Suspension composition and preparation method thereof

Abstract

The invention provides a suspension composition. The suspension composition is prepared from vothioxetine hemipamoate, a wetting agent, a suspending aid, a pH (Potential of Hydrogen) regulator and a solvent. The votioxetine semipamoate suspension composition and the preparation method thereof provided by the invention have the advantages of small burst release of drugs, slow and stable release in vivo, high safety, good resuspension property and the like, and can greatly improve the compliance of patients.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparations, and more specifically to a pharmaceutical suspension composition containing vortioxetine and a method for preparing the same. Background Technology

[0002] Vortioxetine, also known as vortioxetine, was originally developed by Lundbeck in Denmark. It is a novel multimodal antidepressant that exerts its antidepressant effect by acting on six pharmacological targets (antagonizing 5-HT3, antagonizing 5-HT7, antagonizing 5-HT1D, partially activating 5-HT1B, activating 5-HT1A, and inhibiting serotonin transporters) through two different modes of action: inhibiting the reuptake of 5-HT transporters and regulating 5-HT receptors.

[0003] There is a strong demand for long-acting injectable drugs in the treatment of mental illnesses. One technology for long-acting injectable drugs is the sparingly soluble salt technology, which is generally used to further reduce the solubility of insoluble compounds. Currently, the most researched sparingly soluble salt technology is pamoate (dihydroxynaphthyl salt). The formation of pamoate significantly reduces solubility and dissolution rate, prolonging the drug's duration of action in the body. After injection, the sparingly soluble salt of the drug slowly dissolves, and the drug is gradually released into the circulation, maintaining its effect for several weeks.

[0004] CN109311832B mentions administering vortioxetine hemipamoate in suspension form, wherein the preferred pharmaceutical carrier is a viscous injectable carrier, for example, with a viscosity of at least 20 cp at 20°C. High viscosity implies greater difficulty in preparation before clinical use and requires highly skilled operators. Furthermore, the formulation requires vortexing using external equipment such as a vortex mixer, increasing the difficulty and time required for preparation.

[0005] WO2023 / 010410A discloses a lyophilized powder injection of vortioxetine permodate and its preparation method. The prepared powder injection has uniform particle dispersion and normal appearance. The reconstituted solution can pass through a 19-22G needle, exhibiting good needle penetration and stability, providing a more effective treatment option for clinical psychiatric patients. However, the lyophilized powder injection requires a complex reconstitution process before injection, increasing the number of steps and the risk of potential contamination. Furthermore, during the reconstitution process, drug adsorption onto the container walls may occur, leading to loss.

[0006] Therefore, how to obtain a long-acting injectable formulation of vortioxetine hemipamoate with good needle penetration, high stability, good resuspension properties, and simple operation is a problem that needs to be solved by existing technologies. Summary of the Invention

[0007] In a first aspect, the present invention provides a suspension composition comprising vortioxetine hemiparmonate, a wetting agent, a suspending agent, a pH adjuster, and a solvent.

[0008] In some embodiments of the present invention, the suspension composition comprises:

[0009] Vortioxetine hemipamoate 10-50 parts by weight (e.g., 10, 12, 15, 17, 20, 22, 25, 27, 30, 32, 35, 37, 40, 42, 45, 47, 50 parts by weight), preferably 15-45 parts by weight, more preferably 20-40 parts by weight, and even more preferably 20-30 parts by weight;

[0010] The wetting agent is 1-5 parts by weight (e.g., 1, 2, 3, 4, 5 parts by weight), preferably 2-4 parts by weight, more preferably 2-3 parts by weight;

[0011] The suspending agent is 1-15 parts by weight (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 parts by weight), preferably 2-12 parts by weight, more preferably 4-10 parts by weight, and even more preferably 4-8 parts by weight.

[0012] pH adjuster, to adjust the pH value of the suspension composition to 4-8 (e.g. 4, 5, 6, 7, 8), preferably 5-7.5, more preferably 6-7;

[0013] Water 100-300 parts by weight (e.g., 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300 parts by weight), preferably 120-250 parts by weight, more preferably 150-200 parts by weight.

[0014] In some embodiments of the present invention, the wetting agent is selected from one or two of polysorbate, poloxamer, dehydrated sorbitan fatty acid ester, sodium carboxymethyl cellulose, RH40, Soluplus, SDS, HS15, and TPGS; preferably, the wetting agent is selected from poloxamer.

[0015] In some embodiments of the present invention, the suspending agent is selected from one or two of polyethylene glycol, povidone, methylcellulose, sodium carboxymethylcellulose, poloxamer, and hydroxypropylcellulose; preferably, the suspending agent is selected from poloxamer.

[0016] In some embodiments of the present invention, the pH adjuster is selected from one or more of hydrochloric acid, sulfuric acid, citric acid, sodium hydroxide, potassium hydroxide, sodium bicarbonate, and phosphates (such as disodium hydrogen phosphate and sodium dihydrogen phosphate). Preferably, the pH adjuster is selected from one or more of hydrochloric acid, citric acid, phosphates (such as disodium hydrogen phosphate and sodium dihydrogen phosphate), and sodium hydroxide; more preferably, the pH adjuster is selected from citric acid, sodium dihydrogen phosphate, and sodium hydroxide.

[0017] In some embodiments of the present invention, the solvent of the suspension composition is water, preferably water for injection.

[0018] In some embodiments of the present invention, the suspension composition comprises:

[0019] Vortioxetine hemipamoate 10-50 parts by weight (e.g., 10, 12, 15, 17, 20, 22, 25, 27, 30, 32, 35, 37, 40, 42, 45, 47, 50 parts by weight), preferably 15-45 parts by weight, more preferably 20-40 parts by weight, and even more preferably 20-30 parts by weight;

[0020] The wetting agent poloxamer is 1-5 parts by weight (e.g., 1, 2, 3, 4, 5 parts by weight), preferably 2-4 parts by weight, more preferably 2-3 parts by weight;

[0021] The suspending agent poloxamer is 1-15 parts by weight (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 parts by weight), preferably 2-12 parts by weight, more preferably 4-10 parts by weight, and even more preferably 4-8 parts by weight.

[0022] pH adjuster, used to adjust the pH of the suspension composition to 4-8 (e.g., 4, 5, 6, 7, 8), preferably 5-7.5, more preferably 6-7;

[0023] And 100-300 parts by weight of water (e.g., 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300 parts by weight), preferably 120-250 parts by weight, more preferably 150-200 parts by weight.

[0024] In some embodiments of the present invention, the suspension composition comprises:

[0025] 20-30 parts by weight of vortioxetine hemiparmonate;

[0026] Wetting agent: poloxamer, 2-3 parts by weight;

[0027] 4-8 parts by weight of poloxamer, a suspending agent;

[0028] pH adjuster, adjusts the pH value of the suspension composition to 6-7;

[0029] 150-200 parts by weight of water.

[0030] In some embodiments of the present invention, the suspension composition comprises:

[0031] Vortioxetine hemipamoate 10-50 parts by weight (e.g., 10, 12, 15, 17, 20, 22, 25, 27, 30, 32, 35, 37, 40, 42, 45, 47, 50 parts by weight), preferably 15-45 parts by weight, more preferably 20-40 parts by weight, and even more preferably 20-30 parts by weight;

[0032] Poloxamer 2-20 parts by weight (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 parts by weight), preferably 3-16 parts by weight, more preferably 4-12 parts by weight, and even more preferably 5-10 parts by weight;

[0033] pH adjuster, used to adjust the pH of the suspension composition to 4-8 (e.g., 4, 5, 6, 7, 8), preferably 5-7.5, more preferably 6-7;

[0034] And 100-300 parts by weight of water for injection (e.g., 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300 parts by weight), preferably 120-250 parts by weight, more preferably 150-200 parts by weight.

[0035] In some embodiments of the present invention, the suspension composition comprises:

[0036] 20-30 parts by weight of vortioxetine hemiparmonate;

[0037] 5-10 parts by weight of poloxamer;

[0038] pH adjuster, adjusts the pH value of the suspension composition to 6-7;

[0039] 150-200 parts by weight of water for injection.

[0040] Secondly, the present invention also provides a method for preparing a suspension composition, the method comprising the following steps:

[0041] (1) Mix vortioxetine hemipamoate and wetting agent solution evenly, and grind them using a ball mill to obtain grinding fluid;

[0042] (2) Prepare an excipient solution by mixing the suspending agent, pH adjuster and water for injection;

[0043] (3) The grinding liquid and the excipient solution are mixed evenly to obtain a suspension composition.

[0044] Preferably, the wetting agent is poloxamer; the wetting agent solution is an aqueous solution of poloxamer.

[0045] Preferably, in the preparation method, the suspending agent is poloxamer.

[0046] Preferably, the pH adjuster is citric acid, sodium dihydrogen phosphate, and sodium hydroxide.

[0047] In the suspension composition of the present invention, the average particle size of vortioxetine hemipamoate is less than 10 μm, for example, less than 8 μm, preferably less than 6 μm, and more preferably less than 5 μm.

[0048] Thirdly, the present invention also provides the use of the above-described suspension composition in the preparation of medicaments for treating 5-HT receptor-mediated diseases. In some embodiments, the 5-HT receptor-mediated diseases are selected from neurological disorders. Preferably, the neurological disorders are depression, postpartum depression, treatment-resistant depression, depression associated with bipolar disorder, anxiety disorders, obsessive-compulsive disorder, panic disorder, substance abuse, alcoholism, nicotine addiction, carbohydrate addiction, Alzheimer's disease, cognitive impairment, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain, visceral pain, migraine, and cancer-related pain.

[0049] Fourthly, the present invention also provides the use of the above-described suspension composition in the preparation of medicaments for treating neurological disorders. Preferably, the neurological disorders are depression, postpartum depression, treatment-resistant depression, depression associated with bipolar disorder, anxiety disorders, obsessive-compulsive disorder, panic disorder, substance abuse, alcoholism, nicotine addiction, carbohydrate addiction, Alzheimer's disease, cognitive impairment, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain, visceral pain, migraine, and cancer-related pain.

[0050] To provide a more concise description, the term "about" is not used for some quantitative data herein. It should be understood that, whether the term "about" is explicitly used or not, every numerical value given herein includes not only the actual given value (the given value), but also approximations of such a given value that would be reasonably inferred by one of ordinary skill in the art, including equivalents and approximations of such a given value due to experimental and / or measurement conditions. In some embodiments, the approximations are obtained by rounding based on measured values ​​or calculated data based on measured values. In some embodiments, the approximations are preferably ±20%, ±15%, ±10%, ±8%, ±6%, ±5%, ±4%, ±3%, 2%, or ±1% of the given value.

[0051] The vortioxetine hemipamoate suspension composition and its preparation method provided by this invention have five significant advantages: 1. Small burst release of the drug, allowing for slow and stable release in vivo with high safety; 2. Good resuspension properties, easy and uniform mixing with shaking, eliminating the need for complex reconstitution before injection, reducing the risk of introducing contamination; 3. No organic solvents are required in the preparation process, overcoming the problem of residual organic solvents in solvent-antisolvent preparation processes; 4. The wet grinding method allows for precise control of process parameters, high controllability of particle size, and scalable production; 5. By optimizing the dosage form and packaging materials, vortioxetine hemipamoate can be developed into a suspension injection and filled into pre-filled syringes, further improving the feasibility of industrialization, saving production costs, and making clinical use more convenient. Attached Figure Description

[0052] Figure 1 Blood concentration-time curves of vortioxetine hemipamoate suspension 1 and suspension 2 in rats. Detailed Implementation

[0053] The present invention will now be described in detail with reference to embodiments to facilitate understanding of the invention by those skilled in the art. It is particularly important to note that the embodiments are merely illustrative of the invention and should not be construed as limiting the scope of protection of the invention. Non-essential improvements and adjustments made to the invention by those skilled in the art based on the above description should still fall within the scope of protection of the invention. Furthermore, all raw and auxiliary materials mentioned below, unless otherwise specified, are commercially available products; all process steps or preparation methods not mentioned in detail are process steps or preparation methods known to those skilled in the art.

[0054] The raw materials and instruments used in this invention are sourced from the following sources:

[0055] Vortioxetine hemipamoate (homemade);

[0056] Planetary ball mill (Model: XQM-0.4A, Changsha Tianchuang Powder Technology Co., Ltd.);

[0057] Laser particle size analyzer (model: Mastersizer2000, Malvern).

[0058] Example 1: Screening of wetting agents

[0059] Tween 80, Tween 20, poloxamer 338, poloxamer 407, Soluplus, sorbitan laurate, RH40, HS15, sodium dodecyl sulfate, and TPGS were weighed and dissolved in water. Vortioxetine hemipamoate was then mixed with the above solution at a ratio of 1:9 (w / w) (the concentration of the wetting agent after mixing is shown in Table 1). The mixture was then ground using a planetary ball mill to obtain a grinding slurry. The feasibility of preparing the vortioxetine hemipamoate grinding slurry and the concentration of dissolved drug were used as evaluation indicators to determine the optimal wetting agent. Specific results are shown in Table 1.

[0060] Table 1: Experimental Results of Wetting Agent Screening

[0061]

[0062]

[0063] The experimental results showed that, among the 10 wetting agents initially screened, except for poloxamer 388 and poloxamer 407, all exhibited particle aggregation and / or excessively high drug concentrations during grinding. Particle aggregation during grinding indicates that the type and amount of wetting agent were inappropriate and failed to provide stabilization, resulting in uncontrollable particle size in the prepared samples. Excessively high drug concentrations in the grinding solution indicate that the wetting agent has a strong solubilizing effect on the drug, which may cause burst release in vivo, reducing safety and potentially causing sample stability issues. Considering both the solubility of vortioxetine hemipamoate and the wetting efficiency during preparation, poloxamer (e.g., poloxamer 338 or poloxamer 407) was selected as the wetting agent.

[0064] Example 2: Screening of suspending agents

[0065] Weigh 1.0 g of poloxamer 338 into 89 g of water and stir until dissolved. Weigh 10 g of vortioxetine hemipamoate and disperse it in the above poloxamer 338 solution. Mix well and grind using a planetary ball mill to obtain a vortioxetine hemipamoate grinding slurry. Weigh PEG4000, PEG3350, PVP K12, PVP K17, sodium carboxymethyl cellulose, and poloxamer 338 into water to prepare a total of 100 g of aqueous solution. After stirring to dissolve, mix with the vortioxetine hemipamoate grinding slurry (the concentration of the suspending agent after mixing is shown in Table 2) to obtain a vortioxetine hemipamoate suspension. The optimal suspending agent was determined by the particle size change (difference in particle size Dv50 between before and after mixing) and resuspension time (the suspension was allowed to stand at room temperature for 5 days, then vigorously shaken at an amplitude of approximately 25 cm until it was uniformly dispersed without any precipitate or clumps). Specific results are shown in Table 2.

[0066] Table 2: Experimental Results of Suspension Agent Screening

[0067]

[0068]

[0069] The experiment investigated different concentrations of each suspending agent. The results showed that poloxamer had a shorter resuspension time and smaller particle size change, so poloxamer was the preferred suspending agent.

[0070] Example 3: Preparation of vothioxetine hemipamoate suspension 1

[0071] Preparation of grinding slurry: Weigh 2g of poloxamer 338 into 78g of water and stir until dissolved. Weigh 20g of vortioxetine hemipamoate and disperse it in the above poloxamer 338 solution. Mix thoroughly and grind using a planetary ball mill until the average particle size (Dv50) is approximately 4.5μm. Preparation of excipient solution: Weigh 4g of poloxamer 338, 2g of citric acid, and 1.6g of sodium dihydrogen phosphate monohydrate into 92.4g of water. Stir until dissolved and adjust the pH to 7.0 with sodium hydroxide. Mix the grinding slurry and excipient solution thoroughly to obtain suspension 1.

[0072] Example 4: Preparation of vothioxetine hemipamoate suspension 2

[0073] Preparation of grinding slurry: Weigh 3g of poloxamer 338 into 67g of water and stir until dissolved. Weigh 30g of vortioxetine hemipamoate and disperse it in the above poloxamer 338 solution. Mix well and grind using a planetary ball mill until the average particle size (Dv50) is approximately 4.5μm. Preparation of excipient solution: Weigh 6g of poloxamer 338, 2g of citric acid, and 1.6g of sodium dihydrogen phosphate monohydrate into 90.4g of water and stir until dissolved. Adjust the pH to 7.0 with sodium hydroxide. Mix the grinding slurry and excipient solution evenly to obtain suspension 2.

[0074] Example 6: In vivo rat experiment

[0075] Ten male SD rats (purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.) were randomly divided into two groups. After shaking suspensions 1 and 2, the rats were injected vertically into the biceps brachii muscle of their right thigh using a syringe with a 23G needle. The dosage was 103 mg / kg (calculated as vortioxetine hemipamoate). Blood samples of 350 μL were collected from the orbital venous plexus at 0.25 h, 0.5 h, 6 h, 24 h, 96 h, 192 h, 336 h, 408 h, 504 h, 576 h, and 672 h after intramuscular injection. The blood samples were placed in anticoagulant tubes containing heparin sodium and centrifuged to obtain plasma. Centrifugation conditions were 3000 g, 4 °C for 10 min. The plasma samples were stored at -70 °C for analysis. The drug concentration in the plasma was determined using LC-MS / MS, and the pharmacokinetic parameters were calculated using a WinNonlin 8.0 non-compartmental model. The results are as follows: Figure 1 As shown.

[0076] The experimental results show that both final suspension 1 and final suspension 2 can maintain a certain drug concentration in rat plasma for a relatively long time, with stable blood drug concentration and high safety, allowing for administration once every two or four weeks.

Claims

1. A suspension composition comprising: Vortioxetine hemipamoyate, a wetting agent, a suspending agent, a pH adjusting agent, a solvent.

2. The suspension composition of claim 1, comprising: Vortioxetine hemipamoyate 10-50 parts by weight (e.g. 10, 12, 15, 17, 20, 22, 25, 27, 30, 32, 35, 37, 40, 42, 45, 47, 50 parts by weight), preferably 15-45 parts by weight, more preferably 20-40 parts by weight, even more preferably 20-30 parts by weight; A wetting agent 1-5 parts by weight (e.g. 1, 2, 3, 4, 5 parts by weight), preferably 2-4 parts by weight, more preferably 2-3 parts by weight; A suspending agent 1-15 parts by weight (e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 parts by weight), preferably 2-12 parts by weight, more preferably 4-10 parts by weight, even more preferably 4-8 parts by weight; A pH adjusting agent to adjust the pH of the suspension composition to 4-8 (e.g. 4, 5, 6, 7, 8), preferably 5-7.5, more preferably 6-7; Water 100-300 parts by weight (e.g. 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300 parts by weight), preferably 120-250 parts by weight, more preferably 150-200 parts by weight.

3. The suspension composition of claim 1 or 2, wherein the wetting agent is selected from one or two of polysorbate, poloxamer, sorbitan fatty acid ester, sodium carboxymethyl cellulose, RH40, Soluplus, SDS, HS15, TPGS; preferably, the wetting agent is selected from poloxamer.

4. The suspension composition of claim 1 or 2, wherein the suspending agent is selected from one or two of polyethylene glycol, povidone, methyl cellulose, sodium carboxymethyl cellulose, poloxamer, hydroxypropyl cellulose; preferably, the suspending agent is selected from poloxamer.

5. The suspension composition of claim 1 or 2, wherein the pH adjusting agent is selected from one or more of hydrochloric acid, sulfuric acid, citric acid, sodium hydroxide, potassium hydroxide, sodium bicarbonate, phosphate (e.g. disodium hydrogen phosphate, sodium dihydrogen phosphate); preferably, the pH adjusting agent is selected from one or more of hydrochloric acid, citric acid, phosphate (e.g. disodium hydrogen phosphate, sodium dihydrogen phosphate), sodium hydroxide; more preferably, the pH adjusting agent is selected from citric acid, sodium dihydrogen phosphate and sodium hydroxide.

6. A suspension composition comprising: Vortioxetine hemipamoyate 10-50 parts by weight (e.g. 10, 12, 15, 17, 20, 22, 25, 27, 30, 32, 35, 37, 40, 42, 45, 47, 50 parts by weight), preferably 15-45 parts by weight, more preferably 20-40 parts by weight, even more preferably 20-30 parts by weight; wetting agent, poloxamer 1-5 parts by weight (e.g. 1, 2, 3, 4, 5 parts by weight), preferably 2-4 parts by weight, more preferably 2-3 parts by weight; suspending agent, poloxamer 1-15 parts by weight (e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 parts by weight), preferably 2-12 parts by weight, more preferably 4-10 parts by weight, still more preferably 4-8 parts by weight; pH adjusting agent, adjusting the pH of the suspension composition to 4-8 (e.g. 4, 5, 6, 7, 8), preferably 5-7.5, more preferably 6-7; and water 100-300 parts by weight (e.g. 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300 parts by weight), preferably 120-250 parts by weight, more preferably 150-200 parts by weight.

7. A suspension composition comprising: vortioxetine hemipamoyate 20-30 parts by weight; wetting agent, poloxamer 2-3 parts by weight; suspending agent, poloxamer 4-8 parts by weight; pH adjusting agent, adjusting the pH of the suspension composition to 6-7; water 150-200 parts by weight.

8. A suspension composition comprising: vortioxetine hemipamoyate 10-50 parts by weight (e.g. 10, 12, 15, 17, 20, 22, 25, 27, 30, 32, 35, 37, 40, 42, 45, 47, 50 parts by weight), preferably 15-45 parts by weight, more preferably 20-40 parts by weight, still more preferably 20-30 parts by weight; poloxamer 2-20 parts by weight (e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 parts by weight), preferably 3-16 parts by weight, more preferably 4-12 parts by weight, still more preferably 5-10 parts by weight; pH adjusting agent, adjusting the pH of the suspension composition to 4-8 (e.g. 4, 5, 6, 7, 8), preferably 5-7.5, more preferably 6-7; and water for injection 100-300 parts by weight (e.g. 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300 parts by weight), preferably 120-250 parts by weight, more preferably 150-200 parts by weight.

9. A method for preparing the suspension composition according to any one of claims 1-8, the method comprising the following steps: (1) mixing vortioxetine hemipamoyate and the wetting agent solution uniformly, and grinding using a ball mill to obtain a grinding solution; (2) preparing the suspending agent, the pH adjusting agent and the water for injection into a auxiliary solution; (3) mixing the grinding solution and the auxiliary solution uniformly to obtain the suspension composition.

10. Use of a suspension composition according to any one of claims 1 to 8 for the manufacture of a medicament for the treatment of a 5-HT receptor mediated related disease; preferably the 5-HT receptor mediated related disease is selected from the group consisting of a neurological disorder; more preferably the neurological disorder is depression, postpartum depression, treatment resistant depression, depression associated with bipolar disorder, anxiety, obsessive compulsive disorder, panic disorder, drug abuse, alcoholism, nicotine addiction, carbohydrate addiction, Alzheimer's disease, cognitive disorders, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain, visceral pain, migraine and cancer related pain.

11. Use of a suspension composition according to any one of claims 1 to 8 for the manufacture of a medicament for the treatment of a neurological disorder; preferably the 5-HT receptor mediated related disease is selected from the group consisting of a neurological disorder; more preferably the neurological disorder is depression, postpartum depression, treatment resistant depression, depression associated with bipolar disorder, anxiety, obsessive compulsive disorder, panic disorder, drug abuse, alcoholism, nicotine addiction, carbohydrate addiction, Alzheimer's disease, cognitive disorders, chronic pain, neuropathic pain, nociceptive pain, inflammatory pain, visceral pain, migraine and cancer related pain.

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