Polysaccharide-based composition

Abstract

Disclosed is a composition comprising a polysaccharide and a first acid, the polysaccharide comprising sucrose and a maltodextrin, the first acid comprising citric acid, malic acid, and / or tartaric acid, wherein the weight ratio of the maltodextrin to the first acid is 2:1 or higher. Further disclosed a formulation prepared from the composition. Also disclosed is a composition of oral dry powder formulation comprising a polysaccharide and a first acid, the polysaccharide comprising sucrose and a maltodextrin, the first acid comprising citric acid, malic acid, and / or tartaric acid, and the composition further comprising acetaminophen (APAP) and another active pharmaceutical ingredient different from acetaminophen (APAP), wherein the weight ratio of the maltodextrin to the first acid is 2:1 or higher.

Description

POLYSACCHARIDE-BASED COMPOSITIONINVENTION FIELD

[0001] The present invention relates to a polysaccharide-based composition, in particular to a formulation of polysaccharide-based composition.BACKGROUND

[0002] Polysaccharides (such as, sucrose and maltodextrin) can be used as fillers, binders, and sweeteners, which are widely used in oral dry powder formulation products such as drugs, dietary supplements and beverages to balance the taste of products and / or increase the flavor of products. Likewise, pH adjusters such as citric acid and sodium citrate are also common ingredients / additives in such products. However, powder formulation products containing polysaccharide like sucrose and acid share a common challenge of agglomeration, especially under conditions of high temperature (e.g., 30°C or higher) and high humidity (e.g., a relative humidity (RH) of 50% or higher). The agglomeration of powder formulations remarkably affects product quality and consumer's use experience. Thus, it is desired to develop a powder formulation that is not prone to agglomerate, thereby ensuring the product quality and increasing the consumer’s use experience.SUMMARY

[0003] The present inventors have conducted extensive research and developed a composition, from which a formulation prepared has a storage stability and is not prone to agglomerate even under conditions of high temperature and high humidity, ensuring the product quality and the consumer's use experience.

[0004] The present invention provides a composition comprising a polysaccharide and a first acid, the polysaccharide comprising sucrose and a maltodextrin, the first acid comprising citric acid, malic acid, and / or tartaric acid, wherein the weight ratio of the maltodextrin to the first acid is 2: 1 or higher.

[0005] In another embodiment, the present invention relates to a composition comprising a polysaccharide and a first acid, the polysaccharide comprising sucrose and a maltodextrin, the first acid comprising citric acid, malic acid, and / or tartaric acid, wherein the weight ratio of the maltodextrin to the first acid is 2: 1 to 14: 1.

[0006] In another embodiment, the present invention relates to a composition comprising a polysaccharide and a first acid, the polysaccharide comprising sucrose and a maltodextrin, the first acid comprising citric acid, malic acid, and / or tartaric acid, wherein the weight ratio of the maltodextrin to the first acid is 4: 1 to 6: 1.

[0007] The present invention further provides a formulation prepared from the above composition.

[0008] Suitably, the formulation is an oral dry powder formulation.

[0009] The present invention further provides a composition of oral dry powder formulation comprising a polysaccharide and a first acid, the polysaccharide comprising sucrose and a maltodextrin, the first acid comprising citric acid, malic acid, and / or tartaric acid, and the composition further comprising acetaminophen (APAP) and another API different from acetaminophen (APAP), wherein the weight ratio of the maltodextrin to the first acid is 2: 1 or higher.

[0010] In another embodiment, the present invention relates to a composition of oral dry powder formulation comprising a polysaccharide and a first acid, the polysaccharide comprising sucrose and a maltodextrin, the first acid comprising citric acid, malic acid, and / or tartaric acid, and the composition further comprising acetaminophen (APAP) and another API different from acetaminophen (APAP), wherein the weight ratio of the maltodextrin to the first acid is 2: 1 to 14: 1.

[0011] In another embodiment, the present invention relates to a composition of oral dry powder formulation comprising a polysaccharide and a first acid, the polysaccharide comprising sucrose and a maltodextrin, the first acid comprising citric acid, malic acid, and / or tartaric acid, and the composition further comprising acetaminophen (APAP) and another API different from acetaminophen (APAP), wherein the weight ratio of the maltodextrin to the first acid is 4: 1 to 6: 1.

[0012] The features and advantages of the present invention will be particularly presented in detail in the following description of the embodiments.BRIEF DESCRIPTION OF DRAWINGS

[0013] FIG. 1 shows photos of Formulations 1-7 of Example 1 after being placed at 40°C / 75% RH for 3 days.

[0014] FIG. 2 shows photos of Formulations 1-7 of Example 2 after being placed at 40°C / 75% RH for 3 days.

[0015] FIG. 3 shows photos of Formulations 1-7 of Example 3 after being placed at 40°C / 75% RH for 3 days.

[0016] FIG. 4 shows a graph of 5-HMF contents at different weight ratios of maltodextrin to citric acid in the composition formulations containing different APIs.DETAILED DISCRIPTION

[0017] In the present application, unless expressly stated otherwise, the use of a singular comprises a plural and the use of a plural comprises a singular. For example, although “a” polysaccharide is referred to herein, one or more of the specie can be used.

[0018] In the present application, the terms “include,” “comprise,” and “contain” or the like are not intended to limit the invention to exclude any variations or additions. In the present application, unless expressly stated otherwise, the use of “or” means “and / or”, even though “and / or” can be expressly used in some cases.

[0019] Additionally, it should be understood that any numerical range described herein is intended to encompass all the sub-ranges contained therein. For example, a range of “1 to 10” is intended to comprise all the sub-ranges between the listed minimum value of 1 and the listed maximum value of 10 (including the endpoints), namely, all the sub-ranges having a minimum value equal to or great than 1 and a maximum value equal to or less than 10.

[0020] Except those in the examples or otherwise expressly stated, it should be understood that all numerical values representing amounts of components used in the specification and claims can be varied by the term “about” in all cases. Accordingly, the numerical parameters set forth in the following description and claims are approximations that can vary depending upon desired properties to be obtained by the present invention, unless otherwise indicated to be contrary. At the least, it is intended not to limit the application of the doctrine of equivalent to the scope of the claims, and each numerical parameter should at least be construed in terms of its number of significant digits and by applying ordinary rounding.

[0021] Although the numerical ranges and parameters describing the broad scope of the present invention are approximations, the numerical values listed in the particular Examples should be reported as precisely as possible. However, any one value inherently has a certain error, which is an inevitable consequence of standard deviation found in its corresponding measurement method.

[0022] As used herein, the term “polysaccharide” refers to a compound formed by the condensation of at least two monosaccharide molecules. As used herein, the “polysaccharide-based composition” refers to a composition comprising at least one polysaccharide.

[0023] The composition according to the present invention is solid powder at ambient temperature and pressure. The composition according to the present invention can be prepared into a formulation by dry blending, dry granulation, or wet granulation. The formulation prepared by these methods all have storage stability. Suitably, the formulation prepared from the composition can comprise an oral dry powder formulation, such as, electuary, powder, pulvis, and / or granule.

[0024] The present invention relates to a composition comprising a polysaccharide and a first acid, the polysaccharide comprising sucrose and a maltodextrin, the first acid comprising citric acid, malic acid, and / or tartaric acid, wherein the weight ratio of the maltodextrin to the first acid is 2: 1 or higher.

[0025] Surprisingly, the present inventors found that the agglomeration problem of the composition formulation can be ameliorated / solved by modifying the ratio of the maltodextrin to the first acid (such as, citric acid, malic acid, and / or tartaric acid). After study, the present inventors found that the agglomeration of the composition formulation is related to the generation of 5 -hydroxymethyl furfural (5-HMF). With the increase of the weight ratio of the maltodextrin to the first acid, the 5-HMF content decreases, and the agglomeration problem of the formulation is ameliorated / solved.

[0026] As used herein, the amelioration of agglomeration in the composition is evaluated by placing the composition under conditions of high temperature and high humidity (40°C / 75% RH) for 3 days, and determining the 5-HMF content in the composition. In certain embodiments the high temperature is 40°C ± 2°C and / or the high humidity is 75% RH ± 5%. By controlling the weight ratio of the maltodextrin to the first acid, the 5-HMF content in the composition can be reduced to less than 1.0 pg / mL, or even less than 0.6 pg / mL.

[0027] Suitably, in the composition according to the present invention, the weight ratio ofthe maltodextrin to the first acid can be 2: 1 to 18: 1, e.g., 2: 1 to 17: 1, 2: 1 to 16: 1, 2: 1 to 15: 1, 2: 1 to 14: 1, 2: 1 to 13: 1, 2: 1 to 12: 1, 2: 1 to 11 : 1, 2: 1 to 10: 1, 2: 1 to 9: 1, 2: 1 to 8: 1, 2: 1 to 7: 1, 2: 1 to 6: 1, 2: 1 to 5: 1, 2: 1 to 4: 1, or 2: 1 to 3: 1.

[0028] Suitably, in the composition according to the present invention, the weightratio ofthe maltodextrin to the first acid can be 3:1 to 18:1, e.g., 3:1 to 17:1, 3:1 to 16:1, 3:1 to 15:1, 3:1 to 14:1, 3:1 to 13:1, 3:1 to 12:1, 3:1 to 11:1, 3:1 to 10:1, 3:1 to 9:1, 3:1 to 8:1, 3:1 to 7:1, 3:1 to 6:1, 3:1 to 5:1, or 3:1 to 4:1.

[0029] Suitably, in the composition according to the present invention, the weight ratio ofthe maltodextrin to the first acid can be 4:1 to 18:1, e.g., 4:1 to 17:1, 4:1 to 16:1, 4:1 to 15:1, 4:1 to 14:1, 4:1 to 13:1, 4:1 to 12:1, 4:1 to 11:1, 4:1 to 10:1, 4:1 to 9:1, 4:1 to 8:1, 4:1 to 7:1, 4:1 to 6:1, or 4:1 to 5:1.

[0030] Suitably, in the composition according to the present invention, the weight ratio of the maltodextrin to the first acid can be 5:1 to 18:1, e.g., 5:1 to 17:1, 5:1 to 16:1, 5:1 to 15:1, 5:1 to 14:1, 5:1 to 13:1, 5:1 to 12:1, 5:1 to 11:1, 5:1 to 10:1, 5:1 to 9:1, 5:1 to 8:1, 5:1 to 7:1, or 5:1 to 6:1.

[0031] Suitable maltodextrin for use in the composition according to the present invention can have a DE of 20 or lower. Suitably, the maltodextrin can have a DE of 19 or lower, e.g., 18 or lower, 17 or lower, 16 or lower, 15 or lower, 14 or lower, 13 or lower, 12 or lower, 11 or lower, or 10 or lower. Suitably, the maltodextrin can have a DE of 2 or higher, e.g., 3 or higher, such as, 4 or higher, 5 or higher, 6 or higher, 7 or higher, 8 or higher, or 9 or higher. Suitably, the maltodextrin can have a DE of 2-20, 2- 10, or within any range with any of the above values as endpoints. The maltodextrin with the above DE can ameliorate agglomeration in the composition according to the present invention.

[0032] The composition according to the present invention can further comprise another polysaccharide different from sucrose and maltodextrin. Suitable another polysaccharide for use in the present invention can comprise cellulose, starch, hyaluronic acid, chitin, and / or chitosan.

[0033] Suitable first acid for use in the composition according to the present invention can be selected from weak organic acids and have an acceptable taste characteristic. Suitably, the first acid can comprise citric acid, malic acid, and / or tartaric acid. Suitably, based on the unit dosage of the composition, the first acid can be present in a concentration of 350 mg to 1000 mg in the composition. Suitably, based on the unit dosage of the composition, the first acid can have a concentration of 350 mg or higher, 375 mg or higher, 400 mg or higher, 425 mg or higher, 450 mg or higher, 475 mg or higher, 500 mg or higher, 525 mg or higher, 550 mg or higher, or 575 mg or higher. Suitably, based on the unit dosage of the composition, the first acid can have aconcentration of 1000 mg orlower, 975 mg orlower, 950 mg orlower, 925 mg orlower, 900 mg or lower, 875 mg or lower, 850 mg or lower, 825 mg or lower, 800 mg or lower, 775 mg or lower, 750 mg or lower, 725 mg or lower, 700 mg or lower, 675 mg or lower, 650 mg or lower, 625 mg or lower, or 600 mg or lower. Suitably, based on the unit dosage of the composition, the first acid can have a concentration of 375 mg to 700 mg, 400 mg to 600 mg, or within any range with any of the above values as endpoints.

[0034] The composition according to the present invention can further comprise an active pharmaceutical ingredient (API). Suitably, the active pharmaceutical ingredient can comprise one or more selected from the group consisting of acetaminophen (APAP), ibuprofen, chlorpheniramine maleate (CPM), dextromethorphan (Dex), phenylephrine hydrochloride (PE), diphenhydramine, caffeine, and guaifenesin.

[0035] Suitably, the active pharmaceutical ingredient can comprise acetaminophen or ibuprofen, and one or more another active pharmaceutical ingredient selected from the group consisting of chlorpheniramine maleate, dextromethorphan, phenylephrine hydrochloride, diphenhydramine, caffeine, and guaifenesin. For example, the composition according to the present invention can comprise acetaminophen, dextromethorphan, and phenylephrine hydrochloride.

[0036] Suitably, acetaminophen can be present in a concentration of 250 mg / dose to 650 mg / dose in the composition according to the present invention. As used herein, the “ / dose (per dose)” refers to a unit dosage, i.e., a volume in which active pharmaceutical ingredient being present in a mass effective amount. Suitably, the concentration of acetaminophen in the composition according to the present invention can be 250 mg / dose or higher, 270 mg / dose or higher, 290 mg / dose or higher, 310 mg / dose or higher, 330 mg / dose or higher, 350 mg / dose or higher, 370 mg / dose or higher, 390 mg / dose or higher, 410 mg / dose or higher, 420 mg / dose or higher, 430 mg / dose or higher, 440 mg / dose or higher, 450 mg / dose or higher, 460 mg / dose or higher, 470 mg / dose or higher, 480 mg / dose or higher, 490 mg / dose or higher, or 500 mg / dose or higher. Suitably, the concentration of acetaminophen in the composition according to the present invention can be 650 mg / dose or lower, 640 mg / dose or lower, 630 mg / dose or lower, 620 mg / dose or lower, 610 mg / dose or lower, 600 mg / dose or lower, 590 mg / dose or lower, 580 mg / dose or lower, 570 mg / dose or lower, 560 mg / dose or lower, 550 mg / dose or lower, 540 mg / dose or lower, 530 mg / dose or lower, 520 mg / dose or lower, or 510 mg / dose or lower. For example, acetaminophen can be present in aconcentration of 500 mg / dose in the composition according to the present invention.

[0037] Suitably, ibuprofen can be present in a concentration of 200 mg / dose to 400 mg / dose in the composition according to the present invention. As used herein, the “ / dose (per dose)” refers to a unit dosage, i.e., a volume in which active pharmaceutical ingredient being present in a mass effective amount. Suitably, the concentration of ibuprofen in the composition according to the present invention can be 200 mg / dose or higher, 210 mg / dose or higher, 220 mg / dose or higher, 230 mg / dose or higher, 240 mg / dose or higher, 250 mg / dose or higher, 260 mg / dose or higher, 270 mg / dose or higher, 280 mg / dose or higher, 290 mg / dose or higher, or 300 mg / dose or higher. Suitably, the concentration of ibuprofen in the composition according to the present invention can be 400 mg / dose or lower, 390 mg / dose or lower, 380 mg / dose or lower, 370 mg / dose or lower, 360 mg / dose or lower, 350 mg / dose or lower, 340 mg / dose or lower, 330 mg / dose or lower, 320 mg / dose or lower, or 310 mg / dose or lower. For example, ibuprofen can be present in a concentration of 300 mg / dose in the composition according to the present invention.

[0038] Suitably, each of the another active pharmaceutical ingredient (e.g., chlorpheniramine maleate, or dextromethorphan, or phenylephrine hydrochloride, or diphenhydramine, or caffeine, or guaifenesin) can be present in a concentration of 1 mg / dose to 200 mg / dose in the composition according to the present invention. As used herein, the “ / dose (per dose)” refers to a unit dosage, i.e., a volume in which active pharmaceutical ingredient being present in a mass effective amount. Suitably, the concentration of chlorpheniramine maleate can be 1 mg / dose or higher, or 2 mg / dose or higher, and / or 4 mg / dose or lower, or 3 mg / dose or lower. Suitably, the concentration of dextromethorphan can be 15 mg / dose or higher, or 20 mg / dose or higher, and / or 30 mg / dose or lower, or 25 mg / dose or lower. Suitably, the concentration of phenylephrine hydrochloride can be 5 mg / dose or higher, or 10 mg / dose or higher, and / or 50 mg / dose or lower, or 40 mg / dose or lower. Suitably, the concentration of diphenhydramine can be 25 mg / dose or higher, or 35 mg / dose or higher, and / or 50 mg / dose or lower, or 45 mg / dose or lower. Suitably, the concentration of caffeine can be 15 mg / dose or higher, or 30 mg / dose or higher, and / or 65 mg / dose or lower, or 50 mg / dose or lower. Suitably, the concentration of guaifenesin can be 100 mg / dose or higher, or 120 mg / dose or higher, and / or 200 mg / dose or lower, or 150 mg / dose or lower.

[0039] For example, the composition according to the present invention can comprise500 mg of acetaminophen, 30 mg of dextromethorphan, and 10 mg of phenylephrine hydrochloride per dose.

[0040] The composition according to the present invention can further comprise other components. The other components can comprise, but are not limited to, flavorings, artificial sweeteners, anti-caking agents, lubricants, and / or colorants, etc.

[0041] The composition according to the present invention can be prepared by mixing components comprising sucrose, the maltodextrin, the first acid, and the like.

[0042] The present invention further provides a formulation prepared from the above composition. Suitably, the formulation can be an oral dry powder formulation. The formulation can be prepared by dry blending, dry granulation, or wet granulation.

[0043] The present invention further provides a composition of oral dry powder formulation comprising a polysaccharide and a first acid, the polysaccharide comprising sucrose and a maltodextrin, the first acid comprising citric acid, malic acid, and / or tartaric acid, and the composition further comprising acetaminophen and another active pharmaceutical ingredient different from acetaminophen, wherein the weight ratio of the maltodextrin to the first acid is 2: 1 or higher.

[0044] Suitably, in the composition of oral dry powder formulation, the weight ratio of the maltodextrin to the first acid can be 2:1 to 18:1, e.g., 2:1 to 17:1, 2:1 to 16:1, 2:1 to 15:1, 2:1 to 14:1, 2:1 to 13:1, 2:1 to 12:1, 2:1 to 11:1, 2:1 to 10:1, 2:1 to 9:1, 2:1 to 8:1, 2:1 to 7:1, 2:1 to 6:1, 2:1 to 5:1, 2:1 to 4:1, or 2:1 to 3:1.

[0045] Suitably, in the composition of oral dry powder formulation, the weight ratio of the maltodextrin to the first acid can be 3:1 to 18:1, e.g., 3:1 to 17:1, 3:1 to 16:1, 3:1 to 15:1, 3:1 to 14:1, 3:1 to 13:1, 3:1 to 12:1, 3:1 to 11:1, 3:1 to 10:1, 3:1 to 9:1, 3:1 to 8:1, 3:1 to 7:1, 3:1 to 6:1, 3:1 to 5:1, or 3:1 to 4:1.

[0046] Suitably, in the composition of oral dry powder formulation, the weight ratio of the maltodextrin to the first acid can be 4:1 to 18:1, e.g., 4:1 to 17:1, 4:1 to 16:1, 4:1 to 15:1, 4:1 to 14:1, 4:1 to 13:1, 4:1 to 12:1, 4:1 to 11:1, 4:1 to 10:1, 4:1 to 9:1, 4:1 to 8:1, 4:1 to 7:1, 4:1 to 6:1, or 4:1 to 5:1.

[0047] Suitably, in the composition of oral dry powder formulation, the weight ratio of the maltodextrin to the first acid can be 5:1 to 18:1, e.g., 5:1 to 17:1, 5:1 to 16:1, 5:1 to 15:1, 5:1 to 14:1, 5:1 to 13:1, 5:1 to 12:1, 5:1 to 11:1, 5:1 to 10:1, 5:1 to 9:1, 5:1 to 8:1, 5:1 to 7:1, or 5:1 to 6:1.

[0048] Suitably, in the composition of oral dry powder formulation, the another activepharmaceutical ingredient comprises at least one selected from the group consisting of chlorpheniramine maleate, dextromethorphan, phenylephrine hydrochloride and diphenhydramine.

[0049] Suitably, the composition of oral dry powder formulation comprises 500 mg of acetaminophen, 30 mg of dextromethorphan, and 10 mg of phenylephrine hydrochloride per dose.

[0050] Suitably, the composition of oral dry powder formulation comprises less than 1.0 pg / mL of 5-HMF per dose.EXAMPLES

[0051] The following examples are provided to further illustrate the present invention, but should not be construed to limit the present invention to the details of the examples. All parts and percentages in the following examples are by weight, unless otherwise stated.Compositions Comprising Di fferent APIs

[0052] Example 1 : Acetaminophen (APAP) + Dextromethorphan (Dex) + Phenylephrine Hydrochloride (PE)

[0053] Formulations 1-7 of Example 1 were prepared using the components and their respective amounts listed in Table 1 below, specifically by the steps of: (1) mixing acetaminophen, dextromethorphan, phenylephrine hydrochloride, citric acid, maltodextrin, sucrose, and other components (sodium citric acid, silica, calcium phosphate, and aspartame); and (2) further processing the mixed powder obtained in step (1) into a unit formulation.Table 1. Formulations 1-7 of Example 1

[0054] Formulations 1-7 were placed under conditions of high temperature and high humidity (40°C / 75% RH) for 3 days, and then measured for the 5-HMF content in the formulation composition. The results are shown in the table below. Moreover, the photos of Formulations 1-7 underwent high temperature and high humidity are shown in FIG. 1 (Formulations 1-7, in sequence from left to right).EXAMPLE 2: Acetaminophen (APAP) + Diphenhydramine + Phenylephrine Hydrochloride (PE)

[0055] Formulations 1-7 of Example 2 were prepared using the components and their respective amounts listed in Table 2 below, specifically by the steps of: (1) mixing acetaminophen, diphenhydramine, phenylephrine hydrochloride, citric acid, maltodextrin, sucrose, and other components (sodium citrate and aspartame); and (2) further processing the mixed powder obtained in step (1) into a unit formulation. Table 2. Formulations 1-7 of Example 2

[0056] Formulations 1-7 were placed under conditions of high temperature and high humidity (40°C / 75% RH) for 3 days, and then measured for the 5-HMF content in the formulation composition. The results are shown in the table below. Moreover, thephotos of Formulations 1-7 underwent high temperature and high humidity are shown in FIG. 2 (Formulations 1-7, in sequence from left to right).Example 3 : Acetaminophen (APAP) + Dextromethorphan (Dex) + Chlorpheniramine Maleate (CPM)

[0057] Formulations 1-7 of Example 3 were prepared using the components and their respective amounts listed in Table 3 below, specifically by the steps of: (1) mixing acetaminophen, dextromethorphan, chlorpheniramine maleate, citric acid, maltodextrin, sucrose, and other components (sodium citric acid, silica, calcium phosphate, and aspartame); and (2) further processing the mixed powder obtained in step (1) into a unit formulation.Table 3. Formulations 1-7 of Example 3

[0058] Formulations 1-7 were placed under conditions of high temperature and high humidity (40°C / 75% RH) for 3 days, and then measured for the 5-HMF content in the formulation composition. The results are shown in the table below. Moreover, the photos of Formulations 1-7 underwent high temperature and high humidity are shown in FIG. 3 (Formulations 1-7, in sequence from left to right).Compositions Comprising Maltodextrins with Different DEsExample 4: Maltodextrin with DE of 18

[0059] Formulations 1-10 of Example 4 were prepared using the components and their respective amounts listed in Table 4 below, specifically by the steps of: (1) mixing malic acid, maltodextrin, and sucrose; and (2) further processing the mixed particles obtained in step (1) into a unit formulation.Table 4. Formulations 1-10 of Example 4

[0060] Formulations 1-10 were placed under conditions of high temperature and high humidity (40°C / 75% RH) for 3 days, and then measured for the 5-HMF content in the formulation composition. The results are shown in the table below.Example 5: Maltodextrin with DE of 9

[0061] Formulations 1-10 of Example 5 were prepared using the components and their respective amounts listed in Table 5 below, specifically by the steps of: (1) mixing malic acid, maltodextrin, and sucrose; and (2) further processing the mixed powder obtained in step (1) into a unit formulation.Table 5. Formulations 1-10 of Example 5

[0062] Formulations 1-10 were placed under conditions of high temperature and high humidity (40°C / 75% RH) for 3 days, and then measured for the 5-HMF content in the formulation composition. The results are shown in the table below.Example 6: Maltodextrin with DE of 2

[0063] Formulations 1-10 of Example 6 were prepared using the components and their respective amounts listed in Table 6 below, specifically by the steps of: (1) mixing malic acid, maltodextrin, and sucrose; and (2) further processing the mixed powder obtained in step (1) into a unit formulation.Table 6. Formulations 1-10 of Example 6

[0064] Formulations 1-10 were placed under conditions of high temperature and high humidity (40°C / 75% RH) for 3 days, and then measured for the 5-HMF content in the formulation composition. The results are shown in the table below.

[0065] It can be seen from the above Examples 1-3 that with different API compositions, the increase of the weight ratio of maltodextrin to acid reduces the generation of 5-HMF, so that agglomeration is ameliorated (as shown in FIG. 4). It canbe seen from the above Examples 4-6 that the use of maltodextrin with different DEs reduces the generation of 5-HMF.

[0066] Although the particular aspects of the present invention have been illustrated and described, it is obvious to persons skilled in the art that many other variations and modifications can be made without departing the spirit and scope of the present invention. Thus, the accompanying claims are intended to encompass all of these variations and modifications falling within the scope of the present invention.

Claims

CLAIMSWhat is claimed is:

1. A composition comprising a polysaccharide and a first acid, the polysaccharide comprising sucrose and a maltodextrin, the first acid comprising citric acid, malic acid, and / or tartaric acid, wherein the weight ratio of the maltodextrin to the first acid is 2: 1 or higher.

2. The composition of claim 1, wherein the weight ratio of the maltodextrin to the first acid is 2: 1 to 14: 1.

3. The composition of claim 1 or 2, wherein the weight ratio of the maltodextrin to the first acid is 4: 1 to 6: 1.

4. The composition of any one of claims 1-3, wherein the maltodextrin has a DE value of 20 or lower.

5. The composition of any one of claims 1-4, further comprising an active pharmaceutical ingredient.

6. The composition of claim 5, wherein the active pharmaceutical ingredient comprises acetaminophen (APAP), ibuprofen, chlorpheniramine maleate (CPM), dextromethorphan (Dex), phenylephrine hydrochloride (PE), diphenhydramine, caffeine, and / or guaifenesin.

7. The composition of claim 5 or 6, wherein the active pharmaceutical ingredient comprises acetaminophen (APAP) or ibuprofen, and at least one selected from the group consisting of chlorpheniramine maleate (CPM), dextromethorphan (Dex), phenylephrine hydrochloride (PE), diphenhydramine, caffeine, and guaifenesin.

8. The composition of any one of claims 5-7, comprising per dose 250-650 mg of acetaminophen (APAP) or 200-400 mg of ibuprofen, and at least one selected from the group consisting of 1-4 mg of chlorpheniramine maleate (CPM), 15-30 mg of dextromethorphan (Dex), 1-30 mg of phenylephrine hydrochloride (PE), 25-50 mg of diphenhydramine, 15-65 mg of caffeine, and 100-200 mg of guaifenesin.

9. The composition of any one of claims 1-8, wherein the composition is solid powder.

10. A formulation prepared from the composition of any one of claims 1-9.

11. The formulation of claim 10, wherein the formulation is an oral dry powder formulation.

12. The formulation of claim 10 or 11, wherein the formulation is prepared from the composition by dry blending, dry granulation, or wet granulation.

13. A composition of oral dry powder formulation comprising a polysaccharide and a first acid, the polysaccharide comprising sucrose and maltodextrin, the first acid comprising citric acid, malic acid, and / or tartaric acid, and the composition further comprising acetaminophen (APAP) and another active pharmaceutical ingredient different from acetaminophen (APAP), wherein the weight ratio of the maltodextrin to the first acid is 2: 1 or higher.

14. The composition of oral dry powder formulation of claim 13, wherein the weight ratio of the maltodextrin to the first acid is 2: 1 to 14: 1.

15. The composition of oral dry powder formulation of claim 13 or 14, wherein the weight ratio of the maltodextrin to the first acid is 4: 1 to 6: 1.

16. The composition of oral dry powder formulation of any one of claims 13-15, wherein the another active pharmaceutical ingredient comprises at least one selected from the group consisting of chlorpheniramine maleate (CPM), dextromethorphan (Dex), phenylephrine hydrochloride (PE), diphenhydramine, caffeine, and guaifenesin.

17. The composition of oral dry powder formulation of claim 16, comprising per dose 500 mg of acetaminophen (APAP), 30 mg of dextromethorphan (Dex), and 10 mg of phenylephrine hydrochloride (PE).

18. The composition of oral dry powder formulation of any one of claims 13-17, comprising less than 1.0 pg / mL of 5 -hydroxymethyl furfural (5-HMF) after being placed at 40°C / 75% relative humidity for 3 days, particularly 40°C ± 2°C / 75% ± 5% relative humidity for 3 days.

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