Naproxen sodium tablets produced using continuous process
By adopting a continuous manufacturing process in the production of naproxen sodium tablets, using weightless feeder and online mixer, the unnecessaryness of the granulation step and the use of the flow aid in the traditional process are solved, and high efficiency is achieved. Uniform tablet production.
Patent Information
- Application Number
- CN202380048022.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2022-06-20
- Filing Date
- 2023-06-20
- Publication Date
- 2025-02-07
AI Technical Summary
Traditional tableting processes require granulation steps when processing low-flow powders, resulting in uneven product and high cost, and the addition of a glidant to improve fluidity.
The naproxen sodium tablets are produced by continuous manufacturing processes, and the free flow and uniform mixing of materials are achieved through weightless feeders and in-line mixers, eliminating the granulation step without using glidants.
The production of highly efficient Naproxen sodium tablets without glidants is achieved, simplifying the manufacturing process, reducing costs and error risks, and improving product uniformity and fluidity.
Smart Images
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Abstract
Description
[0001] CROSS-REFERENCE TO RELATED APPLICATIONS
[0002] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 353,751, filed on June 20, 2022, which is incorporated herein by reference in its entirety. Technical Field
[0003] The present disclosure relates generally to naproxen sodium tablets, and more particularly, to naproxen sodium tablets produced using a continuous process. Background Art
[0004] Naproxen sodium is a nonsteroidal anti-inflammatory drug (NSAID) used to treat inflammation associated with a variety of conditions and to provide long-term relief of mild to moderate pain. Typically, naproxen sodium is administered in tablet form.
[0005] When using powders with poor flowability, traditional tableting processes require a granulation step. Using low-flow powders can lead to inhomogeneity and separation within the product mixture. Granulation is used to improve the flowability of powder ingredients by increasing the particle size. Granulation can be done using wet granulation (where a liquid binder is added to the powder) or dry granulation (where the powder is pressed or compacted and ground to achieve the desired properties). A commonly used dry granulation process is roller granulation. In roller granulation, the powder mixture is passed through two counter-rotating rollers, the powder is pressed into a ribbon, and then ground into the desired particle size. Alternatively or in addition to granulation, a glidant (e.g., colloidal silicon dioxide) can be added to the mixture to enhance flow. Summary of the invention
[0006] Naproxen sodium tablets without a glidant are described herein, as well as naproxen sodium tablets without a glidant produced using a continuous manufacturing process. Specifically, the continuous manufacturing process allows low-flowing materials (e.g., naproxen sodium) to flow freely without the addition of a glidant (e.g., colloidal silicon dioxide). As described above, conventional tableting processes require the use of a granulation process to convert low-flowing powders into granules that are more easily flowed through downstream processes. However, by using the continuous tableting process described herein (including a loss-in-weight feeder specifically designed for low-flowing materials), naproxen sodium tablets can be manufactured without the addition of a glidant. In addition, the continuous process completely eliminates the need for a granulation process (e.g., wet granulation). Eliminating this pretreatment step can improve the cost and efficiency of producing naproxen sodium tablets.
[0007] In addition, the continuous tableting process described herein includes a tablet press with three rollers that are convenient for direct compression. Traditional tablet presses include two compression / compacting stations (pre-compression and main compression). The pre-compression roller provides densification to remove the air in the mixture by compacting the mixture, and the main compression roller applies force to form tablets. In this case, the third roller is used as the second pre-compression roller to enhance the densification of the mixture to the extent that the needs of pre-roll compacted particles are made up. In other words, after pre-compression and main compression mixture, the third roller serves as an in-situ roller compactor to make tablets.
[0008] In some embodiments, the naproxen sodium tablets described herein may include excipients including stearic acid, sodium starch glycolate, mannitol, microcrystalline cellulose, magnesium stearate, or povidone. However, the naproxen sodium tablets described herein do not include a glidant (e.g., colloidal silicon dioxide).
[0009] In some embodiments, provided herein are oral tablets comprising: naproxen sodium; mannitol; a superdisintegrant; and a lubricant, wherein the oral tablet does not comprise a glidant.
[0010] In some embodiments of the oral tablet, the superdisintegrant comprises sodium starch glycolate.
[0011] In some embodiments of the oral tablet, the oral tablet comprises 70-80 wt. % naproxen sodium.
[0012] In some embodiments of the oral tablet, the oral tablet comprises 15-25 wt. % mannitol.
[0013] In some embodiments of the oral tablet, the oral tablet comprises 3-8 wt.% of a superdisintegrant.
[0014] In some embodiments of the oral tablet, the oral tablet comprises 1-6 wt. % of a lubricant.
[0015] In some embodiments of the oral tablet, the lubricant includes one or more of magnesium stearate or stearic acid.
[0016] In some embodiments of the oral tablet, the mannitol is spray-dried mannitol.
[0017] In some embodiments of the oral tablet, the oral tablet comprises 220 mg naproxen sodium.
[0018] In some embodiments, a naproxen sodium tablet is provided that is formed by: mixing naproxen sodium, mannitol, a super disintegrant, and a lubricant in a continuous in-line mixer to form a tableting mixture; transferring the tableting mixture to a tablet press; and compressing the tableting mixture into naproxen sodium tablets.
[0019] In some embodiments of the naproxen sodium tablet, the naproxen sodium tablet does not include a granulation step.
[0020] In some embodiments of the naproxen sodium tablet, mixing naproxen sodium, mannitol, a super disintegrant, and a lubricant in a continuous in-line mixer comprises feeding naproxen sodium, mannitol, a super disintegrant, and a lubricant into the in-line mixer via a loss-in-weight feeder.
[0021] In some embodiments of the naproxen sodium tablet, mixing naproxen sodium, mannitol, a super disintegrant, and a lubricant in a continuous in-line mixer comprises mixing naproxen sodium, mannitol, and a super disintegrant before adding the lubricant to the in-line mixer.
[0022] In some embodiments of the naproxen sodium tablet, transferring the tableting mixture to a tablet press comprises vacuum transfer.
[0023] In some embodiments of the naproxen sodium tablet, the superdisintegrant includes sodium starch glycolate.
[0024] In some embodiments of the naproxen sodium tablet, the lubricant includes one or more of magnesium stearate or stearic acid.
[0025] In some embodiments of the naproxen sodium tablet, the oral tablet comprises 70-80 wt. % naproxen sodium.
[0026] In some embodiments of the naproxen sodium tablet, the oral tablet comprises 15-25 wt. % mannitol.
[0027] In some embodiments of the naproxen sodium tablet, the oral tablet comprises 3-8 wt. % of a superdisintegrant.
[0028] In some embodiments of the naproxen sodium tablet, the oral tablet comprises 1-6 wt. % of a lubricant.
[0029] In some embodiments of the naproxen sodium tablet, the mannitol is spray-dried mannitol.
[0030] In some embodiments of the naproxen sodium tablet, the oral tablet comprises 220 mg naproxen sodium.
[0031] In some embodiments, any one or more features, characteristics, or elements discussed above with respect to any embodiment may be incorporated into any other embodiment mentioned above or described elsewhere herein. BRIEF DESCRIPTION OF THE DRAWINGS
[0032] Figure 1 A process for manufacturing naproxen sodium tablets according to some embodiments is shown;
[0033] Figure 2 A loss-in-weight feeder designed for handling low-flow materials is shown according to some embodiments;
[0034] Figure 3 shows the volume decay at various agitator speeds using a twin screw at 80% screw speed based on a feed trial of a continuous manufacturing process according to some embodiments;
[0035] Figure 4 shows the volume decay obtained with a double concave screw at 80% screw speed and 50% agitator speed based on a feed trial of a continuous manufacturing process according to some embodiments;
[0036] Figure 5 shows gravimetric feeding data for a twin screw feeder based on feeding trials for a continuous manufacturing process according to some embodiments;
[0037] Figure 6 shows gravimetric feeding data for a twin screw feeder based on feeding trials for a continuous manufacturing process according to some embodiments;
[0038] Figure 7 shows gravimetric feeding data for a twin screw feeder based on feeding trials for a continuous manufacturing process according to some embodiments;
[0039] Fig. 8A shows an image of a hopper after two days of operation, according to some embodiments; and
[0040] Figure 8B An image showing the inlet position of a hopper after two days of operation, according to some embodiments. DETAILED DESCRIPTION OF THE INVENTION
[0042] Described herein are naproxen sodium tablets that do not contain a glidant and naproxen sodium tablets that do not contain a glidant produced using a continuous manufacturing process. Specifically, the continuous manufacturing process is a tableting process that omits the pretreatment granulation step, which is commonly used to form tablets, especially when processing low-flow materials (such as naproxen sodium). Common granulation methods include, for example, roller granulation. However, by using the continuous tableting process described herein to manufacture naproxen sodium tablets, naproxen sodium tablets can be produced in a more efficient and cost-effective manner. Specifically, omitting the granulation step saves a lot of time, reduces waste, and equipment and maintenance costs. In addition, omitting a glidant (such as colloidal silicon dioxide) saves the cost of the material. Fewer components in the final product also simplify the manufacturing process and minimize the possibility of errors.
[0043] As mentioned above, naproxen sodium is a cohesive material with very poor flow properties. Due to the fineness and cohesive nature of naproxen sodium, forming a free-flowing mixture is extremely challenging and difficult to achieve. Therefore, naproxen sodium is usually granulated using a wet or dry granulation process (roller granulation) and then compressed into tablets. Without granulated naproxen sodium, the powdered naproxen sodium mixture has very poor flow properties, which makes it impossible to form tablets on a rotary tablet press (because the mixture sticks to the punches).
[0044] Using the continuous manufacturing process described herein, poorly flowing materials (e.g., naproxen sodium) can be continuously and consistently fed by using a loss-in-weight (LIW) feeder in various configurations, thereby achieving a free-flowing homogeneous mixture using an in-line mixer that keeps the material / mixture in constant fluid motion by preventing any separation and densification of the material. The mixture delivered to the tablet press by a batch transfer mechanism further ensures the homogeneity of the mixture before being pressed into tablets. The mixture is also lubricated by magnesium stearate in the in-line mixer or applied directly to the punch tip by a controlled spray mechanism, so that the mixture is pressed into tablets without any physical defects.
[0045] Naproxen Sodium Tablets Composition
[0046] Active drug ingredient: Naproxen sodium
[0047] The tablets described herein contain naproxen sodium (C 14 H 14 O3), which is a nonsteroidal anti-inflammatory and analgesic drug. Due to its low flow properties, naproxen sodium may be difficult to process. In some embodiments, the naproxen sodium tablets described herein may contain 50-90, 60-85 or 70-80 wt.% of naproxen sodium. In some embodiments, the naproxen sodium tablets described herein may contain less than or equal to 90, 85, 80, 75, 70, 65, 60 or 55 wt.% of naproxen sodium. In some embodiments, the naproxen sodium tablets described herein may contain greater than or equal to 50, 55, 60, 65, 70, 75, 80 or 85 wt.% of naproxen sodium.
[0048] In some embodiments, a naproxen sodium tablet comprising naproxen sodium may include one or more additional active pharmaceutical ingredients. For example, an oral tablet may include a monolayer containing naproxen sodium and one or more additional active pharmaceutical ingredients. Suitable additional active ingredients may include, but are not limited to, active pharmaceutical ingredients indicated for the treatment of pain, fever, and / or colds and flu, such as acetaminophen, phenylephrine, pseudoephedrine, doxylamine, dextromethorphan, and / or guaifenesin, or any pharmaceutically acceptable salt thereof (e.g., pseudoephedrine hydrochloride or pseudoephedrine sulfate).
[0049] excipient
[0050] As described herein, oral tablets prepared using a continuous process may include one or more active pharmaceutical ingredients (API) and a variety of excipients. Suitable excipients may include excipients such as binders, lubricants, disintegrants, and super disintegrants. In some embodiments, the naproxen sodium tablets of the present disclosure produced using a continuous process further include excipients.
[0051] In some embodiments, naproxen sodium tablets contain mannitol as an excipient. Mannitol is a sugar alcohol that can act as a diluent, filler and / or disintegrant. In some embodiments, naproxen sodium tablets contain 5-40, 10-30 or 15-25 wt.% mannitol. In some embodiments, naproxen sodium tablets contain less than or equal to 40, 35, 30, 25, 20, 15 or 10 wt.% mannitol. In some embodiments, naproxen sodium tablets contain greater than or equal to 5, 10, 15, 20, 25, 30 or 35 wt.% mannitol. Suitable commercially available mannitol can include Pearlitol SD200 from Roquette Freres.
[0052] In some embodiments, some characteristics or types of mannitol may be particularly useful. In some embodiments, mannitol is spray-dried mannitol. In some of the aforementioned embodiments, the average particle size of mannitol is at least 50 μm, at least 75 μm, at least 100 μm, at least 125 μm or at least 150 μm. In other embodiments, the average particle size of mannitol is less than or equal to 300 μm, less than or equal to 275 μm, less than or equal to 250 μm, less than or equal to 225 μm or less than or equal to 200 μm. In certain embodiments, the average particle size of mannitol is between 50 μm and 300 μm, between 50 μm and 250 μm, between 50 μm and 200 μm, between 100 μm and 300 μm, between 100 μm and 250 μm, between 100 μm and 200 μm, between 150 μm and 300 μm, between 150 μm and 250 μm, or between 50 μm and 200 μm.
[0053] In some embodiments, the naproxen sodium tablet comprises one or more superdisintegrants. For example, the naproxen sodium tablet may comprise sodium starch glycolate as an excipient. Sodium starch glycolate can be used as a superdisintegrant in a pharmaceutical formulation to facilitate conduction and penetration of the dissolution medium throughout the naproxen sodium tablet. In some embodiments, the naproxen sodium tablet comprises 0.1-20, 1-15, 1-10 or 3-8 wt.% of a superdisintegrant. In some embodiments, the naproxen sodium tablet comprises less than or equal to 20, 18, 16, 15, 14, 12, 10, 8, 6, 5, 4, 3, 2 or 1 wt.% of a superdisintegrant. In some embodiments, the naproxen sodium tablet comprises greater than or equal to 0.1, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 15, 16 or 18 of a superdisintegrant. Suitable commercially available superdisintegrants include superdisintegrants provided by DFE pharma.
[0054] In some embodiments, naproxen sodium tablets contain one or more lubricants. In some embodiments, naproxen sodium tablets contain magnesium stearate as an excipient. Magnesium stearate is an excipient used as a lubricant in various dosage forms to reduce the adhesion of powder materials to processing equipment and facilitate the discharge of tablets from the tablet press. In some embodiments, naproxen sodium tablets contain 0.1-10, 1-5 or 1-2 wt.% of lubricant. In some embodiments, naproxen sodium tablets contain less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 wt.% of lubricant. In some embodiments, naproxen sodium tablets contain greater than or equal to 0.1, 1, 2, 3, 4, 5, 6, 7, 8 or 9 wt.% of lubricant. Suitable commercially available lubricants may include lubricants provided by Peter Greven Fett-Chemie.
[0055] In some embodiments, naproxen sodium tablets include stearic acid. Like magnesium stearate, stearic acid acts as a lubricant. Specifically, stearic acid is both a lubricant and a solubilizer, which can help achieve the desired fluidity of the powder mixture during manufacturing and the desired dissolution curve in the actual use of the tablet. In some embodiments, naproxen sodium tablets include 0.1-10, 1-5 or 2-4wt.% of stearic acid. In some embodiments, naproxen sodium tablets include less than or equal to 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1wt.% of naproxen sodium. In some embodiments, naproxen sodium tablets include greater than or equal to 0.1, 1, 2, 3, 4, 5, 6, 7, 8 or 9wt.% of stearic acid.
[0056] In some embodiments, the naproxen sodium tablets described herein may comprise 70-75 wt.% naproxen sodium, 15-25 wt.% mannitol, 3-8 wt.% super disintegrant such as sodium starch glycolate, and 1-2 wt.% magnesium stearate.
[0057] In some embodiments, the naproxen sodium tablets described herein may comprise 73-74 wt.% naproxen sodium, 19-21 wt.% mannitol, 4-6 wt.% super disintegrant such as sodium starch glycolate, and 1-2 wt.% magnesium stearate.
[0058] In some embodiments, the naproxen sodium tablets described herein may include 73.33 wt.% naproxen sodium, 20 wt.% mannitol, 5 wt.% super disintegrant such as sodium starch glycolate, and 1.67 wt.% magnesium stearate.
[0059] The following table shows two examples of naproxen sodium formulations according to some embodiments.
[0060] mg / tablet ％ Naproxen Sodium, USP 220 73.33 Mannitol 60 20.00 Sodium starch glycolate 15 5.00 Magnesium Stearate 5 1.67 Total: 300 100
[0061] mg / tablet ％ Naproxen Sodium, USP 220 72.6 Mannitol 60 19.8 Sodium starch glycolate 15 4.95 Magnesium Stearate 5 1.65 Stearic acid 3 0.99 Total: 303 100
[0062] Naproxen Sodium Tablets Specifications
[0063] Several target specifications for naproxen sodium tablets manufactured using a continuous manufacturing process according to some embodiments are described below. Specifically, the target specifications described include target tablet weight, single tablet weight range, average tablet weight range, tablet thickness, tablet diameter, tablet hardness, and naproxen sodium content.
[0064]
[0065]
[0066] Method for manufacturing naproxen sodium tablets
[0067] The naproxen sodium tablets provided herein do not contain a glidant, such as colloidal silicon dioxide. In conventional tableting processes, a granulation step is required, especially for low-flow materials such as naproxen sodium. A glidant can be introduced during the granulation step to improve the flowability of the material, thereby improving the processability of the downstream material. Here, the naproxen sodium tablets are manufactured using a continuous manufacturing process that explicitly eliminates the pretreatment granulation step and, therefore, also eliminates the addition of a glidant. Therefore, the naproxen sodium tablets described herein do not contain a glidant in their formulation.
[0068] Figure 1An example of a process 100 for making naproxen sodium tablets according to some embodiments described herein is shown. The process can include a loss-in-weight (LIW) feeder, an in-line (continuous) mixer, and a tablet press.
[0069] In step 102, naproxen sodium, mannitol, a super disintegrant (e.g., sodium starch glycolate), and magnesium stearate are mixed. In some embodiments, these components are all introduced into an inline mixer at the same time. In some embodiments, these components are introduced into the mixer at different times.
[0070] For example, naproxen sodium, mannitol and super disintegrant can be first fed into an inline mixer through a LIW feeder and mixed. A lubricant (e.g., magnesium stearate) can then be added to the inline mixer through a LIW feeder and mixed with the naproxen sodium-mannitol-super disintegrant mixture.
[0071] In some embodiments, naproxen sodium and the super disintegrant are mixed first, and the mannitol is added to the in-line mixer at a later time. Magnesium stearate is added as a separate component. In some embodiments, naproxen sodium and mannitol are mixed first, and the super disintegrant is added to the in-line mixer at a later time. Magnesium stearate is added as a separate component. In some embodiments, mannitol and the super disintegrant are mixed first, and the naproxen sodium and mannitol are added to the in-line mixer at a later time. Magnesium stearate is added as a separate component.
[0072] By using a LIW feeder designed for low-flowing materials, components, regardless of their cohesive properties, can be accurately and consistently added to the inline mixer without the need to add flow aids. In addition, using an inline continuous mixer allows the material to maintain a constant fluidization state and consistent flow during the manufacturing process to prevent separation and densification of the mixture.
[0073] Figure 2 One embodiment of a LIW feeder 200 is shown that can be used in a continuous process for making naproxen sodium tablets without the addition of glidants, as described herein. A loss-in-weight feeder is a gravimetric feeder that measures the weight of the material to achieve and maintain a predetermined feed rate.
[0074] Figure 2 The LIW feeder shown is specially designed for handling low flow materials.
[0075] In step 104, the naproxen sodium-mannitol-super disintegrant-magnesium stearate mixture (i.e., tableting mixture) is transferred to a tablet press using a batch transfer mechanism. The batch transfer mechanism keeps the mixture uniform for tableting. In some embodiments, the tableting mixture is transferred to a tablet press using a vacuum transfer technique.
[0076] In step 106, the tableting mixture is compressed into naproxen sodium tablets using a tablet press. In some embodiments, the tablet press can be a FE55 tablet press from Fette Compacting.
[0077] In some embodiments, using the continuous manufacturing process described herein, 100-2000, 100-1000, 100-500, 200-400 or 300-350 tablets can be produced per hour. In some embodiments, the continuous manufacturing process described herein can obtain less than or equal to 2000, 1500, 1000, 900, 800, 700, 600, 500, 400, 350, 300, 250, 200 or 150 tablets per hour. In some embodiments, the continuous manufacturing process described herein can obtain greater than or equal to 100, 150, 200, 250, 300, 350, 400, 500, 600, 700, 800, 900, 100 or 1500 tablets per hour. In some embodiments, the continuous manufacturing process described herein can obtain 320 tablets / hour.
[0078] Example: Manufacturing Naproxen Sodium Tablets Using a Continuous Manufacturing Process
[0079] 220 mg of Naproxen Sodium, 60 mg of Mannitol and 15 mg of Sodium Starch Glycol were fed from a LIW feeder to an inline continuous mixer and mixed. 5 mg of Magnesium Stearate was added from a LIW feeder to the inline mixer, and the Naproxen Sodium, Mannitol and Sodium Starch Glycol mixture was further mixed with Magnesium Stearate to form a tableting mixture.
[0080] The tableting mixture was vacuum transferred to a Fette Compacting FE55 tablet press equipped with 10 mm round standard concave punches.
[0081] The tableting mixture is compressed into tablets on a high-speed rotary tablet press (FE55 from Fette) which includes three compression rollers. Standard tablet presses usually include only two compression rollers (pre-compression and main compression). The pre-compression force of the pre-compression roller can reduce the trapped air that affects the integrity of the tablet. The main compression force of the main compression roller affects the hardness of the tablet. The second pre-compression roller (i.e. the third roller) present on the FE55 is not only used to control degassing, but also used to adjust the tablet hardness in combination with the first pre-compression roller. This in turn helps the main compression roller to compress the tablet to the desired hardness.
[0082] Lubrication of tablet press punch tips
[0083] As mentioned above, in some embodiments, lubricant (e.g., magnesium stearate) is added directly to the online mixer. However, in other embodiments, lubricant can be directly applied to the punch tip of the tablet press to prevent the tabletting mixture from adhering to the punch tip of the tablet press. In some embodiments, controlled spraying technology can be used to apply lubricant to the punch tip. External lubrication refers to applying lubricant to the tablet surface only by a device with compressed air and a powder delivery point to the punch tip. In some embodiments, some lubricants are added to the online mixer, and some lubricants are added to the punch tip of the tablet press. Example
[0084] Figure 3-7 The graph shown in Figure 1 shows naproxen sodium feed data under various conditions to achieve a mass flow rate of 71.094 kg / hr (volume flow rate of 151.26 dm 3 / h), thereby producing naproxen sodium tablets with a target weight of 300 mg at a production rate of 320,000 tablets / hr (98 kg / hr). All tests were conducted using naproxen sodium only. The performance of the LIW feeder depends on the density of the material, and the density of naproxen sodium was determined to be 0.47 kg / dm 3 (Unless otherwise specified). Naproxen Sodium has moderate to poor flow properties, fluidizes easily, and degases quickly. A TS2024 twin helical screw was used as indicated, and a TC2020 twin concave screw was used as indicated. The feeder used was a DDSR20-QR (6 kg load cell, 7 liter hopper volume).
[0085] Figure 3 and Figure 4 Volume decay data is shown. Such tests include checking the maximum feed rate, analyzing the effect of hopper fill level on screw filling, and determining the optimum refill level. Figure 5-7 Gravimetric data is shown, which includes analysis of the impact of refilling and a check on overall gravimetric feeding accuracy.
[0086] Figure 3 The volume decay at different agitator speeds (20%, 50% and 80%) using a TS2024 twin screw at 80% screw speed is shown according to some embodiments. As shown, the target of 71 kg / h can be achieved at 80% screw speed. The behavior depicted at 30-40% hopper level can be attributed to the influence of the agitator, when the powder surface begins to move within the hopper. This is a unique behavior for naproxen sodium.
[0087] Figure 4 The volume decay at 80% screw speed and 50% agitator speed using a TS2020 twin concave screw is shown according to some embodiments. As shown, the twin concave screw is not shown in Figure 3 The subtle behavior of Naproxen Sodium is depicted at 30-40% hopper level. In addition, at 80% screw speed, a single double concave screw can achieve the target of 35 kg / h.
[0088] Figure 5 Gravity feed data for a TS2024 twin screw according to some embodiments is shown. The mass flow rate for this run was 71.094 kg / h. The two shaded bars extending vertically through the graph represent the time when the bins were changed on the reference scale. The peaks in mass flow (about 4% overshoot) represent refilling.
[0089] Figure 6 Gravity feed data for a TS2024 twin screw according to some embodiments is shown. The mass flow rate for this run was 35.547 kg / h. The two shaded bars running vertically through the graph represent the time when the bins were changed on the reference scale. The peak in mass flow (about 2.5% overshoot) represents refilling.
[0090] Figure 7 Gravity feed data for a TC2020 dual concave screw is shown according to some embodiments. The shaded bar running vertically through the graph shows when the bin is changed on a reference scale. As shown, the mass flow rate data line shows little effect from refilling.
[0091] Fig. 8A and 8B Both images shown in were taken immediately after idling. Fig. 8A An image of a LIW feeder according to some embodiments after two days of operation is shown. As shown, there is almost no naproxen sodium powder remaining in the hopper. Therefore, this indicates that after two days of operation without cleaning, the naproxen sodium powder did not adhere to the wall. The hopper filled with powder was also kept still overnight, and it still did not adhere. Figure 8B An image of the inlet position of a hopper according to some embodiments after two days of operation is shown. As shown, there is some powder / dust accumulation along the upper corners of the hopper, but it is very minimal.
[0092] The above description sets forth exemplary systems, methods, techniques, parameters, etc. However, it should be recognized that such description is not intended to limit the scope of the present disclosure, but is provided as a description of exemplary embodiments.
[0093] Although the description herein uses the terms first, second, etc. to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another element.
Claims
1. An oral tablet comprising: Naproxen sodium; Mannitol; super disintegrants; and A lubricant, wherein the oral tablet does not contain a glidant.
2. The oral tablet of claim 1, wherein the super disintegrant comprises sodium starch glycolate.
3. The oral tablet according to claim 1 or 2, wherein the oral tablet comprises 70-80 wt.% of naproxen sodium.
4. The oral tablet of any one of claims 1-3, wherein the oral tablet comprises 15-25 wt.% of mannitol.
5. The oral tablet of any one of claims 1-4, wherein the oral tablet comprises 3-8 wt.% of a super disintegrant.
6. The oral tablet of any one of claims 1-5, wherein the oral tablet comprises 1-6 wt.% of a lubricant.
7. The oral tablet of any one of claims 1-6, wherein the lubricant comprises one or more of magnesium stearate or stearic acid.
8. The oral tablet of any one of claims 1-7, wherein the mannitol is spray-dried mannitol.
9. The oral tablet of any one of claims 1-8, wherein the oral tablet comprises 220 mg naproxen sodium.
10. Naproxen sodium tablets, formed by the following process: mixing naproxen sodium, mannitol, a super disintegrant, and a lubricant in a continuous in-line mixer to form a tableting blend; transferring the tableting mixture to a tableting machine; and The tableting mixture is compressed into naproxen sodium tablets.
11. The naproxen sodium tablet of claim 10, wherein the process does not include a granulation step.
12. The naproxen sodium tablet of claim 10 or 11, wherein mixing naproxen sodium, mannitol, a super disintegrant, and a lubricant in a continuous in-line mixer comprises feeding the naproxen sodium, the mannitol, the super disintegrant, and the lubricant to the in-line mixer via a loss-in-weight feeder.
13. The naproxen sodium tablet of any one of claims 10-12, wherein mixing naproxen sodium, mannitol, a super disintegrant, and a lubricant in a continuous in-line mixer comprises mixing the naproxen sodium, the mannitol, and the super disintegrant before adding the lubricant to the in-line mixer.
14. The naproxen sodium tablet of any one of claims 10-13, wherein transferring the tableting mixture to a tablet press comprises vacuum transfer.
15. The naproxen sodium tablet of any one of claims 10-14, wherein the super disintegrant comprises sodium starch glycolate.
16. The naproxen sodium tablet of any one of claims 10-15, wherein the lubricant comprises one or more of magnesium stearate or stearic acid.
17. The naproxen sodium tablet of any one of claims 10-16, wherein the oral tablet comprises 70-80 wt.% of naproxen sodium.
18. The naproxen sodium tablet of any one of claims 10-17, wherein the oral tablet comprises 15-25 wt.% mannitol.
19. The naproxen sodium tablet of any one of claims 10-18, wherein the oral tablet comprises 3-8 wt.% of a superdisintegrant.
20. The naproxen sodium tablet of any one of claims 10-19, wherein the oral tablet comprises 1-6 wt.% of a lubricant.
21. The naproxen sodium tablet of any one of claims 10-20, wherein the mannitol is spray-dried mannitol.
22. The naproxen sodium tablet of any one of claims 10-21, wherein the oral tablet comprises 220 mg naproxen sodium.