use of purification by membrane filtration and isolation by spray drier techniques.

[0022] Other features and advantages of the present invention will become apparent from the following more detailed description, which illustrate, by way of example, the principle of the invention.DETAILED OF THE INVENTION

[0023] The following detailed description is merely exemplary in nature and is not intended to limit the disclosed invention described herein. Furthermore, there is no intention to be bound by any theory presented in the preceding background or the following detailed description.

[0024] The term “about” as used in connection with a numerical value throughout the specification and the claims denotes an interval of accuracy, familiar and acceptable to a person skilled in the art. In general, such interval of accuracy is ±10%. Thus, “about ten” means 9 to 11. All numbers in this description indicating amounts, ratios of materials, physical properties of materials, and / or use are to be understood as modified by the word “about,” except as otherwise explicitly indicated.

[0025] “At least one”, as used herein, means one or more, i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, or more. If used in combination with a compound, the term does not mean the absolute number of molecules but rather to the number of different types of said compound.

[0026] The term “substantially”, as used herein, means at least about 80%, preferably at least about 90%, more preferably at least about 99%, for example at least about 99.9%. In some embodiments, the term substantially can mean completely, or about 100%.

[0027] As used herein, the term “comprising” means including, made up of, composed, characterized by or having.

[0028] The expression “weight average molecular weight”, unless otherwise indicated, is one expression of the molecular weight of a substance which comprises a distribution of molecular weights rather than a single molecular weight. The “weight average molecular weight” is calculated as a summation of the squares of the weights of a fraction of the molecular weight distribution, divided by the total weight of the molecules. The weight averagemolecular weight may be determined by gel permeation chromatography (GPC), using refractive index, light scattering, small angle neutron scattering (SANS), or by sedimentation velocity.

[0029] The expression “alkali metal,” as used herein, refers to metals or ions of metals found in Group I of the periodic table. Some examples of preferred alkali metals include, but are not limited to, lithium, sodium and potassium.

[0030] The term “base”, as used herein, refers to a chemical species that donates electrons or hydroxide ions (Arrhenius definition) or that accepts protons (Brönsted definition). Bases include strong bases, i.e., bases that are completely dissociated in aqueous solution, and weak bases, i.e., bases that are only partially dissociated in aqueous solution. Examples of strong bases include, but are not limited to, sodium hydroxide and potassium hydroxide. Examples of weak bases include, but are not limited to, ammonia and alkyl amines.

[0031] The term “oligosaccharide”, as used herein, refers to a carbohydrate, or a reduced and / or oxidized and / or derivatized variant thereof, having a small number, typically 3-10, monosaccharide units, or to a mixture of two or more carbohydrates, or reduced and / or oxidized and / or derivatized variants thereof, wherein the majority (e.g., at least 60%, at least 70%, at least 80% or more) of the molecules have a small number, typically 3-10, monosaccharide units.

[0032] The term “monomer saccharide”, as used herein, refers to a monosaccharide or a reduced and / or oxidized and / or derivatized variant thereof, or to a mixture of two or more monosaccharides and / or variants thereof.

[0033] The term “dimer saccharide”, as used herein, refers to a carbohydrate having two monosaccharide units (such as a disaccharide) or a reduced and / or oxidized and / or derivatized variant thereof, or to a mixture oftwo or more carbohydrates, or and / or oxidized and / or derivatized variants thereof, wherein the majority (e.g., at least 60%, at least 70%, at least 80% or more) of the molecules have two monosaccharide units.

[0034] The phrase “water-miscible organic solvent,” unless otherwise indicated, refers to an organic solvent which is soluble in water in all proportions at standard temperature and pressure. Examples of suitable water-miscible organic solvents include, for example, methanol, ethanol, isopropanol, acetone, acetonitrile, tetrahydrofuran, dioxane, dimethyl formamide, dimethylacetamide and N-methyl pyrrolidinone.

[0035] The terms “aqueous medium” and “aqueous solvent” refer, unless otherwise indicated, to a solvent or medium that is water, or a mixture of water and one or more water-miscible organic solvents.

[0036] One embodiment of the present invention provides a novel process for isolation of solid ferric derisomaltose, which includes the steps of: a) reacting a reduced dextran with an iron salt in presence of at least one base; and b) isolating ferric derisomaltose obtained in step (a) by at least one organic solvent.

[0037] In some embodiments, the process further includes the steps of: i) preparing a reduced dextran from a reaction between dextran and at least one reducing agent under basic conditions; and ii) isolating the reduced dextran obtained in step (i) by at least one organic solvent.

[0038] The suitable organic solvent used for the isolation of reduced dextran may be selected from methanol, ethanol, isopropanol, acetone, acetonitrile and mixtures thereof. In some preferred embodiments, thesuitable organic solvent is and mixtures thereof, and more preferably, the suitable organic solvent is methanol.

[0039] The reducing agent used in step (i) may be selected from sodium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, lithium borohydride and mixtures thereof.

[0040] A base used in step (i) for providing the basic conditions may be selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate and mixtures thereof, and in some preferred embodiments is sodium hydroxide.

[0041] The suitable iron salt used in step (a) may be selected from ferric chloride, ferrous chloride, ferric nitrate, ferrous nitrate, ferric sulfate, ferrous sulfate, ferric bromide, ferrous bromide and mixtures thereof. In some preferred embodiments, the iron salt is selected from ferric chloride hexahydrate, ferric chloride tetra hydrate and mixtures thereof, and more preferably is ferric chloride hexahydrate.

[0042] The base used in step (a) may be selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate and mixtures thereof, and in some preferred emboidments is selected from sodium carbonate, sodium hydroxide and mixtures thereof.

[0043] The suitable organic solvent used in step (b) for the isolation of ferric derisomaltose may be selected from methanol, ethanol, isopropanol, acetone, acetonitrile, tetrahydrofuran, dioxane, dimethyl formamide, dimethylacetamide, N-methyl pyrrolidinone and mixtures thereof. In some preferred embodiments, the suitable organic solvent is acetone, methanol, ethanol and mixtures thereof, and more preferably is acetone.

[0044] Surprisingly, it was observed that isolation of solid ferric derisomaltose through the use of a suitable organic solvent results in theremoval of undesired inorganic unreacted starting materials. The isolation process of solid ferric derisomaltose by using an organic solvent is cost effective and commercially viable as compared to the membrane filtration and spray drier techniques.

[0045] In some embodiments, the method of isolation of solid ferric derisomaltose in accordance with the present invention does not require a membrane filtration step. In additional embodiments, the method of isolation of solid ferric derisomaltose does not require a spray drier process step.

[0046] The molecular weight in accordance with the present invention may be measured by using Gel permeation chromatography (GPC) by using appropriate standard as per general method disclosed, for example, in US Patent No. 7,674,780. In the present invention, the inventors have used following parameters of Gel permeation chromatography (GPC) as shown in Table-1: Table-1: GPC parameterspresent invention and MONOFERRIC®brand is shown in Table-2:Table-2: Molecular Weight between Ferric Derisomaltose prepared by present invention and MONOFERRIC® ty

[0047] EXAMPLES

[0048] Example-1: Preparation of reduced dextran.

[0049] Dextran 1 (100.0 g) was dissolved in 250 mL of purified water at 25°C to 30°C. 2.5 g of sodium hydroxide solution (50%) was added in the reaction mixture and was stirred for 10-20 minutes at 25°C to 30°C. Sodium borohydride (10.0 g) was added in portions within 15-30 minutes to the reaction mixture, followed by flushing with 50 mL of purified water at 40°C to 45°C reaction temperature. The reaction mass was stirred at 40°C to 45°C for 4 hours. The reaction mass was cooled to 25°C to 30°C and the pH was adjusted to between 6 to 7 by adding concentrated hydrochloric acid (17 mL) at and the reaction mass was maintained for 10-20 minutes at 25°C to 30°C. The reaction mixture was added to 8000 mL of methanol at 25°C to 30°C and stirred for 10-20 minutes. The precipitated solid was filtered and washed with methanol to get wet material. The wet material was dried in a vacuum tray dryer (VTD) at 50°C to 55°C to obtain 76 g of reduced dextran.

[0050] Example-2: Preparation of solid Ferric derisomaltose.

[0051] Ferric chloride hexahydrate (20.0 g) was added to purified water (150 mL) at 25-30°C and stirred until dissolved. Reduced dextran (20.0 g)obtained in example-1 was added reaction mixture. Then, 140 mL of sodium carbonate solution (20%) was added at 25°C to 30°C for 10-30 minutes and stirred further for 5-10 minutes. The pH was adjusted to be between 10 to 11 by using sodium hydroxide solution (50%). The reaction mass was heated to 95°C to 105°C and maintained for 4 hours. The reaction mass was then cooled to 25°C to 30°C and the pH was adjusted between 5.5- 6.0 by using concentrated hydrochloric acid (40 mL) and the reaction mass was maintained for 10-20 minutes at 25°C to 30°C. Acetone (680 mL) was added into the reaction mixture at 25°C to 30°C and stirred for 10-20 minutes. The precipitated solid was filtered and washed with acetone to get wet material. The wet material was dried in VTD at 50°C to 55°C to obtain 16 g of ferric derisomaltose.

[0052] Example-3: Preparation of solid Ferric derisomaltose.

[0053] (Step A) Ferric chloride hexahydrate (40.0 g) was added into purified water (275 mL) at 25-30°C and stirred until dissolved. Reduced dextran (40.0 g) obtained in example-1 was added, followed by rinsing with 25 mL of purified water.280 mL of sodium carbonate solution (20%) was then added at 25°C to 30°C for 10-30 minutes. The pH was adjusted to be between 10.2 to 10.7 by using sodium hydroxide solution (50%). The reaction mass was heated to between 95°C to 105°C and maintained for 4 hours. Then, the reaction mass was cooled to 25°C to 30°C and the pH was adjusted between 5.5-6.0 by using concentrated hydrochloric acid. Next, the reaction mass was stirred for 10-20 minutes at 25°C to 30°C and solid ferric derisomaltose was isolated by using various solvent(s) as mentioned below.

[0054] (Step B-1) Solid Ferric derisomaltose isolation through Dimethyl formamide as a solvent.

[0055] Dimethyl formamide (2400 mL) was added into the reaction mixture as obtained above in example-3A at 25°C to 30°C and stirred for 10- 20 minutes. The precipitated solid was filtered and washed with acetone (800mL) to get wet material. The wet was dried in VTD at 50°C to 55°C to obtain 28.8 g of ferric derisomaltose. Molecular weight (Mw): 58058; Mn: 34565; and Polydispersity (PDI): 1.68.

[0056] (Step B-2) Solid Ferric derisomaltose isolation through Dimethyl acetamide as a solvent.

[0057] Dimethyl acetamide (2400 mL) was added into the reaction mixture as obtained above in example-3A at 25°C to 30°C and stirred for 10- 20 minutes. The precipitated solid was filtered and washed with acetone (800 mL) to get wet material. The wet material was dried in VTD at 50°C to 55°C to obtain 38.8 g of ferric derisomaltose. Molecular weight (Mw): 58428; Mn: 36147; and Polydispersity (PDI): 1.62.

[0058] (Step B-3) Solid Ferric derisomaltose isolation through N- methyl pyrrolidone as a solvent.

[0059] N-methyl pyrrolidone (2400 mL) was added into the reaction mixture as obtained above in example-3 at 25°C to 30°C and stirred for 10-20 minutes. The precipitated solid was filtered and washed with acetone (1280 mL) to get wet material. The wet material was dried in VTD at 50°C to 55°C to obtain 42.4 g of ferric derisomaltose. Molecular weight (Mw): 64437; Mn: 38459; and Polydispersity (PDI): 1.68.

[0060] (Step B-4) Solid Ferric derisomaltose isolation through Methanol as a solvent.

[0061] Methanol (1200 mL) was added into the reaction mixture as obtained above in example-3 at 25°C to 30°C and stirred for 10-20 minutes. The precipitated solid was filtered and washed with methanol (800 mL) to get wet material. The wet material was dried in VTD at 50°C to 55°C to obtain 32.8 g of ferric derisomaltose. Molecular weight (Mw): 54332; Mn: 34716; and Polydispersity (PDI): 1.57.

[0062] Example-4: solid Ferric derisomaltose.

[0063] Ferric chloride hexahydrate (10.0 g) was added into purified water (75 mL) at 25-30°C and stirred until dissolved. Reduced dextran (10.0 g) as obtained in example-1 was then added. 70 mL of sodium carbonate solution (20%) was added at 25°C to 30°C for 10-30 minutes. The pH was adjusted between 10 to 11 by using sodium hydroxide solution (50%). Then, citric acid (0.2 g) was added at 25°C to 30°C and the reaction mass was heated to between 95°C to 105°C and maintained for 4 hours. The reaction mass was then cooled to 25°C to 30°C and the pH was adjusted between 5 - 6 by using concentrated hydrochloric acid. Next, the reaction mass was stirred for 10-20 minutes at 25°C to 30°C. Acetone (172 mL) was added into the reaction mixture at 25°C to 30°C and stirred for 10-20 minutes. The precipitated solid was filtered and washed with acetone to get wet material. The wet material was dried in VTD at 50°C to 55°C to obtain 6.7 g of ferric derisomaltose. Molecular weight (Mw): 84441; Mn: 41163; and Polydispersity (PDI): 2.05.

[0064] Example 5: Gel permeation chromatography data for MONOFERRIC®

[0065] Molecular weight, Mn and polydispersity of Ferric Derisomaltose sold under MONOFERRIC® brand were measured using gel permeation chromatography. The measured data are as follows: Molecular weight (Mw): 82009; Mn: 55442; Polydispersity (PDI): 1.47.

[0066] The solid ferric derisomaltose prepared by the method of the present invention may be used for preventing or treating iron-deficiency anaemia in animal or human subjects by parenterally or orally administering a pharmacologically effective amount of a therapeutical composition including the solid ferric derisomaltose. When using the solid ferric derisomaltose powder for producing injection or infusion liquids, the powder may be re- dissolved in an aqueous medium, the pH is checked and, if necessary,adjusted, and the solution is filled or vials after being sterilized by a suitable method, such as filtration. Alternatively, the sterilization may be accomplished by autoclaving after filling into ampoules or vials.

[0067] It should be noted that the invention in its broader aspects is not limited to the specific details, representative compositions, methods, and processes, and illustrative examples described in connection with the preferred embodiments and preferred methods. Modifications and equivalents will be apparent to practitioners skilled in this art and are encompassed within the spirit and scope of the appended claims.

Claims

AMENDED CLAIMS received by the International Bureau on 15 April 2025 (15.04.2025)What is claimed is:

1. A method for isolation of solid ferric derisomaltose, comprising the steps of: a) reacting a reduced dextran with at least one iron salt in presence of at least one base; and b) isolating the solid ferric derisomaltose by treatment with at least one organic solvent.

2. The method according to claim 1 , wherein the at least one organic solvent used in step (b) is selected from methanol, ethanol, isopropanol, acetone, acetonitrile, tetrahydrofuran, dioxane, dimethyl formamide, dimethylacetamide, N-methyl pyrrolidinone and mixtures thereof.

3. The method according to claim 2, wherein the at least one organic solvent is acetone.

4. The method according to claim 1 , further comprising the steps of: i) preparing the reduced dextran from a reaction between dextran and at least one reducing agent in presence of at least one base; and ii) isolating the reduced dextran obtained in step (i) by treatment with at least one organic solvent.

5. The method according to claim 4, wherein the at least one organic solvent is selected from methanol, ethanol, isopropanol, acetone, acetonitrile and mixtures thereof.

6. The method according to claim 5, wherein the at least one organic solvent is methanol.AMENDED SHEET (ARTICLE 19)7. The method according to claim 1 , wherein the at least one iron salt is selected from ferric chloride, ferrous chloride, ferric nitrate, ferrous nitrate, ferric sulfate, ferrous sulfate, ferric bromide, ferrous bromide and mixtures thereof.

8. The method according to claim 1 , wherein the at least one iron salt is selected from ferric chloride hexahydrate, ferric chloride tetrahydrate and mixtures thereof.

9. The method according to claim 8, wherein the at least one iron salt is ferric chloride hexahydrate.

10. The method according to claim 4, wherein at least one base used in step (i) is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate and mixtures thereof.

11. The method according to claim 4, wherein the reducing agent used in step (i) is selected from sodium borohydride, sodium cyanoborohydride, lithium borohydride and mixtures thereof.

12. The method according to claim 1 , wherein the at least one base used in step (a) is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate and mixtures thereof.

13. The method according to claim 12, wherein the at least one base is selected from sodium hydroxide, sodium carbonate and mixtures thereof.

14. The method according to claim 1 , wherein the solid ferric derisomaltose has polydispersity of about 1 .5 to about 2.5.AMENDED SHEET (ARTICLE 19)15. The method according to claim 1 , wherein the solid ferric derisomaltose has an average molecular weight in a range from about 50,000 to about 100,000 Daltons as measured by gel permeation chromatography.

16. A method for isolation of solid ferric derisomaltose, comprising the steps of: preparing a reduced dextran from a reaction between dextran and at least one reducing agent in presence of at least one first base; isolating the reduced dextran by at least one first organic solvent; reacting the reduced dextran with at least one iron salt in presence of at least one second base; and isolating the solid ferric derisomaltose with at least one second organic solvent.

17. The method according to claim 16, wherein the method does not require a step of spray drying.

18. The method according to claim 16, wherein the method does not require a membrane filtration step.

19. A method of preventing or treating iron-deficiency anaemia, comprising parenterally or orally administering a pharmacologically effective amount of a therapeutical composition including the solid ferric derisomaltose of claim 1 to animal or human subjects in need thereof.AMENDED SHEET (ARTICLE 19)

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