Multicompartment compositions in the treatment of parkinson's disease

Abstract

The present invention relates to a solid composition for use in the treatment of Parkinson's disease comprising at least two compartments, a first active pharmaceutical ingredient (API) and a second API, preferably for increasing uptake of the second API and reducing side effects associated with the treatment of Parkinson's disease.

Description

As PD advances, the remaining cells may become less responsive to levodopa, requiring higher doses to achieve the same level of symptom control. Furthermore, as the duration of treatment with levodopa increases, higher doses maybe needed to maintain efficacy. Higher doses of levodopa are also associated with an increased risk of side effects and complications. Long-term use of levodopa is associated with the development of motor fluctuations, including wearing-off periods and on-off fluctuations. Wearing-off or end-of-dose-wearing-off refers to the diminishing effect of levodopa before the next dose is due, leading to a return of symptoms. Specifically, patients often suffer from the so-called freezing of gait symptom in this context. Accordingly, a common disadvantage of the prior art in treating PD with levodopa is that higher doses are necessarily required as the disease progresses. With long-term use of levodopa, individuals may experience “end-of-dose” periods where the effects of the drug before the next dose is taken, leading to a return of symptoms. In particular, patients may experience a decline in the therapeutic effects of levodopa towards the end of each dosing interval. This is known as “end-of-dose wear-off’ and can manifest as a return of PD symptoms, such as freezing of gait, before the next dose is due. In addition, some patients may experience 'on-off fluctuations, characterized by unpredictable swings between improved mobility (“on state”) and worsening symptoms (“off state”). Another common drawback is that they have limited effect on non-motor symptoms such as cognitive impairment, depression and autonomic dysfunction. Therefore, the underlying problem of the present invention is to provide an improved treatment of PD in order to at least partly overcome the above mentioned deficiencies of the prior art. A solution is provided according to the subject matter of claim i. 3. Summary of the invention While in the following, several compositions for use in the treatment of a disease are described, it is to be noted that the described subject-matter is to be understood as equivalents to methods of treatment, methods in treating, mode of treatment or any alternative wording. The above-mentioned problem is at least partly solved by a solid composition for use in the treatment of a condition associated with Parkinson’s disease, the composition comprising: at least two compartments separately arranged in the solid composition; a first active pharmaceutical ingredient, API, provided in a first compartment of the at least two compartments, wherein the first API is selected form the group of DOPA-decarboxylase inhibitors or catechol-O-methyltransferase (C0MT-) inhibitors; and a second API provided in a second compartment of the at least two compartments, wherein the second API is an amino acid. In the prior art mentioned above, the treatment of PD is based on orally administered formulations which usually requires increasing the individual dose during the course of the disease. In order to milder the symptoms of the individuals, the number of daily doses of the medical formulation is usually raised. This leads inevitably to increased side effects and “end of dose wearing off’ phenomena, in particular the “early morning off state” (EMO) such as freezing of gait. The patients experience a return of Parkinson's symptoms in the morning, which is usually the period just before the next scheduled dose. The present invention is based on a different approach. The advantageous effect is in particular that the pharmacokinetic characteristic of the solid composition is significantly altered. Furthermore, the bioavailability properties of the APIs in the solid composition are enhanced as compared to conventional compositions in the art. Specifically, the solid composition allows for a sequential release of the APIs, which may be desired when administering one or more individual APIs. In this manner, the solid composition allows for a convenient and efficient administration. In particular, the inventors have found that the solid composition according to present disclosure exhibits a 50 to 100% increase of area under the curve (AUC) of the second API when using the solid composition according to present disclosure. Moreover, when using the solid composition according to present disclosure, the total number of intakes of API is reduced in the course of the disease. This has the beneficial effect that when using the solid composition according to present disclosure, side effects associated with the second API are reduced or even removed. This is due to the fact that, due to the lowering of the second APIs dose, less API is degraded in peripheral tissues, which are responsible for API related side effects (immediate benefit). There is likely another positive effect. In case side effects are associated with the overall dose of the second API (e.g., dyskinesias), solid composition may substantially prolong the dyskinesia-free interval. Furthermore, the inventors have found that the solid composition allows for reducing the total dosage, for example required to reach a therapeutic benefit as compared with common compositions in the art. Furthermore, when, for example, a patient who is suffering from PD is treated with the solid composition according to present disclosure, a reduced number of daily doses is required as compared with the common composition as known in the art. This leads to reduced side effects in the patients when treating according to the method of present disclosure. Moreover, the solid composition reduces “end of dose wearing off’ phenomena, and in particular EMO such as freezing of gait. Accordingly, when for example patients are treated with the solid composition according to the present disclosure, the patients won’t suffer from returning PD symptoms, particularly in the morning. The inventors have found that the treatment of patients with PD by using the solid composition according to present disclosure increases and at the same time may enhance the bioavailability of the second API within the patients. Through this, the inevitable increase in dosage of the API during the course of the disease is postponed or even diminished. The inventors could show that due to this postponement and reduction in dosage, the total daily doses are further reduced as compared to the total daily doses required with conventional compositions. Accordingly, when using the solid composition of present disclosure, undesired side effects associated with the treatment by the specific APIs are successfully reduced and moreover, disease specific symptoms alleviated. “Using the solid composition”, “the solid composition when used” and / or “administering the solid composition” or “the solid composition when administered” according to present disclosure is to be understood and not limited to, as the intake and / or the ingestion of the solid composition by an individual. Furthermore, “Using the solid composition”, “the solid composition when used” and / or “administering the solid composition” or “the solid composition when administered” according to present disclosure is to be understood and not limited to, the process of dissolution of the solid composition. In some embodiments, use maybe prevention and / or treatment of Parkinson’s disease. The group of DOPA-decarboxylase inhibitors according to present disclosure comprises for example one or more of benserazide, carbidopa, methyl dopa, alpha-Difluoromethyl-DOPA (DFMD), 3',4',5,7-Tetrahydroxy-8-methoxyisoflavone, epigallocatechin gallate (EGCG) or epigallocatechin (EGC). The group of catechol-O-methyltransferase (C0MT-) inhibitors according to present disclosure comprises for example one or more of entacapone, nitecapone, opicapone or tolcapone. The amino acid according to present disclosure may be preferably an aromatic amino acid, a non-proteinogenic amino acid, and / or an ct-amino acid. The amino acid according to present disclosure may be preferably levodopa. In some embodiments, the first and / or second API may be selected from the groups of dopamine agonists, anticholinergics and / or MAO inhibitors. The compartments are preferably constituted such that they dissolve upon use. For example, when the composition is orally administered, the compartments dissolve in body fluids. The compartments may also dissolve in water. Accordingly, the compartments may comprise a base component being soluble in body liquids and / or water. The composition itself may thus also be soluble in body liquids and / or water. In some embodiments, the first compartment is arranged adjacent to the second compartment. The inventors have found that such an arrangement of the compartment positively impacts and increases the bioavailability of the APIs, and in particular the AUC of the APIs. Further, the adjacent arrangement of the compartments allows for a precise design of the composition to provide for customized and desired release characteristics of the APIs. The APIs may each be homogeneously arranged within the respective compartment. “Adjacent” according to present disclosure is to be understood and not limited to, as being arranged next to each other, either in direct contact, or separated from each other by for example another layer or compartment. For example, the first compartment may be arranged on top of the second compartment, or the first compartment may be also arranged under the second compartment. The first compartment maybe in direct contact with the second compartment. The first and the second compartment may be separated from each other by an additional layer which is located between the compartments. This additional layer may be for example a coating layer. In some embodiments the first compartment may encompass the second compartment. For instance, the first compartment maybe covering the second compartment such that the second compartment forms a core of the composition, while the first compartment forms a shell around the second compartment. In this manner, when using and / or administering the solid composition, the first compartment may dissolve before the second compartment. In some embodiments, the composition may have a plate-like structure, wherein a length of the structure may be larger than a height of the structure. This allows for convenient arrangement of the compartments, for example in an adjacent arrangement. Specifically, release and dissolution characteristics of the platestructures can be easily modified in this way. “Plate-like structure” according to present disclosure is to be understood and not limited to as a structure being rather planar, i.e. having a planar dimension being larger than its height. For instance, a plate-like structure may be a rectangular, squared or oval structure. In some embodiments, the compartments may be arranged adjacent to one another along the height of the plate-like structure of the composition. For example, the compartments may also be plate-like, and be arranged on top of each other to form the composition. This allows for specifically designing the solid composition in terms of its compartments. For instance, the same and / or different compartments maybe arranged adjacent to each other. In this manner, individual compositions can be achieved thereby allowing for efficient and patient-individualized usage (e.g., treatment). Moreover, the manufacturing process is simplified, as the compartments can be manufactured with similar manufacturing procedures. It is also conceivable that the composition maybe manufactured by using one single manufacturing step. In some embodiments, the second compartment may provide for at most 20%, preferably for at most 15%, more preferably for at most 10% of the total surface of the solid composition. The total surface of the solid composition impacts the pharmacokinetics, and in particular the bioavailability of the APIs. Specifically, in this way, the release characteristics of the second API is improved. Specifically, it has been found that the pharmacokinetic characteristic of the solid composition is improved. The solid composition comprising at most 20%, preferably at most 15%, more preferably at most 10%, for example of the second compartment, allows for an increase in total bioavailability of the second API. In some embodiments, the first API may be further arranged in a third compartment of the at least two compartments. Thus, the composition may comprise at least three separate compartments. In this way, the bioavailability of the second API is further improved when compared with the bioavailability of the individual APIs. The provision of the first API in a third compartment allows for better tailoring of the release profile of the first API. The compartments may be arranged such to encompass the In some embodiments the first and third compartments may have the same dimensions and API release characteristics. For example, the first and third compartment may have the same structural dimensions (length, width, height, form), and may consist of the same composition. This allows for simple manufacturing of the composition, and simple design of the release characteristics. In some embodiments, the first and third compartments may provide for at least 80%, preferably for at least 85%, more preferably for at least 90% of the total surface of the solid composition. The inventors have found that the total surface of the solid composition impacts the pharmacokinetics of the solid composition. Moreover, in this way, the bioavailability and the release characteristics of the different APIs is improved. Specifically, it has been found that in this way the pharmacokinetic characteristic of the solid composition is improved. The solid composition comprising at least 8o%, preferably for at least 85%, more preferably for at least 90% for example of the first and third compartment allows for an increase in total bioavailability of the solid composition. In some embodiments, the second compartment may be located between the first and the third compartment. For example, the second compartment maybe arranged as a layer in between the first and the third compartment leading to a sandwich-like structure. In this context, the first and third composition may be also arranged in layers. It is also conceivable that the second compartment is encapsulated within the first and third compartment. The inventors discovered that the bioavailability of the second API is increased as a consequence and that the therapeutic benefit is significantly increased. In some embodiments, the second compartment may have the same width and the same length as the first compartment. This has a positive impact on the dissolution characteristics, as well as on the release characteristics. Accordingly, these characteristics have a beneficial effect on the therapeutic use of the solid composition. In some embodiments, the first compartment is free of the second API, and wherein the second compartment is free of the first API. In this manner, it is ensured that the bioavailability of the second API is increased. In some embodiments, the composition for use maybe administered orally. For example, the solid composition may be orally administered by an individual. The individual may be a patient. Oral administration represents the most convenient and safest route of drug administration. In this way, convenient, non-invasive and patient compliant administration is enabled. Moreover, the independency of the patient during the course of the treatment is maintained. Furthermore, it has been found that the oral bioavailability of the APIs is increased as compared with the bioavailability of the individual APIs. In some embodiments, the first compartment maybe characterized by a first dissolution rate. In some embodiments the second compartment may be characterized by a second dissolution rate different from the first dissolution rate. The dissolution of the solid composition can be patient-individual designed. This allows for a better compliance and possibly to a beneficial course during the usage, i.e. treatment of the disease. In some embodiments, the first API and the second API may be released simultaneously or sequentially. “Sequential release”, “released sequentially” or “releasing in a sequential manner”, according to present disclosure is to be understood and not limited to as a subsequent and / or ordered release. For example, the first API is released first and / or before the second API. However, the second API may be also released meanwhile the first API is released. The sequential release allows for a more efficient dosage regimen during the course of the treatment. For example, the sequential release allows that the patient may not need to increase the dosage of the APIs to achieve the same therapeutic effect for example during the course of the disease. Accordingly, higher doses are not necessarily required as the disease progresses. Furthermore, the inventors have found that a sequential release reduces ”end-of-dose” periods. Accordingly, a decline in the therapeutic effect of the APIs towards the end of each dosing interval is diminished and / or even prevented. For example, freezing of gait symptoms, in particular in the morning before the first dose is due, is relieved. In some embodiments, the release of the first API may have a first peak maximum of API release in % over time, and the release of the second API may have a different, second peak maximum of API release in % over time. In this way, the individual peak maxima of API release in % occur in a sequential manner. The sequential release allows for a more efficient dosage regimen during the course of the treatment. In some embodiment, the second peak maximum may be subsequent to the first peak maximum. This has the particular advantage that the first API is released and can pharmacologically affect in higher concentrations than the second API. This is because the second peak maximum of API release in % for the second API is delayed as compared with the first peak maximum of API release in % for the first API. In some embodiments, the treatment may be characterized in a reduction of a side effect associated with Parkinson’s disease. The side effect may be related to API 1 and / or API 2. Further, the side effect maybe a long-term and / or a shortterm side effect. Accordingly, side effects associated with Parkinson’s disease are reduced. This has the advantage, that the therapeutic and clinical benefit is increased in patients when treating with the solid composition according to present invention. In some embodiments, the side effect associated with Parkinson’s disease may be a side effect selected from a motor and / or a non-motor symptom. The treatment in particular reduces motor and / or non-motor symptoms. These symptoms occur usually in the course of the disease and negatively affect the therapeutic benefits. Accordingly, by reducing motor and / or non-motor symptoms, the therapeutic benefit can be raised. In some embodiments, the motor and / or the non-motor symptom may be selected from one or more of bradykinesia, impaired mobility, tremor, rigidity, dysphagia or freezing of gait, FOG, preferably bradykinesia, impaired mobility, tremor or FOG, more preferably FOG. Specifically, by reducing one or more of these symptoms, the compliance and the overall therapeutic benefit is increased. In some embodiments, the use maybe in prevention and / or treatment of Parkinson’s disease. In particular, it is desirable to prevent and / or treat Parkinson’s disease, which can result in an improved quality of life. In some embodiments, the total dosage of the first API may be between 5 mg and 50 mg, preferably between 10 mg and 40 mg, more preferably between 15 mg and 35 mg. Specifically, it has been shown that these dosages impact the pharmacokinetics and moreover, allow for an increased bioavailability of the APIs. Moreover, this allows for an improved course in the treatment. In some embodiments, the total dosage of the second API may be between 50 mg and 500 mg, preferably between 80 mg and 250 mg, more preferably between 90 mg and 150 mg; or preferably between 120 mg and 450 mg, more preferably between 150 mg and 400 mg. The inventors have shown that these dosages for the second API improve the pharmacokinetics of the API and of the solid composition and in particular improves the bioavailability of the APIs. In some embodiments, the first API may be carbidopa and the second API may be levodopa. The inventors have found that when the first and the second API may be carbidopa and levodopa, the therapeutic benefit as compared to a conventional composition is increased. In some embodiments, the solid composition according to present disclosure may be administered daily, and wherein the total daily dose of carbidopa may be between 30 mg and 300 mg, preferably between 50 mg and 250 mg, more preferably between 80 mg and 200 mg. This allows for reduced side effects as compared to conventional total daily doses. Moreover, this leads to reduced intakes of the solid composition during the day. For example, the solid composition maybe administered 5 times during the day, preferably 4 times, more preferably 3 times. In some embodiments, the solid composition according to present disclosure may be administered daily, and wherein the total daily dose of levodopa may be between 150 mg and 2000 mg, preferably between 250 mg and 1200 mg, more preferably between 300 mg and 1000 mg. In this way, side effects associated with levodopa are decreased while maintaining the same or even enhanced therapeutic effect. Moreover, it has been shown that freezing of gait symptoms can be significantly reduced in patients during the course of the treatment. In some embodiments, when used, the first API may be released immediately upon use of the composition. Accordingly, this enhances the bioavailability of the APIs and lead to an improved treatment of PD. In some embodiments when the solid composition is used, the first API is released in less than 3 hours, preferably 2 hours, more preferably 1 hour. In this manner, an immediate release of the first API takes place. This has shown to lead to an enhanced bioavailability of the second API and, overall, of the solid composition. In some embodiments when the solid composition is used, the second API is released in less than 6 hours, preferably 3 hours, more preferably 2 hours. Accordingly, the extended release of the second API allows for the enhancement in bioavailability of the API. In some embodiments, the solid composition may further comprise one or more of: a pharmaceutically acceptable coating, a pharmaceutically acceptable carrier, or a pharmaceutically acceptable substituent. In this way, the solid composition can be provided in a pharmaceutically acceptable form. This allows for the pharmaceutical application of the solid composition for an improved treatment. 12 In some embodiments the composition maybe a tablet. In this way, a userfriendly and convenient administration is provided. In particular, this embodiment can be manufactured in a time and cost-efficient way. In some embodiments, the tablet may have a toroidal, oval and / or rectangular shape. The inventors have found that the shape may impact the pharmacokinetics of the solid composition. In this way, it is possible to design and tailor a therapeutic treatment based on individual needs of the patients. 4.     Short description of the figures Possible embodiments of the present invention are further described in the following detailed description, with reference to the following figures, wherein: Fig. 1: illustrates schematically a solid composition according to an embodiment of the present disclosure. Figs. 2a and 2b: illustrate the release characteristics and the bioavailability of a solid composition according to an embodiment of the present disclosure and illustrates the improvement in bioavailability of a solid composition according to an embodiment of the present disclosure. Fig. 3: illustrates the dissolution profile of a solid composition in comparison with conventional release modified compositions. Fig. 4a and 4b: illustrate multicompartment compositions according to an embodiment of the present disclosure. Fig. 5: illustrates the dissolution profiles and AUCs of a composition comprising levodopa and carbidopa according to an embodiment of the present disclosure in comparison to conventional release modified compositions. Fig. 6: illustrates the dissolution profiles of shaped tablets comprising different compartments according to an embodiment of the present disclosure. Fig. 7:                illustrates the dissolution profiles of shaped tablets comprising different compartments according to an embodiment of the present disclosure. 5. Detailed description of possible embodiments It is to be noted that individual embodiments of the invention are described in greater detail below. However, it is clear to the person skilled in the art that the design possibilities and optional features described in relation to these specific embodiments can be further modified and combined with one another in a different manner within the scope of the present invention and that individual steps or features can also be omitted where they appear to be unnecessary. In order to avoid redundancies, reference is made to the explanations in the previous sections, which also apply to the following detailed description. In Fig. 1, a tablet (10) being a solid composition (left in Fig. 1) is shown next to a conventional composition in the art (right in Fig. 1). Specifically, Fig. 1 illustrates a tablet (10) for use in the treatment of a condition associated with Parkinson’s disease is shown. The tablet comprises three compartments (11,12,13), which are separately arranged in the tablet (10). A first API is provided in the first compartment (11), wherein the first API is carbidopa, which is a DOPA-decarboxylase inhibitor. In the embodiment shown in Fig. 1, carbidopa is further arranged in the third compartment (13). The second API is provided in the second compartment (12) of the tablet (10), wherein the second API is levodopa. Accordingly, in the embodiment of Fig. 1, the first API is carbidopa which is provided in the first (11) and the third (13) compartment, and the second API is levodopa which is provided in the second compartment (12). The compartments are arranged adjacent to each other, such that the second compartment (12) is arranged between the first (11) and third (13) compartment. The compartments are in direct contact with each other and are of the same structure. The tablet (10) as shown in Fig. 1 comprise a plate-like structure and has an oval shape. Specifically, the plate-like structure has a length that is greater than the height of the structure. The three compartments (11,12,13) are also plate-like, and are arranged such that they are stacked on top of each other. The three compartments (11,12,13) are arranged adjacent to one another along the height of the plate-like structure, i.e. they are arranged on top of one another. As can be seen, the first (11) and the third (13) compartment have the same structural dimensions. In particular, the first (11) and the third (13) compartment have the same length, width and height. The second compartment (12) has the same planar characteristics as the first (11) and the third (13) compartment, i.e. the same length and width, but has a different height. The second compartment (12) provides for 20% of the total surface of the tablet (10), namely at the edge of the tablet (10). The first (11) and third (13) compartment together provide for 80% of the total surface of the tablet (10). The top and bottom surfaces of the tablet (10) are defined by the first compartment (11) and the third compartment (13), respectively. The main surfaces of the second compartment (12) are fully covered by the first compartment (11) and the third compartment (13). The side of the tablet (10) is defined by all three compartments. At its side, the second compartment (12) is not covered by the other two compartments (11,13). The compartments are constituted such that they dissolve when used, for example when orally administered. Accordingly, when the tablet (10) is used, the tablet is dissolving. As will be appreciated by the skilled person, when the compartments are dissolving, the respective APIs are released. The initial dissolution phase is characterized by release of the carbidopa arranged in the outer compartments of the tablet (10). Minor amounts of levodopa are also be released during the initial dissolution phase, at the edge side of the tablet (10). When the first and third compartments are fully dissolved, the subsequent dissolution phase is characterized by a strong release of the levodopa. In the embodiment shown in Fig. 1, the first compartment (11) has the same dimensions and API release characteristics as the third compartment (13). They differ from the dimensions and API release characteristics of the second compartment (12). This is in particular illustrated in Fig. 2a. Fig. 2a illustrates the blood level profiles (bottom) for carbidopa (API 1) and levodopa (API 2) and their corresponding AUC profiles (top). In Fig. 2a, bottom two curves are shown (dotted lines), each curve indicating the measured concentration of API over time. The first curve indicating the blood level of carbidopa raises immediately and reaches a plateau before the curve for levodopa. In turn, the second curve indicating the blood level for levodopa, raises slower over time and reaches a higher maximal concentration (Cmax) as compared to the first curve. In other words, the measured blood level of carbidopa which is released from the first compartment (n) has a blood level that is different from the measured blood level of levodopa, which is released from the second compartment (12) (Fig. 2a bottom). Specifically, carbidopa is faster released as compared to levodopa. Moreover, carbidopa reaches a plateau (Cmax) when approximately ¥2 of the total levodopa is released. When the tablet (10) as shown in Fig. 1 is used, carbidopa (Fig. 2a, “API 1”) and levodopa (Fig. 2a, “API2”) are released simultaneously. The amount of carbidopa which is released is greater than the amount of levodopa. This can be seen in Fig. 2 top, wherein the AUC profiles for carbidopa and levodopa after administration of a tablet are shown. Carbidopa has a peak maximum which occurs before the peak maximum of levodopa. The release of carbidopa is characterized by a first peak maximum of API release in % over time and the release of levodopa has a different, second peak maximum of API release in % over time. This second peak maximum is subsequent to the first peak maximum (Fig. 2a top). Since carbidopa is arranged in the first compartment (11) and the third compartment (13), it is faster released than levodopa when the tablet (10) is used. Returning to Fig. 1, the second compartment (12) of the tablet (10) has the same length as the first compartment (11), but a different width. The first compartment (11) is free of the second API, and the second compartment (12) is free of the carbidopa. Also, the third compartment (13) is free of the levodopa. However, it is conceivable that in some embodiments the third compartment (13) also comprises the levodopa. The following table illustrates preferred characteristics (diameter d, height h, width b, surface area SA, hardness in N, mass in g and the dissolution in %) of a tablet according to the present disclosure: d [mm] h [mm] b [mm] SA [mm2] Oval 14 2.72 5 220.96 Oval 14 0.44 5 144.10 Total 3.6 V [mmd SA / V [mm*] m [mg] m API [mg] Oval 175.81 1.26 167.02 100.2 Owl 28.44 5.07 27.017 12.5 Hardness       78.3 N (+4.0¾) Friability         0.066% Mass uniformity m (gj h [mm] d [mm] b [mm] 214.6 + 3.4(1.6%) 3.85 40.04 (1.1%) 13.52 ± 0.05 (0.4%) 4.69 + 0.05(1.0%) Dissolution 100 % CAR release after 60 min 100% LEV release after 120 min Comparative dissolution studies Fig. 2b shows in a comparative manner the AUC profile of a conventional composition (left in Fig. 2b) in the art as compared to the solid composition of 5             present disclosure (right in Fig. 2b). Specifically, it can be seen that the AUC curves for carbidopa (API i) and levodopa (API 2) in the solid composition are arranged in a sequential manner (Fig. 2b on the right). Particularly, the APIs can reach a higher increase in the maximum concentration (Cmax) as compared to the conventional composition in vivo (Cmax). Moreover, Fig. 2b shows that the 10            use of the solid composition not only leads to an increase in concentration of levodopa which is present after use but also in the total AUC of the APIs. These results show that the solid composition according to present disclosure can effectively increase the bioavailability of levodopa in vivo. In Fig. 3 the dissolution profiles of the solid composition are compared to 15            conventional compositions known in the art. In particular, dissolution profiles for a tablet are shown. The material released (shown as average API content in %) of the tablet comprising carbidopa (API 1) and levodopa (API 2) of two conventional compositions has been measured in vitro over 300 minutes. The conventional compositions shown in Fig. 3 are 1) an immediate release formulation and 2) a retard formulation. As can be seen in Fig. 3, the release characteristics of the two compartments in the tablet are comparable with the release characteristics of an immediate and extended release formulation. In particular, it is shown that carbidopa in the tablet is quickly released resembling the conventional immediate composition. This quick release can be seen in the steep rise of the first graph. Levodopa (API 2) is, on the other hand, released more slowly as compared to carbidopa (API 1). Levodopa resembles a release-modified composition, such as a retard formulation. Accordingly, the tablet combines the release characteristics of two different formulations. In a further embodiment, the tablet combines more than two release characteristics. Multicompartment compositions In Figs. 4a and 4b several preferred embodiments are shown. In particular, tablets (10) are shown that comprise two or three compartments. These compartments comprise either the same or different APIs and release characteristics. Particularly, tablets (10) in form of a multi compartment tablet are shown. These multicompartment tablets are produced by using common printing methods. Printing methods comprise screen printing, 3D printing, or 3D screen printing. As can be seen, the compartments of the tablets (10) are either adjacent to each other along the plate-like structure (in the Figs. 4a and 4b, on the right) or arranged in a coating manner (in the Figs. 4a and 4b, on the left). In Fig. 4a on the left, a tablet (10) is shown in which the first compartment (11) encompasses the second compartment (12). The first compartment (11) comprises the first API, and the second compartment (12) comprises the second API. The first compartment (11) is free of the second API and the second compartment (12) is free of the first API. In this particular embodiment, the first (11) and the second (12) compartment have different dimensions and API release characteristics. In particular, the compartments have different height, width and length. Specifically, the second compartment (12) provides for 0% of the total surface of the solid composition and the first compartment (11) provides for 100% of the total surface of the tablet (10). In this manner, when the tablet is used, the first API is released completely before the second API is released. Accordingly, the uptake of the first API occurs before the uptake of the second API. In this way, the bioavailability for the second API is enhanced. In Fig. 4a on the right, a tablet (io) is shown in which the first compartment (ii) is adjacent to the second compartment (12) along the plate-like structure. In this particular embodiment, the first compartment (11) has a different height than the second compartment (12). The height of the first compartment (11) is larger than the height of the second compartment (12). As can be seen, the second compartment (12) is arranged on top of the first compartment (11). The compartments are in direct contact to each other. The first compartment (11) comprises the first API, and the second compartment (12) comprises the second API. The first compartment (11) is free of the second API and the second compartment (12) is free of the first API. In this particular embodiment, the compartments have different API release characteristics. Further embodiments may comprise a third compartment (13), which is illustrated in Fig. 4b. Specifically, Fig. 4b on the left shows a tablet (10) for use according to present disclosure, and in particular a tablet (10) which can be orally administered. The tablet comprises three compartments (11,12,13). The third compartment (13) of the at least two compartments is encompassed by the second compartment (12), which itself is encompassed by the first compartment (11). In this manner, the first compartment (11) provides for 100% of the total surface of the tablet (10). On the other hand, the second (12) and the third compartment (13) provide for 0% of the total surface of the tablet (10). In particular, the compartments have different height, width and length. The tablet (10) shown in Fig. 4b, comprises a first API, which is arranged in the first (11) and the third compartment (13). These compartments are free from the second API, which is arranged in the second, middle, compartment (12). In this manner, the total amount of the first API is not released before the second API. In this particular embodiment, the second API is released when the first API has completely been released from the first compartment (11). After complete release of the second API, the first API is further released from the third compartment (13). It is conceivable, that the third compartment (13) comprise a third API which is different from the first and second API. In this particular embodiment shown in Fig. 4b on the left, the compartments are arranged in a centrosymmetric manner. It is conceivable, that the compartments are differently arranged, which changes the release characteristics. In Fig. 4b on the right, a tablet (10) is shown which comprises three compartments. The first (11), second (12) and third (13) compartment are arranged on top of each other and in particular, adjacent to each other along the plate-like structure of the tablet (10). These compartments (11,12,13) are in direct contact to each other. The first (11) and third (13) compartments have the same dimensions and API release characteristics. The second compartment (12) has different dimensions and API release characteristics. Specifically, the first (11) and the third (13) compartment provide for at least 80% of the total surface of the tablet (10). In this particular embodiment, when the tablet is used, the two APIs are released simultaneously. However, the first API is released in a larger amount, which is due to the larger portion of the total surface. During this stage, small amount of the second API is released. After the first API is released completely from the first (11) and the third (13) compartment, the second API is released in a larger amount (“sequential”). In this way, the peak maxima of the AUC curves for the first and the second APIs occur subsequently, i.e. the peak maximum of the first API occurs before the peak maximum of the second API. Increased bioavailability and reduction of dose In vitro dissolution testing Dissolution experiments were performed according to the USP monograph “Acetaminophen tablets” section dissolution of the US Pharmacopeia. A Vankel® VK 7000 dissolution paddle apparatus equipped with a VK750D heater were used for the dissolution experiments. Dissolution was performed using 900 mL phosphate buffer, pH = 5.8 at 37.0 ± 0.5 °C, with stirring at 50 rpm. Wire claps were used to fix the tablets at the bottom of the vessel during the experiment. Analysis (n=6) was performed using a Thermo® Evolution 300 UV / Vis spectrophotometer equipped with flow-through cuvettes run by an Ismatec® IPS multichannel peristaltic pump. Absorption at X=243 nm was measured continuously over 8h using the Thermo vision Pro software. A calibration curve in the range of 2 - i50mg Paracetamol was made, which correlated with R = 0-9999 In vivo testing Tablet administration: • Measurement of drug uptake after tablet application using gastroscopic technique directly into the stomach of pigs • Active ingredient concentrations are measured in the blood up to 24 hours after application. • Measuring points: 30, 60, 90, 120, 180, 240, 360, 480 minutes and 24 hours Analytical method: Plasma samples were prepared according to Cesar et al.; “Development and validation of a high-performance liquid chromatography-electrospray ionization MS / MS method for the simultaneous quantitation of levodopa and carbidopa in human plasma” J. Mass. Spectrom. 2011, (46), 943-948 by protein precipitation with perchlorate and addition of methyldopa as an internal standard; centrifugation was performed at 2000 rpm and 5°C for 15 minutes. Samples were analyzed by ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry using a THERMO (Bremen, Germany) UltiMate HPG-3400 RS binary pump and a WPS-3000 auto-sampler set at 10 °C and equipped with a 25 pL injection syringe and a 100 pL sample loop. The column was stored at 25 °C in the column chamber TCC-3200. THERMO Accucore® C-18 RP (too x 2.1 mm; 2.6 pm) was used as the chromatography column using the gradient in Table 2 at a constant flow rate of 0.4 mL / min. Eluent A was water with 2% acetonitrile and 0.1% formic acid. Eluent B was pure acetonitrile. Mass spectra were recorded using a THERMO QExactive plus Orbitrap mass spectrometer coupled to a heated electrospray source (HESI). The solid composition of present disclosure has been studied towards its release characteristics in vitro and its bioavailability in vivo. For the in vitro and in vivo experiments, the tablet (io) has been used and administered. Following dosages were used and administered respectively: a tablet with the total dosage of carbidopa between io mg and 15 mg, and the total dosage of the levodopa between 90 mg and 150 mg was used in the in vitro study and administered in the in vivo study. The average API content in % of the tablet comprising carbidopa as the first API (“API 1 in a solid composition”) and levodopa as the second API (“API 1 in a solid composition”) has been measured in vitro over 200 min and were compared to two conventional compositions (“API 1 conventional / API 2 conventional” and “API 1 retard / API 2 retard”). The corresponding dissolution profiles for these conventional formulations are depicted in Fig. 5 on the left. As can be seen, the release characteristics of carbidopa (“API 1 in a solid composition”) of the tablet is comparable with the dissolution profile of an immediate release formulation of carbidopa (“API 1 conventional”). Further, the release characteristics of levodopa (“API 1 in a solid composition”) of the tablet is comparable with the dissolution profile of an extended-release formulation of levodopa (“API 2 retard”). In particular, it is shown that the tablet releases carbidopa immediately upon use of the tablet. The dissolution profile for this immediate release of carbidopa upon use resembles the dissolution profile of the conventional immediate composition. Levodopa is on the other hand released slower as compared to carbidopa in the tablet and in particular is resembling a release-modified composition, such as a retard formulation. Particularly, as can be seen in Fig. 5 on the left, the carbidopa of the tablet has an average API release of too wt. % in less than 1 hour, preferably 2 hours, more preferably 1 hour. Levodopa in the tablet is characterized by an average API release of too wt. % in less than 2 hours. For the in vivo study, the tablet is administered orally. After administration, the API content has been measured over 24 hours (1600 min) after administration. In Fig. 5 on the right, the in vivo data for the tablet (indicated as “LD sandwich table!’) as discussed in Fig. 5 on the left is shown. From these measured data, the bioavailability has been calculated by plotting the AUC which can be seen in Fig. 5 on the right. In particular, the tablet reaches 89 (AUC 89) which is an 100% increase in bioavailability for levodopa when compared to the conventional immediate release composition (AUC 40) (e.g. Sinemet). In comparison to a release-modified composition, the tablet according to the present disclosure reaches a 50% increase in bioavailability for levodopa when compared to the conventional retard composition, which reaches (AUC 60) (e.g. Dopadura Retard). Consequently, the AUC of the tablet is significantly different as compared to the individual AUC of the conventional formulations (indicated as “LD Dopadura retard” and “LD Sinemet” in Fig. 5 on the right). Specifically, the AUC of levodopa when administered in the tablet is enlarged as compared to the conventional compositions. Accordingly, the bioavailability for levodopa when administering the tablet differs significantly in vivo from the bioavailability of the individual APIs in conventional formulations. In this way, when using the tablet of present disclosure, the treatment of a patient who requires for example 6 conventional doses per day is reduced drastically, to only 3 doses per day by using the solid composition of present disclosure. At the same time, the prolonged bioavailability reduces freezing of gait symptoms in the morning, when the first dose of the day is due. In conclusion, the in vitro and in vivo data demonstrate the enhanced pharmacokinetics and increase in bioavailability, when compared to conventional compositions. These results further demonstrate the potential effective use of the tablet in the treatment of PD. Particularly, the solid composition is used in the prevention and treatment of PD. As a higher bioavailability is reached (Fig. 5 on the right), the dosage required to achieve a therapeutic benefit can be reduced. In this way, a treatment with reduced side effects associated with PD can be achieved. In particular, the side effects, such as motor and / or a non-motor symptom is consequently reduced. In this manner, “end of dose wearing off’ phenomena such as freezing of gait (FOG) is reduced as the bioavailability is even prolonged as compared to the conventional compositions (see Fig. 5 on the right and Fig. 2b). Shape and composition In Fig. 6 the dissolution profile for three preferred embodiments, i.e. for tablets with a rectangular shape, a toroidal shape and an oval shape are shown. As can be seen the different shaped tablets comprise one or more compartments with different API release characteristics. In particular and as compared to the known dissolution profiles for an immediate and extended-release formulation, the dissolution profile for the rectangular composition resembles an immediate release formulation. On the other hand, the dissolution profile of the oval shaped composition is similar to an extended-release formulation. The toroidal shaped composition is a “mixed-type”, which shows a dissolution which resembles an immediate profile in the first 20 mins and subsequently to the extended release profile. In Fig. 7 the dissolution profiles for a toroidal shaped tablet according to present disclosure are shown. In particular, it is shown that the toroidal tablet comprises one API in two different compartments with two different API release characteristics (immediate and extended). Specifically, embodiments with the following proportions are used: 100% immediate, 75% immediate and 25% extended, 50% immediate and 50% extended, 25% immediate and 75% extended and 100% extended. By changing the proportion between the two compartments within the toroidal tablet, different dissolution profiles are achieved. While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided byway of example only. It is not intended that the invention be limited by the specific examples provided within the specification. While the invention has been described with reference to the aforementioned specification, the descriptions and illustrations of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. Furthermore, it shall be understood that all aspects of the invention are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the invention described herein maybe employed in practicing the invention. It is therefore contemplated that the invention shall also cover any such alternatives, modifications, variations or equivalents. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

1. A solid composition for use in the treatment of a condition associated with Parkinson’s disease, the composition comprising:at least two compartments separately arranged in the solid composition;a first active pharmaceutical ingredient, API, provided in a first compartment (n) of the at least two compartments, wherein the first API is selected from the group of DOPA-decarboxylase inhibitors and / or catechol-O-methyltransferase (C0MT-) inhibitors; anda second API provided in a second compartment (12) of the at least two compartments, wherein the second API is an amino acid.

2. The solid composition for use according to claim 1, wherein the first compartment (11) is arranged adjacent to the second compartment ¢12).

3. The solid composition for use according to claim 1 or 2, wherein the first compartment (11) encompasses the second compartment (12).

4. The solid composition for use according to claim 1 or 2, wherein the composition has a plate-like structure, wherein a length of the structure is larger than a height of the structure.

5. The solid composition for use according to claim 4, wherein the compartments are arranged adjacent to one another along the height of the plate-like structure of the composition.

6. The solid composition for use according to claim 4 or 5, wherein the second compartment (12) provides for at most 20%, preferably for at most 15%, more preferably for at most 10% of the total surface of the solid composition.

7. The solid composition for use according to any one of claims 4 to 6, whereinthe first API is further arranged in a third compartment (13) of the at least two compartments.

8. The solid composition for use according to claim 7, wherein the first and third compartments (11,13) have the same dimensions and API release characteristics.

9. The solid composition for use according to claim 7 or 8, wherein the first and third compartments (11,13) provide for at least 80%, preferably for at least 85%, more preferably for at least 90% of the total surface of the solid composition.

10. The solid composition for use according to any one of claims 7-9, wherein the second compartment (12) is arranged between the first compartment (11) and third compartment (13).

11. The solid composition for use according to any one of claims 4 to 9, wherein the second compartment (12) has the same width and length as the first compartment (11).

12. The solid composition for use according to any of the preceding claims, wherein the first compartment (11) is free of the second API, and wherein the second compartment (12) is free of the first API.

13. The solid composition for use according to any of the preceding claims, wherein the composition is administered orally.

14. The solid composition for use according to any of the preceding claims, wherein the first compartment (11) is characterized by a first dissolution rate; and wherein the second compartment (12) is characterized by a second dissolution rate different from the first dissolution rate.

15. The solid composition for use according to any one of the preceding claims, wherein, when used, the first API and the second API are released simultaneously or sequentially.

16. The solid composition for use according to the preceding claim, wherein, when used, the release of the first API has a first peak maximum of API release in % over time, and the release of the second API has a different, second peak maximum of API release in % over time.

17. The solid composition for use according to the preceding claim, wherein the second peak maximum is subsequent to the first peak maximum.

18. The solid composition for use according to any of the preceding claims, wherein the treatment is characterized in a reduction of a side effect associated with Parkinson’s disease.

19. The solid composition for use according to the preceding claim, wherein the side effect associated with Parkinson’s disease is a side effect selected from a motor and / or a non-motor symptom.

20. The solid composition for use according to the preceding claim, wherein the motor and / or the non-motor symptom is selected from one or more of bradykinesia, impaired mobility, tremor, rigidity, dysphagia, or freezing of gait, FOG, preferably bradykinesia, impaired mobility, tremor or FOG, more preferably FOG.

21. The solid composition for use according to any of the preceding claims, characterized in that the use is in prevention and / or treatment of Parkinson’s disease.

22. The solid composition for use according to any of the preceding claims, wherein the total dosage of the first API is between 5 mg and 50 mg,preferably between io mg and 40 mg, more preferably between 15 mg and 35 mg.

23. The solid composition for use according to any of the preceding claims, wherein the total dosage of the second API is between 50 mg and 500 mg, preferably between 80 mg and 250 mg, more preferably between 90 mg and 150 mg; or preferably between 120 mg and 450 mg, more preferably between 150 mg and 400 mg.

24. The solid composition for use according to the preceding claim, wherein the first API is carbidopa and the second API is levodopa.

25. The solid composition for use according to the preceding claim, wherein said composition is administered daily, and wherein the total daily dose of carbidopa is between 30 mg and 300 mg, preferably between 50 mg and 250 mg, more preferably between 80 mg and 200 mg.

26. The solid composition for use according to claim 24 or 25, wherein said composition is administered daily, and wherein the total daily dose of levodopa is between 150 mg and 2000 mg, preferably between 250 mg and 1200 mg, more preferably between 300 mg and 1000 mg.

27. The solid composition for use according to any of the preceding claims, wherein, when used, the first API is released immediately upon use of the composition.

28. The solid composition for use according to any of the preceding claims, wherein, when used, the first API is released in less than 3 hours, preferably 2 hours, more preferably 1 hour.

29. The solid composition for use according to any of the preceding claims, wherein, when used, the second API is released in less than 6 hours, preferably 3 hours, more preferably 2 hours.

30. The solid composition for use according to any of the preceding claims, further comprising one or more of: a pharmaceutically acceptable coating, a pharmaceutically acceptable carrier, or a pharmaceutically acceptable substituent.1031. The solid composition for use according to any of the preceding claims,wherein the composition is a tablet (10).

32. The solid composition for use according to the preceding claim, wherein the15tablet (10) has a toroidal, oval and / or rectangular shape.

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