Apparatus and method for evaluating the physical strength or robustness of a solid dosage form based on an impact strike test

Abstract

A solid dosage form testing apparatus and method are presented. The solid dosage form testing apparatus includes a striker component, an impact platform, a sensor data acquisition system, and a solid dosage form positioning mechanism. The solid dosage form positioning mechanism has first and second push components movable toward each other to position the solid dosage form at an impact site. The method includes performing an impact strike test on a first plurality of solid dosage forms and measuring a plurality of peak impact force values. The method may include performing a drop test on a second plurality of solid dosage forms and measuring a plurality of physical failure rates. The method may include determining a model describing a relationship between the peak impact force values ​​and the physical failure rate, and determining a predicted physical failure rate based on the model.

Description

Technical Field

[0001] The present invention is directed to an apparatus and method for evaluating the physical strength or robustness of solid pharmaceutical dosage forms such as tablets, mini - tablets, pills, chewable gums, wafers, disks, caplets, medicated candies, troches, implants, granules, and pellets based on an impact strike test.

Background Art

[0002] Solid pharmaceutical dosage forms, such as tablets, mini - tablets, pills, chewable gums, wafers, disks, caplets, medicated candies, troches, implants, granules, and pellets, provide a means by which a drug or other compound can be delivered into a user's body. Various pharmaceutical or drug formulations can be manufactured or formed into tablets, mini - tablets, pills, chewable gums, wafers, disks, caplets, medicated candies, troches, implants, granules, and pellets. In some cases, different formulations can produce tablets, mini - tablets, pills, chewable gums, wafers, disks, caplets, medicated candies, troches, implants, granules, and pellets having different mechanical or other physical properties.

Summary of the Invention

[0003] In view of the above, provided herein is a solid dosage form testing apparatus and method for evaluating the toughness of solid dosage forms, such as tablets, mini - tablets, pills, chewable gums, wafers, disks, caplets, medicinal candies, troches, implants, granules, and pellets. In one aspect, the solid dosage form testing apparatus includes a striker component, an impact platform, a sensor data acquisition system, and an arrangement mechanism for holding and properly positioning the solid dosage form under the striker component. The arrangement mechanism has a first push component and a second push component that are movable towards each other to position the solid dosage form at the impact site. The method includes performing an impact strike test on a first plurality of solid dosage forms or a set of the first plurality of solid dosage forms, and measuring a plurality of peak impact force values. The method may further include performing a drop test on a second set of a plurality of solid dosage forms and measuring a plurality of physical defect rates. The method may further include determining a model that describes the relationship between the peak impact force value and the physical defect rate, and determining a physically predicted defect rate based on the model.

Brief Description of the Drawings

[0004] The above - mentioned and other characteristics and aspects of the present technology can be better understood from the following description of the embodiments and as shown in the accompanying drawings. The accompanying drawings are incorporated herein and form a part of this specification, but further function to explain the essence of the present technology. The drawings are not necessarily to scale.

[0005]

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DETAILED DESCRIPTION OF THE INVENTION

[0006] The specific examples shown and described in this specification are examples of solid pharmaceutical forms and their tests, and it should be understood that they are not intended to limit the scope of this application in any way. As used in this specification, the singular forms "a", "an", and "the" strictly include the plural forms of the terms they refer to as well, unless the context clearly indicates otherwise.

[0007] The following detailed description is merely exemplary in nature and is not intended to limit the present invention or its application and uses. The description of this embodiment is in the context of evaluating or calculating the physical strength or robustness of a solid pharmaceutical dosage form such as tablets of a batch of tablets or samples, etc., but the present invention may be used in the context of evaluating or calculating the physical strength or robustness of solid pharmaceutical dosage forms such as small tablets, pills, chewable gums, wafers, disks, caplets, medicinal candies, lozenges, implants, granules, and pellets, etc., and samples of batches thereof. Further, there is no intention to be bound by any theory, whether explicit or implicit, shown in the prior art field, background art, summary of the invention, or the following detailed description.

[0008] One aspect of the present application relates to evaluating or calculating the physical strength or robustness of a solid pharmaceutical dosage form that is a sample or subset of a batch of tablets to withstand forces or situations in various environments to which the tablets can be exposed, such as during the coating process, packaging process, and / or inspection process of a tablet core, in a manufacturing facility, warehouse facility, pharmacy, hospital, patient's home, or during delivery from a tablet manufacturing facility to a pharmacy, hospital, home, or another location. As used herein, the term "tablet" may refer to a tablet core, a coated tablet, and an uncoated tablet. For example, tablets may be accidentally dropped onto a solid surface in these environments or may be exposed to forces during processing, such as the forces that a tablet core undergoes during the coating process. Evaluating the physical strength or robustness of these tablets may include, for example, predicting or otherwise determining the physical defect rate associated with the tablets when dropped from a specific height and / or dropped a specific number of times. Such evaluation or calculation may be used to determine whether a pharmaceutical formulation, such as a tablet, produces sufficiently robust mechanical or other physical properties to enable the tablet to withstand the situations or events to which the tablet can be exposed. In some cases, calculating the physical strength of a sample or subset of a batch of tablets may include, for example, determining their tensile strength via a hardness test and using the tensile strength as an indicator of the strength of the tablet (the tensile strength may be calculated, for example, from pharmacopeial hardness test data generated from a Sotax HT100, tablet dimensions, and compression tool dimensions using the Pit equation discussed on pages 169 - 175 of "Powder Technology" by K.T. Pitt & M.G. Heasley). However, parameters such as tensile strength do not cover the rapid transfer of energy, such as when a freely falling tablet collides with a solid surface. Such events may impart an impact or other force to the falling tablet, which may crush or otherwise break the tablet. In some cases, a tablet or pharmaceutical formulation of a tablet may be determined via a hardness test to have a high tensile strength, but may still have a low ability to cope with other events, including impacts, collisions, or rapid transfer of energy.Thus, the hardness test and tensile strength parameters may not be sufficient to predict the physical defect rate of tablets in large-scale manufacturing settings, leading to a discrepancy between the predicted physical robustness and the actual physical robustness of the tablets to be manufactured.

[0009] In certain embodiments, the peak impact force parameter may be used to calculate the physical strength of a tablet. More specifically, the value of the peak impact force parameter, also referred to as the peak impact force value, may be used to predict the physical defect rate for a batch of tablets. The peak impact force value may be measured, for example, by conducting an impact strike test in which a striker component strikes and breaks one or more samples of a batch of tablets. During the test, the peak amount of force applied to the tablet or the average of the peak amounts of force applied to a set of tablets may be measured. This is because these measurements may be better indicators of the rapid transfer of energy and may provide a better ability to calculate the physical strength of the tablet or, more specifically, to predict the physical defect rate for the tablet.

[0010] In certain embodiments, the peak impact force parameter may be used as an indirect measurement result or approximation of the impact toughness, also referred to as toughness, of a tablet (e.g., a plain tablet, a coated tablet, an uncoated table, etc.) or a batch of tablets (e.g., a tablet core, a coated tablet, an uncoated table, etc.). In some cases, the toughness of a sample or subset of a batch of tablets may be measured directly, such as by determining the area under the stress-strain curve of the tablet. In such cases, the directly measured toughness of the tablets or samples of the batch of tablets may be used to predict the physical defect rate for the batch of tablets. In certain embodiments, a computer system or other device may receive sensor data indicating the force a tablet receives during an impact strike test. In some implementations, the computer system may be configured to determine, based on the sensor data, whether the tablet was broken or otherwise suffered another physical defect during the impact strike test.

[0011] In one embodiment, the impact strike test may be performed with a solid dosage form or tablet testing apparatus that uses a striker component that is removably suspended above the impact site. In some implementations, the tablet testing apparatus may include a solid dosage form or tablet placement mechanism (also referred to as a tablet centering mechanism or tablet holder) for placing the solid dosage form or tablet such that the solid dosage form or tablet is centered directly below the striker component about the impact site. When implemented as a tablet placement mechanism, the mechanism may thus place the tablet at a location where the center of the tablet is aligned with the center of the tip of the striker component such that the center of the tablet is struck by the falling striker component. In some implementations, the tablet placement mechanism may have a recess for accommodating the curvature of the tablet. The recess may push the tablet toward the impact site when engaged with the tablet. In some implementations, the tablet testing apparatus may include a channel for directing an air stream toward an impact chamber surrounding the impact site. The air stream may reduce the likelihood that fragments or other material generated during the impact strike test exit the housing of the tablet testing apparatus. In one embodiment, the tablet testing apparatus may include a waste collection device or component configured to perform waste collection or waste removal after each impact strike test or after several impact strike tests. Waste collection or waste removal may include, for example, automatically removing the tablet from the impact site, and the tablet removed may be broken or, if not, may have been subjected to an impact strike test. In some cases, the tablet placement mechanism may be configured to automatically acquire a new tablet and place the new tablet at the impact site after the tablet has been removed so that the impact strike test can be performed on the new tablet.In one embodiment, the tablet testing apparatus may be configured to automate the tablet testing process by automatically placing a tablet onto an impact platform, automatically arranging the tablet by a tablet placement mechanism at an impact site on the impact platform, releasing a striker component onto the tablet to strike the tablet, collecting sensor data or other measurements related to striking the tablet, automatically removing the tablet from the impact platform by a waste collection device, and repeating the process by placing the next tablet onto the impact platform. In such a manner, the tablet testing apparatus may be able to automatically test a batch sample or subset of tablets in a carousel manner.

[0012] FIG. 1A provides a configuration diagram of a system 1000 for evaluating one or more mechanical properties of a batch of tablets or a solid pharmaceutical dosage form such as a sample of tablets, and / or for calculating the mechanical or physical strength or robustness of a tablet. In some cases, system 1000 may be part of a pharmaceutical or other manufacturing facility that manufactures any of such dosage forms for pharmaceutical tablets, dietary tablets, or other ingestible tablets or pills, chewable gum, wafers, disks, caplets, medicinal candies, lozenges, implants, granules, and pellets. For example, system 1000 may be used within a manufacturing facility or a research / development facility to provide a quality control process by being used by a manufacturer to predict whether a batch of tablets is strong enough to withstand handling by a pharmacist, doctor, patient, or other person, or if not, whether it will become robust. Such handling may include events such as a tablet dropping onto a hard surface, or other events that may subject the tablet to an impact or force that may break the tablet or, if not, introduce physical defects into the tablet.

[0013] In the embodiment of FIG. 1A, the system 1000 may include a solid dosage form testing device 1100 and a computer system 1200. As will be described in more detail below, the solid dosage form testing device 1100 may be used to perform an impact strike test on a tablet, and more specifically, to generate sensor data that measures the amount of force or energy involved in striking the tablet. In one embodiment, the solid dosage form testing device 1100 may include a housing 1110 in which various components of the solid dosage form testing device 1100, such as a striker component 1120 and an impact platform 1130, are disposed. The impact platform 1130 may be configured as a substrate or surface on which a solid dosage form can be placed. More specifically, the impact platform 1130 may include an impact site where the striker component 1120 strikes the impact platform 1130 or a solid dosage form disposed directly above the impact site. For example, the striker component 1120 may be suspended above the impact platform 1130. In this example, the impact site may be a position on the upper surface of the impact platform 1130 directly below the striker component 1120. The housing 1110 may include a striker mechanism configured to removably suspend the striker component 1120 above the impact site on the impact platform 1130. The striker mechanism may be able to release the striker component 1120 as part of the impact strike test, allowing the striker component 1120 to fall or descend towards the impact site under the influence of gravity. The falling striker component 1120 may strike a solid dosage form (if present) disposed at the impact site or, if not, may strike the impact site. In some cases, the striker component 1120 may strike the tablet with sufficient momentum or energy to crush or, if not, break the tablet into multiple pieces.

[0014] In one embodiment, the solid dosage form testing apparatus 1100 may include a sensor data acquisition system 1140 for acquiring, or otherwise generating, sensor data related to an impact strike test performed using the solid dosage form testing apparatus 1100. As described above, the sensor data may measure, or otherwise indicate, parameters such as the speed or kinetic energy of the striker component 1120 as it falls towards the solid dosage form at the impact site, and / or the amount of force imparted to the solid dosage form by the striker component 1120. In some cases, the sensor data acquisition system 1140 may include one or more sensors for generating the sensor data. For example, the one or more sensors may include a first sensor configured to measure the speed or kinetic energy of the striker component 1120 as it falls, and / or a second sensor configured to measure the amount of energy imparted to the solid dosage form by the striker component 1120 when the striker component 1120 strikes the solid dosage form. In some implementations, the sensor data acquisition system 1140 may be configured to store the sensor data. For example, the sensor data acquisition system 1140 may include circuitry, such as an analog-to-digital converter (DAC) and / or digital signal processing (DSP) circuitry configured to receive sensor data from one or more sensors, and / or a non-transitory computer-readable medium (e.g., solid state drive or hard disk drive) for storing the sensor data.

[0015] FIG. 1B shows a solid pharmaceutical dosage form testing device 1100A according to an embodiment herein, which may be an embodiment of the solid pharmaceutical dosage form testing device 1100 including a solid dosage form placement mechanism 1150 and an impact chamber 1115. In certain embodiments, the solid dosage form placement mechanism 1150 is configured to push a solid dosage form, such as a tablet, mini-tablet, pill, chewable gum, wafer, disk, caplet, medicinal candy, troche, implant, granule, or pellet, toward an impact site on the impact platform 1130 so as to place the solid dosage form directly below the striker component 1120 prior to the start of an impact strike test, or otherwise move it. In some implementation examples, the impact chamber 1115 may be part of the housing 1110 and may be a chamber surrounding the impact platform 1130. The impact chamber 1115 may be used to collect, or otherwise contain, debris that may occur when the solid dosage form is struck by the striker component 1120. More specifically, the impact chamber 1115 may prevent debris from spreading into the environment outside the housing 1110 to protect skilled workers or other personnel monitoring the impact strike test from being exposed to pharmaceuticals or other substances within the debris.

[0016] In certain embodiments, the computer system 1200 of FIGS. 1A and 1B may be configured to process sensor data. In some implementation examples, data processing may include, for example, determining a model that explains (i) how much impact force a solid dosage form can withstand before breaking and (ii) the relationship, or another relationship, between the physical defects a solid dosage form may experience as a result of the drop. In some implementation examples, data processing may include generating a prediction regarding the physical defect rate of a solid dosage form or batch of solid dosage forms, where the physical defects may indicate the likelihood of physical defects experienced when one of the batches of solid dosage forms is dropped onto a hard surface or experiences another type of physical impact.

[0017] In one embodiment, computer system 1200 may include, for example, at least one processing circuit (e.g., a computer processor) and a non-transitory computer-readable medium (e.g., a solid-state drive). The processing circuit may be configured to process sensor data. In some cases, the processing circuit may process sensor data by executing instructions stored on or in the non-transitory computer-readable medium. Computer system 1200 may be a stand-alone device (e.g., a desktop computer or a server) separated from the solid dosage form testing apparatus 1100, or it may be a part of the solid dosage form testing apparatus 1100 (e.g., an arithmetic circuit or a chip embedded within the solid dosage form testing apparatus 1100).

[0018] Figures 2A and 2B show a tablet testing device 2100 according to an embodiment of the present specification, which may be an embodiment of the solid dosage form testing devices 1100 and 1100A. The tablet testing device 2100 is configured as a floor-standing system, which is by way of example and not limiting, and a bench-top or table-top system as described below is also within the scope of the present disclosure. More specifically, FIG. 2A is a front view of the tablet testing device 2100, while FIG. 2B is a cross-sectional view of the tablet testing device 2100 taken along line A-A of FIG. 2A. As shown in FIG. 2A, the tablet testing device 2100 includes a housing 2110 in which various components of the tablet testing device 2100 are disposed. In certain embodiments, the housing 2110 may form one or more chambers such as a striker component chamber 2111 and an impact chamber 2115, which are described in more detail below. As shown in FIG. 2B, the striker component chamber 2111 may be surrounded by one or more walls such as walls 2111A and 2111B, while the impact chamber 2115 may be surrounded by one or more walls such as walls 2115A and 2115B. FIG. 2A further shows the tablet testing device 2100 having a user input device 2170 configured to receive user instructions or other user inputs. For example, the user input device 2170 may be configured to receive one or more user instructions related to performing an impact strike test.

[0019] In one embodiment, the striker component chamber 2111 may be a chamber that houses an impact striker 2120 (also referred to as a tap), as shown in FIG. 2B. The striker component chamber 2111 may further house a striker mechanism 2113 that removably suspends the striker component 2120 above the impact chamber 2115. The striker mechanism 2113 is configured to release the striker component 2120 such that the striker component 2120 may fall or descend through an opening 2114 in the impact chamber 2115 onto the impact site 2132, where the striker component 2120 may strike a tablet 2300 or other object disposed at the impact site 2132, or otherwise impact. Thus, the impact chamber 2115 may house the impact site 2132 and may be used to collect or otherwise contain debris that may be generated by the impact. In some implementations, the solid dosage form or tablet testing apparatuses 1100, 1100A, 2100 may include a motor or other actuator configured to raise the striker component after it has been lowered such that the striker component may be released again to perform another impact strike test.

[0020] In one embodiment, the impact site 2132 may be provided by an impact platform 2130 that may be an embodiment of the impact platform 1130. The impact platform 2130 may be housed in the impact chamber 2115 and may provide a substrate for receiving an impact or other collision with the striker component 2120. For example, the impact platform 2132 may be an object or device that provides an upper surface that is flat (to form a flat upper surface) or curved outwardly or inwardly (to form a convex or concave upper surface). In such a case, the impact site 2132 may be at a position such as a central position on the flat upper surface of the impact platform 2130. The impact platform 2130 may have a cylindrical shape, a rectangular shape, or any other shape. In one embodiment, the tablet testing device 2100 may include a tablet placement mechanism 2150 that may be an embodiment of the tablet placement mechanism 1150. The tablet placement mechanism 2150 is disposed on the upper surface of the impact platform 2130. The tablet placement mechanism 2150 may have components that surround the impact site 2132 and / or are equidistant from the impact site 2132, and may push the tablet towards the impact site 2132 or, if not, move it. More specifically, the tablet may be configured to be disposed centered on the impact site 2132 such that the center of the tablet is directly above the impact site 2132. In some implementation examples, once the tablet 2300 placement mechanism moves the tablet to the impact site, the components may move away from the tablet 2300 so as to disengage from the tablet. As a result, the tablet placement mechanism 2150 is no longer in contact with the tablet 2300. By disengaging from contact with the tablet 2300, the tablet placement mechanism 2150 may avoid interfering with the impact test and may avoid affecting the sensor data generated during the impact test. The tablet placement mechanism is described in more detail below.

[0021] In one embodiment, the striker component 2120 (also referred to as a tap) may be a rigid component such as an elongated rod made of a metal such as stainless steel. The striker component 2120 is configured to be released or lowered to create an impact with the impact site 2132 of the impact platform 2130. In some implementation examples, the striker component 2120 may have a tip 2121 such as a flat tip or a rounded tip, or more specifically, a tip facing the impact site 2132, and the impact site 2132 is configured to contact the center of the tablet 2300 disposed at the impact site 2132 when the striker component 2120 impacts the tablet 2300 or otherwise strikes. In the embodiments of the present specification, the tip 2121 may be made of a metal such as stainless steel.

[0022] In one embodiment, the striker component 2120 may have a body in the shape of an elongated cylinder with a tip 2121 having a circular profile. FIG. 2D shows a flat tap insert 2121A attached to the striker component 2120D and functioning as its tip on a flat surface, and a hemispherical tap insert 2121B attached to the striker component 2120D and functioning as its tip on a rounded surface. Thus, in some cases, the striker tip may be formed by a metal insert or tap insert such as stainless steel, which may be inserted into or otherwise attached to a shaft forming the elongated cylinder or other configuration of the striker component as shown in FIG. 2D for the striker component 2120D. Simply repeating the above, for example, the flat tip 2121 may be formed from the flat tap insert 2121A, while the rounded tip 2121 may be formed from the hemispherical tap insert 2121B or other curved tap insert. In some cases, the diameter of the cylinder may be similar to the diameter of various tablets or alternatively another dimension (e.g., length or width). As an example, the diameter of the cylinder may range from, for example, 5 mm to 12 mm.

[0023] In embodiments herein, the striker component, tip, and / or tip or tap insert may be made of a non-rigid material selected to mimic substances that the tablets may contact at various stages of manufacturing, packaging, storage, and transportation. In such embodiments, the striker component, tip and / or tip or tap insert may be made of a non-rigid or soft elastomer or polymer material. In other embodiments, the striker component, tip and / or tip or tap insert may be formed from non-rigid cardboard or other such packaging material.

[0024] In one embodiment, referring to FIGS. 2B and 2C, the striker component 2120 may include one or more objects 2122 that are removably attached to the body of the striker component 2120 so as to provide additional mass or weight to the striker component 2120. For example, the one or more objects 2122 may include one or more disks that may slide around a portion of the body of the striker component 2120. In some implementations, for a particular drop distance, the total mass of the striker component 2120 including the one or more objects 2122 may be small enough to apply a force of impact between the striker component 2120 and a pharmaceutical tablet or other tablet within a range that is sufficient to break the tablet but not large enough to completely crush the tablet. In some cases, for a particular drop distance, the total mass of the striker component 2120 may be 1 kg or less or 0.5 kg or less.

[0025] In one embodiment, the striker component 2120E shown in FIG. 2E may have a number of tips or tap inserts configured to simultaneously impact a number of tablets. As such, the number of tips or tap inserts may be used for the execution of parallel processing of a number of tablets so as to increase the rate at which impact strike tests can be performed on a sample or subset of a batch of tablets or other solid dosage forms. In FIG. 2E, the striker component 2120E includes tips or tap inserts 2121A, 2121B, 2121C, 2121D, 2121E. In some cases, the number of tips may form a 2D array of tips (also referred to as the parent body of the number of tips). In this embodiment, the weight of the striker component, or more specifically the tap weight or tap mass, may increase in relation to the striker component of FIG. 2C. The weight or mass of the striker component 2120E may be increased to a level such that when the striker component 2120E of FIG. 2E falls from a particular height and collides with a number of tablets, it can provide sufficient force to have a reasonable expectation of breaking all of the tablets. In this embodiment further, each sensor may be disposed within or attached to each of the tips or tap inserts 2121A, 2121B, 2121C, 2121D, 2121E so as to collect sensor data indicating the amount of force applied by each tip to each tablet struck by the tip.

[0026] In the embodiments of this specification, the tablet testing apparatuses 2100F and 2100G may include sample filling stations 2400F and 2400G such as those shown in FIGS. 2F and 2G. In the examples of FIGS. 2F and 2G, the sample filling stations 2400F and 2400G may form a carousel for supplying one or more tablets to one or more positions on their impact platforms. In some cases, the sample filling station 2400G may supply one tablet at a time to the position 2131G (also referred to as the tablet supply position) of the impact platform 2130G, as shown in FIG. 2G. In some cases, the sample filling station 2400F may be configured to supply multiple tablets simultaneously to multiple tablet supply positions 2131F of the impact platform 2130F, as shown in FIG. 2F. In some cases, the tablet supply position may be a well or other indentation within the surface of the impact platforms 2130F and 2130G, and the well may hold the supplied tablets. In the example of FIG. 2F, the multiple tablet supply positions 2131F may be arranged in a line (e.g., a column) of wells. In some cases, the sample filling stations 2400F and 2400G may be configured as grooved carousels, and each groove may contain each set of tablets to be supplied. For example, each groove may be used to accommodate different types of tablets.

[0027] In the embodiments of this specification, the impact platforms 2130F and 2130G in FIGS. 2F and 2G may be rotatable to rotate one or more supplied tablets from one or more tablet supply positions 2131F and 2131G to one or more impact sites 2132F and 2132G. In some cases, the impact platforms 2130F and 2130G may rotate one or more supplied tablets to an intermediate position or, more specifically, to the alignment stations 2402F and 2402G. At the alignment stations 2402F and 2402G, the tablet testing apparatus may include a tablet placement mechanism that uses a pair of push components or multiple pairs of push components to ensure that, for example, a single supplied tablet or multiple supplied tablets are placed at the center of a desired position, such as the center of each well into which they are supplied. Such an alignment operation can make it more certain that when the supplied tablets are rotated to the impact test stations 2404F and 2404G, they will gather centered directly below each tip 2121A, 2121B, 2121C, 2121D, 2121E of the striker component 2120E as shown in FIG. 2F or centered below the tip 2121 of the striker component 2120 as shown in FIG. 2G.

[0028] In the embodiments of this specification, the impact test stations 2404F and 2404G are configured to include one or more impact sites that may receive an impact from one or more tips of the striker components 2120 and 2120E when the striker components fall towards the impact platforms 2130F and 2130G. The striker components 2120 and 2120E may be used as part of an impact strike test as disclosed herein and may be intended to break the supplied tablets when the tablets are rotated to the impact test stations.

[0029] In the embodiments of this specification, the rotatable impact platforms 2130F, 2130G are configured to further rotate one or more supplied tablets from the impact test stations 2404F, 2404G to the clearing stations 2406F, 2406G after the one or more supplied tablets are broken by each striker component or, if not, after being struck. The clearing stations 2406F, 2406G are configured to remove fragments of the broken tablets or other debris so as to prevent the fragments of the broken tablets or other debris from contaminating other areas of the tablet testing apparatuses 2100F, 2100G towards the portion within the impact chamber for one or more supplied tablets (which may be the tablets broken at this point). In the example of FIG. 2F, the clearing station 2406F may include a vacuum configured to generate a negative pressure that may, for example, suck fragments of the broken tablets or other debris towards the waste compartment of the tablet testing apparatus 2100F. In such an example, the tablet testing apparatus 2100F may be airtight so as to facilitate creating a negative pressure in its impact chamber (with respect to the remaining area of the tablet testing apparatus). In the example of FIG. 2G, the clearing station 2406G may include a scraper 2408 configured to sweep fragments of one or more broken tablets or other debris from the upper surface of the impact platform 2130G. The fragments or other debris may, for example, be scraped off and fall towards the waste compartment disposed under the impact platform 2130G.

[0030] In the embodiments of this specification, with further reference to FIGS. 2B and 2C, the striker mechanism 2113 may be configured to removably suspend the striker component 2120 within the housing 2110 and on the impact site 2132. For example, the striker mechanism 2113 may include a base 2113C, which may be a device, block, or other object from which the striker component 2120 hangs, or is otherwise suspended. In some implementations, the base 2113C may include a movable latch, stopper, or other component on which the striker component 2120 rests. Such a component may prevent the striker component 2120 from falling towards the impact site 2132. In one embodiment, the base 2113C may include an actuator such as a solenoid configured to retract or otherwise move the latch or stopper to a position where it no longer supports the striker component 2120. Such movement of the latch or stopper may release the striker component 2120 and thus permit the striker component 2120 to fall towards the impact site 2132. In some cases, the actuator in this example may be activated, stopped, or otherwise controlled based on a user instruction such as a user instruction received via the user input device 2170. For example, the user input device 2170 may provide a user interface that enables the user to input a user instruction that causes the descent of the striker component 2120. In such an example, the actuator of the base 2113C may be activated in response to the user instruction.

[0031] In one embodiment, the base 2113C may be a lifter device (also called a tap lifter) configured to control the height at which the striker component 2120 is suspended above the impact site 2132, and thus the release height RH (also called the drop height) at which the striker component 2120 is released to descend toward the impact site 2132. Increasing the release height RH can increase the amount of energy or the impact force imparted by a striker component 2120 of an appropriate / specific mass to the tablet 2300 at the impact site 2132, while decreasing the release height can decrease the amount of energy or the impact force imparted by a striker component 2120 of an appropriate / specific mass to the tablet 2300. In embodiments according to the present specification, the desired impact force may be achieved by selecting an appropriate release height RH for the mass of the striker component, and any desired impact force may also be achieved by correctly selecting the weight of the striker component that provides the desired impact force at the impact site and each release height. In some implementation examples, the base 2113C may control the release height RH of the striker component 2120 by moving along or being moved along one or more rails 2113A, 2113B that may form a support frame or support structure of the striker mechanism 2113. More specifically, the one or more rails 2113A, 2113B may be or include elongated bars or rods that guide the movement of the base 2113C as the base 2113C raises or lowers the striker component 2120. In one embodiment, the mechanism 2130 may include an actuator such as a motor or a pneumatic actuator configured to generate a force to raise or lower the base 2113C along the one or more rails 2113A, 2113B. This actuator may be disposed within the base 2113C, or may be disposed at other locations within the housing 2110 or outside the housing 2110. If the actuator is disposed outside the base 2113C, the tablet testing device 2100 may include a transmission component such as a chain configured to transmit the force generated by the actuator to the base 2113C.If an actuator is disposed within base 2113C, such an actuator may be separated from any actuator used to release striker component 2120 from base 2113C.

[0032] In one embodiment, the tablet testing device 2100 may have a size small enough to provide a device suitable as a bench top or table top device such as the bench top tablet testing device 2100BB shown in front and side views in FIG. 2BB. The bench top tablet testing device 2100BB may include a housing 2110BB having a relatively short height, for example, a height H of 130 cm to 140 cm suitable for installation and operation on a laboratory bench or table. In one example, the height H may be such that a striker component (not shown) that may be weighted as described above can be removably suspended above the impact site 2132BB (release height RH) to a maximum distance of 120 cm, 110 cm, 100 cm, 90 cm, 80 cm, 70 cm, 60 cm, 50 cm, 40 cm, 30 cm, 20 cm, 10 cm, 5 cm or less. By way of example, the height H of the housing 2110BB may be 140 cm, 130 cm, 120 cm, 110 cm, 100 cm, 90 cm, 80 cm, 70 cm, 60 cm, or a smaller numerical value. The reduced release height RH described above may require a striker component of greater mass to provide sufficient impact force at the impact site for the impact strike test to be performed, i.e., specifically, to break a pharmaceutical tablet or other tablet during the impact strike test. The greater mass may be achieved, as previously explained, by adding mass to an existing striker component or by selecting a striker component of a heavier material. The bench top tablet testing device 2100BB may include all or most of the features described herein with reference to the tablet testing devices 2100, 3100, for example, one or more chambers such as a striker component chamber and an impact chamber, a striker mechanism for removably suspending a striker component above the impact chamber, additional mass or weight for adding to the striker component, and an impact platform located within the impact chamber and having a tablet placement mechanism, each of these structures being appropriately sized for bench or table top use.

[0033] In one embodiment, the tablet testing apparatus 2100 may be an embodiment of the sensor data acquisition system 1140 configured to generate sensor data for measuring various aspects of the impact strike test, and may include a sensor data acquisition system 2140 as shown in FIG. 2C. For example, the sensor data acquisition system 2140 may include at least a sensor 2141 and a sensor 2142. The sensor 2141 is configured to measure the impact force applied by the striker component 2120 to the tablet 2300 or other object at the impact site 2132 when the striker component 2120 collides with, impacts, or strikes the object. For example, it may be a strain gauge force sensor or other sensor. In one example, as shown in FIG. 2C, the sensor 2141 may be disposed at the tip 2121 of the striker component 2120. In one embodiment, the sensor 2142 may be a laser sensor or other sensor configured to measure the kinetic energy or velocity of the striker component 2120 as it falls towards or otherwise moves towards the impact site 2132. In some cases, the sensor data acquisition system 2140 may include a communication circuit 2143 configured to receive or collect sensor data generated by the sensors 2141, 2142 via a wired or wireless connection 2144. If the sensor data is to be processed by the computer system 1200 of FIGS. 1A and 1B, the computer system 1200 may receive the sensor data via the communication circuit 2143. In one embodiment, the sensor of the sensor data acquisition system (e.g., 2141) may be disposed on or within the impact platform and configured to measure the force with which the striker component 2120 impacts the impact site 2132. In a particular implementation example, the sensor may be statically disposed at a fixed position such as directly below the impact site 2132 and within the impact platform.

[0034] FIG. 3A shows a tablet testing device 3100 that may be an embodiment of the solid dosage form or tablet testing devices 1100, 1100A, 2100. The tablet testing device 3100 includes a housing 3100 that forms a striker component chamber 3111 and an impact chamber 3115. The striker component chamber 3111 may include a striker component 3120 and a mechanism 3113 configured to removably suspend the striker component 3120 above the impact chamber 3115. The impact chamber 3115 may include an impact platform 3130 and a tablet placement mechanism 3150 disposed on the upper surface of the impact platform 3130. In some cases, the components shown in FIG. 3A may be embodiments of similar components described above with respect to the embodiments shown in FIGS. 2A-2C.

[0035] As described above, the solid dosage form or tablet testing apparatus 1100 / 2100 / 3100 may include a solid dosage form or tablet placement mechanism 1150 / 2150 / 3150. FIGS. 3B and 3C show an embodiment of the tablet placement mechanism 3150 that may be configured to push the tablet toward the impact site or, if not, move it, and more specifically, place the tablet centered on the impact site. Such placement may place the tablet directly beneath the striker component prior to initiation of the impact strike test. More specifically, the tablet placement mechanism 3150 may be disposed on the upper surface of the impact platform 3130, attached to the upper surface of the impact platform 3130, or otherwise connected, and may include a first push component 3151 and a second push component 3152. In this example, the impact site 3132 may be disposed between the first push component 3151 and the second push component 3152. The first push component 3151 and the second push component 3152 in this example may be movable toward each other manually or via an actuator (e.g., a motor) along the directions indicated by the arrows 3701, 3702 in FIG. 3B. More specifically, the tablet placement mechanism 3150 may have an open configuration, as shown in FIGS. 3B and 3C, in which the first component 3151 and the second component 3152 have a space therebetween for placing the tablet in that space. The tablet placement mechanism 3150, as shown in FIG. 3D, may be movable or adjustable from the open configuration to a closed configuration (e.g., via a motor) by moving the push components 3151, 3152 toward each other and toward the impact site 3132 such that the tablet is pushed toward the impact site 3132, and more specifically, the tablet is centered on the impact site 3132. In some cases, the first push component and the second push component may be equidistant from the impact site such that when they are moved toward each other by an equal amount, the tablet is pushed toward the impact site thereby.Once the tablet is centrally placed at the impact site 3132, the push components 3151, 3152 may be moved to return to the open configuration, and in the open configuration, the push components 3151, 3152 are moved away from the tablet so that they no longer contact the tablet.

[0036] In some cases, the impact platform 3130 may include one or more connecting components, such as springs, that connect the first push component 3151 and the second push component 3152 to the impact platform 3130, yet permit the first push component 3151 and the second push component 3152 to move toward or away from each other along the upper surface of the impact platform 3130.

[0037] In one embodiment, the first push component 3151 may have a first recess 3151A that may provide a recess that may be used to fit on one side (e.g., the left side) of the tablet when the tablet is on a particular side (e.g., the left side) of the impact site. In such a scenario, when the first push component 3151 is moved in the rightward direction towards the second push component 3152, the first push component 3151 may push the tablet in the rightward direction towards the impact site. Similarly, the second push component 3152 may have a second recess 3152A that may provide a recess that may be used to fit on the other side (e.g., the right side) of the tablet. When the second push component 3152 is moved in the leftward direction towards the first push component and the tablet is on the other side (e.g., the right side) of the impact site, the second push component 3152 may push the tablet in the leftward direction towards the impact site. More specifically, the recess formed by the first recess 3151A of the first push component 3151 may extend inwardly towards the interior 3151D such as the central portion of the first push component 3151 and, as a result, may extend away from the impact site 3132. Similarly, the recess formed by the second recess 3152A of the second push component 3152 may extend inwardly towards the interior 3152D of the second push component 3152 and, as a result, may extend away from the impact site 3152. As shown in FIGS. 3B and 3C, the first push component 3151 and the second push component 3152 may surround the impact site 3132 such that the impact site 3132 may be disposed between the first recess 3151A of the first push component 3151 and the second recess 3152A of the second push component 3152. More particularly, the impact site may remain as the central position of the space between the first push component 3151 and the second push component 3152.When the first push component 3151 and the second push component 3152 are moved towards each other, their movement may position the first recess 3151A and the second recess 3152A at the impact site 3132. Accordingly, the tablet may be placed at the impact site 3132 such that the tablet is centered around the impact site 3132.

[0038] In one embodiment, the first push component 3151 and the second push component 3152 may be well-suited for receiving a tablet and positioning or otherwise placing the tablet centered around the impact site 3132. More particularly, various tablets may have a convex side or, more generally, a convex shape. For example, some tablets may have an annular or elliptical shape where the opposite side is curved outwardly. The first push component 3151 and the second push component 3152 may have a concave shape that complements the convex shape of the tablet. As an example, the first recess 3151A of the first push component 3151 in FIGS. 3B and 3C may form a first concave corner 3151E configured to receive the first convex side of the tablet. In this example, the second recess 3152A of the second push component 3152 may form a second concave corner 3152E configured to receive the second convex side of the tablet. The concave corners 3151E, 3152E may each be a curved angle having a curve angle or each be a sharper angle without a curve angle. The concave corners 3151E, 3152E may be such that when one or both corners receive the tablet, the tablet is pushed towards the impact site 3132 when the first push component 3151 and the second push component 3152 are moved towards each other. In one embodiment, the first push component 3151 and the second push component 3152 may be arranged such that the impact site 3132 is equidistant from the push components 3151, 3152. For example, the impact site 3132 may be equidistant from the first concave corner 3151E and the second concave corner 3152E.

[0039] In one embodiment, the first push component 3151 and the second push component 3152 may have complementary portions that are fitted together, or not, such that the tablet placement mechanism 3150 moves from an open configuration to a closed configuration to allow the push components 3151, 3152 to be brought close enough to the impact site to centrally position the tablet at the impact site. For example, as shown in FIG. 3C, the first recess 3151A of the first push component 3151 may form one or more grooves 3151B, 3151C. The one or more grooves 3151B, 3151C may be configured to receive the second recess 3152 when the first push component 3151 and the second push component 3152 are moved towards each other. More specifically, the second recess 3152 may include a first sub-portion 3152B and a second sub-portion 3152C that project from the second push component 3152. In this example, the groove 3151B may be configured to receive the first sub-portion 3152B, while the groove 3151C may be configured to receive the second sub-portion 3152C. In other words, the sub-portions 3152B, 3152C may be slidable into the grooves 3151B, 3151C. These complementary structures of the first push component 3151 and the second push component 3152 may allow them to move towards each other and towards the impact site 3132 to push an object towards the impact site 3132 such that, as shown in FIG. 3D, the object is positioned centered on the impact site 3132. In one embodiment, once the push components 3151, 3152 have been moved from the open configuration to the closed configuration, the push components may return to the open configuration to place a tablet or other object at the impact site 3132. When the push components return to the open configuration, they may disengage from the tablet such that they do not contact the tablet when the striker component is falling towards the tablet during the impact strike test.

[0040] Figures 4A and 4B show a striker component 3120 that strikes the tablet 3300 by dropping onto the tablet 3300 under the influence of gravity. Figures 4A and 4B show a scenario where the tablet placement mechanism 3150 is in an open configuration such that the tablet placement mechanism 3150 disengages from the tablet 3300 while the striker component 3120 is being dropped or falling onto the tablet 3300. In such a configuration, the tablet placement mechanism 3150, specifically, the first push component 3151 and the second push component 3152, may avoid interference with the striker component 3120 and avoid interference with the measurement of how much force is applied from the striker component 3120 to the tablet 3300. Figure 4C shows the results of an impact strike test being performed on the tablet 3300. More specifically, the impact strike test may include a striker component 3120 having sufficient mass and / or being released from a sufficient height such that when the striker component 3120 is released to impact the tablet 3300, the striker component 3120 applies sufficient force or energy to break the tablet 3300. For example, Figure 4C shows the result of the force of the impact from the striker component 3120 and a gap 3300A in the tablet 3300 created when a portion of the tablet 3300 breaks away from the tablet 3300. As will be described in more detail below, some embodiments of the present specification may include detecting a tablet breakage event by determining whether the tablet was actually broken as a result of the impact strike test based on measurements made with sensor data.

[0041] As described above, the impact chambers 1115, 2115, 3115 may surround the impact sites 2132, 3132 and may be used to contain fragments that may be created during the impact strike test. For example, an impact from a striker component, such as 2120, may create fragments in the form of dispersed powder. If the powder were to be exposed to personnel outside of the enclosures 1110, 2110, 3100 of the solid dosage form or tablet testing apparatus, there is a risk that it may contain pharmaceutical substances that may have an adverse effect on health. Thus, the impact chambers 1115, 2115, 3115 may be used to collect fragments therein. In one embodiment, as shown in FIG. 2F, the impact chamber may be connected to a vacuum to create a negative pressure to prevent contaminated air from leaking out of the impact chamber.

[0042] For example, FIG. 5 shows a tablet testing device 2100 that may be configured to generate an air flow that can prevent fragments from leaking out of the impact chamber 2115. More specifically, the tablet testing device 2100 may include an opening 2114, that is, specifically, a hole through which a striker component 2120 can pass through the impact chamber 2115 and reach the impact site 2132. In this embodiment, the impact chamber 2115 may have walls 2115A, 2115B, 211C, and 2115D that are airtight and connected to each other and airtight to the upper and bottom walls. In one example, walls 2115D and 2115C may be the front and rear walls of the impact chamber 2115, respectively, while walls 2115A and 2115B may be the side walls of the impact chamber, respectively. In this way, walls 2115A, 2115B, 2115C, and 2115D may prevent fragments from leaking laterally out of the impact chamber 2115. However, the fragments may leak out through the opening 2114. To reduce the possibility of such a situation occurring, the tablet testing device 2100 may include an air flow generator 2180 such as a fan or a pneumatic pump or a conduit connected to compressed air configured to generate an air flow. In this embodiment, the tablet testing device may have one or more channels 2123A, 2123B (e.g., tubes, hoses, or pipes) that are directly or indirectly connected to the air flow generator 2180. The one or more channels 2123A, 2123B may have outlets around the opening 2114, and the air flow generated by the air flow generator 2180 may reach a region near the opening 2114 (e.g., just above the opening 2114 as shown in FIG. 5). In this way, the air flow generator 2180 and the one or more channels 2123A, 2123B may apply air pressure into the impact chamber 2115 through the opening 2114. The air pressure may reduce the possibility of fragments leaking out of the impact chamber 2115. In some implementation examples, the impact chamber 2115 may include a filter 2116 that provides an outlet for the air flow entering the impact chamber 2115 through the opening 2114.The filter 2116 may be made by an impact strike test and configured to remove any debris carried by the airflow, thus further preventing debris from leaking out of the impact chamber 2115. In some implementations, the impact chamber 2115 may be configured to provide environmental control. More specifically, the impact chamber 2115 may be configured to control the temperature or other environmental conditions at the impact site to create a situation standardized for the impact strike test.

[0043] FIG. 6 shows a method 6000 that may use a tablet testing apparatus to evaluate the strength of a sample or subset of a tablet or batch of tablets. The method may include determining how much impact force various tablets can absorb before physically breaking, or, if not, withstand. In one embodiment, the method 6000 may include determining the relationship between such impact force and a physical defect rate indicative of the likelihood of physical defects occurring in the tablets in a particular situation or series of situations. In some cases, the method 6000 may use this relationship to predict the physical defect rate for other situations and / or other batches of tablets or types of tablets. In one embodiment, the method 6000 may be performed, for example, by a manufacturing facility that manufactures pharmaceutical tablets or other tablets, and / or a research / development facility, i.e., specifically by the personnel of the facility. In some cases, the method 600 may be performed as part of a tablet manufacturing process or tablet (formulation) development.

[0044] In one embodiment, method 6000 may begin at step 6002 where an impact shock test is performed on a first plurality of tablets or a set of the first plurality of tablets, or may include step 6002 if not. In some cases, the first plurality of tablets or the set of the first plurality of tablets may be associated with a plurality of tablet types having different physical characteristics. In other words, each tablet of the first plurality of tablets may be associated with each tablet type of the plurality of tablet types, or each set of tablets of the set of the first plurality of tablets may be associated with each tablet type of the plurality of tablet types. For example, if the impact shock test is performed on the first plurality of tablets, the first plurality of tablets may include a first tablet belonging to a first tablet type, e.g., tablet type 1, a second tablet belonging to a second tablet type, e.g., tablet type 2, and so on. If the impact shock test is performed on a set of the first plurality of tablets, the set of the first plurality of tablets may include a first set of tablets belonging to a first tablet type, e.g., 10 or 20 tablets, a second set of tablets belonging to a second tablet type, and so on. Thus, the impact shock test may be used to generate sensor data associated with different tablet types.

[0045] In some cases, the tablet type may be related to the batch of tablets being manufactured. In other words, tablets of the same batch may belong to a common tablet type. In some cases, the physical characteristics related to the tablet type may be related to the physical characteristics of the tablets related to the tablet type, such as the shape and / or size of the tablets. For example, the shape of the tablet may be related to whether the tablet is oval or circular and / or whether the tablet has a flat surface. In some cases, the physical characteristics related to a particular tablet or tablet type may be affected, for example, by the formulation of the tablet or tablet type, the shape of the tablet, and / or the method by which the tablet is manufactured. The method by which the tablet is manufactured may be related to or affected by the parameter values or the manufacturing techniques used to manufacture the tablet. For example, if the tablet is manufactured based on compressing a powder, the parameter value is related to the amount of compression pressure used to compress the powder. The powder may be compressed directly by direct compression or granulated to form granules using dry granulation or wet granulation techniques prior to compression. In such examples, the method of manufacturing the tablet may affect physical characteristics such as the porosity of the tablet or tablet type. In other examples, the method by which the tablet is manufactured may be related to the use of a coating process on the tablet core that can be subjected to various forces. In such examples, the method of coating the tablet may further affect physical characteristics such as the porosity of the tablet or tablet type. In still other examples, the method by which the tablet is manufactured may be related to the use of molding or additive manufacturing such as 3D printing using, for example, hot melt extrusion.

[0046] In one embodiment, the formulation of the tablet may relate to what materials are included in the tablet or, more generally, to the qualitative and / or quantitative composition of the tablet. The materials included in the tablet may be divided into one of the categories of pharmaceutical active ingredient (API) or excipient. The excipients within the tablet formulation may be further classified into one or more of the following categories. Filler, disintegrant, binder (solution binder or dry binder), glidant, lubricant / anti-adherent (see, for example, M.E. Aulton, Pharmaceutics - The Science of Dosage Form Design, 2nd Edition).

[0047] In certain embodiments, the qualitative composition describing the tablet formulation may list such classifications of excipients and / or specific substances. Examples of fillers include MCC (e.g., MCC Avicel PH 102 101, Emcocel 90M, etc.), mannitol (e.g., Pearlitol 50c, Pearlitol 120c, or Pearlitol 160c). Examples of disintegrants include sodium starch glycolate, e.g., ExploTab or Glycolys LV. Examples of binders include Plasdone K29 / 32, povidone, and Kolidon K30. Examples of glidants include colloidal silica and talc. Examples of lubricants include magnesium stearate and glyceryl dibehenate.

[0048] In certain embodiments, the quantitative composition may list the specific substances along with the amounts of each substance. The amounts may be expressed as weight or percentage. The filler, when employed, is in the range of about 10 to about 75 weight percent (e.g., about 15 to about 70 weight percent) of the dry formulation, the disintegrant, when employed, is in the range of between about 0.5 and 10.0 weight percent (e.g., about 5 weight percent) of the dry formulation, the binder, when employed, is in the range of, e.g., between about 2 and about 8 weight percent of the dry formulation, the glidant, when employed, is in the range of between about 0.1 and 10.0 weight percent of the dry formulation, and the lubricant, when employed, is in the range of between about 0.25 and 2.5 weight percent of the dry formulation.

[0049] In some examples, fillers (also called diluents / carriers) used in oral formulations such as in the form of immediate release tablets may include monocalcium phosphate, dicalcium phosphate (including dicalcium phosphate dihydrate and anhydrous calcium hydrogen phosphate), tricalcium phosphate, lactose, microcrystalline cellulose, siliconized microcrystalline cellulose, mannitol, sorbitol, starch (e.g., corn, potato, or rice), glucose, calcium lactate, calcium carbonate, and the like. In one example, the diluent / carrier may include dicalcium phosphate and microcrystalline cellulose, which may be used alone or in combination with other diluents / carriers such as mannitol. In certain embodiments, the formulation of the immediate release tablets may include one or more excipients to improve the physical and / or chemical properties of the final composition of the tablets and / or to facilitate the manufacturing process.Such a complementary medicine may be used in the formulation of an immediate-release formulation for oral drug delivery and contains one or more lubricants (e.g., magnesium stearate, stearic acid, calcium stearate, stearyl alcohol, or sodium stearyl fumarate), glidants (e.g., talc or colloidal silica), one or more binders (e.g., polyvinylpyrrolidone, microcrystalline cellulose, polyethylene glycol (PEG), polyethylene oxide, low molecular weight hydroxypropylmethylcellulose (HPMC), low molecular weight methylcellulose (MC), low molecular weight hydroxypropylcellulose (HPC), low molecular weight hydroxyethylcellulose (HEC), starch (e.g., corn, potato, or rice), or sodium carboxymethylcellulose of low molecular weight, polyvinylpyrrolidone or low molecular weight HPMC as a binder), one or more pH adjusters (e.g., organic acids (e.g., citric acid) or their alkali metal (e.g., sodium) salts, magnesium oxide, alkalis or alkaline earth metal (e.g., sodium, calcium, or potassium) sulfates, metabisulfites, propionates, or sorbates), one or more disintegrants (e.g., sodium starch glycolate, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose, starch (e.g., corn, potato, or rice) or alginates), coloring agents, flavoring agents, isotonic agents, coating agents, or preservatives.

[0050] As an example, the composition of tablets in some cases may include one or more of diluents such as calcium phosphate (monocalcium phosphate, dicalcium phosphate, and tricalcium phosphate), lactose, microcrystalline cellulose, mannitol, sorbitol, titanium dioxide, aluminum silicate, etc. In some cases, the diluent may also include microcrystalline cellulose and mannitol. In some cases, the composition of the tablets may include one or more of the following lubricants. Magnesium stearate, sodium stearyl fumarate, etc. In some cases, the composition of the tablets may include a flow promoter such as colloidal silica. In some cases, the composition of the tablets may include one or more of the following binders. Polyvinylpyrrolidone, lactose, mannitol, microcrystalline cellulose, polyethylene glycol (PEG), low molecular weight HPMC, low molecular weight MC, low molecular weight HPC, etc. A preferred binder includes microcrystalline cellulose. In some cases, the composition of the tablets may include one or more of the following pH adjusters. Organic acids (e.g., citric acid, etc.) or their alkali metal (e.g., sodium) salts, pharmaceutically acceptable salts of inorganic acids (e.g., carbonic acid or phosphoric acid) (e.g., sodium, magnesium, or calcium salts), magnesium oxide, and further, alkalis, and alkaline earth metal (e.g., sodium, calcium, potassium, etc.) sulfates, metabisulfites, propionates, and sorbinates. Other additional excipients may include coloring agents, flavoring agents, solubilizers (e.g., SDS), coating agents, preservatives, etc.

[0051] In a further example, one formulation of the tablets may include a composition containing materials such as microcrystalline cellulose (MCC), mannitol (MAN), and / or dicalcium phosphate (CDPA). The formulation may further include a coating around the tablet core, or such a coating may be absent.

[0052] Thus, in one example, different tablet types may be related to different respective formulations, or different respective combinations of formulations, and the porosity of the tablets being manufactured. For example, FIG. 7 shows various data points 701, 702, 703, 704, 711, 712, 713, 714, 721, 722, 723, 724, 731, 732, 733, 734 associated with different respective tablet types (e.g., tablet type 1, tablet type 2, tablet type 3, etc.). In this example, each tablet type may be related to a particular combination of a particular porosity and a particular formulation. As an example, data point 701 may indicate the peak impact force value of a first tablet type associated with a tablet having a porosity of about 7.5% and a formulation in which a powder having mannitol (and no MCC) is compressed to a target tensile strength of 1 MPa to form a tablet having a flat surface. The peak impact force value may indicate how much impact force a tablet of the first tablet type can absorb before breaking, or otherwise withstand, as described in more detail below.

[0053] In certain embodiments, if an impact strike test is performed on a first plurality of tablets, such an impact strike test may include, for example, only a single tablet per tablet type. For example, the first plurality of tablets may include a single tablet belonging to the first tablet type, a single tablet belonging to the second tablet type, a single tablet belonging to the third tablet type, and so on. In such an example, the impact strike test may generate, for example, a single peak impact force value, as described below, indicating the amount of force required to break each of the tablets. The single peak impact force value may be related to each tablet type to which the broken tablet belongs.

[0054] In one embodiment, if an impact strike test is performed on a first plurality of sets of tablets, the impact strike test may generate an average peak impact force value for each set. The average peak impact force value for a particular set of tablets may indicate the average amount of force required to break the set of tablets. For example, if one of the sets includes, for example, 10 tablets associated with a particular tablet type, the impact strike test may be performed to determine each of the 10 peak impact force values required to break the 10 tablets in that set. In such an example, the impact strike test may be used to determine the average peak impact force value associated with the tablet type, and the average peak impact force value may be the average of the 10 peak impact force values.

[0055] As described above, the impact strike test may be performed with solid dosage form or tablet test apparatuses such as apparatuses 1100, 2100, 3100. For example, the impact strike test may include placing a first tablet or solid dosage form of a first plurality of tablets or solid dosage forms on impact sites 2132, 3132 on impact platforms 1130, 2130, 3130, and centrally placing the first tablet or solid dosage form on the impact sites 2132, 3132 with solid dosage form or tablet placement mechanisms 1150, 2150, 3150. As an example, the tablet placement mechanisms 1150, 2150, 3150 may be moved from the open configuration described above to a closed configuration in which various components of the solid dosage form or tablet placement mechanisms 1150, 2150, 3150, such as the first push component 3151 and the second push component 3152, are moved closer to the impact sites 2132, 3132. The solid dosage form or tablet test apparatus may have striker components 1120, 2120, 3120 that are initially suspended above the impact site 2132, and step 6002 may include releasing the striker components 1120, 2120, 3120 of the solid dosage form or tablet test apparatuses 1100, 2100, 3100 to drop the striker components 1120, 2120, 3120 and strike the first tablet or solid dosage form. For example, the striker components 1120, 2120, 3120 may be released via a user instruction input into the user input device 2170. In this example, the impact strike test may further include removing the first tablet or solid dosage form after being struck by the striker components 1120, 2120, 3120. In some cases, the removal may be performed manually. In other cases, the removal may be performed automatically. For example, the tablet test apparatus 2100 may include a waste removal device or component. The waste removal device or component may include a waste filtration component configured to remove possible tablet fragments or other waste resulting from the impact strike test from the tablet test apparatus 2100. In some cases, the removal may include, for example, moving the solid dosage form or tablet placement mechanisms 1150, 2150, 3150 from the closed configuration to the open configuration.

[0056] In one embodiment, the impact strike test may repeat the above operation, step 6002, with more tablets or solid dosage forms. As an example, if the first plurality of tablets includes 10 tablets each associated with 10 tablet types, then all 10 tablets are placed at the impact sites 2132, 3132 and struck by the striker components 1120, 3120, 3120, the above operation may be repeated 9 more times. As another example, if the impact strike test is performed on 10 sets of tablets, each set is associated with a different tablet type, includes 5 tablets, and all 50 tablets are placed at the impact sites 2132, 3132 and struck by the striker component, the above operation may be repeated 49 more times. As yet another example, if the tablet testing device includes a striker component having a number of tips, the tablet testing device may perform the impact strike test on a number of tablets simultaneously. For example, if the striker component has a 2D array of 5×5 tips (i.e., 25 tips), the tablet testing device may be able to perform the impact strike test on 25 tablets simultaneously, and then repeat the impact strike test on another 25 tablets so that the impact strike test is performed on a total of 50 tablets.

[0057] In one embodiment, the impact strike test may be performed in a manner that maximizes the likelihood that each tablet of the first plurality of tablets or set of first plurality of tablets is broken as a result of the impact strike test. For example, the impact strike test may include a striker component 1120, 2120, 3120 having a sufficient total mass, e.g., 1 kg, and / or suspended at a sufficient height, e.g., 30 cm, above the impact sites 2132, 3132 such that the accumulated momentum and / or kinetic energy when the striker component reaches the impact site is sufficient to break the tablet. For example, by creating a gap 3300A, when the striker components 1120, 2120, 3120 are released and fall towards the impact sites 2132, 3132, it may be ensured that the striker components 1120, 2120, 3120 accumulate sufficient momentum and / or kinetic energy during the fall. In one embodiment, as described in more detail below with respect to FIG. 8C, the computer system 1200 may be configured to detect or determine whether the tablet has actually been broken based on sensor data that measures a force profile during the impact strike test.

[0058] In one embodiment, method 6000 may include step 6004 of measuring, during the impact strike test, a plurality of peak impact force values indicative of each peak amount of the impact force received by the first plurality of tablets or solid dosage forms from the striker components 1120, 2120, 3120 during the impact strike test, or each average peak amount of the impact force received by the set of the first plurality of tablets or solid dosage forms during the impact strike test. In some cases, the peak impact force may indicate the peak amount of force endured by the tablet until it disintegrates during the impact strike test, or the average of the peak amounts of force endured by the set of tablets until they disintegrate during the impact strike test. The plurality of peak impact force values in this example may be associated with each of the first plurality of tablet types.

[0059] As described above, method 6000 may include detecting an event in which a tablet or solid dosage form is damaged. Such a detection operation may include determining, based on sensor data that measures the impact force applied to the tablet, whether force has actually broken the tablet. Such a determination may be made, for example, based on a profile of the impact force that may be related to the force function applied to the tablet by the striker component as a function of time. More specifically, FIG. 8E shows the profiles of the impact forces associated with three cases in which each of three tablets is broken by the impact force from the striker component and three other cases in which each of three tablets remains intact without being broken despite the impact force from the striker component. In some implementations, such a determination may include detecting whether the force profile has a period during which the value of the force remains substantially flat as a function of time and forms a plateau shape having a duration exceeding a predetermined threshold. Such a shape of the force profile may indicate that the tablet associated with the force profile has not been broken. On the other hand, if the force profile has a shape in which the value of the force increases toward a peak and then decreases without forming a plateau, such a force profile may indicate that the tablet associated with the force profile has been broken by the force applied thereto during the impact strike test.

[0060] In some cases, when the impact strike test is performed on a single tablet or solid dosage form of a particular tablet type, step 6004 may include measuring a peak impact force value indicating the peak amount of force applied to the tablet by the striker component, and more specifically, how much impact force is required to break a single tablet. In some cases, when the impact strike test is performed on a set of tablets of a particular tablet type, step 6004 may include measuring the average of the peak amounts of the impact forces applied to the set of tablets, that is, more specifically, how much impact force is required on average to break the set of tablets.

[0061] In some cases, step 6004 may be performed with the assistance of or assisted by a sensor data acquisition system, such as sensor data acquisition systems 1140, 2140. For example, a strain gauge force sensor 2141 embedded within striker component 2120 may measure each peak impact force for each of the first plurality of tablets or set of the first plurality of tablets. In this example, step 6004 may further include personnel and / or a computer system, such as computer system 1200, at a manufacturing or research / development facility that receives sensor data generated by sensor 2141. The sensor data may be received directly from sensor 2141 or via a communication circuit, such as communication circuit 2143.

[0062] Figures 8A and 8B show graphs of data that may indicate how much force is applied to a tablet, such as tablet 3300, at impact sites 2132, 3132 by striker components 1120, 2120, 3120 and / or how much force is absorbed by the tablet from the striker components at different points in time. The graphs may represent or be based on, for example, sensor data collected at step 6004. For example, Figure 8A may represent data collected or generated when an impact strike test is breaking the first tablet, while Figure 8B may represent data collected or generated when an impact strike test is breaking the second tablet. In one example, when striker components 1120, 2120, 3120 collide with, impact, or otherwise strike a tablet, such as tablet 3300, striker components 1120, 2120, 3120 may suddenly decelerate. Sensor 2141 or another sensor may measure how much striker components 1120, 2120, 3120 accelerate or decelerate at different points in time. Such measurements may be used to approximate or otherwise indicate how much force (also called impact force) striker components 1120, 2120, 3120 are applying to tablet 3300 as a function of time. More specifically, the sensor data may indicate peak impact force values applied to tablet 3300 by striker components 1120, 2120, 3120 and / or the energy absorbed by the tablet from striker components 1120, 2120, 3120. In some cases, step 6004 may include the computer system 1200 calculating force values, such as those forming the graphs of Figures 8A and 8B, based on sensor data generated by a sensor data acquisition system, such as sensor data acquisition system 2140. As described above, the impact strike test may be performed in a way that maximizes the likelihood of breaking each of a first plurality of tablets. Further as described above, a computer system or other device may determine whether a tablet has actually been broken based on sensor data collected by performing an impact strike test on the tablet.Thus, step 6004 may include measuring peak impact force values associated with breaking the first plurality of tablets. For example, if step 6004 is based on the data shown in FIGS. 8A and 8B, step 6004 may include determining a peak impact force value of 799 N associated with breaking the first tablet and a peak impact force value of 804 N associated with breaking the second tablet. FIGS. 8C and 8D show examples of average peak impact force values determined from sets of 10 tablets of various formulations and various tablet shapes.

[0063] FIGS. 9A-9F show peak impact force values that may be measured as a result of step 6006 of method 6000. More particularly, the drawings represent on the X-axis the average peak impact force values associated with breaking tablets of different tablet types. For example, the graph of FIG. 9A represents data indicating that a set of tablets associated with tablet type 1 has an average peak impact force value of about 400 N. This data point may be determined, for example, by performing an impact strike test in step 6002 on a set of, for example, 5 tablets belonging to or otherwise associated with tablet type 1, and determining the average of the peak impact force values applied to or absorbed by the 5 tablets. As described above, the peak impact force value may represent the maximum force that 5 tablets withstood before breaking. In one embodiment, FIGS. 9A-9F may each show the average peak impact force value associated with each of tablet types 1 through 10, although, as will be described in more detail below, they may be associated with different situations in which the tablet drop test is performed.

[0064] In some implementation examples, step 6004 may include measuring, or alternatively or in addition to measuring the peak impact force value, the amount of energy absorbed by the tablet or solid dosage form during the impact strike test, or if not, determining. As shown in FIGS. 8A and 8B, the amount of energy absorbed may be determined by integrating the force values in the drawing so as to determine the area under the curve in FIGS. 8A and 8B. For example, FIGS. 8C and 8D show data indicating both the peak impact force applied to or absorbed by the tablet and the amount of energy applied to or absorbed by the tablet. In some implementation examples, step 6004 may include measuring, instead of or in addition to measuring the peak impact force value, the toughness parameters of a first plurality of tablets or a first set of a plurality of tablets. In some cases, the toughness parameter of the tablet may be measured based on calculating the area under the stress-strain curve of the tablet, such as the stress-strain curves shown in FIGS. 10A and 10B.

[0065] Returning to FIG. 6, method 6000 may, in one embodiment, include step 6006 of performing a tablet or solid dosage form drop test on a second plurality of tablets or a set of solid dosage forms. The second plurality of sets of tablets may also be associated with the plurality of tablet types described above with respect to step 6002. In other words, each set of the second plurality of sets of tablets may be associated with each tablet type of the plurality of tablet types. For example, the second plurality of tablets may include a set of tablets belonging to a first tablet type, such as tablet type 1, for example, 100 tablets, or a set of tablets belonging to a second tablet type, such as tablet type 2, for example, 100 tablets, and so on.

[0066] In one embodiment, the tablet drop test may include dropping a second plurality of sets of tablets onto a solid, or otherwise rigid surface, and examining what percentage of the tablets break or experience physical defects as a result of the drop. For example, the tablet drop test may be performed on a set of tablets associated with a particular tablet type by holding a number of sets of tablets, e.g., 100 tablets, above a solid surface and permitting the sets of tablets to be released and dropped onto the solid surface. The holding and dropping of the tablets may be done manually, automatically, one tablet at a time, or simultaneously for some or all of the sets of tablets.

[0067] In one embodiment, the tablet drop test may simulate different situations in which the tablets are dropped. The situations may relate to, for example, the drop height, the number of drops, or a combination thereof. In such an embodiment, the different situations may relate to different drop heights, different numbers of drops, or different combinations thereof. By way of example, the different situations may include a first combination in which the tablets are dropped only once from a height of 1 meter, a second situation in which the tablets are dropped 5 times from a height of 1 meter, a third situation in which the tablets are dropped 10 times from a height of 1 meter, a fourth situation in which the tablets are dropped only once from a height of 2 meters, a fifth situation in which the tablets are dropped 5 times from a height of 2 meters, and a sixth situation in which the tablets are dropped 10 times from a height of 2 meters. These situations may be used, for example, to generate the data shown in FIGS. 9A-9F. For example, the tablet drop test may be performed on a set of, for example, 600 tablets associated with a particular tablet type, such as tablet type 1. In this example, the tablet drop test may include dropping different subsets of the tablets for each of the situations described above. Thus, in this example, the tablet drop test includes dropping a first subset of 100 tablets onto a solid surface using the first situation described above, dropping a second subset of 100 tablets onto a solid surface using the second situation described above, dropping a third subset of 100 tablets onto a solid surface using the third situation described above, dropping a fourth subset of 100 tablets onto a solid surface using the fourth situation described above, dropping a fifth subset of 100 tablets onto a solid surface using the fifth situation described above, and dropping a sixth subset of 100 tablets onto a solid surface using the sixth situation described above. In the example above, the tablet drop test may include dropping other sets of tablets that may be associated with other tablet types, such as tablet type 2, tablet type 3, etc.

[0068] Returning to FIG. 6, method 6000 may include step 6008 which, in certain embodiments, may include measuring a plurality of physical defect rates associated with a plurality of tablet types based on a tablet drop test. For example, FIG. 9A shows data points representing a plurality of physical defect rates associated with tablet types 1 through 10. As an example, the data point shows tablet type 1 having a physical defect rate of 69%. FIGS. 9B-9F may each show another plurality of physical defect rates associated with a plurality of tablet types and with other situations in which the tablet drop test is performed.

[0069] In certain embodiments, measuring the physical defect rate of a tablet type may include automatically or manually counting how many tablets in a set or subset of tablets associated with the tablet type are broken or, if not, have experienced a physical defect as a result of the drop, and calculating what proportion or percentage of the set of tablets has experienced a physical defect. As an example, if the tablet drop test includes dropping, just once, a first subset of, for example, 100 tablets associated with tablet type 1, as described above, step 6008 may include counting how many of the subset of tablets were broken or experienced a physical defect as a result of the drop. For example, if 69 tablets are counted as having experienced a physical defect, step 6008 may include determining that there is a related tablet type 1 with a physical defect percentage (also referred to as a physical defect rate) of 69% if the tablets associated with tablet type 1 are dropped just once from a height of 1 meter.

[0070] In one embodiment, the plurality of physical defect rates described above may be the first plurality of physical defect rates, and step 6008 may include measuring or determining the second plurality of physical defect rates, the third plurality of physical defect rates, and the like. Each of the plurality of physical defect rates may be related to a specific situation such as a combination of the drop height and the number of drops at which the tablet is dropped. As an example, FIG. 9A may represent data showing a first plurality of physical defect rates associated with each of tablet types 1 to 10 when the tablet is dropped only once from a height of 1 meter in a tablet drop test, while FIG. 9B may represent data showing a second plurality of physical defect rates associated with each of tablet types 1 to 10 when the tablet is dropped 5 times from a height of 1 meter in a tablet drop test. Although the above embodiment describes obtaining the physical defect rate by performing a drop test, the physical defect rate may be obtained using any other test.

[0071] Returning to FIG. 6, method 6000 may, in one embodiment, include step 6010 of determining a model that describes the relationship between the peak impact force value and the physical defect rate based on the plurality of peak impact force values and the plurality of physical defect rates. In one embodiment, the model may include or be described by a mathematical formula or function that describes the relationship between the peak impact force value and the physical defect rate. For example, FIG. 9A shows a curve 901 representing a mathematical formula or function between the peak impact force value and the physical defect rate. Curve 901 or its corresponding mathematical formula may be determined by performing a curve fitting operation. Such an operation may include determining a curve that best fits the data points in FIG. 9A. As described above, each of the data points in FIG. 9A may represent each average peak impact force value associated with one of tablet types 1 to 10 and each physical defect rate associated with the tablet type. The average peak impact force value may be determined via an impact test, while the physical defect rate may be determined via a tablet drop test.

[0072] In one embodiment, the model may be determined based on a number of curves or mathematical formulas, each of which may be related to a particular situation in which a tablet drop test, such as a particular combination of drop height and number of drops, is performed. For example, the model may include, or be described by, curves 901, 902, 903, 904, 905, and 906 of FIGS. 9A-9F, respectively, or the mathematical formulas represented by the curves. Curves 901-906 may be related to different situations in which the tablet drop test is performed.

[0073] In one embodiment, method 6000 may include determining, based on the model of step 6010, the predicted physical defect rate for other situations in which the tablets are dropped and / or for other tablet types. For example, the prediction may be made for other tablet types, such as tablet type 11, and / or for other combinations of number of drops and drop height, such as 5 drops from a height of 1.5 meters or 4 drops from a height of 2 meters. In some cases, such steps may be performed by personnel in a manufacturing facility and / or by computer system 1200.

[0074] In some cases, determining such a prediction may involve performing an impact test on an additional tablet or set of tablets to determine a peak impact force value and using the peak impact force value to determine the predicted physical defect rate, or more generally, to determine the physical strength or robustness of the additional tablet or set of tablets. For example, the step may include performing an impact test on an additional tablet or set of tablets associated with tablet type 11, and measuring a peak impact force value that indicates the peak amount of impact force that the additional tablet or set of tablets received from the striker component during the impact test, i.e., specifically, the amount of the maximum force that the additional tablet withstood before breaking during the impact test. In this example, the step may determine the predicted physical defect rate of tablet type 11 based on the model described above and based on the peak impact force value. In some cases, the peak impact force value may be an average peak impact force value related to breaking a set of additional tablets. FIG. 11A shows the predicted physical defect rates of various tablet types, and the prediction may be based on peak impact force values derived from performing impact tests on tablets belonging to the tablet type. In some cases, the predicted physical defect rate may relate to a specific situation in which the tablet is dropped, such as a situation where the tablet is dropped 5 times from a height of 2 meters. In such cases, the prediction may include using a curve associated with such a situation, such as curve 905 in FIG. 9E or curve 1105 in FIG. 11B. For example, the prediction in FIG. 11A may include determining the values of the physical defect rates corresponding to 508N, 234N, and 128N of curve 1105.

[0075] As another example, step 6010 may include determining a predicted physical defect rate in an additional situation different from the situation where the tablet was dropped during the tablet drop test of step 6006. For example, the step may include determining the predicted physical defect rate of tablet type 1, tablet type 2, tablet type 11, tablet type 12, or yet another tablet type in a situation where tablets of the tablet type are dropped 4 times from a height of 2 meters. Such a situation may be different from that shown in FIGS. 9A-9F, which represents the situation in which the tablet drop test is performed for step 6006. In such an example, the step may be a physical defect rate associated with a situation directly represented by the model of step 6010, and may include determining one or more intermediate physical defect rates closest to the additional situation described above. For example, if the additional situation relates to the tablet being dropped 4 times from a height of 2 meters, the intermediate physical defect rate may include a first physical defect rate associated with the situation where the tablet is dropped once from a height of 2 meters and a second physical defect rate associated with the situation where the tablet is dropped 5 times from a height of 2 meters, as shown in FIGS. 9D and 9E. In this example, the prediction step described above may estimate the physical defect rate in the additional situation (4 drops from a height of 2 meters) based on the intermediate physical defect rate described above.

[0076] As described above, one aspect of the present disclosure relates to using the measurement of the peak impact force related to breaking a tablet to determine the physical strength or robustness of a tablet or a batch of tablets, i.e., specifically, predicting the physical defect rate of a batch of tablets (or another parameter indicating the likelihood that a tablet will experience a physical defect). More specifically, the peak impact force value may provide a strong indicator or a strong predictor of the physical defect rate predicted to be experienced by a batch of tablets. For example, FIG. 12A shows the p-value and R 2 value associated with the peak impact force, and the p-value and R 2Shows data for comparison with values. The p-value for a parameter may indicate how beneficial the parameter is for explaining the variation in the physical defect rate, that is, specifically, whether the parameter supports the hypothesis that the physical defect rate is affected by the parameter. As shown in FIG. 12A, the peak impact force value may have a low p-value. A low p-value, for example, a p-value less than 0.05, may indicate that the null hypothesis, such as the null hypothesis that the physical defect rate is not affected by the variation in the peak impact force value, is likely to be inaccurate. In other words, a low p-value for the peak impact force value may indicate the hypothesis that the physical defect rate is affected by the variation in the peak impact force value or has a correlation with the variation in the peak impact force value, and may be at least consistent with that hypothesis. As further shown in FIG. 12A, the p-value of the tensile strength may be much higher than the p-value of the peak impact force value. A high p-value for a parameter, for example, a p-value greater than 0.05, may indicate that the parameter has only a limited effect or no effect on the physical defect rate. FIG. 12B provides additional data showing that there is no correlation between the tensile strength and the physical defect rate in the tablets. FIG. 12A has a higher R 2 value than the curve or mathematical formula explaining the relationship between the tensile strength and the physical defect rate. A higher R 2 value may indicate that the approximation curve has a lower error level when compared to the data points used for curve fitting. FIG. 12C shows the R 2 value of the approximation curve used in an attempt to relate the tensile strength and the physical defect rate. As shown in FIG. 12C, the R 2 value of such a curve is the R 2For, it is lower. Thus, the data in FIGS. 11B, 12A, and 12C have a greater impact on peak impact force values with respect to other parameters such as tensile strength and a higher ability to accurately predict the physical defect rate. More generally speaking, the peak impact force value may exhibit a higher ability than other parameters to judge the physical strength or robustness of the tablet. FIG. 15 further illustrates the limited ability of other parameters such as abrasion degree to predict the physical defect rate. The abrasion degree test is a qualitative test that gives pass or fail criteria for the mechanical strength of the tablet (for example, pass: no broken tablets and less than 1% weight loss, or fail: any single tablet is broken and / or more than 1% weight loss). Such a test only provides data under test conditions (fixed drop height and fixed number of drops) and may have no or limited ability to be used to estimate beyond the test conditions (number of impacts). Furthermore, the abrasion degree test may lack the ability to measure the energy absorbed by the broken tablets, so the reason why a particular tablet is broken or chipped may not be explained.

[0077] FIG. 13 shows a method 13000 that may be performed to make a prediction regarding the physical defect rate using the peak impact force value. As described in more detail below, the method 13000 may be performed based on a model such as the model determined above using an impact strike test and a tablet drop test. In some implementations, the method 13000 may be performed by a computer system such as the computer system 1200.

[0078] In one embodiment, method 13000 may include step 13002 in which computer system 1200 receives a peak impact force value measured by a sensor of a tablet testing device, such as 1100, 2100, 3100, during an impact strike test in which a striker component of the tablet testing device strikes or breaks a tablet or a set of tablets. The tablet or set of tablets may belong to a specific tablet type, such as tablet type 11. The peak impact force value may indicate the peak amount of the impact force received by the tablet or set of tablets from a striker component, such as 1120, 2120, 3120, during the impact strike test. If the impact strike test is performed on a set of tablets, the peak impact force value may be the average of the peak amounts of the forces received by each of the tablets in the set. In some cases, the peak impact force may be the maximum amount of force that a tablet withstands until it breaks during the impact strike test or the average of the maximum amounts of force that each of the tablets in the set withstands until they break.

[0079] In one embodiment, method 13000 may include step 13004 in which computer system 1200 determines at least one predicted physical defect rate of a tablet type, such as tablet type 11, associated with the tablet or set of tablets used in the impact strike test, based on the peak impact force value. As described above, the tablet type is associated with the physical characteristics of the tablet or a set of physical characteristics, such as the combination of the formulation and the physical shape or porosity. In this example, the at least one predicted physical defect rate may predict the likelihood that a tablet belonging to the tablet type breaks when dropped on a solid surface.

[0080] In one embodiment, at least one physical defect rate may be determined based on a stored model that describes the relationship between the peak impact force value and the physical defect rate, such as the model described above. For example, the model may include or be described by a curve or mathematical formula that describes the relationship between the peak impact force value and the physical defect rate, such as the curve shown in FIG. 14. As described above, the peak impact force value may describe the peak amount of force applied to a single tablet or the average of the peak amounts of force applied to a set of tablets. In the example of FIG. 14, at least one physical defect rate may be determined as the value on the curve corresponding to the peak impact force determined in step 13002.

[0081] In one embodiment, at least one predicted physical defect rate may include a first predicted physical defect rate associated with a particular situation where the tablet is dropped or can be dropped onto a solid surface, such as when it is dropped 5 times and / or dropped from a height of 2 meters. In some cases, method 13000 may determine a plurality of predicted physical defect rates for a plurality of situations where the tablet is dropped or can be dropped onto a solid surface. For example, the plurality of predicted physical defect rates of the tablet may be related to a plurality of different drop heights, a plurality of different drop times, and / or a plurality of different combinations of drop height and drop time where the tablet can be dropped onto a solid surface. As described above, performing such predictions may, in some cases, involve inferring the predicted physical defect rate from the intermediate physical defect rate.

[0082] In one embodiment, method 13000 may include determining a predicted maximum height at which a tablet of a tablet type can be dropped without breaking or without at least one predicted physical defect rate exceeding a predetermined defect rate threshold, and / or a predicted maximum number of times at which a tablet of a tablet type can be dropped without breaking or without at least one predicted physical defect rate exceeding a predetermined defect rate threshold, based on a peak impact force value. Such determination may be used to evaluate the physical strength or robustness of the tablet or tablet formulation, and / or whether the formulation needs to be adjusted to enhance its physical strength.

[0083] Although various embodiments have been described above, they are presented only as an illustration and example of the technology and not for purposes of limitation. It will be apparent to those skilled in the relevant art that various changes can be made to the form and details without departing from the spirit and scope of the technology. Thus, the breadth and scope of the technology should not be limited by any of the above-described embodiments, but should be defined only in accordance with the appended claims and their equivalents. Also, it will be understood that each feature of each embodiment described herein and each reference cited herein can be used in combination with the features of any other embodiment. All patents and incorporated publications described herein are hereby incorporated by reference in their entirety.

Claims

1. A striker component, an impact platform configured to provide an impact site, a housing in which the striker component and the impact platform are disposed, the housing including a mechanism configured to removably suspend the striker component above the impact site within the housing, a sensor data acquisition system configured to acquire sensor data indicative of a speed or kinetic energy of the striker component when the striker component is released to descend toward the impact site, a solid dosage form placement mechanism having a first push component and a second push component connected to the impact platform, the first push component having a first recess, the second push component having a second recess, and the impact site being disposed between the first recess of the first push component and the second recess of the second push component, wherein the recess of the first recess of the first push component extends inwardly toward the interior of the first push component remote from the impact site, the recess of the second recess of the second push component extends inwardly toward the interior of the second push component remote from the impact site, and the first push component and the second push component are configured to be movable toward each other to position a solid dosage form disposed between the first recess and the second recess at the impact site, a solid drug dosage form testing device.

2. The first recess forms a first concave angle, and the second recess forms a second concave angle, wherein the first push component and the second push component are configured to surround the solid dosage form when the solid dosage form is disposed at the impact site, the solid drug dosage form testing device according to claim 1.

3. The first recess forms a groove adapted to receive the second recess when the first push component and the second push component are moved toward each other, the solid drug dosage form testing device according to claim 1.

4. The housing forms an impact chamber surrounding the impact site for accommodating fragments created during the impact strike test. The solid dosage form testing apparatus The solid dosage form testing apparatus according to claim 1, further comprising at least one of: (i) an air flow generator configured to generate an air flow applying air pressure into the impact chamber, or a vacuum configured to generate a negative pressure for preventing the fragments from leaving the impact chamber. **Claim 5** The solid dosage form testing apparatus according to claim 1, wherein the striker component has a rounded tip facing the impact site. **Claim 6** The solid dosage form testing apparatus according to claim 1, wherein the striker component has a mass of 1 kg or less. **Claim 7** The solid dosage form testing apparatus according to claim 6, wherein the striker component has a mass of 0.5 kg or less. **Claim 8** The solid dosage form testing apparatus according to claim 1, wherein the housing has a height limiting the maximum distance at which the striker component is detachably suspended above the impact site to 120 cm or less.

Images