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

Abstract

To present a solid pharmaceutical dosage form testing apparatus and method.SOLUTION: The solid pharmaceutical dosage form testing apparatus includes a striker component, an impact platform, a sensor data acquisition system, and a solid dosage form placement mechanism. The solid dosage form placement mechanism has first and second push components that are movable toward each other to position a 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 defect rates. The method may include determining a model that describes the relationship between peak impact force values and physical defect rates, and determining, on the basis of the model, a predicted physical defect rate.SELECTED DRAWING: Figure 2B

Description

[Technical Field]

[0001] The present invention is directed to an apparatus and method for evaluating the physical strength or robustness of solid pharmaceutical forms such as tablets, mini-tablets, pills, chewable gum, wafers, discs, caplets, lozenges, troches, implants, granules, and pellets based on impact impact testing. [Background technology]

[0002] Solid dosage forms, such as tablets, mini-tablets, pills, chewable gum, wafers, discs, caplets, lozenges, troches, implants, granules, and pellets, provide a manner in which drugs or other compounds can be delivered into a user's body. Various drug or drug formulations can be manufactured or formed into tablets, mini-tablets, pills, chewable gum, wafers, discs, caplets, lozenges, troches, implants, granules, and pellets. In some cases, different formulations can produce tablets, mini-tablets, pills, chewable gum, wafers, discs, caplets, lozenges, troches, implants, granules, and pellets with different mechanical or other physical properties. Summary of the Invention

[0003] In view of the above, provided herein are solid dosage form testing devices and methods for evaluating the toughness of solid dosage forms, such as tablets, mini-tablets, pills, chewable gum, wafers, discs, caplets, lozenges, troches, implants, granules, and pellets. In one embodiment, the solid dosage form testing device includes a striker component, an impact platform, a sensor data acquisition system, and a positioning mechanism for holding and properly positioning the solid dosage form under the striker component. The positioning mechanism has a first push component and a second push component that are movable toward each other to position the solid dosage form at the impact site. The method includes performing an impact impact 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 plurality of solid dosage forms and measuring a plurality of physical failure rates. The method may further include determining a model describing the relationship between the peak impact force value and the physical failure rate and determining a predicted physical failure rate based on the model. [Brief explanation of the drawings]

[0004] The above and other features and aspects of the present technology can be better understood from the following description of embodiments and as illustrated in the accompanying drawings, which are incorporated into and form a part of this specification and further serve to explain the principles of the present technology. The drawings are not necessarily to scale.

[0005] [Figure 1A] 1 shows a block diagram of a solid drug test device according to an embodiment herein. [Figure 1B] 1 shows a block diagram of a solid drug test device according to an embodiment herein. [Figure 2A] 1 shows a diagram of a tablet testing apparatus according to embodiments herein. [Figure 2B] 1 shows a diagram of a tablet testing apparatus according to embodiments herein. [Figure 2BB]1A-1D show front and side views of a tablet testing apparatus sized for benchtop use according to embodiments herein. [Figure 2C] 1 illustrates a sensor data acquisition system according to embodiments herein. [Figure 2D] 10A-10C illustrate various tap inserts for striker components according to embodiments herein. [Figure 2E] 1 illustrates a striker component having multiple tips for striking multiple tablets simultaneously according to embodiments herein. [Figure 2F] 1 illustrates a carousel for feeding tablets and a vacuum-based clearing system according to embodiments herein. [Figure 2G] 1 illustrates a carousel for feeding tablets and a scraper-based clearing system according to embodiments herein. [Figure 3A] 1 illustrates a tablet testing apparatus according to embodiments herein. [Figure 3B] 1 illustrates a tablet placement mechanism according to embodiments herein. [Figure 3C] 1 illustrates a tablet placement mechanism according to embodiments herein. [Figure 3D] 1 illustrates a tablet placement mechanism according to embodiments herein. [Figure 4A] 1 illustrates an impact impact test being performed on a tablet testing apparatus according to embodiments herein. [Figure 4B] 1 illustrates an impact impact test being performed on a tablet testing apparatus according to embodiments herein. [Figure 4C] 1 illustrates an impact impact test being performed on a tablet testing apparatus according to embodiments herein. [Figure 5] 1 illustrates an airflow generator for providing airflow toward an opening of an impact chamber according to embodiments herein. [Figure 6] 1 is a flow chart illustrating a method for assessing the strength of tablets or a sample of a batch of tablets according to embodiments herein. [Figure 7]1 shows peak impact force values ​​associated with various formulations and porosities according to embodiments herein. [Figure 8A] 1 illustrates the force being applied to a tablet by a striker component during an impact impact test according to embodiments herein. [Figure 8B] 1 illustrates the force being applied to a tablet by a striker component during an impact impact test according to embodiments herein. [Figure 8C] 1 shows various values ​​of peak impact force and energy imparted to tablets during impact impact testing according to embodiments herein. [Figure 8D] 1 shows various values ​​of peak impact force and energy imparted to tablets during impact impact testing according to embodiments herein. [Figure 8E] 1 shows force profiles for situations where a tablet breaks and does not disintegrate during an impact impact test according to embodiments herein. [Figure 9A] 1 shows various values ​​of peak impact force and physical defect rate associated with various tablet types according to embodiments herein. [Figure 9B] 1 shows various values ​​of peak impact force and physical defect rate associated with various tablet types according to embodiments herein. [Figure 9C] 1 shows various values ​​of peak impact force and physical defect rate associated with various tablet types according to embodiments herein. [Figure 9D] 1 shows various values ​​of peak impact force and physical defect rate associated with various tablet types according to embodiments herein. [Figure 9E] 1 shows various values ​​of peak impact force and physical defect rate associated with various tablet types according to embodiments herein. [Figure 9F] 1 shows various values ​​of peak impact force and physical defect rate associated with various tablet types according to embodiments herein. [Figure 10A] 1 shows stress strain curves that may be used to measure toughness associated with various tablet types according to embodiments herein. [Figure 10B] 1 shows stress strain curves that may be used to measure toughness associated with various tablet types according to embodiments herein. [Figure 11A] 10 illustrates predicted physical defect rates based on various peak impact force values ​​according to embodiments herein. [Figure 11B] 10 illustrates predicted physical defect rates based on various peak impact force values ​​according to embodiments herein. [Figure 12A] 1 shows a comparison between p-values ​​and R2 values ​​associated with peak impact force and p-values ​​and R2 values ​​associated with tensile strength, according to embodiments herein. [Figure 12B] 1 illustrates the relative lack of correlation between tensile strength and physical defect rate for tablets according to embodiments herein. [Figure 12C] 10 shows error values ​​associated with curves that attempt to relate tensile strength to physical defect rate according to embodiments herein. [Figure 13] 1 is a flowchart illustrating a method for predicting physical defect rates based on peak impact force values ​​according to embodiments herein. [Figure 14] 10 illustrates a prediction of physical defect rate based on a model describing the relationship between physical defect rate and peak impact force according to embodiments herein. [Figure 15] 1 illustrates the relative lack of correlation between friability values ​​and physical defect rates for tablets according to embodiments herein. DETAILED DESCRIPTION OF THE INVENTION

[0006] It should be understood that the specific examples shown and described herein are examples of solid dosage forms and testing thereof and are not intended to limit the scope of this application in any way. As used herein, the singular forms "a," "an," and "the" strictly include the plural forms of the terms they refer to, unless the content clearly dictates otherwise.

[0007] The following detailed description is merely exemplary in nature and is not intended to limit the invention or its application and uses. Although this embodiment is described in the context of evaluating or calculating the physical strength or robustness of solid dosage forms, such as tablets or samples of a batch of tablets, the invention may be used in the context of evaluating or calculating the physical strength or robustness of solid dosage forms, such as mini-tablets, pills, chewable gum, wafers, discs, caplets, lozenges, troches, implants, granules, and pellets, as well as samples of such batches, where deemed useful. Furthermore, there is no intention to be bound by any expressed or implied theory presented in the preceding technical field, background, brief summary, or the following detailed description.

[0008] One aspect of the present application relates to evaluating or assessing the physical strength or robustness of a solid dosage form that is a sample or subset of a batch of tablets to assess their ability to withstand forces or conditions in various environments to which the tablets may be exposed, such as, for example, the environment of a manufacturing facility, warehouse facility, pharmacy, hospital, patient's home, during tablet core coating, packaging, and / or inspection processes, or during delivery from the tablet manufacturing facility to a pharmacy, hospital, home, or elsewhere; as used herein, "tablet" may refer to tablet cores, coated tablets, and uncoated tablets. For example, tablets may be accidentally lowered onto a solid surface in these environments or exposed to forces during processing, such as those experienced by tablet cores during a coating process; assessing the physical strength or robustness of these tablets may include, for example, predicting or otherwise determining the physical defect rate associated with tablets when lowered from a particular height and / or lowered a particular number of times. Such evaluations or calculations may be used to determine whether a tablet formulation, such as a drug or pharmaceutical formulation, produces sufficiently robust mechanical or other physical properties to enable the tablet to withstand conditions or events to which it may be exposed. In some cases, calculating the physical strength of a sample or subset of a batch of tablets may involve, for example, determining their tensile strength via hardness testing and using the tensile strength as an indicator of tablet strength (tensile strength may be calculated, for example, from pharmacopoeial hardness test data and tablet dimensions generated from a Sotax HT100 and compression tool dimensions using Pitt's equation, discussed in K.T. Pitt & M.G. Heasley, "Powder Engineering," pp. 169-175). However, parameters such as tensile strength do not cover the rapid transfer of energy, such as a freely falling tablet impacting a solid surface. Such an event may impart impact or other forces to the falling tablet, causing it to fracture or otherwise break. In some cases, a tablet or tablet formulation may have high tensile strength as determined via hardness testing, yet may still have a poor ability to handle an impact, collision, or other event involving the rapid transfer of energy.Thus, hardness testing and tensile strength parameters may be poor predictors of the physical defect rate of tablets in a large-scale manufacturing setting, leading to discrepancies between the predicted and actual physical robustness of the manufactured tablets.

[0009] In some embodiments, the peak impact force parameter may be used to assess 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 performing an impact impact 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 imparted to a tablet or the average of the peak amount of force imparted to a set of tablets may be measured. Because these measurements are a better indicator of the rapid transfer of energy, they may provide a better ability to assess the physical strength of a tablet, or more specifically, to predict the physical defect rate for a tablet.

[0010] In some embodiments, the peak impact force parameter may be used as an indirect measure or approximation of the impact toughness, also referred to as toughness, of a tablet (e.g., plain tablet, coated tablet, uncoated tablet, etc.) or a batch of tablets (e.g., tablet core, coated tablet, uncoated tablet, 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 tablets. In such cases, the directly measured toughness of a tablet or sample of a batch of tablets may be used to predict the physical defect rate for the batch of tablets. In some embodiments, a computer system or other device may receive sensor data indicative of the force experienced by the tablets during impact impact testing. In some implementations, the computer system may be configured to determine whether the tablets broke or suffered another physical defect during impact impact testing based on the sensor data.

[0011] In some embodiments, the impact impact test may be performed on 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 positioning mechanism (also referred to as a tablet centering mechanism or tablet holder) for positioning the solid dosage form or tablet so that it is centered at the impact site and positioned directly below the striker component. When implemented as a tablet positioning mechanism, the mechanism may thus position the tablet so that its center is aligned with the center of the tip of the striker component so that the center of the tablet is struck by the falling striker component. In some implementations, the tablet positioning mechanism may have a recess to accommodate the curvature of the tablet. When engaged with the tablet, the recess may push the tablet toward the impact site. In some implementations, the tablet testing apparatus may include a channel for directing airflow toward an impact chamber surrounding the impact site. The airflow may reduce the likelihood of debris or other material that may be generated during the impact impact test escaping the housing of the tablet testing apparatus. In some embodiments, the tablet testing apparatus may include a waste collection device or component configured to perform waste collection or waste removal after each impact impact test or after several impact impact tests. Waste collection or waste removal may include, for example, automatically removing tablets from the impact site, where the removed tablets may be destroyed or otherwise subjected to the impact impact test. In some cases, the tablet placement mechanism may be configured to automatically retrieve a new tablet and place the new tablet at the impact site after the tablet is removed so that the impact impact test can be performed on the new tablet.In some embodiments, the tablet testing apparatus may be configured to automate the tablet testing process by automatically loading a tablet onto the impact platform, having a tablet placement mechanism automatically place the tablet 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 the tablet striking, having a waste collection device automatically remove the tablet from the impact platform, and repeating the process by loading the next tablet onto the impact platform. In this manner, the tablet testing apparatus may be able to automatically test a sample or subset of a batch of tablets in a carousel manner.

[0012] FIG. 1A provides a block diagram of a system 1000 for evaluating a mechanical property or properties of a solid dosage form, such as tablets or a sample of a batch of tablets, and / or for assessing 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 produces pharmaceutical tablets, dietary tablets, or other ingestible tablets or any of such dosage forms for pills, chewable gums, wafers, discs, caplets, lozenges, troches, implants, granules, and pellets. For example, system 1000 may be used to provide a quality control process within a manufacturing facility or research / development facility by being used to predict whether a batch of tablets will be strong or otherwise robust enough to withstand handling by the manufacturer, pharmacists, doctors, patients, or others. Such handling may include events such as the tablet being dropped onto a hard surface or other events that may subject the tablet to impacts or forces that could break the tablet or otherwise introduce physical defects into the tablet.

[0013] In the embodiment of FIG. 1A , system 1000 may include a solid dosage form testing device 1100 and a computer system 1200. As described in more detail below, solid dosage form testing device 1100 may be used to perform impact impact testing on tablets, and more specifically, to generate sensor data measuring the amount of force or energy involved in impacting the tablets. In one embodiment, solid dosage form testing device 1100 may include a housing 1110 in which various components of 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 upon which a solid dosage form may be placed. More specifically, the impact platform 1130 may include an impact site where the striker component 1120 impacts 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 location 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 capable of releasing the striker component 1120 as part of the impact impact test, allowing the striker component 1120 to fall or descend under the influence of gravity toward the impact site. The falling striker component 1120 may strike or otherwise impact a solid dosage form (if present) located at the impact site. In some cases, the striker component 1120 may strike the tablet with sufficient momentum or energy to fracture or otherwise break the tablet into multiple individual pieces.

[0014] In some embodiments, 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 impact 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 velocity or kinetic energy of the striker component 1120 as it falls toward a solid dosage form at an impact site and / or the amount of force imparted by the striker component 1120 to the solid dosage form. 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 velocity or kinetic energy of the striker component 1120 as it falls and a second sensor configured to measure the amount of energy imparted by the striker component 1120 to the solid dosage form as it 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 may include a non-transitory computer-readable medium (e.g., a solid-state drive or a hard disk drive) for storing the sensor data.

[0015] 1B illustrates a solid dosage form testing apparatus 1100A according to embodiments herein, which may be an embodiment of the solid dosage form testing apparatus 1100, including a solid dosage form positioning mechanism 1150 and an impact chamber 1115. In certain embodiments, the solid dosage form positioning mechanism 1150 may be configured to push or otherwise move a solid dosage form, such as a tablet, mini-tablet, pill, chewable gum, wafer, disc, caplet, lozenge, troche, implant, granule, or pellet, toward an impact site on the impact platform 1130 so that the solid dosage form is positioned directly beneath the striker component 1120 prior to the start of the impact impact test. In some implementations, the impact chamber 1115 may be a chamber that is part of the housing 1110 and surrounds the impact platform 1130. The impact chamber 1115 may be used to capture or otherwise contain debris that may be generated when the solid dosage form is struck by the striker component 1120. More particularly, the impact chamber 1115 may prevent the dispersion of debris into the environment outside the enclosure 1110 to protect technicians or other personnel monitoring the impact impact test from exposure to pharmaceuticals or other substances within the debris.

[0016] 1A and 1B may be configured to process sensor data. In some implementations, data processing may include, for example, determining a model that describes the relationship between (i) how much impact force a solid dosage form can withstand before breaking and (ii) the likelihood of a physical defect the solid dosage form will experience as a result of being dropped, or another relationship. In some implementations, data processing may include generating a prediction regarding the physical defect rate of the solid dosage form or a batch of solid dosage forms, where the physical defect may indicate the likelihood of a physical defect being 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 some embodiments, 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 the sensor data. In some cases, the processing circuit may process the sensor data by executing instructions stored on or in the non-transitory computer-readable medium. Computer system 1200 may be a stand-alone device separate from solid drug test device 1100 (e.g., a desktop computer or server) or may be part of solid drug test device 1100 (e.g., a computing circuit or chip embedded within solid drug test device 1100).

[0018] 2A and 2B illustrate a tablet testing apparatus 2100 according to an embodiment herein, which may be an embodiment of the solid dosage form testing apparatus 1100, 1100A. The tablet testing apparatus 2100 is configured as a floor-standing system, although by way of example and not limitation, benchtop or tabletop systems are also within the scope of the present disclosure, as described below. More specifically, FIG. 2A is a front view of the tablet testing apparatus 2100, while FIG. 2B is a cross-sectional view of the tablet testing apparatus 2100 taken along line AA in FIG. 2A. As shown in FIG. 2A, the tablet testing apparatus 2100 includes a housing 2110 within which various components of the tablet testing apparatus 2100 are disposed. In certain embodiments, the housing 2110 may define 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 Figure 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. Figure 2A further shows the tablet testing apparatus 2100 having a user input device 2170 that may be configured to receive user instructions or other user input. For example, the user input device 2170 may be configured to receive one or more user instructions related to conducting an impact impact test.

[0019] 2B , the striker component chamber 2111 may be a chamber that houses the impact striker 2120 (also referred to as a tap). 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 may be configured to release the striker component 2120 such that the striker component 2120 drops or descends through an opening 2114 in the impact chamber 2115 and onto the impact site 2132, where it may strike or otherwise impact a tablet 2300 or other object disposed at the impact site 2132. In this manner, the impact chamber 2115 may house the impact site 2132 and may be used to capture or otherwise contain debris that may be generated by the strike. In some implementations, the solid dosage form or tablet testing apparatus 1100, 1100A, 2100 may include a motor or other actuator configured to raise the striker component after it has been lowered so that the striker component can be released again to perform another impact strike test.

[0020] In certain embodiments, the impact site 2132 may be provided by an impact platform 2130, which may be an embodiment of the impact platform 1130, which may be housed in the impact chamber 2115 and 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 a top surface that is flat (to form a flat top surface) or that curves outwardly or inwardly (to form a convex or concave top surface). In such a case, the impact site 2132 may be a location, such as a central location, on the flat top surface of the impact platform 2130. The impact platform 2130 may have a cylindrical shape, a rectangular shape, or any other shape. In certain embodiments, the tablet testing apparatus 2100 may include a tablet placement mechanism 2150, which may be an embodiment of the tablet placement mechanism 1150, which is disposed on the top surface of the impact platform 2130. The tablet placement mechanism 2150 may have components that surround and / or are equidistant from the impact site 2132 and may be configured to push or otherwise move the tablet toward the impact site 2132, and more specifically, to center the tablet about the impact site 2132 so that the center of the tablet is directly above the impact site 2132. In some implementations, once the tablet 2300 placement mechanism moves the tablet to the impact site, its components may move away from the tablet 2300 to disengage from the tablet. As a result, the tablet placement mechanism 2150 is no longer in contact with the tablet 2300. By moving out of contact with the tablet 2300, the tablet placement mechanism 2150 may avoid interfering with the impact impact test and may avoid affecting sensor data generated during the impact impact test. Tablet placement mechanisms are described in more detail below.

[0021] In certain embodiments, the striker component 2120 (also referred to as a tap) may be a rigid part, 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 an impact site 2132 of the impact platform 2130. In some implementations, the striker component 2120 may have a tip 2121, such as a flat or rounded tip, or more specifically, a tip facing the impact site 2132, which is configured to contact the center of a tablet 2300 placed at the impact site 2132 when the striker component 2120 impacts or otherwise strikes the tablet 2300. In embodiments herein, the tip 2121 may be made of a metal, such as stainless steel.

[0022] In certain embodiments, 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 that may be attached to the striker component 2120D and serve as its tip with a flat surface, and a hemispherical tap insert 2121B that may be attached to the striker component 2120D and serve as its tip with a rounded surface. Thus, in some cases, the striker tip may be formed by a metallic insert or tap insert, such as stainless steel, that may be inserted into or otherwise attached to a shaft that forms the elongated cylinder or other configuration of the striker component, as shown in FIG. 2D for the striker component 2120D. Simply restating the above, for example, the flat tip 2121 may be formed from a flat tap insert 2121A, while the rounded tip 2121 may be formed from a hemispherical tap insert 2121B or other curved tap insert. In some cases, the diameter of the cylinder may be similar to the diameter or another dimension (e.g., length or width) of various tablets. 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 comprised of a non-rigid material selected to mimic substances that tablets may come into contact with during various stages of manufacturing, packaging, storage, and shipping. In such embodiments, the striker component, tip, and / or tip or tap insert may be comprised of a non-rigid or soft elastomeric or polymeric 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 materials.

[0024] 2B and 2C , the striker component 2120 may include one or more objects 2122 that may be removably attached to the body of the striker component 2120 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 an impact force between the striker component 2120 and the pharmaceutical tablet or other tablet 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 some embodiments, the striker component 2120E shown in FIG. 2E may have multiple tips or tap inserts configured to impact multiple tablets simultaneously. In this manner, multiple tips or tap inserts may be used for parallel processing of multiple tablets to increase the rate at which impact impact testing 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, and 2121E. In some cases, the multiple tips may form a 2D array of tips (also referred to as a matrix of multiple tips). In this embodiment, the weight of the striker component, or more specifically, the tap weight or tap mass, may be increased relative to the striker component of FIG. 2C. The weight or mass of the striker component 2120E may be increased to a certain level so that when the striker component 2120E of FIG. 2E is dropped from a particular height and impacts a number of tablets, it will exert enough force to have a reasonable chance of breaking all of the tablets. Further in this embodiment, sensors may be disposed within or attached to each of the tips or tap inserts 2121A, 2121B, 2121C, 2121D, 2121E to collect sensor data indicative of the amount of force exerted by each tip on each tablet struck by the tip.

[0026] In embodiments herein, the tablet testing apparatus 2100F, 2100G may include a sample loading station 2400F, 2400G, such as that shown in FIGS. 2F and 2G. In the example of FIGS. 2F and 2G, the sample loading station 2400F, 2400G may form a carousel for supplying one or more tablets to one or more positions on its impaction platform. In some cases, the sample loading station 2400G may supply one tablet at a time to a position 2131G (also referred to as a tablet supply position) of the impaction platform 2130G, as shown in FIG. 2G. In some cases, the sample loading station 2400F may be configured to simultaneously supply multiple tablets to multiple tablet supply positions 2131F of the impaction platform 2130F, as shown in FIG. 2F. In some cases, the tablet supply positions may be wells or other indentations in the surface of the impaction platform 2130F, 2130G, and the wells may hold the supplied tablets. In the example of Figure 2F, multiple tablet dispensing locations 2131F may be arranged in a line (e.g., column) of wells. In some cases, sample filling stations 2400F, 2400G may be configured as a grooved carousel, with each groove containing a respective set of tablets to be dispensed. For example, each groove may be used to accommodate a different type of tablet.

[0027] In embodiments herein, the impaction platforms 2130F, 2130G of Figures 2F and 2G may be rotatable to rotate one or more fed tablets from one or more tablet feed positions 2131F, 2131G to one or more impact sites 2132F, 2132G. In some cases, the impaction platforms 2130F, 2130G may rotate one or more fed tablets to an intermediate position, or more specifically, to an alignment station 2402F, 2402G. At the alignment station 2402F, 2402G, the tablet testing apparatus may include a tablet placement mechanism that uses a pair of pushing components or multiple pairs of pushing components to ensure that a single fed tablet or multiple fed tablets are centered at a desired location, such as the center of each of the wells into which they are fed. Such alignment action can more reliably ensure that when the fed tablets rotate into the impact testing stations 2404F, 2404G, they are centered directly beneath each of the tips 2121A, 2121B, 2121C, 2121D, 2121E of the striker component 2120E as shown in FIG. 2F, or beneath the tip 2121 of the striker component 2120 as shown in FIG. 2G.

[0028] In embodiments herein, the impact testing stations 2404F, 2404G are configured to include one or more impact sites that may receive an impact from one or more tips of the striker component 2120, 2120E as the striker component falls toward the impact platform 2130F, 2130G. The striker component 2120, 2120E may be used as part of an impact impact test as disclosed herein and may be intended to break a fed tablet as the tablet is rotated into the impact testing station.

[0029] In embodiments herein, the rotatable impact platform 2130F, 2130G may be configured to further rotate one or more fed tablets from the impact testing station 2404F, 2404G to the clearing station 2406F, 2406G after the one or more fed tablets have been broken or otherwise struck by the respective striker components. The clearing station 2406F, 2406G may be configured to remove fragments or other pieces of the one or more fed tablets (which may now be broken tablets) toward a portion within the impact chamber to prevent the fragments or other pieces of the broken tablets from contaminating other areas of the tablet testing apparatus 2100F, 2100G. 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 or other pieces of the broken tablets toward a waste compartment of the tablet testing apparatus 2100F. In such an example, the tablet testing apparatus 2100F may be airtight to facilitate creating a negative pressure in its impaction chamber (relative to the rest of the tablet testing apparatus). In the example of FIG. 2G, the clearing station 2406G may include a scraper 2408 that may be configured to sweep shards or other fragments of one or more broken tablets from the upper surface of the impact platform 2130G. The shards or other fragments may, for example, be scraped off and fall toward a waste compartment located below the impact platform 2130G.

[0030] 2B and 2C , in embodiments herein, the striker mechanism 2113 may be configured to removably suspend the striker component 2120 within the housing 2110 and above 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 toward the impact site 2132. In certain embodiments, 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, thus permitting the striker component 2120 to drop toward the impact site 2132. In some cases, the actuator in this example may be activated, deactivated, 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 allows a user to input a user instruction that causes the drop of the striker component 2120. In such an example, the actuator in the base 2113C may be activated in response to the user instruction.

[0031] In certain embodiments, the base 2113C may be a lifter device (also referred to as a tap lifter) configured to control the height at which the striker component 2120 is suspended above the impact site 2132, and therefore the release height RH (also referred to as a drop height) at which the striker component 2120 is released and lowered toward the impact site 2132. Increasing the release height RH may increase the amount of energy or impact force that a striker component 2120 of a suitable / specific mass imparts to the tablet 2300 at the impact site 2132, while lowering the release height may decrease the amount of energy or impact force that a striker component 2120 of a suitable / specific mass imparts to the tablet 2300. In embodiments according to the present disclosure, a desired impact force may be achieved by selecting an appropriate release height RH relative to the mass of the striker component, and any desired impact force may be achieved by properly selecting the weight and respective release height of the striker components to provide the desired impact force at the impact site. In some implementations, the base 2113C may control the release height RH of the striker component 2120 by moving or being moved along one or more rails 2113A, 2113B, which may form a support frame or support structure for the striker mechanism 2113. More specifically, the one or more rails 2113A, 2113B may be or may include elongated bars or rods that guide the movement of the base 2113C as it raises or lowers the striker component 2120. In certain embodiments, the mechanism 2130 may include an actuator, such as a motor or pneumatic actuator, configured to generate a force to raise or lower the base 2113C along the one or more rails 2113A, 2113B. The actuator may be located within the base 2113C, elsewhere within the housing 2110, or even outside the housing 2110. If the actuator is located outside the base 2113C, the tablet testing apparatus 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 located within the base 2113C, such actuator may be separate from any actuator used to release the striker component 2120 from the base 2113C.

[0032] In certain embodiments, the tablet testing apparatus 2100 may have a size small enough to provide an apparatus suitable as a benchtop or tabletop instrument, such as the benchtop tablet testing apparatus 2100BB shown in front and side views in FIG. 2BB. The benchtop tablet testing apparatus 2100BB includes a housing 2110BB that may have a relatively short height, for example, a height H of 130 cm to 140 cm, more suitable for placement and operation on a laboratory bench or table. In one example, the height H may limit the maximum distance that a striker component (not shown), which may be weighted as described above, can be removably suspended above the impact site 2132BB (release height RH) to 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 less. The reduced release height RH described above may require a strike component of greater mass to provide sufficient impact force at the impact site for the impact impact test to be performed, i.e., specifically, to fracture pharmaceutical tablets or other tablets during the impact impact test. The greater mass may be achieved by adding mass to an existing striker component, as previously described, or by selecting a striker component of a heavier material. The benchtop tablet testing apparatus 2100BB may include all or most of the features described herein with reference to the tablet testing apparatus 2100, 3100, such as one or more chambers, such as a striker component chamber and an impact chamber, a striker mechanism for removably suspending the striker component above the impact chamber, an additional mass or weight for adding 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 tabletop use.

[0033] In one embodiment, the tablet testing apparatus 2100 may include a sensor data acquisition system 2140, as shown in FIG. 2C , which may be an embodiment of the sensor data acquisition system 1140, configured to generate sensor data measuring various aspects of the impact impact test. For example, the sensor data acquisition system 2140 may include at least a sensor 2141 and a sensor 2142. The sensor 2141 may be, for example, a strain gauge force sensor or other sensor configured to measure the impact force that the striker component 2120 imparts to the tablet 2300 or other object at the impact site 2132 when the striker component 2120 collides with, impacts, or otherwise strikes the object. In one example, as shown in FIG. 2C , the sensor 2141 may be located 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 drops or otherwise moves toward 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 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 (e.g., 2141) of the sensor data acquisition system 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 certain implementations, the sensor may be statically positioned in a fixed location, such as directly below the impact site 2132 and within the impact platform.

[0034] FIG. 3A shows a tablet testing apparatus 3100, which may be an embodiment of the solid dosage form or tablet testing apparatus 1100, 1100A, 2100, including a housing 3100 forming 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 an upper surface of the impact platform 3130. In some cases, the components shown in FIG. 3A may be embodiments of similar components described above for 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 a tablet placement mechanism 3150 that may be configured to push or otherwise move a tablet toward an impact site, and more specifically, to center the tablet at the impact site. Such placement may position the tablet directly beneath the striker component prior to the start of the impact impact test. More specifically, the tablet placement mechanism 3150 may be disposed on an upper surface of the impact platform 3130 and may include a first push component 3151 and a second push component 3152 attached to or otherwise coupled to the upper surface of the impact platform 3130. 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 one another manually or via an actuator (e.g., a motor) along the directions indicated by 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 a tablet in that space. The tablet placement mechanism 3150, 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 relative to one another and toward the impact site 3132 to push a tablet or other object toward the impact site 3132, and more specifically, to center the tablet at the impact site 3132. In some cases, the first and second push components may be equidistant from the impact site such that when moved toward each other an equal amount, they push the tablet toward the impact site.Once the tablet is centrally located at the impact site 3132, the push components 3151, 3152 may be moved back to the open configuration in which the push components 3151, 3152 are moved away from the tablet so that they are no longer in contact with 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 but still allow the first push component 3151 and the second push component 3152 to move toward or away from each other along the top surface of the impact platform 3130.

[0037] In some embodiments, the first push component 3151 may have a first recess 3151A that may provide a recess that may be used to fit onto 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 being moved in a rightward direction toward the second push component 3152, the first push component 3151 may push the tablet in a rightward direction toward 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 onto the other side (e.g., the right side) of the tablet. When the second push component 3152 is being moved in a leftward direction toward the first push component, the second push component 3152 may push the tablet in a leftward direction toward the impact site if the tablet is on the other side (e.g., the right side) of the impact site. More specifically, the recess formed by the first recess 3151A of the first push component 3151 may extend inward toward the interior 3151D, such as the center of the first push component 3151, thereby extending away from the impact site 3132. Similarly, the recess formed by the second recess 3152A of the second push component 3152 may extend inward toward the interior 3152D of the second push component 3152, thereby extending 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 located between the first recess 3151A of the first push component 3151 and the second recess 3152A of the second push component 3152. More specifically, the impact site may remain as a central location in 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, the movement may position the first recess 3151A and the second recess 3152A at the impact site 3132, and therefore may place the tablet at the impact site 3132 so that the tablet is centered at the impact site 3132.

[0038] In certain embodiments, the first push component 3151 and the second push component 3152 may be well-suited to engage a tablet to center or otherwise locate the tablet at the impact site 3132. More specifically, various tablets may have convex sides or, more generally, convex shapes. For example, some tablets may have a circular or oval shape with the opposite side curving outward. The first push component 3151 and the second push component 3152 may have concave shapes that complement the convex shape of the tablet. By way of 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 engage a 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 engage a second convex side of the tablet. The concave corners 3151E, 3152E may each be a curved corner with a curved angle, or may each be a sharper corner without a curved angle. The concave corners 3151E, 3152E may be such that, when one or both corners engage, the tablet is pushed toward the impact site 3132 when the first push component 3151 and the second push component 3152 are moved toward each other. In some embodiments, the first push component 3151 and the second push component 3152 may be positioned 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 certain embodiments, the first push component 3151 and the second push component 3152 may have complementary portions that temporarily mate or otherwise fit with each other as the tablet positioning mechanism 3150 moves from the open configuration to the closed configuration to allow the push components 3151, 3152 to approach the impact site close enough to centrally locate 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 as the first push component 3151 and the second push component 3152 are moved toward each other. More specifically, the second recess 3152 may include a first sub-portion 3152B and a second sub-portion 3152C that protrude from the second push component 3152. In this example, groove 3151B may be configured to receive first sub-portion 3152B, while groove 3151C may be configured to receive second sub-portion 3152C. In other words, sub-portions 3152B, 3152C may be slidable into grooves 3151B, 3151C. These complementary structures of first push component 3151 and second push component 3152 may push an object toward impact site 3132 and allow them to move toward each other and toward impact site 3132 so that the object is centered at impact site 3132, as shown in FIG. 3D . In some embodiments, once push components 3151, 3152 are 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 impact site 3132. When the push components return to the open configuration, they may disengage from the tablet and not come into contact with the tablet when the striker component is dropped toward the tablet during an impact impact test.

[0040] 4A and 4B show the striker component 3120 descending onto the tablet 3300 under the influence of gravity, striking the tablet 3300. Figures 4A and 4B show a scenario illustrating the tablet placement mechanism 3150 in an open configuration while the striker component 3120 is being lowered or dropped onto the tablet 3300, such that the tablet placement mechanism 3150 disengages from the tablet 3300 while the striker component 3120 is being lowered or dropped onto the tablet 3300. In such a configuration, the tablet placement mechanism 3150, i.e., specifically the first push component 3151 and the second push component 3152, may avoid interference with the striker component 3120 and the measurement of how much force is imparted by the striker component 3120 to the tablet 3300. Figure 4C shows the results of an impact impact test being performed on the tablet 3300. More specifically, the impact impact 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 and impacts the tablet 3300, the striker component 3120 applies sufficient force or energy to break the tablet 3300. For example, FIG. 4C shows a gap 3300A in the tablet 3300 created when a portion of the tablet 3300 breaks away from the tablet 3300 as a result of the force of the impact from the striker component 3120. As described in more detail below, some embodiments herein may include detecting a tablet breakage event by determining whether the tablet actually broke as a result of the impact impact test based on measurements made with sensor data.

[0041] As mentioned above, the impact chamber 1115, 2115, 3115 may surround the impact site 2132, 3132 and may be used to contain debris that may be created during impact impact testing. For example, impact from a striker component, e.g., 2120, may create debris in the form of dispersed powder. The powder may contain pharmaceutical substances that may have adverse health effects if exposed to personnel outside the solid dosage form or tablet testing apparatus enclosure 1110, 2110, 3100. As such, the impact chamber 1115, 2115, 3115 may be used to capture debris therein. In certain embodiments, as shown in FIG. 2F, the impact chamber may be connected to a vacuum to create a negative pressure to prevent contaminated air from escaping the impact chamber.

[0042] 5 shows a tablet testing apparatus 2100 that may be configured to generate an airflow that may prevent debris from escaping the impact chamber 2115. More specifically, the tablet testing apparatus 2100 may include an opening 2114, i.e., specifically, a hole that may allow the striker component 2120 to pass through the impact chamber 2115 to reach the impact site 2132. In this embodiment, the impact chamber 2115 may have walls 2115A, 2115B, 2115C, and 2115D that are airtightly connected to each other and to a top wall and a bottom wall. In one example, the walls 2115D and 2115C may be the front and back walls of the impact chamber 2115, respectively, while the walls 2115A and 2115B may be the side walls of the impact chamber, respectively. In this manner, the walls 2115A, 2115B, 2115C, and 2115D may prevent debris from leaking laterally out of the impact chamber 2115. However, debris may still escape through the opening 2114. To reduce the likelihood of this occurring, the tablet testing apparatus 2100 may include a conduit connected to an airflow generator 2180, such as a fan or air pressure pump, or compressed air configured to generate the airflow. In this embodiment, the tablet testing apparatus may have one or more channels 2123A, 2123B (e.g., tubes, hoses, or pipes) directly or indirectly connected to the airflow generator 2180. The one or more channels 2123A, 2123B may have outlets around the opening 2114 to allow the airflow generated by the airflow generator 2180 to reach an area proximate to the opening 2114 (e.g., immediately above the opening 2114 as shown in FIG. 5 ). In this manner, the airflow generator 2180 and 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 likelihood of debris escaping from the impact chamber 2115. In some implementations, the impact chamber 2115 may include a filter 2116 that provides an outlet for the airflow entering the impact chamber 2115 through the opening 2114.The filter 2116 may be configured to remove any debris produced by the impact percussion test and carried by the airflow, thus further preventing the debris from escaping the impact chamber 2115. In some implementations, the impact chamber 2115 may be configured to provide environmental control. More particularly, the impact chamber 2115 may be configured to control the temperature or other environmental conditions at the impact site to create standardized conditions for the impact percussion test.

[0043] FIG. 6 illustrates a method 6000 that may use tablet testing equipment to evaluate the strength of a sample or subset of tablets or a batch of tablets. The method may include determining how much impact force various tablets can absorb or otherwise withstand before physically breaking. In certain embodiments, method 6000 may include determining a relationship between such impact force and a physical defect rate that indicates the likelihood of a tablet experiencing physical defects under a particular circumstance or set of circumstances. In some cases, method 6000 may use this relationship to predict physical defect rates for other situations and / or other tablet batches or tablet types. In certain embodiments, method 6000 may be performed by, for example, a manufacturing facility that produces pharmaceutical tablets or other tablets, and / or a research / development facility, i.e., specifically by facility personnel. In some cases, method 6000 may be performed as part of a tablet manufacturing process or tablet (formulation) development.

[0044] In some embodiments, method 6000 may begin with or include step 6002, in which an impact impact test is performed on a first plurality of tablets or a first set of tablets. In some cases, the first plurality of tablets or the first set of tablets may relate to multiple tablet types having different physical characteristics. In other words, each tablet of the first plurality of tablets may relate to a respective tablet type of the multiple tablet types, and each set of tablets of the first set of tablets may relate to a respective tablet type of the multiple tablet types. For example, if the impact impact 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, etc. If the impact impact test is performed on a first set of tablets, the first set of tablets may include a first set of tablets belonging to the first tablet type, e.g., 10 or 20 tablets, and a second set of tablets belonging to the second tablet type, etc. In this manner, impact impact testing may be used to generate sensor data associated with different tablet types.

[0045] In some cases, a tablet type may be related to the batch of tablets produced. In other words, tablets from the same batch may belong to a common tablet type. In some cases, a physical characteristic of a tablet type may relate to physical characteristics of tablets associated with the tablet type, such as tablet shape and / or size. For example, tablet shape may relate to whether the tablet has an oval or round shape and / or whether the tablet has a flat surface. In some cases, a physical characteristic of a particular tablet or tablet type may be influenced by, for example, the tablet or tablet type formulation, tablet shape, and / or the method by which the tablet is manufactured. The method by which the tablet is manufactured may be related to or influenced by parameter values ​​or manufacturing techniques used to manufacture the tablet. For example, if the tablet is manufactured based on compressing a powder, the parameter value relates to the amount of compression pressure used to compress the powder. The powder may be directly compressed by direct compression or may be granulated to form granules using dry granulation or wet granulation techniques before 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 involve the use of a coating process on the tablet core, which may subject the tablet core to various forces. In such examples, the method of coating the tablet may further affect the physical properties, such as the porosity, of the tablet or tablet type. In yet other examples, the method by which the tablet is manufactured may involve the use of molding or additive manufacturing, such as 3D printing, for example, using hot melt extrusion.

[0046] In certain embodiments, a tablet formulation may relate to which 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 active pharmaceutical ingredients (API) or excipients. Excipients in tablet formulations may be further divided into one or more of the following categories: fillers, disintegrants, binding agents (solution binders or dry binders), glidants, lubricants / anti-adherents (see, e.g., ME Olton, Pharmaceutics - The Science of Formulation Design, 2nd Edition).

[0047] In some 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 102101, 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 Kollidon K30. Examples of glidants include colloidal silica and talc. Examples of lubricants include magnesium stearate and glyceryl dibehenate.

[0048] In some embodiments, the quantitative composition may list specific substances along with the amount of each substance. The amounts may be expressed as weights or percentages. Fillers, if used, range from about 10 to about 75 weight percent (e.g., about 15 to about 70 weight percent) of the dry formulation; disintegrants, if used, range from about 0.5 to 10.0 weight percent (e.g., about 5 weight percent) of the dry formulation; binders, if used, range from, for example, about 2 to about 8 weight percent of the dry formulation; glidants, if used, range from about 0.1 to 10.0 weight percent of the dry formulation; and lubricants, if used, range from about 0.25 to 2.5 weight percent of the dry formulation.

[0049] In some examples, fillers (also called diluents / carriers) used in oral formulations, such as those in the form of immediate-release tablets, may include monocalcium phosphate, dicalcium phosphate (including dicalcium phosphate dihydrate and dibasic calcium phosphate anhydrous), tricalcium phosphate, lactose, microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, sorbitol, starch (e.g., corn, potato, or rice), glucose, calcium lactate, calcium carbonate, etc. 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, immediate-release tablet formulations may include one or more excipients to improve the physical and / or chemical properties of the final tablet composition and / or to facilitate the manufacturing process.Such excipients may be used in the formulation of immediate release formulations for oral drug delivery and may include 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 low molecular weight hydroxyethylcellulose (HEC). The composition may comprise one or more of the following: high molecular weight sodium carboxymethylcellulose, polyvinylpyrrolidone or low molecular weight HPMC for use as a binder; one or more pH adjusters (e.g., organic acids (e.g., citric acid) or alkali metal (e.g., sodium) salts thereof, magnesium oxide, alkali or alkaline earth metal (e.g., sodium, calcium, or potassium) sulfates, metabisulfites, propionates, or sorbates); one or more disintegrating agents (e.g., sodium starch glycolate, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose, starches (e.g., corn, potato, or rice) or alginates); colorants; flavorings; isotonicity agents; coating agents; or preservatives.

[0050] For example, in some cases, the tablet composition may include one or more 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 also includes microcrystalline cellulose and mannitol. In some cases, the tablet composition may include one or more of the following lubricants: magnesium stearate, sodium stearyl fumarate, etc. In some cases, the tablet composition may include a glidant such as colloidal silica. In some cases, the tablet composition 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 suitable binder includes microcrystalline cellulose. In some cases, the tablet composition may include one or more of the following pH adjusters. Pharmaceutically acceptable salts of organic acids (e.g., citric acid, etc.) or alkali metal (e.g., sodium) salts thereof, inorganic acids (e.g., carbonates or phosphates) (e.g., sodium, magnesium, or calcium salts), magnesium oxide, as well as alkali and alkaline earth metal (e.g., sodium, calcium, potassium, etc.) sulfates, metabisulfites, propionates, and sorbates. Other additional excipients may include colorants, flavors, solubilizers (e.g., SDS), coating agents, preservatives, etc.

[0051] In a further example, one tablet formulation may include a composition including 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 may lack such a coating.

[0052] Thus, in one example, different tablet types may be associated with different respective formulations, or different respective combinations of formulations, and porosity of the tablets produced. For example, Figure 7 shows various data points 701, 702, 703, 704, 711, 712, 713, 714, 721, 722, 723, 724, 731, 732, 733, and 734 associated with each of the different tablet types (e.g., Tablet Type 1, Tablet Type 2, Tablet Type 3, etc.). In this example, each tablet type may be associated with a particular combination of porosity and particular formulation. By way of example, data point 701 may represent the peak impact force value for a first tablet type associated with a tablet having a porosity of approximately 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 with flat surfaces. The peak impact force value may indicate how much impact force a tablet of the first tablet type can absorb or otherwise withstand before breaking, as described in more detail below.

[0053] In some embodiments, if a first plurality of tablets is impact-tested, such impact testing 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 a first tablet type, a single tablet belonging to a second tablet type, a single tablet belonging to a third tablet type, etc. In such an example, the impact testing may produce, for example, a single peak impact force value, as described below, indicating the amount of force required to break each of the tablets. A single peak impact force value may be associated with each tablet type to which a broken tablet belongs.

[0054] In some embodiments, if the impact impact test is performed on a first set of tablets, the impact impact 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 impact test may be performed to determine the 10 peak impact force values ​​required to break the 10 tablets in that set. In such an example, the impact impact 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, impact impact testing may be performed on a solid dosage form or tablet testing apparatus, such as apparatus 1100, 2100, 3100. For example, impact impact testing may include placing a first tablet or solid dosage form of a first plurality of tablets or solid dosage forms at an impact site 2132, 3132 on an impact platform 1130, 2130, 3130, and centrally placing the first tablet or solid dosage form at the impact site 2132, 3132 with a solid dosage form or tablet placement mechanism 1150, 2150, 3150. By way of example, the tablet placement mechanism 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 mechanism 1150, 2150, 3150, such as the first push component 3151 and the second push component 3152, are moved closer to the impact site 2132, 3132. The solid dosage form or tablet testing apparatus may have a striker component 1120, 2120, 3120 initially suspended above the impact site 2132, and step 6002 may include releasing the striker component 1120, 2120, 3120 of the solid dosage form or tablet testing apparatus 1100, 2100, 3100 to drop the striker component 1120, 2120, 3120 and strike the first tablet or solid dosage form. For example, the striker component 1120, 2120, 3120 may be released via a user instruction entered into the user input device 2170. In this example, the impact impact testing may further include removing the first tablet or solid dosage form after it has been struck by the striker component 1120, 2120, 3120. In some cases, the removal may be manual. In other cases, the removal may be automatic. For example, the tablet testing apparatus 2100 may include a waste removal device or component. The waste removal device or component may include a waste filtering component configured to remove tablet debris or other waste that may have been created as a result of impact impact testing from the tablet testing apparatus 2100. In some cases, the removal may include, for example, moving the solid dosage form or tablet placement mechanism 1150, 2150, 3150 from a closed configuration to an open configuration.

[0056] In some embodiments, the impact impact test may repeat the above operation, step 6002, with more tablets or solid dosage forms. By way of example, if the first plurality of tablets includes 10 tablets associated with 10 tablet types, the above operation may be repeated 9 more times so that all 10 tablets are placed at the impact site 2132, 3132 and struck by the striker component 1120, 3120, 3120. As another example, if the impact impact test is performed on 10 sets of tablets, each set associated with a different tablet type and including 5 tablets, the above operation may be repeated 49 more times so that all 50 tablets are placed at the impact site 2132, 3132 and struck by the striker component. As yet another example, if the tablet testing apparatus includes a striker component with multiple tips, the tablet testing apparatus may perform the impact impact test on multiple tablets simultaneously. For example, if the striker component has a 2D array of 5x5 tips (i.e., 25 tips), the tablet testing apparatus may be capable of simultaneously impact testing 25 tablets, and then repeating the impact testing on another 25 tablets, for a total of 50 tablets.

[0057] In certain embodiments, the impact impact test may be conducted in a manner that maximizes the likelihood that each tablet in the first plurality of tablets or set of first plurality of tablets will break as a result of the impact impact test. For example, the impact impact 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 site 2132, 3132 to ensure that when the striker component 1120, 2120, 3120 is released and falls towards the impact site 2132, 3132, the striker component 1120, 2120, 3120 accumulates sufficient momentum and / or kinetic energy during its fall, e.g., by creating a gap 3300A such that the accumulated momentum and / or kinetic energy when the striker component reaches the impact site is sufficient to break the tablets. 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 measuring the force profile during the impact impact test.

[0058] In certain embodiments, method 6000 may include step 6004, which includes measuring, during the impact impact test, a plurality of peak impact force values ​​from striker component 1120, 2120, 3120, each representing a peak amount of impact force experienced by the first plurality of tablets or solid dosage forms during the impact impact test, or a respective average peak amount of impact force experienced by the set of first plurality of tablets or solid dosage forms during the impact impact test. In some cases, the peak impact force may represent a peak amount of force a tablet withstands before disintegrating during the impact impact test, or an average of a peak amount of force a set of tablets withstands before disintegrating during the impact impact 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 a tablet or solid dosage form breakage event. Such a detection operation may include determining whether a force actually broke a tablet based on sensor data measuring the impact force applied to the tablet. Such a determination may be made based on an impact force profile, which may relate, for example, to the force function applied to the tablet by the striker component as a function of time. More specifically, FIG. 8E shows impact force profiles associated with three cases in which three tablets were broken by the impact force from the striker component and three cases in which three tablets remained unbroken 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 force value remains substantially flat as a function of time and forms a plateau shape with 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 broken. On the other hand, if the force profile has a shape in which the force value increases towards a peak and then decreases without forming a plateau, such a force profile may indicate that the tablet associated with the force profile was fractured by the force applied to it during the impact impact test.

[0060] In some cases, if the impact impact 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 imparted to the tablet by the striker component, more specifically, how much impact force it takes to break a single tablet. In some cases, if the impact impact test is performed on a set of tablets of a particular tablet type, step 6004 may include measuring the average peak amount of impact force imparted to the set of tablets, i.e., more specifically, how much impact force it takes, on average, to break the set of tablets.

[0061] In some cases, step 6004 may be performed with or with the assistance of a sensor data acquisition system, e.g., sensor data acquisition system 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 first plurality of tablets. In this example, step 6004 may further include manufacturing or research / development facility personnel and / or a computer system, e.g., computer system 1200, receiving sensor data generated by sensor 2141. The sensor data may be received directly from sensor 2141 or via a communication circuit, e.g., communication circuit 2143.

[0062] 8A and 8B show graphs of data that may indicate how much force is applied by the striker component 1120, 2120, 3120 to a tablet at the impact site 2132, 3132, e.g., tablet 3300, and / or how much force is absorbed by the tablet from the striker component at different points in time. The graphs may represent or be based on sensor data collected in step 6004, for example. For example, FIG. 8A may represent data collected or generated when the impact impact test is breaking a first tablet, while FIG. 8B may represent data collected or generated when the impact impact test is breaking a second tablet. In one example, the striker component 1120, 2120, 3120 may suddenly decelerate as it collides, impacts, or otherwise strikes the tablet, e.g., tablet 3300. The sensor 2141 or another sensor may measure how much the striker component 1120, 2120, 3120 accelerates or decelerates at different points in time. Such measurements may be used to approximate or otherwise indicate how much force (also referred to as impact force) the striker component 1120, 2120, 3120 is imparting to the tablet 3300 as a function of time. More particularly, the sensor data may indicate the peak impact force value imparted to the tablet 3300 by the striker component 1120, 2120, 3120 and / or the energy absorbed by the tablet from the striker component 1120, 2120, 3120. In some cases, step 6004 may include the computer system 1200 calculating force values ​​such as those forming the graphs of FIGS. 8A and 8B based on the sensor data generated by the sensor data acquisition system, e.g., the sensor data acquisition system 2140. As described above, the impact impact test may be performed in a manner that maximizes the likelihood of breaking each tablet of the first plurality of tablets. Further, as described above, a computer system or other device may determine whether a tablet has actually broken based on sensor data collected from subjecting the tablets to the impact impact test.Thus, step 6004 may include measuring peak impact force values ​​associated with breaking a first plurality of tablets. For example, if step 6004 were based on the data depicted in Figures 8A and 8B, step 6004 may include determining a peak impact force value of 799 N associated with breaking a first tablet and a peak impact force value of 804 N associated with breaking a second tablet. Figures 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] 9A-9F illustrate peak impact force values ​​that may be measured as a result of step 6006 of method 6000. More specifically, the figures depict average peak impact force values ​​associated with breaking tablets of different tablet types along the X-axis. For example, the graph in FIG. 9A depicts data showing that a set of tablets associated with tablet type 1 had an average peak impact force value of approximately 400 N. This data point may have been determined, for example, by subjecting a set of, for example, five tablets belonging to or otherwise associated with tablet type 1 to an impact impact test in step 6002 and determining the average peak impact force value applied to or absorbed by the five tablets. As discussed above, the peak impact force value may represent the maximum force the five tablets withstood before breaking. In some embodiments, FIGS. 9A-9F may depict average peak impact force values ​​associated with each of tablet types 1 through 10, respectively, but may also be associated with different situations in which tablet drop tests are performed, as described in more detail below.

[0064] In some implementations, step 6004 may include measuring or otherwise determining the amount of energy absorbed by the tablet or solid dosage form during the impact impact test, instead of or in addition to measuring the peak impact force value. As shown in Figures 8A and 8B, the amount of energy absorbed may be determined by integrating the force values ​​in the diagrams to determine the area under the curves in Figures 8A and 8B. For example, Figures 8C and 8D show data showing both the peak impact force imparted to or absorbed by the tablet and the amount of energy imparted to or absorbed by the tablet. In some implementations, step 6004 may include measuring a toughness parameter of the first plurality of tablets or set of first plurality of tablets, instead of or in addition to measuring the peak impact force value. In some cases, the toughness parameter of the tablet may be determined based on calculating the area under the tablet's stress-strain curve, such as the stress-strain curves shown in Figures 10A and 10B.

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

[0066] In some embodiments, the tablet drop test may involve dropping the second plurality of tablets onto a solid or otherwise rigid surface and examining the percentage of tablets that break or experience physical defects as a result of being dropped. For example, the tablet drop test may be performed on a large set of tablets, e.g., 100 tablets, associated with a particular tablet type by holding the set above a solid surface and releasing and allowing the set to drop onto the solid surface. The holding and dropping of the tablets may be performed manually or automatically, one tablet at a time, or several or all of the set of tablets simultaneously.

[0067] In some embodiments, the tablet drop test may simulate different situations in which a tablet is dropped. The situations may relate, for example, to drop height, number of drops, or a combination thereof. In such embodiments, the different situations may relate to different drop heights, different number of drops, or different combinations thereof. By way of example, the different situations may include a first situation in which the tablet is dropped only once from a height of 1 meter, a second situation in which the tablet is dropped five times from a height of 1 meter, a third situation in which the tablet is dropped ten times from a height of 1 meter, a fourth situation in which the tablet is dropped only once from a height of 2 meters, a fifth situation in which the tablet is dropped five times from a height of 2 meters, and a sixth situation in which the tablet is dropped ten 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, e.g., 600 tablets associated with a particular tablet type, e.g., tablet type 1. In this example, the tablet drop test may include dropping a different subset of tablets for each of the situations described above. Thus, the tablet drop test, in this example, may include lowering a first subset of 100 tablets onto a solid surface using the first situation described above, lowering a second subset of 100 tablets onto a solid surface using the second situation described above, lowering a third subset of 100 tablets onto a solid surface using the third situation described above, lowering a fourth subset of 100 tablets onto a solid surface using the fourth situation described above, lowering a fifth subset of 100 tablets onto a solid surface using the fifth situation described above, and lowering a sixth subset of 100 tablets onto a solid surface using the sixth situation described above. In the above example, the tablet drop test may include lowering other sets of tablets that may relate to other tablet types, tablet type 2, tablet type 3, etc.

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

[0069] In some embodiments, determining 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 broke or otherwise experienced a physical defect as a result of the drop, and calculating what proportion or percentage of the set of tablets experienced a physical defect. By way of example, if a tablet drop test includes dropping a first subset of, say, 100 tablets associated with tablet type 1, described above, from a height of one meter just once, step 6008 may include counting how many of the tablets in the subset broke or experienced a physical defect as a result of the drop. For example, if 69 tablets were counted as having experienced a physical defect, step 6008 may include determining that if tablets associated with tablet type 1 were dropped from a height of one meter just once, there would be an associated tablet type 1 with a physical defect rate (also referred to as a physical defect rate) of 69%.

[0070] In some embodiments, the plurality of physical defect rates described above may be a first plurality of physical defect rates, and step 6008 may include measuring or determining a second plurality of physical defect rates, a third plurality of physical defect rates, etc. Each of the plurality of physical defect rates may be associated with a particular situation, such as a combination of the height and number of drops from which the tablets are dropped. By way of example, FIG. 9A may represent data showing a first plurality of physical defect rates associated with each of tablet types 1 through 10 when the tablets are dropped only once from a height of one 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 through 10 when the tablets are dropped five times from a height of one meter in a tablet drop test. Although the above embodiments describe obtaining physical defect rates from performing a drop test, physical defect rates may be obtained using any other test.

[0071] Returning to FIG. 6 , in some embodiments, method 6000 may include step 6010, which includes determining a model describing the relationship between the peak impact force values ​​and the physical defect rate based on the plurality of peak impact force values ​​and the plurality of physical defect rates. In some embodiments, the model may include or be described by a mathematical equation or function describing the relationship between the peak impact force values ​​and the physical defect rate. For example, FIG. 9A shows curve 901 representing a mathematical equation or function between the peak impact force values ​​and the physical defect rate. Curve 901 or its corresponding mathematical equation may be determined by performing a curve fitting procedure. Such a procedure 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 a respective average peak impact force value associated with one of tablet types 1 through 10 and a respective physical defect rate associated with the tablet type. The average peak impact force value may be determined via an impact impact test, whereas the physical defect rate may be determined via a tablet drop test.

[0072] In some embodiments, the model may be determined based on multiple curves or equations, each of which may be associated with a particular situation in which the tablet drop test is performed, such as a particular combination of drop height and drop number. For example, the model may include or be described by curves 901, 902, 903, 904, 905, and 906 in Figures 9A-9F, respectively, or the equations represented by the curves. Curves 901-906 may be associated with different situations in which the tablet drop test is performed.

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

[0074] In some cases, determining such a prediction may include performing an impact 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 a 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 impact test on an additional tablet or set of additional tablets associated with, for example, tablet type 11, and measuring a peak impact force value indicative of the peak amount of impact force the additional tablet or set of additional tablets received from the striker component during the impact impact test, i.e., specifically, the maximum amount of force endured by the additional tablet before breaking during the impact impact test. In this example, the step may determine a predicted physical defect rate for 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 for breaking the set of additional tablets. FIG. 11A shows predicted physical defect rates for various tablet types, where the prediction may be based on peak impact force values ​​derived from performing impact impact tests on tablets belonging to the tablet type. In some cases, the predicted physical defect rate may be for a particular situation in which a tablet is dropped, such as a situation in which a tablet is dropped five times from a height of two meters. In such cases, the prediction may include using a curve associated with such a situation, such as curve 905 in Figure 9E or curve 1105 in Figure 11B. For example, the prediction in Figure 11A may include determining physical defect rate values ​​corresponding to, e.g., 508N, 234N, and 128N of curve 1105.

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

[0076] As explained above, one aspect of the present disclosure relates to using measurements of peak impact force associated with breaking tablets to determine the physical strength or robustness of a tablet or batch of tablets, i.e., specifically, to predict the physical defect rate of a batch of tablets (or another parameter indicative of the likelihood that tablets will experience physical defects). More specifically, peak impact force values ​​may provide a strong indicator or predictor of the physical defect rate that a batch of tablets is expected to experience. For example, FIG. 12A shows the p-value and R associated with peak impact force. 2 values ​​and the p-values ​​and R associated with tensile strength 212A shows data comparing the peak impact force value with the peak impact force value. The p-value for a parameter may indicate how useful the parameter is for explaining the variation in physical defect rate, i.e., 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, e.g., a p-value less than 0.05, may indicate that a 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, or may at least be consistent with, the hypothesis that the physical defect rate is affected by or correlated with the variation in the peak impact force value. As further shown in FIG. 12A, the p-value for the tensile strength may be much higher than the p-value for the peak impact force value. A high p-value for a parameter, e.g., a p-value greater than 0.05, may indicate that the parameter has limited or no effect on the physical defect rate. Figure 12B provides additional data showing the lack of correlation between tensile strength and physical defect rate in tablets. Figure 12A shows that the fitted curve or equation describing the relationship between peak impact force value and physical defect rate has a higher R than the curve or equation describing the relationship between tensile strength and physical defect rate. 2 Further indicating that there is a higher R 2 The R value may indicate that the fitted curve has a lower level of error compared to the data points used to perform the curve fit. Figure 12C shows the R value of the fitted curve used in an attempt to link tensile strength to physical defect rate. 2 As shown in Figure 12C, the R 2 The R value is the R of a curve like that in Figure 11B, which relates peak impact force to physical defect rate. 2, is lower. Thus, the data in Figures 11B, 12A, and 12C show that peak impact force has a greater impact on physical defect rate and a higher ability to accurately predict physical defect rate than other parameters, such as tensile strength. More generally, peak impact force may have a greater ability than other parameters to determine tablet physical strength or robustness. Figure 15 further illustrates the limited ability of other parameters, such as friability, to predict physical defect rate. Friability testing is a qualitative test that provides a pass or fail criterion for tablet mechanical strength (e.g., 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 tests only provide data at test conditions (fixed drop height and fixed drop count) and may have no or limited ability to be used to extrapolate beyond test conditions (high or low impact). Furthermore, friability testing may lack the ability to measure the energy absorbed by broken tablets and therefore may not explain why a particular tablet is broken or chipped.

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

[0078] In some embodiments, 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 apparatus, e.g., 1100, 2100, 3100, during an impact impact test in which a striker component of the tablet testing apparatus strikes or breaks a tablet or set of tablets. The tablet or set of tablets may belong to a particular tablet type, such as tablet type 11. The peak impact force value may indicate the peak amount of impact force experienced by the tablet or set of tablets from a striker component, e.g., 1120, 2120, 3120, during the impact impact test. If the impact impact test is performed on a set of tablets, the peak impact force value may be an average of the peak amounts of force experienced by each of the set of tablets. In some cases, the peak impact force may be the maximum amount of force a tablet withstands before breaking or the average of the maximum amount of force each of the set of tablets withstands before breaking during the impact impact test.

[0079] In some embodiments, method 13000 may include a step 13004 in which computer system 1200 determines, based on the peak impact force value, at least one predicted physical defect rate for a tablet type, e.g., tablet type 11, associated with a tablet or set of tablets used in the impact impact test. As explained above, a tablet type is associated with a physical characteristic or set of physical characteristics of the tablet, such as a combination of formulation and 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 will break when lowered onto a solid surface.

[0080] In some embodiments, the at least one physical defect rate may be determined based on a stored model describing the relationship between peak impact force values ​​and physical defect rates, such as the model described above. For example, the model may include or be described by a curve or formula describing the relationship between peak impact force values ​​and physical defect rates, 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 amount of force applied to a set of tablets. In the example of FIG. 14, the 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 certain embodiments, the at least one predicted physical defect rate may include a first predicted physical defect rate associated with a particular situation in which the tablet is or can be dropped onto the solid surface, such as when dropped five times and / or dropped from a height of two meters. In some cases, method 13000 may determine multiple predicted physical defect rates for multiple situations in which the tablet is or can be dropped onto the solid surface. For example, the multiple predicted physical defect rates for the tablet may be associated with multiple different drop heights, multiple different number of drops, and / or multiple different combinations of drop heights and number of drops at which the tablet can be dropped onto the solid surface. As noted above, making such a prediction may in some cases include extrapolating the predicted physical defect rate from intermediate physical defect rates.

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

[0083] Various embodiments have been described above, but they have been presented only as illustrations and examples of the present technology, and are not intended to be limiting. It will be apparent to those skilled in the relevant art that various changes in form and detail can be made therein without departing from the spirit and scope of the present technology. Thus, the breadth and scope of the present 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. It should also 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 mentioned herein are incorporated herein by reference in their entirety.

Claims

1. performing an impact impact test on a first plurality of tablets or a first set of tablets, the impact impact test comprising a striker component of a solid dosage form testing device striking and breaking the first plurality of tablets or the first set of tablets, each tablet of the first plurality of tablets or each set of the first plurality of sets being associated with a respective tablet type of a plurality of tablet types having respective different physical characteristics; measuring, during the impact impact test, a plurality of peak impact force values ​​indicating peak amounts of impact force received by the first plurality of tablets or the set of first plurality of tablets from the striker component during the impact impact test, the plurality of peak impact force values ​​being associated with the plurality of tablet types; performing a tablet drop test on a second plurality of sets of tablets, the tablet drop test comprising lowering the second plurality of sets of tablets onto a solid surface, each set of the second plurality of sets being associated with a respective tablet type of the plurality of tablet types; determining a plurality of physical defect rates associated with the plurality of tablet types based on the tablet drop test; determining a model that describes a relationship between peak impact force values ​​and physical defect rates based on the plurality of peak impact force values ​​and the plurality of physical defect rates; determining a predicted physical defect rate for one or additional tablet types of the plurality of tablet types based on the model.

2. 2. The computer-implemented method of claim 1, wherein the different physical characteristics associated with the plurality of tablet types include, for each of the plurality of tablet types, at least one of: (i) a respective formulation of the tablet type; or (ii) a respective porosity of the tablet type.

3. 2. The computer-implemented method of claim 1, wherein the plurality of physical defectivity rates is a first plurality of physical defectivity rates associated with a first drop height, the method further comprising measuring a second plurality of physical defectivity rates associated with a second drop height.

4. 2. The computer-implemented method of claim 1, wherein the plurality of physical defect rates are a first plurality of physical defect rates associated with a first number of drops indicating the number of times tablets of the second plurality of set of tablets are lowered onto the solid surface during the tablet drop test, and the method further comprises measuring a second plurality of physical defect rates associated with a second number of drops.

5. Determining the predicted physical defect rate of the additional tablet type comprises: performing the impact impact test on additional tablets associated with the additional tablet type, the impact impact test including the striker component striking and breaking the additional tablets; measuring an additional peak impact force value indicative of the peak amount of impact force received by the additional tablet from the striker component during the impact impact test to break the tablet; 2. The computer-implemented method of claim 1, wherein the predicted physical defect rate for the additional tablet type is determined based on the model and the additional peak impact force value.

6. The impact impact test is Stryker components; an impact platform configured to provide an impact site; a housing within which the striker component and the impact platform are disposed, the housing including a mechanism configured to removably suspend the striker component within the housing above the impact site; a sensor data acquisition system configured to acquire sensor data indicative of the velocity or kinetic energy of the striker component as it is released to descend toward the impact site; and a solid dosage form placement mechanism having a first push component and a second push component coupled to the impact platform, the first push component having a first recess and the second push component having a second recess, the impact site being disposed between the first recess of the first push component and the second recess of the second push component; a recess of the first recess of the first push component extending inward toward an interior of the first push component away from the impact site; a recess of the second recess of the second push component extending inward toward an interior of the second push component away from the impact site; 2. The computer-implemented method of claim 1, wherein 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, using the solid dosage form testing device.

7. receiving a peak impact force value measured by a sensor of the solid dosage form testing device during an impact impact test in which a striker component of the solid dosage form testing device strikes and breaks a set of tablets, the peak impact force value indicating an average peak amount of impact force received by the set of tablets from the striker component during the impact impact test; A computer-implemented method comprising: determining, based on the peak impact force value, at least one predicted physical defect rate for a tablet type associated with the set of tablets used in the impact impact test, the tablet type being associated with a physical characteristic or set of physical characteristics of the set of tablets, and the at least one predicted physical defect rate predicting the likelihood that the set of tablets belonging to the tablet type will break when lowered onto a solid surface.

8. 8. The computer-implemented method of claim 7, wherein determining the at least one predicted physical defect rate comprises determining a plurality of predicted physical defect rates for the set of tablets, the plurality of predicted physical defect rates being associated with a plurality of different drop heights to which the set of tablets can be lowered onto the solid surface.

9. 8. The computer-implemented method of claim 7, wherein determining the at least one predicted physical defect rate comprises determining a plurality of predicted physical defect rates for the set of tablets, the plurality of predicted physical defect rates being associated with a plurality of different numbers of drops of the set of tablets, each of the plurality of different numbers of drops indicating a number of times one or more of the set of tablets are lowered onto the solid surface.

10. 8. The computer-implemented method of claim 7, further comprising determining, based on the peak impact force value, a predicted maximum height that the set of tablets of the tablet type can be dropped to without breaking or without the at least one predicted physical defect rate exceeding a predetermined defect rate threshold.

11. The computer-implemented method of claim 7 , wherein the at least one predicted physical defect rate is determined based on a stored model that describes a relationship between peak impact force values ​​and physical defect rates.

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