Apparatus and method for evaluating the physical strength or robustness of solid drug dosage forms based on an impact shock test

Abstract

A solid drug dosage form testing apparatus and method are presented. The solid drug dosage form testing apparatus includes an impactor 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 pusher components that are movable toward each other to place a solid dosage form at an impact site. The method includes performing an impact-impact test on a first plurality of solid dosage forms and measuring a plurality of peak impact force values. The method can include performing a drop test on a second plurality of solid dosage forms and measuring a plurality of physical defect rates. The method can include determining a model that describes a relationship between the peak impact force values and the physical defect rates and determining a predicted physical defect rate based on the model.

Description

Technical Field

[0001] This invention relates to an apparatus and method for evaluating the physical strength or robustness of solid pharmaceutical dosage forms, such as tablets, mini tablets, pills, chewing gum, sheets, discs, capsules, lozenges, implants, granules, and pellets, based on an impact test. Background Technology

[0002] Solid drug dosage forms (such as tablets, mini tablets, pills, chewing gum, thin sheets, discs, capsules, lozenges, implants, granules, and pellets) provide a means of delivering medicines or other compounds into a user's body. Many medicines or pharmaceutical formulations can be manufactured or formed as tablets, mini tablets, pills, chewing gum, thin sheets, discs, capsules, lozenges, implants, granules, and pellets. In some cases, different formulations can produce tablets, mini tablets, pills, chewing gum, thin sheets, discs, capsules, lozenges, implants, granules, and pellets with different mechanical or other physical properties. Summary of the Invention

[0003] In view of the foregoing, this document provides a solid drug dosage form testing apparatus and method for evaluating the toughness of solid drug dosage forms, such as tablets, mini tablets, pills, chewing gum, sheets, discs, capsules, lozenges, implants, granules, and pellets. In one aspect, the solid drug dosage form testing apparatus includes an impactor component, an impact platform, a sensor data acquisition system, and a placement mechanism for holding and correctly positioning the solid drug dosage form below the impactor component. The placement mechanism has a first pushing component and a second pushing component, which are movable toward each other to position the solid drug dosage form at the impact site. The method includes performing impact tests on a first plurality of solid drug dosage forms or a first plurality of groups of solid drug dosage forms and measuring a plurality of peak impact force values. The method may further include performing drop tests on a second plurality of groups of solid drug dosage forms and measuring a plurality of physical defect rates. The method may further include determining a model describing the relationship between peak impact force values ​​and physical defect rates, and determining a predicted physical defect rate based on the model. Attached Figure Description

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

[0005] Figure 1A and 1B A block diagram of a solid drug dosage form testing apparatus according to embodiments herein is depicted.

[0006] Figure 2A and 2B A view of a tablet testing apparatus according to an embodiment of this document is depicted.

[0007] Figure 2BB A front view and a side view of a tablet testing device of a size suitable for benchtop use according to embodiments of this document are depicted.

[0008] Figure 2C A sensor data acquisition system according to embodiments herein is described.

[0009] Figure 2D Various hammer inserts for impactor components according to embodiments herein are depicted.

[0010] Figure 2E An impactor component having multiple ends for simultaneously impacting multiple tablets is depicted according to embodiments herein.

[0011] Figure 2F A rotary table for dispensing tablets according to embodiments herein is described, and a vacuum-based cleaning system is also described.

[0012] Figure 2G A rotary table for dispensing tablets according to embodiments herein is described, and a scraper-based cleaning system is also described.

[0013] Figure 3A A tablet testing apparatus according to embodiments herein is described.

[0014] Figure 3B-3D A tablet placement mechanism according to an embodiment of this document is described.

[0015] Figures 4A-4C An impact test performed using a tablet testing apparatus according to embodiments of this document is described.

[0016] Figure 5 An airflow generator for applying airflow toward an opening in an impact chamber, according to an embodiment of this document, is described.

[0017] Figure 6 This is a flowchart depicting a method for evaluating the strength of a sample of tablets or a batch of tablets according to embodiments of this document.

[0018] Figure 7 The illustration shows the peak impact force values ​​associated with various formulations and porosities according to embodiments of this article.

[0019] Figure 8A and 8B The force imparted to the tablet by the impactor component during an impact test according to embodiments herein is depicted.

[0020] Figure 8C and8D Various values ​​of peak impact force and energy imparted to the tablet during impact testing according to the embodiments herein are described.

[0021] Figure 8E The force distribution during an impact test, assuming the tablet breaks, is depicted according to the embodiments herein, as well as the force distribution when the tablet does not break.

[0022] Figures 9A-9F The illustrations show various values ​​of peak impact force and physical defect rate associated with various tablet types according to embodiments of this article.

[0023] Figure 10A and 10B The figure illustrates a stress-strain curve according to an embodiment of this document, which can be used to measure the toughness associated with various tablet types.

[0024] Figure 11A and 11B The illustration shows the predicted physical defect rate based on various peak impact force values ​​according to embodiments of this document.

[0025] Figure 12A The figure illustrates the p-value and R-value associated with the peak impact force according to the embodiments described herein. 2 Values ​​and p-values ​​and R-values ​​associated with tensile strength 2 Comparison between values.

[0026] Figure 12B The illustration shows a relatively weak correlation between the tensile strength and physical defect rate of tablets according to embodiments of this article.

[0027] Figure 12C The figure illustrates the error value associated with a curve attempting to correlate tensile strength with physical defect rate according to embodiments of this article.

[0028] Figure 13 This is a flowchart depicting a method for predicting physical defect rate based on peak impact force values ​​according to embodiments of this document.

[0029] Figure 14 The illustration shows the prediction of the physical defect rate based on a model describing the relationship between the physical defect rate and the peak impact force, according to an embodiment of this paper.

[0030] Figure 15 The illustration shows a relative lack of correlation between the fragility value and physical defect rate of the tablets according to embodiments herein. Detailed Implementation

[0031] It should be understood that the specific embodiments shown and described herein are examples of solid pharmaceutical dosage forms and their testing, and are not intended to limit the scope of this application in any way. As used in this specification, the singular forms “a,” “an,” and “the” specifically also cover the plural forms of the terms they refer to, unless expressly specified otherwise.

[0032] The following detailed description is exemplary in nature only and is not intended to limit the invention or its application and use. Although the description of the embodiments herein is made in the context of evaluating or assessing the physical strength or robustness of solid pharmaceutical dosage forms (such as tablets or samples of a batch of tablets), the invention may also be used in the context of evaluating or assessing the physical strength or robustness of solid pharmaceutical dosage forms such as mini tablets, pills, chewing gum, sheets, discs, capsules, lozenges, implants, granules, and pellets, and samples of their batches, where it is deemed useful. Furthermore, it is not intended to be limited by any express or implied theory presented in the foregoing technical field, background art, summary of the invention, or the following detailed description.

[0033] One aspect of this application relates to evaluating or assessing the physical strength or robustness of solid pharmaceutical dosage forms, which are samples or subsets of a batch of tablets, wherein "tablet" as used herein can refer to tablet cores, coated tablets, and uncoated tablets, to assess their ability to withstand forces or conditions in various environments in which the tablets may be exposed, such as manufacturing facilities, for example, during the coating, packaging, and / or inspection processes of tablet cores, in warehouse facilities, pharmacies, hospitals, patients' homes, or during the transport of tablets from manufacturing facilities to pharmacies, hospitals, homes, or other locations. For example, in these environments, tablets may accidentally fall onto solid surfaces or be subjected to forces during processing, such as forces received by the tablet core during the coating process, and evaluating the physical strength or robustness of these tablets may involve predicting or otherwise determining the rate of physical defects associated with the tablets in the event of a tablet being dropped from, for example, a specific height and / or a specific number of drops. This evaluation or assessment can be used to determine whether a tablet formulation (such as a pharmaceutical formulation or drug formulation) possesses sufficiently robust mechanical or other physical properties to allow the tablet to withstand conditions or events in which it may be exposed. In some cases, assessing the physical strength of a sample or subset of tablets may include determining their tensile strength via, for example, a hardness test, and using tensile strength as an indicator of tablet strength (tensile strength can be calculated from, for example, pharmacopoeia hardness test data and tablet dimensions generated by Sotax HT100 and compression tool dimensions using the Pitt equation, discussed in KTPitt & M.G. Heasley's "Powder Technology," pp. 169-175). However, parameters such as tensile strength cannot account for rapid energy transfer, such as a tablet falling freely and impacting a solid surface. Such events may impart impact or other forces to the falling tablet and may cause it to shatter or otherwise break. In some cases, a tablet or tablet formulation may have high tensile strength, as determined by a hardness test, but may still have poor ability to withstand vibration, impact, or other events involving rapid energy transfer. Therefore, hardness testing and tensile strength parameters may be poor predictors of the physical defect rate of tablets in large-scale production, and may lead to a discrepancy between the predicted physical strength and the actual physical strength of the produced tablets.

[0034] In one embodiment, the peak impact force parameter can be used to assess the physical strength of a tablet. More specifically, the value of the peak impact force parameter, also known as the peak impact force value, can be used to predict the physical defect rate of a batch of tablets. The peak impact force value can be measured, for example, by performing an impact test in which an impactor component strikes and causes one or more samples of a batch of tablets to break. During the test, the peak amount of force applied to the tablet, or the average of the peak amounts of force applied to a group of tablets, can be measured. Because these measurements are better indicators of rapid energy transfer, they provide a better ability to assess the physical strength of the tablet, or more specifically, to predict the physical defect rate of the tablet.

[0035] In one embodiment, the peak impact force parameter can be used as an indirect measure or approximation of the impact toughness of a tablet (e.g., chip tablets, coated tablets, uncoated tablets, etc.) or a batch of tablets (e.g., tablet cores, coated tablets, uncoated tablets, etc.), also referred to as toughness. In some cases, the toughness of a sample or a subset of a batch of tablets can be measured directly, such as by determining the area under the stress-strain curve of the tablet. In this case, the directly measured toughness of a sample of the tablet or the batch of tablets can be used to predict the physical defect rate of the batch of tablets. In one embodiment, a computing system or other device can receive sensor data indicating the forces received by the tablet during an impact test. In some embodiments, the computing system can be configured to determine, based on the sensor data, whether the tablet fractured or suffered some other physical defect during the impact test.

[0036] In one embodiment, the impact test can be performed using a solid dosage form or tablet testing device that uses an impactor component releasably suspended above the impact site. In some embodiments, the tablet testing device may include a solid dosage form or tablet placement mechanism (also referred to as a tablet centering mechanism or tablet holder) for placing a solid dosage form or tablet such that the solid dosage form or tablet is centered around the impact site and directly below the impactor component. When implemented as a tablet placement mechanism, this mechanism can thus place the tablet at a position where the center of the tablet is aligned with the center of the end of the impactor component, such that the center of the tablet will be impacted by the falling impactor component. In some embodiments, the tablet placement mechanism may have a recessed portion for accommodating the curvature of the tablet. The recessed portion pushes the tablet toward the impact site upon engagement with the tablet. In some embodiments, the tablet testing device may include a channel for guiding airflow toward an impact chamber surrounding the impact site. The airflow can reduce the likelihood of debris or other substances that may be generated during the impact test escaping from the housing of the tablet testing device. In one embodiment, the tablet testing device may include a waste collection device or component configured to perform waste collection or removal after each impact test or after several impact tests. Waste collection or removal may include, for example, automatically removing tablets from the impact site, where the removed tablets may have been broken or otherwise subjected to an impact test. In some cases, the tablet placement mechanism may be configured to automatically retrieve a new tablet after a tablet has been removed and place it at the impact site, allowing an impact test to be performed on the new tablet. In one embodiment, the tablet testing device may be configured to automate the tablet testing process by automatically loading tablets onto an impact platform, having the tablet placement mechanism automatically place tablets at the impact site on the impact platform, having an impactor component released onto and impacting the tablet, collecting sensor data or other measurements related to tablet impact, having a waste collection device automatically remove tablets from the impact platform, and repeating the process by loading the next tablet onto the impact platform. In this way, the tablet testing device may be able to automatically test a sample or a subset of a batch of tablets in a rotary manner.

[0037] Figure 1AA block diagram of System 1000 is provided, which is used to evaluate one or more mechanical properties of solid pharmaceutical dosage forms (such as tablets or samples of a batch of tablets) and / or to assess the mechanical or physical strength or robustness of tablets. In some cases, System 1000 may be part of a pharmaceutical manufacturing facility or other manufacturing facility that manufactures pharmaceutical tablets, dietary tablets or other ingestible tablets, or any such formulation for pills, chewing gum, thin sheets, discs, capsules, lozenges, implants, granules, and pellets. For example, System 1000 may be used within a manufacturing facility or research / development facility to provide a quality control process by predicting whether a batch of tablets will be sufficiently robust or otherwise strong to withstand handling by a manufacturer, pharmacist, physician, patient, or other person. Such handling may involve events such as tablets being dropped onto a hard surface or other events that may subject the tablets to impacts or forces that could cause the tablets to break or otherwise introduce physical defects into the tablets.

[0038] exist Figure 1A In some embodiments, system 1000 may include a solid drug dosage form testing device 1100 and a computing system 1200. As discussed in more detail below, the solid drug dosage form testing device 1100 may be used to perform impact tests on tablets, and more specifically, to generate sensor data that measures the force or energy involved in impacting the tablet. In one embodiment, the solid drug dosage form testing device 1100 may include a housing 1110 in which various components of the solid drug dosage form testing device 1100, such as an impactor component 1120 and an impact platform 1130, are disposed. The impact platform 1130 may be configured as a substrate or surface on which a solid drug dosage form may be disposed. More specifically, the impact platform 1130 may include an impact portion at which the impactor component 1120 will collide with the impact platform 1130 or with a solid drug dosage form disposed directly above the impact portion. For example, the impactor component 1120 may be suspended above the impact platform 1130. In this example, the impact site may be a location on the top surface of the impact platform 1130, directly below the impactor component 1120. The housing 1110 may include an impactor mechanism configured to releasably suspend the impactor component 1120 above the impact site on the impact platform 1130. As part of an impact test, the impactor mechanism may be able to release the impactor component 1120, allowing it to fall or drop towards the impact site under the influence of gravity. The falling impactor component 1120 may strike or otherwise impact a solid pharmaceutical dosage form (if present) positioned at the impact site. In some cases, the impactor component 1120 may impact the tablet with sufficient momentum or energy to shatter the tablet or otherwise break it into multiple pieces.

[0039] In one embodiment, the solid drug dosage form testing apparatus 1100 may include a sensor data acquisition system 1140 for acquiring or otherwise generating sensor data associated with an impact test performed using the solid drug 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 solid drug dosage form as the impactor component 1120 falls toward the impact site, and / or the amount of force exerted by the impactor component 1120 on the solid drug 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 impactor component 1120 as it falls, and a second sensor configured to measure the amount of energy exerted by the impactor component 1120 on the solid drug dosage form when the impactor component 1120 impacts the solid drug dosage form. In some embodiments, 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 configured to receive sensor data from one or more sensors, such as analog-to-digital converter (DAC) and / or digital signal processing (DSP) circuitry, and / or may include non-transitory computer-readable media (e.g., solid-state drive or hard disk drive) for storing the sensor data.

[0040] Figure 1B The illustration shows a solid dosage form testing apparatus 1100A according to an embodiment of the present invention, which may be an embodiment of the solid dosage form testing apparatus 1100, including a solid dosage form placement mechanism 1150 and an impact chamber 1115. In one embodiment, the solid dosage form placement mechanism 1150 may be configured to push or otherwise move a solid dosage form (such as tablets, mini tablets, pills, chewing gum, sheets, discs, capsules, lozenges, implants, granules, and pellets) toward an impact site on an impact platform 1130 so that the solid dosage form is positioned directly below the impactor component 1120 before the impact test begins. In some embodiments, the impact chamber 1115 may be a chamber that is part of a housing 1110 and surrounds the impact platform 1130. The impact chamber 1115 may be used to trap or otherwise contain debris that may be generated when the solid dosage form is impacted by the impactor component 1120. More specifically, the impact chamber 1115 can prevent debris from spreading to the environment outside the housing 1110 in order to protect technicians or other personnel monitoring the impact impact test from exposure to drug compounds or other materials in the debris.

[0041] In one embodiment, Figure 1A and 1BThe computing system 1200 can be configured to process sensor data. In some embodiments, data processing may include, for example, determining a model describing, or some other relationship, between: (i) the magnitude of impact force a solid dosage form can withstand before breaking, and (ii) the likelihood of a solid dosage form experiencing physical defects due to a fall. In some embodiments, data processing may include generating a prediction of the physical defect rate of a solid dosage form or a batch of solid dosage forms, wherein the physical defect rate may indicate the likelihood of physical defects occurring when one of the solid dosage forms in a batch falls onto a hard surface or when subjected to some other type of physical impact.

[0042] In one embodiment, the computing system 1200 may include, for example, at least one processing circuitry (e.g., a computer processor) and a non-transitory computer-readable medium (e.g., a solid-state drive). The processing circuitry may be configured to perform processing of sensor data. In some cases, the processing circuitry may process the sensor data by executing instructions stored on or in a non-transitory computer-readable medium. The computing system 1200 may be a separate device (e.g., a desktop computer or server) independent of the solid-state drug form testing device 1100, or it may be part of the solid-state drug form testing device 1100 (e.g., computing circuitry or a chip embedded within the solid-state drug form testing device 1100).

[0043] Figure 2A and 2B The illustration shows a tablet testing device 2100 according to an embodiment thereof, which may be an embodiment of solid drug dosage form testing devices 1100, 1100A. The tablet testing device 2100 is configured as a floor-standing system; this is by way of example and not limitation, and as described below, benchtop or desktop systems also fall within the scope of this disclosure. More specifically, Figure 2A This is a front view of the tablet testing equipment 2100, and Figure 2B It is a tablet testing device 2100. Figure 2A A cross-sectional view taken along line AA. (Example) Figure 2A The tablet testing device 2100 depicted includes a housing 2110, within which various components of the tablet testing device 2100 are disposed. In one embodiment, the housing 2110 may form one or more chambers, such as an impactor component chamber 2111 and an impact chamber 2115, which will be discussed in more detail below. Figure 2B As depicted, the impactor component chamber 2111 may be enclosed by one or more walls, such as walls 2111A and 2111B, and the impact chamber 2115 may also be enclosed by one or more walls, such as walls 2115A and 2115B. Figure 2AThe tablet testing apparatus 2100 is further described with a user input device 2170, which can be configured to receive user commands or other user input. For example, the user input device 2170 can be configured to receive one or more user commands associated with performing an impact test.

[0044] In one embodiment, the impactor component chamber 2111 may be a chamber containing an impact impactor 2120 (also referred to as a hammer), such as... Figure 2B As shown. The impactor component chamber 2111 may also include an impactor mechanism 2113 that releasably suspends the impactor component 2120 above the impact chamber 2115. The impactor mechanism 2113 may be configured to release the impactor component 2120 so that the impactor component 2120 falls or drops through the opening 2114 onto an impact portion 2132 within the impact chamber 2115, at which the impactor component 2120 may strike or otherwise impact a tablet 2300 or other object disposed at the impact portion 2132. Thus, the impact chamber 2115 may include the impact portion 2132 and may be used to trap or otherwise contain debris that may be generated by the impact. In some embodiments, solid drug dosing or tablet testing devices 1100, 1100A, 2100 may include a motor or other actuator configured to lift the impactor component after it has fallen, such that the impactor component can be released again to perform another impact test.

[0045] In one embodiment, the impact portion 2132 may be provided by an impact platform 2130, which may be an embodiment of impact platform 1130, may be contained within an impact chamber 2115, and may provide a base for receiving impacts or other collisions with the impactor component 2120. For example, the impact platform 2132 may be an object or device providing a flat (to form a flat upper surface) or outwardly or inwardly curved (to form a convex or concave upper surface) upper surface. In this case, the impact portion 2132 may be a location on the flat upper surface of the impact platform 2130, such as a central location. The impact platform 2130 may have a cylindrical, rectangular, or any other shape. In one embodiment, the tablet testing device 2100 may include a tablet placement mechanism 2150, which may be an embodiment of tablet placement mechanism 1150 disposed on the upper surface of the impact platform 2130. The tablet placement mechanism 2150 may have components surrounding and / or equidistant from the impact portion 2132, and may be configured to push or otherwise move the tablet toward the impact portion 2132, and more specifically, to center the tablet around the impact portion 2132 such that the center of the tablet is directly above the impact portion 2132. In some embodiments, once the tablet placement mechanism 2300 has moved the tablet to the impact portion, its components may move away from the tablet 2300 to detach from the tablet. As a result, the tablet placement mechanism 2150 is no longer in contact with the tablet 2300. By moving away from contact with the tablet 2300, the tablet placement mechanism 2150 can avoid interfering with the impact test and avoid affecting the sensor data generated during the impact test. The tablet placement mechanism will be discussed in detail below.

[0046] In one embodiment, the impactor component 2120 (also referred to as a hammer) may be a rigid component, such as an elongated rod made of metal, such as stainless steel. The impactor component 2120 is configured to be released or dropped to impact the impact portion 2132 of the impact platform 2130. In some embodiments, the impactor component 2120 may have an end 2121, such as a flat end or a rounded end, or more specifically, an end facing the impact portion 2132, configured to contact the center of the tablet 2300 disposed at the impact portion 2132 when the impactor component 2120 impacts or otherwise strikes the tablet 2300. In its embodiments, the end 2121 may be made of metal, such as stainless steel.

[0047] In one embodiment, the impactor component 2120 may have a body shaped as an elongated cylinder with an end 2121 having a circular profile. Figure 2DA flat hammer insert 2121A is depicted that can be attached to the impactor component 2120D as its end having a flat surface, and a hemispherical hammer insert 2121B can be attached to the impactor component 2120D as its end having a rounded surface. Thus, in some cases, the impactor end can be formed from an insert or hammer insert made of metal (such as stainless steel), which can be inserted into or otherwise attached to a shaft forming an elongated cylinder or other structure of the impactor component, such as... Figure 2D The impactor component 2120D is shown. To reiterate the foregoing, for example, the flat end 2121 can be formed by a flat hammer insert 2121A, while the rounded end 2121 can be formed by a hemispherical hammer insert 2121B or other curved hammer inserts. In some cases, the diameter of the cylinder can be similar to the diameter of various tablets or some other dimension (e.g., length or width). As an example, the diameter of the cylinder can range from, for example, 5 mm to 12 mm.

[0048] In embodiments of the invention, the impactor component, end and / or end or punch insert may be formed of a non-rigid material selected to mimic the materials that the tablet may come into contact with at various stages of its manufacture, packaging, storage, and transport. In such embodiments, the impactor component, end and / or end or punch insert may be formed of a non-rigid or soft elastic or polymeric material. In another embodiment, the impactor component, end and / or end or punch insert may be formed of a non-rigid cardboard or other such packaging material.

[0049] In one embodiment, and referring to Figure 2B and 2C The impactor component 2120 may include one or more objects 2122 that may be removably attached to the body of the impactor component 2120 to provide additional mass or weight to the impactor component 2120. For example, the one or more objects 2122 may include one or more discs that may slide around a portion of the body of the impactor component 2120. In some embodiments, for a given drop distance, the total mass of the impactor component 2120 including the one or more objects 2122 may be small enough to generate an impact force within a range between the impactor component 2120 and the pharmaceutical tablet or other tablet, a range of impact forces sufficient to break the tablet but not large enough to completely crush the tablet. In some cases, for a given drop distance, the total mass of the impactor component 2120 may be less than or equal to 1 kg, or less than or equal to 0.5 kg.

[0050] In one embodiment, Figure 2EThe impactor component 2120E shown may have multiple end or hammer inserts configured to simultaneously impact multiple tablets. Therefore, multiple end or hammer inserts can be used to perform parallel processing of multiple tablets to increase the speed of performing impact tests on a batch of tablets or other solid drug dosage forms or samples or subsets. Figure 2E In this embodiment, the impactor component 2120E includes end pieces or hammer inserts 2121A, 2121B, 2121C, 2121D, and 2121E. In some cases, the multiple ends may form a 2D array of ends (also referred to as a matrix of multiple ends). In this embodiment, the weight of the impactor component, or more specifically the hammer weight or hammer mass, may be relative to... Figure 2C The impactor components are increased. The weight or mass of the impactor component 2120E can be increased to such a level that when Figure 2E When the impactor component 2120E falls from a certain height and collides with multiple tablets, it is able to impart sufficient force to have a reasonable probability of breaking all the tablets. Furthermore, in this embodiment, corresponding sensors may be disposed within or attached to each of the end caps or impact inserts 2121A, 2121B, 2121C, 2121D, 2121E to collect sensor data indicating the amount of force imparted by the respective end cap to the respective tablet impacted by the end cap.

[0051] In its embodiments, the tablet testing devices 2100F and 2100G may include sample filling stations 2400F and 2400G, such as Figure 2F and 2G The sample filling station is shown. Figure 2F and 2G In the examples, sample filling stations 2400F and 2400G can form a turntable for dispensing one or more tablets onto one or more locations on their impact platform. In some cases, sample filling station 2400G can dispense one tablet at a time onto location 2131G of impact platform 2130G (also known as the tablet dispensing location), such as... Figure 2G As shown. In some cases, the sample filling station 2400F can be configured to simultaneously dispense multiple tablets to multiple tablet dispensing positions 2131F of the impact platform 2130F, such as... Figure 2F As shown. In some cases, the tablet dispensing location may be a groove or other notch within the surface of the impact platform 2130F, 2130G, wherein the groove can hold the dispensed tablet. Figure 2FIn the example, multiple tablet dispensing positions 2131F can be arranged in a row (e.g., a row) of recesses. In some cases, sample filling stations 2400F, 2400G can be constructed as turntables with slots, each slot accommodating a corresponding set of tablets to be dispensed. For example, each slot can be used to accommodate different types of tablets.

[0052] In its embodiments, Figure 2F and 2G The impact platforms 2130F, 2130G may be rotatable to rotate one or more dispensed tablets from one or more tablet dispensing positions 2131F, 2131G to one or more impact sites 2132F, 2132G. In some cases, the impact platforms 2130F, 2130G may rotate one or more dispensed tablets to a central position, or more specifically, to an alignment station 2402F, 2402G. At the alignment station 2402F, 2402G, the tablet testing apparatus may, for example, include a tablet placement mechanism that uses one or more pairs of actuating elements to ensure that a single dispensed tablet or multiple dispensed tablets are centered in a desired position, such as being dispensed into the corresponding center of a recess therein. This alignment operation better ensures that, when the dispensed tablets are rotated to the impact test stations 2404F and 2404G, they are centered directly below the corresponding ends 2121A, 2121B, 2121C, 2121D, and 2121E of the impactor component 2120E, as shown below. Figure 2F As shown, or directly below the end 2121 of the impactor component 2120, such as Figure 2G As shown.

[0053] In its embodiments, impact test stations 2404F, 2404G are configured to include one or more impact portions that can receive impacts from one or more ends of impactor components 2120, 2120E when the impactor components fall toward the impact platforms 2130F, 2130G. Impactor components 2120, 2120E can be used as part of an impact impact test, as disclosed herein, and are intended to cause the dispensed tablet to fracture when the tablet is rotated into the impact test station.

[0054] In its embodiments, the rotatable impact platforms 2130F, 2130G can be configured to further rotate from impact test stations 2404F, 2404G to cleaning stations 2406F, 2406G after one or more dispensed tablets have been broken or otherwise impacted by the corresponding impactor component. Cleaning stations 2406F, 2406G can be configured to remove debris or other fragments of one or more dispensed tablets (which may now be broken tablets) toward portions within the impact chamber to prevent debris or other fragments from broken tablets from contaminating other areas of the tablet testing equipment 2100F, 2100G. Figure 2F In one example, the cleaning station 2406F may include a vacuum configured to generate negative pressure, which could draw debris or other fragments of broken tablets toward, for example, the waste compartment of the tablet testing device 2100F. In such an example, the tablet testing device 2100F may be airtight to facilitate the generation of negative pressure (relative to the rest of the tablet testing device) in its impact chamber. Figure 2G In the example, the cleaning station 2406G may include a scraper 2408 configured to remove debris or other fragments of one or more broken tablets from the top surface of the impact platform 2130G. The debris or other fragments may be scraped off and fall toward a waste compartment located below the impact platform 2130G.

[0055] For further reference Figure 2B and 2C In one embodiment, the impactor mechanism 2113 may be configured to releasably suspend the impactor component 2120 within the housing 2110 and above the impact site 2132. For example, the impactor mechanism 2113 may include a base 2113C, which may be a device, block, or other object from which the impactor component 2120 is suspended or otherwise suspended. In some embodiments, the base 2113C may include a movable latch, stop, or other component on which the impactor component 2120 rests. Such a component may prevent the impactor component 2120 from falling toward the impact site 2132. In one embodiment, the base 2113C may include an actuator, such as a solenoid, configured to retract or otherwise move the latch or stop to a position where it no longer supports the impactor component 2120. Such movement of the latch or stop may release the impactor component 2120, thereby allowing the impactor component 2120 to fall toward the impact site 2132. In some cases, the actuator in this example can be activated, deactivated, or otherwise controlled based on user commands, such as user commands received via user input device 2170. For example, user input device 2170 can provide a user interface that allows a user to input user commands to trigger the drop of impactor component 2120. In such an example, the actuator in base 2113C can be activated in response to a user command.

[0056] In one embodiment, the base 2113C may be a lifting device (also known as a hammer lift) configured to control the height at which the impactor component 2120 is suspended above the impact site 2132, and thus control the release height RH (also known as the drop height) at which the impactor component 2120 is released to fall toward the impact site 2132. Increasing the release height RH can increase the amount of energy or impact force that the appropriate / specific mass of the impactor component 2120 will impart to the tablet 2300 at the impact site 2132, while decreasing the release height can decrease the amount of energy or impact force that the appropriate / specific mass of the impactor component 2120 will impart to the tablet 2300. In a consistent embodiment, the desired impact force can be achieved by selecting an appropriate release height RH for the mass of the impactor component, wherein any desired impact force can be achieved by appropriately selecting the weight of the impactor component and the corresponding release height to provide the desired impact force at the impact site. In some embodiments, the base 2113C can control the release height RH of the impactor component 2120 by moving or being moved along one or more tracks 2113A, 2113B, which can form a support frame or support structure for the impactor mechanism 2113. More specifically, the one or more tracks 2113A, 2113B can be or may include elongated rods or bars that guide the movement of the base 2113C as the impactor component 2120 is raised or lowered. In one embodiment, the mechanism 2130 may include an actuator, such as a motor or pneumatic actuator, configured to generate a force for raising or lowering the base 2113C along one or more tracks 2113A, 2113B. The actuator may be located within the base 2113C, or elsewhere within the housing 2110, or even outside the housing 2110. If the actuator is located outside the base 2113C, the tablet testing device 2100 may include a transmission component, such as a chain, configured to transmit the force generated by the actuator to the base 2113C. If the actuator is located inside the base 2113C, such actuator may be separate from any actuator used to release the impactor component 2120 from the base 2113C.

[0057] In one embodiment, the tablet testing device 2100 may be small enough to be suitable as a benchtop or desktop instrument, such as in a tabletop or desktop setting. Figure 2BBThe benchtop tablet testing device 2100BB is shown in the front and side views. The benchtop tablet testing device 2100BB includes a housing 2110BB, which can have a relatively short height, such as 130cm to 140cm, H, which is more suitable for placement and operation on a laboratory workbench or table. In one example, the height H can limit the maximum distance (release height RH) at which an impactor component (not shown) that can be weighted as described above can be releasably suspended above the impact point 2132BB to 120cm, 110cm, 100cm, 90cm, 80cm, 70cm, 60cm, 50cm, 40cm, 30cm, 20cm, 10cm, 5cm, or less. As an example, the height H of the housing 2110BB can be a value of 140cm, 130cm, 120cm, 110cm, 100cm, 90cm, 80cm, 70cm, 60cm, or less. The reduced release height RH discussed above may require a larger mass impactor component to provide sufficient impact force at the impact site to perform an impact test, or more specifically, sufficient to rupture a drug tablet or other tablet during an impact impact test. As previously mentioned, a larger mass can be achieved by increasing the mass of an existing impactor component, or by selecting an impactor component made of a heavier material. The benchtop tablet testing apparatus 2100BB may include all or most of the features described herein with reference to tablet testing apparatuses 2100, 3100, such as one or more chambers (such as an impactor component chamber and an impact chamber), an impactor mechanism for releasably suspending the impactor component above the impact chamber, additional mass or weight to be added to the impactor component, and an impact platform located within the impact chamber and having a tablet placement mechanism, wherein the dimensions of each of these structures are adapted for benchtop or desktop applications.

[0058] In one embodiment, the tablet testing device 2100 may include a sensor data acquisition system 2140, such as Figure 2C As shown, this can be an embodiment of sensor data acquisition system 1140, configured to generate sensor data measuring various aspects of an impact test. For example, sensor data acquisition system 2140 may include at least sensor 2141 and sensor 2142. Sensor 2141 may be, for example, a strain gauge force sensor or other sensor, configured to measure the impact force imparted by impactor component 2120 at impact site 2132 to tablet 2300 or other object when impactor component 2120 collides, impacts, or otherwise strikes an object. In one example, as... Figure 2CAs depicted, sensor 2141 may be disposed at the end 2121 of impactor component 2120. In one embodiment, sensor 2142 may be a laser sensor or other sensor configured to measure the kinetic energy or velocity of impactor component 2120 as it falls or otherwise moves toward impact site 2132. In some cases, sensor data acquisition system 2140 may include communication circuitry 2143 configured to receive or collect sensor data generated by sensors 2141, 2142 via a wired or wireless connection 2144. If the sensor data is generated by... Figure 1A and 1B If the computing system 1200 processes the data, the computing system 1200 can receive sensor data via communication circuit 2143. In one embodiment, the sensor (e.g., 2141) of the sensor data acquisition system can be disposed on or within the impact platform and configured to measure the force of the impactor component 2120 impacting the impact point 2132. In some embodiments, the sensor can be statically located in a fixed position, such as directly below the impact point 2132 and within the impact platform.

[0059] Figure 3A The illustration shows a tablet testing apparatus 3100, which may be an embodiment of solid drug dosage form or tablet testing apparatus 1100, 1100A, 2100, including a housing 3100 forming an impactor component chamber 3111 and an impact chamber 3115. The impactor component chamber 3111 may include an impactor component 3120 and a mechanism 3113 configured to releasably suspend the impactor component 3120 above the impact chamber 3115. The impact chamber 3115 may include an impact platform 3130 and a tablet placement mechanism 3150 disposed on the upper surface of the impact platform 3130. In some cases, Figure 3A The components depicted in the text can be those mentioned above. Figure 2A-2C The embodiments described herein are examples of similar components discussed in the embodiments.

[0060] As described above, the solid dosage form or tablet testing equipment 1100 / 2100 / 3100 may include a solid dosage form or tablet placement mechanism 1150 / 2150 / 3150. Figure 3B and 3CAn embodiment of a tablet placement mechanism 3150 is depicted, which may be configured to push or otherwise move a tablet toward an impact site, or more specifically, to place the tablet such that it is centered around the impact site. This placement results in the tablet being positioned directly beneath the impactor component before the impact test begins. More specifically, the tablet placement mechanism 3150 may be disposed on the upper surface of an impact platform 3130 and may include a first pushing member 3151 and a second pushing member 3152, which are attached to or otherwise coupled to the upper surface of the impact platform 3130. In this example, the impact site 3132 may be located between the first pushing member 3151 and the second pushing member 3152. In this example, the first pushing member 3151 and the second pushing member 3152 may be manually or via an actuator (e.g., a motor) along a path formed by… Figure 3B Arrows 3701 and 3702 indicate directions in which the tablets move toward each other. More specifically, the tablet placement mechanism 3150 can have an open configuration, such as... Figure 3B and 3C As shown, a space exists between the first component 3151 and the second component 3152 for placing a tablet within that space. The tablet placement mechanism 3150 can be moved from an open configuration to a closed configuration (e.g., via a motor) by moving the pushing components 3151 and 3152 closer to each other and closer to the impact point 3132. Figure 3D As shown, this is to push the tablet or other object toward the impact site 3132, and more specifically, to center the tablet around the impact site 3132. In some cases, the first and second pushing members can be equidistant from the impact site, such that when they move toward each other by an equal amount, they cause the tablet to be pushed toward the impact site. Once the tablet has been centered at the impact site 3132, the pushing members 3151, 3152 can also be moved back to the open configuration, wherein the pushing members 3151, 3152 are moved away from the tablet so that they are no longer in contact with the tablet.

[0061] In some cases, the impact platform 3130 may include one or more connecting components, such as springs, that connect the first pusher 3151 and the second pusher 3152 to the impact platform 3130, but still allow the first pusher 3151 and the second pusher 3152 to move toward or away from each other along the upper surface of the impact platform 3130.

[0062] In one embodiment, the first pushing member 3151 may have a first recessed portion 3151A that provides a recess that can be used to engage one side of the tablet (e.g., the left side) if the tablet is on a particular side of the impact site (e.g., the left side). In this scenario, when the first pushing member 3151 moves to the right toward the second pushing member 3152, the first pushing member 3151 may also push the tablet toward the impact site in a rightward direction. Similarly, the second pushing member 3152 may have a second recessed portion 3152A that provides a recess that can be used to engage the other side of the tablet (e.g., the right side). When the second pushing member 3152 moves to the left toward the first pushing member, if the tablet is on the other side of the impact site (e.g., the right side), the second pushing member 3152 may push the tablet toward the impact site in a leftward direction. More specifically, the recess formed by the first recessed portion 3151A of the first pushing member 3151 can extend inward toward the interior 3151D (such as the center) of the first pushing member 3151, thereby extending away from the impact portion 3132. Similarly, the recess formed by the second recessed portion 3152A of the second pushing member 3152 can extend inward toward the interior 3152D of the second pushing member 3152, thereby extending away from the impact portion 3152. Figure 3B and 3C As depicted, the first pushing member 3151 and the second pushing member 3152 can surround the impact portion 3132, such that the impact portion 3132 can be located between the first recessed portion 3151A of the first pushing member 3151 and the second recessed portion 3152A of the second pushing member 3152. More specifically, the impact portion can be maintained at the center of the space between the first pushing member 3151 and the second pushing member 3152. When the first pushing member 3151 and the second pushing member 3152 move toward each other, this movement can position the first recessed portion 3151A and the second recessed portion 3152A at the impact portion 3132, and thus place the tablet at the impact portion 3132, such that the tablet is centered around the impact portion 3132.

[0063] In one embodiment, the first actuating member 3151 and the second actuating member 3152 are well-suited for engaging and centering the tablet or otherwise positioning it at the impact site 3132. More specifically, various tablets may have convex sides, or more generally, a convex shape. For example, some tablets may have a circular or elliptical shape, wherein opposite sides curve outward. The first actuating member 3151 and the second actuating member 3152 may have a concave shape complementary to the convex shape of the tablet. As an example, Figure 3B and 3CThe first recessed portion 3151A of the first pushing member 3151 can form a first concave corner 3151E, which is configured to engage a first convex side of the tablet. In this example, the second recessed portion 3152A of the second pushing member 3152 can form a second concave corner 3152E, which is configured to engage a second convex side of the tablet. The concave corners 3151E and 3152E can each be a curved corner with a certain curvature, or they can each be a sharper corner without curvature. As the first pushing member 3151 and the second pushing member 3152 move toward each other, when the tablet engages one or both of the corners, the concave corners 3151E and 3152E can cause the tablet to be pushed toward the impact portion 3132. In one embodiment, the first pushing member 3151 and the second pushing member 3152 can be positioned such that the impact portion 3132 is equidistant from the pushing members 3151 and 3152. For example, the impact portion 3132 can be equidistant from the first concave corner portion 3151E and the second concave corner portion 3152E.

[0064] In one embodiment, the first actuating member 3151 and the second actuating member 3152 may have complementary portions that temporarily engage or otherwise interlock with each other when the tablet placement mechanism 3150 moves from an open configuration to a closed configuration, allowing the actuating members 3151, 3152 to approach the impact site close enough to centrally place the tablet at the impact site. For example, as... Figure 3C As depicted, the first recessed portion 3151A of the first pushing member 3151 may form one or more grooves 3151B, 3151C. The one or more grooves 3151B, 3151C may be configured to receive the second recessed portion 3152 when the first pushing member 3151 and the second pushing member 3152 move toward each other. More specifically, the second recessed portion 3152 may include a first sub-portion 3152B and a second sub-portion 3152C protruding from the second pushing member 3152. In this example, groove 3151B may be configured to receive the first sub-portion 3152B, and groove 3151C may be configured to receive the second sub-portion 3152C. In other words, sub-portions 3152B, 3152C may slide into grooves 3151B, 3151C. These complementary structures of the first pushing member 3151 and the second pushing member 3152 allow them to move closer to each other and closer to the impact point 3132 in order to push the object toward the impact point 3132 and center it around the impact point 3132, such as... Figure 3DAs shown. In one embodiment, once the actuating components 3151, 3152 have moved from the open configuration to the closed configuration to place a tablet or other object at the impact site 3132, the actuating components can return to the open configuration. When the actuating components return to the open configuration, they can disengage from the tablet so that they do not contact the tablet when the impactor components fall toward the tablet during an impact test.

[0065] Figure 4A and 4B The illustration shows the impactor component 3120 impacting the tablet 3300 by falling onto it under the influence of gravity. Figure 4A and 4B A scenario is depicted in which the tablet placement mechanism 3150 is shown in an open configuration when the impactor component 3120 falls or lands on the tablet 3300, such that the tablet placement mechanism 3150 disengages from the tablet 3300 when the impactor component 3120 falls or lands on the tablet 3300. In this configuration, the tablet placement mechanism 3150, or more specifically the first pushing component 3151 and the second pushing component 3152, can avoid interfering with the impactor component 3120 and avoid interfering with the measurement of how much force is applied to the tablet 3300 from the impactor component 3120. Figure 4C The illustration shows the results of an impact test performed on tablet 3300. More specifically, the impact test may include an impactor component 3120 having sufficient mass and / or releasing from a sufficient height, such that when the impactor component 3120 is released and impacts tablet 3300, the impactor component 3120 imparts sufficient force or energy to cause tablet 3300 to fracture. For example, Figure 4C The illustration shows a gap 3300A in tablet 3300, which is created when a portion of tablet 3300 is separated from tablet 3300 due to an impact force from impactor component 3120. As discussed in more detail below, some embodiments herein may include detecting a tablet breakage event by determining whether the tablet has actually broken due to an impact test based on measurements made with sensor data.

[0066] As described above, impact chambers 1115, 2115, and 3115 can surround impact portions 2132 and 3132, and can be used to contain debris that may be generated during impact testing. For example, an impact from an impactor component (e.g., 2120) may produce debris in the form of dispersed powder. This powder may contain pharmaceutical substances that may have adverse health effects on personnel exposed outside the housings 1110, 2110, and 3100 of a solid drug dosage form or tablet testing device. Therefore, impact chambers 1115, 2115, and 3115 can be used to trap debris within them. In one embodiment, such as Figure 2FAs shown, the impact chamber can be connected to a vacuum to generate negative pressure and prevent any contaminated air from escaping the impact chamber.

[0067] For example, Figure 5 The illustration shows a tablet testing apparatus 2100 configured to generate an airflow that prevents debris from escaping from an impact chamber 2115. More specifically, the tablet testing apparatus 2100 may include an opening 2114, or more specifically, an aperture, allowing an impactor component 2120 to enter the impact chamber 2115 and reach the impact site 2132. In this embodiment, the impact chamber 2115 may have walls 2115A, 2115B, 2111C, and 2115D that are hermetically connected to each other and hermetically connected to a top and bottom wall. In one example, walls 2115D and 2115C may be the front and rear walls of the impact chamber 2115, respectively, while walls 2115A and 2115B may be the side walls of the impact chamber. Therefore, walls 2115A, 2115B, 2115C, and 2115D prevent debris from escaping from the impact chamber 2115 in a lateral direction. However, debris can escape through opening 2114. To reduce the likelihood of this, the tablet testing device 2100 may include an airflow generator 2180, such as a fan or pneumatic pump, or a conduit connected to compressed air, configured to generate an airflow. In this embodiment, the tablet testing device may have one or more channels 2123A, 2123B (e.g., tubes, hoses, or pipes) directly or indirectly connected to the airflow generator 2180. One or more channels 2123A, 2123B may have outlets surrounding opening 2114 and may allow the airflow generated by the airflow generator 2180 to reach areas near opening 2114 (e.g., such as...). Figure 5 As shown, directly above opening 2114. Therefore, airflow generator 2180 and one or more channels 2123A, 2123B can apply air pressure to impact chamber 2115 via opening 2114. The air pressure can reduce the likelihood of debris escaping from impact chamber 2115. In some embodiments, impact chamber 2115 may include filter 2116, which provides an outlet for airflow entering impact chamber 2115 via opening 2114. Filter 2116 may be configured to filter out any debris generated by the impact test and carried by the airflow, thereby further preventing debris from escaping from impact chamber 2115. In some embodiments, impact chamber 2115 may be configured to provide environmental control. More specifically, impact chamber 2115 may be configured to control the temperature or other environmental conditions at the impact site to create standardized conditions for impact testing.

[0068] Figure 6The illustration illustrates method 6000, which uses tablet testing equipment to evaluate the strength of a tablet or sample, or a subset of a batch of tablets. The method may include determining how much impact force various tablets can absorb or otherwise withstand before physical breakage. In one embodiment, method 6000 may include determining a relationship between such impact force and physical defect rate, indicating the likelihood that a tablet will experience physical defects in a particular situation or set of situations. In some cases, method 6000 may use this relationship to predict the physical defect rate of another situation and / or another batch of tablets or another tablet type. In one embodiment, method 6000 may be performed by, for example, a manufacturing facility and / or research / development facility for manufacturing pharmaceutical tablets or other tablets, or more specifically by personnel at that facility. In some cases, method 600 may be performed as part of a tablet manufacturing process or tablet (formulation) development.

[0069] In one embodiment, method 6000 may begin with step 6002, or otherwise include step 6002, in which an impact test is performed on a first plurality of tablets or a first plurality of groups of tablets. In some cases, the first plurality of tablets or the first plurality of groups of tablets may be associated with multiple tablet types having different physical properties. In other words, each tablet of the first plurality of tablets may be associated with a corresponding tablet type of multiple tablet types, or each group of tablets of the first plurality of tablets may be associated with a corresponding tablet type of multiple tablet types. For example, if an impact test is performed on the first plurality of tablets, the first plurality of tablets may include a first tablet of a first tablet type (e.g., tablet type 1), a second tablet of a second tablet type (e.g., tablet type 2), and so on. If an impact test is performed on the first plurality of tablets, the first plurality of tablets may include a first group of tablets of a first tablet type (e.g., 10 or 20 tablets), a second group of tablets of a second tablet type, and so on. Thus, impact testing can be used to generate sensor data associated with different types of tablets.

[0070] In some cases, tablet type can be associated with a batch of tablets produced. In other words, tablets in the same batch can belong to a common tablet type. In some cases, the physical properties of tablet type can refer to the physical structure of the tablets associated with that tablet type, such as the shape and / or size of the tablets. For example, the shape of a tablet can refer to whether the tablet has an oval or round shape, and / or whether the tablet has a flat surface. In some cases, the physical properties of a particular tablet or tablet type may be affected by, for example, the formulation of the tablet or tablet type, the shape of the tablet, and / or the method of manufacturing the tablet. The method of manufacturing a tablet can refer to, or be affected by, the parameter values ​​used to manufacture the tablet. For example, if the tablet is based on compressed powder, the parameter values ​​can include the amount of compression pressure used to compress the powder. The powder can be directly compressed, or it can be granulated into particles using dry granulation or wet granulation techniques before compression. In such an example, the method of manufacturing a tablet can affect the physical properties of the tablet or tablet type, such as porosity. In another example, the method of manufacturing a tablet can refer to the use of a coating process on the tablet core, which can subject the tablet core to various forces. In such an example, the way tablets are coated can further affect the physical properties of the tablet or tablet type, such as porosity. In yet another example, the way tablets are manufactured can refer to the use of molding or additive manufacturing, such as 3D printing using, for example, hot melt extrusion.

[0071] In one embodiment, the formulation of a tablet may refer to the materials contained in the tablet, or more generally to the qualitative and / or quantitative composition of the tablet. Materials contained in a tablet may be categorized into one of the following classes: active pharmaceutical ingredient (API) or excipient. Excipients in a tablet formulation may be further classified into one or more of the following categories: fillers, disintegrants, binders (solution binders or dry binders), flow aids, lubricants / anti-sticking agents. (See, for example, MEAulton, Pharmaceutics: The Science of Dosage Form Design, 2nd Edition).

[0072] In one embodiment, describing the qualitative composition of a tablet formulation may list such categories of excipients and / or specific substances. Examples of fillers include: MCC (e.g., MCC Avicel PH 102101, Emcocel 90M, etc.), mannitol (e.g., Perlitol 50c, Perlitol 120c, or Perlitol 160c). Examples of disintegrants include sodium starch glycolate, such as ExploTab or Glycolys LV. Examples of binders include Plasdone K29 / 32, povidone, and Kollidon K30. Examples of flow aids include silica gel and talc. Examples of lubricants include magnesium stearate and benzoyl diglycerides.

[0073] In one embodiment, the quantitative composition may list specific substances and the amount of each substance. The quantity may be expressed as weight or percentage. When fillers are used, the range is, for example, from about 10 to about 75 weight percent (e.g., from about 15 to about 70 weight percent) of the dry formulation; when disintegrants are used, the range is from about 0.5 to 10.0 weight percent (e.g., about 5 weight percent) of the dry formulation; when binders are used, the range is, for example, from about 2 to about 8 weight percent of the dry formulation; when gliding agents are used, the range is from about 0.1 to 10.0 weight percent of the dry formulation; and when lubricants are used, the range is from about 0.25 to 2.5 weight percent of the dry formulation.

[0074] In some examples, fillers (also called diluents / carriers) used in oral formulations (such as formulations in the form of immediate-release tablets) may include dicalcium phosphate, calcium dihydrogen phosphate (including calcium dihydrogen phosphate dihydrate and anhydrous calcium dihydrogen phosphate), calcium trihydrogen phosphate, lactose, microcrystalline cellulose, silicified microcrystalline cellulose, mannitol, sorbitol, starch (such as 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 another diluent / carrier (such as mannitol). In one embodiment, the formulation of an immediate-release tablet may include one or more excipients to improve the physical and / or chemical properties of the final tablet composition and / or facilitate the manufacturing process. This excipient can be used in formulations of oral, immediate-release preparations and may include one or more of the following substances: one or more lubricants (such as magnesium stearate, stearic acid, calcium stearate, stearyl alcohol, or sodium stearyl fumarate); flow aids (such as talc or colloidal silica); one or more binders (such as polyvinylpyrrolidone, microcrystalline cellulose, polyethylene glycol (PEG), polyethylene oxide, low molecular weight hydroxypropyl methylcellulose (HPMC), low molecular weight methylcellulose (MC), low molecular weight hydroxypropyl cellulose (HPC), low molecular weight hydroxyethyl cellulose (HEC), starch (such as corn starch), etc.); and other similar substances. Rice, potato, or rice) or low molecular weight sodium carboxymethyl cellulose; polyvinylpyrrolidone or low molecular weight HPMC used as a binder; one or more pH control agents (such as organic acids (e.g., citric acid) or their alkali metal (e.g., sodium) salts, magnesium oxide, alkali metal or alkaline earth metal (e.g., sodium, calcium, or potassium) sulfates, metabisulfites, propionates, or sorbates); one or more disintegrants (e.g., sodium starch glycolate, croscarmellose, croscarmellose sodium, starch (such as corn, potato, or rice) or alginate); colorants, flavorings, tension modifiers, coating agents, or preservatives.

[0075] For example, in some cases, the tablet composition may include one or more of the following diluents: calcium phosphate (monocalcium phosphate, dicalcium phosphate, and tricalcium phosphate), lactose, microcrystalline cellulose, mannitol, sorbitol, titanium dioxide, aluminum silicate, etc. In some cases, the diluent includes microcrystalline cellulose and mannitol. In some cases, the tablet composition may include one or more of the following lubricants: magnesium stearate, sodium stearoyl fumarate, etc. In some cases, the tablet composition may include a flow aid, 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. Preferred binders include microcrystalline cellulose. In some cases, the tablet composition may contain one or more of the following pH control agents: organic acids (e.g., citric acid) or their alkali metal (e.g., sodium) salts, pharmaceutically acceptable salts of inorganic acids (e.g., carbonates or phosphoric acids, such as sodium, magnesium, or calcium salts), magnesium oxides, and sulfates, metasulfites, propionates, and sorbates of alkali metals and alkaline earth metals (e.g., sodium, calcium, potassium, etc.). Other additional excipients may include colorants, flavoring agents, solubilizers (such as SDS), coating agents, preservatives, etc.

[0076] As another example, a formulation for tablets may include a composition comprising materials such as microcrystalline cellulose (MCC), mannitol (MAN), and / or dicalcium phosphate (CDPA). The formulation may further include a coating surrounding the tablet core, or may not have such a coating.

[0077] Therefore, in one example, different tablet types can refer to different corresponding formulations, or different corresponding combinations of formulation and porosity of the manufactured tablets. For example, Figure 7 The illustration shows various data points 701, 702, 703, 704, 711, 712, 713, 714, 721, 722, 723, 724, 731, 732, 733, 734, respectively, associated with different tablet types (e.g., tablet type 1, tablet type 2, tablet type 3, etc.). In this example, each tablet type can be associated with a specific combination of porosity and a specific formulation. As an example, data point 701 can indicate the peak impact force value of a first tablet type associated with a tablet having a porosity of approximately 7.5% and a formulation in which powder containing mannitol (and without MCC) is compressed to a target tensile strength of 1 MPa to form a tablet with a planar surface. The peak impact force value can indicate how much impact force a tablet of the first tablet type can absorb or otherwise withstand before breaking, as discussed in more detail below.

[0078] In one embodiment, if an impact test is performed on a first plurality of tablets, such an impact test may include, for example, a single tablet of each 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, and so on. In such an example, the impact test may generate, for example, a single peak impact force value, which will be discussed below, indicating the amount of force required to break each tablet. The single peak impact force value may be associated with the corresponding tablet type to which the broken tablet belongs.

[0079] In one embodiment, if an impact test is performed on a first plurality of groups of tablets, the impact test can generate an average peak impact force value for each group. The average peak impact force value for a particular group of tablets can indicate the amount of average force required to break the tablets in that group. For example, if one of the groups includes, for instance, ten tablets associated with a particular tablet type, an impact test can be performed to determine ten corresponding peak impact force values ​​required to break the ten tablets in that group. In such an example, the impact test can be used to determine an average peak impact force value associated with a tablet type, where the average peak impact force value can be the average of ten corresponding peak impact force values.

[0080] As described above, impact testing can be performed using solid dosage form or tablet testing equipment, such as devices 1100, 2100, and 3100. For example, impact testing may include placing a first tablet or solid dosage form of a first plurality of tablets or solid dosage forms at impact sites 2132, 3132 on impact platforms 1130, 2130, and 3130, and centering the first tablet or solid dosage form at impact sites 2132, 3132 using solid dosage form or tablet placement mechanisms 1150, 2150, and 3150. As an example, tablet placement mechanisms 1150, 2150, and 3150 may be moved from the open configuration discussed above to a closed configuration, in which various components of the solid dosage form or tablet placement mechanisms 1150, 2150, and 3150 (such as the first pusher 3151 and the second pusher 3152) are moved closer to impact sites 2132, 3132. A solid dosage form or tablet testing device may have impactor components 1120, 2120, 3120 initially suspended above impact site 2132, and step 6002 may include releasing the impactor components 1120, 2120, 3120 of the solid dosage form or tablet testing device 1100, 2100, 3100 so as to cause the impactor components 1120, 2120, 3120 to fall and impact a first tablet or solid dosage form. For example, the impactor components 1120, 2120, 3120 may be released via a user command input into user input device 2170. In this example, the impact test may also include removing the first tablet or solid dosage form after it has been impacted by the impactor components 1120, 2120, 3120. In some cases, removal may be performed manually. In other cases, removal may be performed automatically. For example, tablet testing device 2100 may include a waste removal device or component. Waste removal equipment or components may include waste filtering components configured to remove tablet debris or other waste from tablet testing equipment 2100, which may have been generated due to impact testing. In some cases, removal may include, for example, moving solid dosage form or tablet placement mechanisms 1150, 2150, 3150 from a closed configuration to an open configuration.

[0081] In one embodiment, the impact test can be repeated for more tablets or solid dosage forms, step 6002. As an example, if the first plurality of tablets comprises ten tablets associated with ten different tablet types, the above operation can be repeated nine times, such that all ten tablets are placed at impact sites 2132, 3132 and impacted by impactor components 1120, 3120, 3120. As another example, if the impact test is performed on ten groups of tablets, each group associated with a different corresponding tablet type and comprising five tablets, the above operation can be repeated forty-nine times, such that all fifty tablets are placed at impact sites 2132, 3132 and impacted by the impactor components. As yet another example, if the tablet testing device includes impactor components with multiple ends, the tablet testing device can perform impact tests on multiple tablets simultaneously. For example, if the impactor component has a 2D array of 5×5 ends (i.e., 25 ends), the tablet testing equipment can perform impact tests on 25 tablets simultaneously, and then repeat the impact test on another 25 tablets, thereby performing impact tests on a total of 50 tablets.

[0082] In one embodiment, the impact test can be performed in a manner that maximizes the probability that each tablet in a first plurality of tablets or a first plurality of groups of tablets will break due to the impact test. For example, the impact test may include impactor components 1120, 2120, 3120 having a sufficient total mass (e.g., 1 kg), and / or being suspended at a sufficient height (e.g., 30 cm) above impact sites 2132, 3132 to ensure that when impactor components 1120, 2120, 3120 are released and fall toward impact sites 2132, 3132, they accumulate sufficient momentum and / or kinetic energy during the fall, such that when the impactor components reach the impact site, the accumulated momentum and / or kinetic energy is sufficient to break the tablet, for example by creating a gap 3300A. In one embodiment, reference is made as follows. Figure 8C In more detail, the computing system 1200 can be configured to detect or determine whether a tablet has actually broken based on sensor data that measures the force distribution during an impact test.

[0083] In one embodiment, method 6000 may include step 6004, which includes measuring a plurality of peak impact force values ​​during an impact test. These peak impact force values ​​indicate the corresponding peak amount of impact force received by a first plurality of tablets or solid dosage forms from impactor components 1120, 2120, 3120 during the impact test, or the corresponding average peak amount of impact force received by a first plurality of groups of tablets or solid dosage forms during the impact test. In some cases, the peak impact force may indicate the peak amount of force experienced by a tablet before breakage during the impact test, or the average of the peak amounts of force experienced by a group of tablets before breakage during the impact test. In this example, the plurality of peak impact force values ​​may be associated with a first plurality of tablet types, respectively.

[0084] As described above, method 6000 may include detecting a tablet or solid dosage form breakage event. This detection operation may include determining whether the force actually caused the tablet to break based on sensor data measuring the impact force applied to it. This determination may be based on an impact force distribution, which may refer to, for example, a function of the force applied to the tablet by the impactor component as a function of time. More specifically, Figure 8E The illustration depicts impact force distributions associated with three cases where three corresponding tablets fractured due to impact forces from an impactor component, and three other cases where three corresponding tablets remained intact despite impact forces from the impactor component. In some embodiments, this determination may include detecting whether the force distribution has a period of time during which the force values ​​remain substantially flat as a function of time and form a smooth shape lasting for a predetermined threshold. Such a shape of the force distribution may indicate that the tablet associated with that force distribution has not fractured. On the other hand, if the force distribution has a shape in which the force values ​​increase toward a peak and then decrease without forming a smooth shape, such a force distribution may indicate that the tablet associated with the force distribution has been broken by the force imparted to it during the impact test.

[0085] In some cases, if an 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, which indicates the peak amount of force imparted to the tablet by the impactor component, or more specifically, how much impact force is involved in breaking a single tablet. In some cases, if an impact test is performed on a group of tablets of a particular tablet type, step 6004 may include measuring a peak impact force value, which indicates the average of the peak impact force values ​​imparted to the group of tablets, or more specifically, the average of the impact forces involved in breaking the group of tablets.

[0086] In some cases, step 6004 may be performed by a sensor data acquisition system (e.g., sensor data acquisition systems 1140, 2140) or with the assistance of a sensor data acquisition system. For example, a strain gauge force sensor 2141 embedded within the impactor component 2120 may measure the corresponding peak impact force for each of the first plurality of tablets or the first plurality of groups of tablets. In this example, step 6004 may also include personnel at a manufacturing or research / development facility and / or computing system (e.g., computing system 1200) receiving sensor data generated by sensor 2141. The sensor data may be received directly from sensor 2141 or via communication circuitry (e.g., communication circuitry 2143).

[0087] Figure 8A and 8B The diagram illustrates a data graph that shows how much force the impactor components 1120, 2120, and 3120 apply to the tablet, for example, tablet 3300, at impact sites 2132 and 3132 at different time points, and / or how much force the tablet is absorbing from the impactor components. This graph can be represented or based on sensor data collected, for example, at step 6004. Figure 8A This can represent the data collected or generated while the impact test is causing the first tablet to break, and Figure 8B This can represent data collected or generated while an impact test is causing a second tablet to break. In one example, when impactor components 1120, 2120, 3120 collide, impart, or otherwise impact a tablet (e.g., tablet 3300), impactor components 1120, 2120, 3120 may suddenly decelerate. Sensor 2141 or some other sensor can measure the degree to which impactor components 1120, 2120, 3120 are accelerating or decelerating at different points in time. This measurement can be used to approximate or otherwise indicate how much force (also called impact force) impactor components 1120, 2120, 3120 are imparting to tablet 3300 as a function of time. More specifically, sensor data can indicate the peak impact force value imparted to tablet 3300 by impactor components 1120, 2120, 3120, and / or the energy absorbed by the tablet from impactor components 1120, 2120, 3120. In some cases, step 6004 may include the calculation system 1200 calculating the force value based on sensor data generated by the sensor data acquisition system (e.g., sensor data acquisition system 2140), such as forming Figure 8A and 8BThe force value of the curve. As described above, the impact test can be performed in a manner that maximizes the probability of each of the first plurality of tablets breaking. As further described above, a computing system or other device can determine whether a tablet actually breaks based on sensor data collected by performing an impact test on the tablets. Therefore, step 6004 may include measuring the peak impact force value associated with causing the first plurality of tablets to break. For example, if step 6004 is based on Figure 8A and 8B If the data is as shown in the figure, then step 6004 may include determining a peak impact force of 799 N associated with breaking the first tablet and a peak impact force of 804 N associated with breaking the second tablet. Figure 8C and 8D The illustration shows an example of the average peak impact force value determined for a set of ten tablets based on various formulations or tablet shapes.

[0088] Figures 9A-9F The figures illustrate peak impact force values ​​that can be measured as a result of step 6006 of method 6000. More specifically, these figures depict curves where the X-axis represents the average peak impact force value associated with causing tablets of different tablet types to break. For example, Figure 9A The graph in the figure represents data showing an average peak impact force of approximately 400 N for a group of tablets associated with tablet type 1. This data point may have been determined, for example, by performing an impact test on a group of, for example, five tablets belonging to or otherwise associated with tablet type 1 in step 6002, and determining the average of the peak impact force values ​​imparted to or absorbed by the five tablets. As described above, the peak impact force value can indicate the maximum force that the five tablets withstand before breaking. In one embodiment, Figures 9A-9F Each can indicate the average peak impact force value associated with tablet type 1 to 10, but can be associated with different circumstances under which a tablet drop test is performed, as discussed in more detail below.

[0089] In some embodiments, instead of measuring the peak impact force value, or in addition to measuring the peak impact force value, step 6004 may include measuring or otherwise determining the amount of energy absorbed by the tablet or solid dosage form during the impact test. Figure 8A and 8B The amount of energy absorbed can be determined by integrating the force values ​​in the diagram, in order to determine... Figure 8A and 8B The area under the curve. For example, Figure 8C and 8DThe illustration shows data indicating both the peak impact force imparted to or absorbed by the tablet and the energy imparted to or absorbed by the tablet. In some embodiments, instead of measuring the peak impact force value, or in addition to measuring the peak impact force value, step 6004 may include measuring the toughness parameters of a first plurality of tablets or a first plurality of groups of tablets. In some cases, the toughness parameters of the tablet may be measured based on calculating the area under the stress-strain curve of the tablet, such as... Figure 10A and 10B The stress-strain curve shown.

[0090] Back Figure 6 In one embodiment, method 6000 may include step 6006, which includes performing a tablet or solid dosage form drop test on the second plurality of tablets or solid dosage forms. The second plurality of tablets may also be associated with the various tablet types discussed above with respect to step 6002. In other words, each of the second plurality of tablets may be associated with a corresponding tablet type among the various 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), a set of tablets (e.g., 100 tablets) belonging to a second tablet type (e.g., tablet type 2), and so on.

[0091] In one embodiment, a tablet drop test may include dropping a second set of tablets onto a solid or other rigid surface and examining the percentage of tablets that break or experience physical defects due to the drop. For example, a tablet drop test may be performed on a set of tablets associated with a specific tablet type by holding the set of multiple tablets (e.g., 100 tablets) above a solid surface and releasing the set of tablets to allow them to fall onto the solid surface. The holding and dropping of tablets may be performed manually or automatically, and may be performed one tablet at a time, or may be performed simultaneously on some or all of the tablets in a set.

[0092] In one embodiment, a tablet drop test can simulate different scenarios of tablet drops. These scenarios can refer to, for example, drop height, number of drops, or combinations thereof. In such embodiments, different scenarios can refer to different drop heights, different drop counts, or different combinations thereof. For example, different scenarios might include: a first combination where the tablet drops only once from a height of one meter; a second scenario where the tablet drops five times from a height of one meter; a third scenario where the tablet drops ten times from a height of one meter; a fourth scenario where the tablet drops only once from a height of two meters; a fifth scenario where the tablet drops five times from a height of two meters; and a sixth scenario where the tablet drops ten times from a height of two meters. These scenarios can be used to generate, for example... Figures 9A-9FThe data shown. For example, a tablet drop test can be performed on a set (e.g., 600 tablets) associated with a specific tablet type (e.g., tablet type 1). In this example, the tablet drop test can include dropping different corresponding subsets of tablets for each of the above scenarios. Thus, in this example, the tablet drop test can include dropping 100 tablets of a first subset onto a solid surface using the first scenario described above; dropping 100 tablets of a second subset onto a solid surface using the second scenario described above; dropping 100 tablets of a third subset onto a solid surface using the third scenario described above; dropping 100 tablets of a fourth subset onto a solid surface using the fourth scenario described above; dropping 100 tablets of a fifth subset onto a solid surface using the fifth scenario described above; and dropping 100 tablets of a sixth subset onto a solid surface using the sixth scenario described above. In the above example, the tablet drop test can include dropping other tablet groups, which can be associated with other tablet types, such as tablet type 2, tablet type 3, etc.

[0093] Back Figure 6 In one embodiment, method 6000 may include step 6008, which may include measuring multiple physical defect rates associated with multiple tablet types based on a tablet drop test. For example, Figure 9A The diagram illustrates data points representing multiple physical defect rates associated with tablet types 1 through 10. For example, a data point indicates that type 1 tablets have a physical defect rate of 69%. Figure 9B-9F Each can indicate a corresponding number of physical defect rates associated with various tablet types, as well as with other circumstances related to the performance of tablet drop tests.

[0094] In one embodiment, measuring the physical defect rate of a tablet type may include automatically or manually counting how many tablets in a subset of a group of tablets or tablets associated with that tablet type broke or otherwise experienced physical defects due to a drop, and calculating the rate or percentage of that group of tablets that experienced physical defects. As an example, if the tablet drop test includes dropping a first subset (e.g., 100 tablets) associated with tablet type 1 from a height of 1 meter only once, as discussed above, step 6008 may include counting how many tablets in that subset broke or experienced physical defects due to a drop. For example, if 69 of the tablets are counted as experiencing physical defects, step 6008 may include determining that when the tablets associated with tablet type 1 are dropped from a height of 1 meter only once, the tablets associated with tablet type 1 have a 69% physical defect percentage (also referred to as the physical defect rate).

[0095] In one embodiment, the plurality of physical defect rates as discussed 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 specific circumstance of tablet drop, such as a combination of drop height and drop count. As an example, Figure 9A This can represent data indicating the first plurality of physical defect rates associated with tablet types 1 to 10, respectively, when a tablet is dropped from a height of 1 meter only once in a tablet drop test. Figure 9B This can represent data indicating a second plurality of physical defect rates associated with tablet types 1 to 10, respectively, when a tablet is dropped a total of 5 times from a height of 1 meter in a tablet drop test. While the above embodiments discuss obtaining physical defect rates based on performing drop tests, any other test can be used to obtain physical defect rates.

[0096] Back Figure 6 In one embodiment, method 6000 may include step 6010, which includes determining a model describing the relationship between the peak impact force values ​​and the physical defect rates based on a plurality of peak impact force values ​​and a plurality of physical defect rates. In one embodiment, the model may include, or may be described by, an equation or function describing the relationship between the peak impact force values ​​and the physical defect rates. For example, Figure 9A The diagram illustrates curve 901, representing the equation or function relating the peak impact force and the physical defect rate. Curve 901, or its corresponding equation, can be determined by performing a curve fitting operation. This operation may include determining the best fit. Figure 9A The curve of the data points in the data. As discussed above, Figure 9A Each data point indicates the corresponding average peak impact force value associated with one of tablet types 1 to 10, and the corresponding physical defect rate associated with the tablet type. The average peak impact force value may have been determined by an impact test, while the physical defect rate may have been determined by a tablet drop test.

[0097] In one embodiment, the model can be determined based on multiple curves or equations, each of which can be associated with specific circumstances of performing a tablet drop test, such as a specific combination of drop height and drop count. For example, the model may include or may be derived from... Figures 9A-9F The curves 901, 902, 903, 904, 905, and 906 describe the situation, or the equations represented by the curves. Curves 901-906 can be associated with different scenarios in which a tablet drop test is performed.

[0098] In one embodiment, method 6000 may include a step of determining a predicted physical defect rate for another tablet drop scenario and / or another tablet type based on the model of step 6010. For example, predictions may be performed for another tablet type (such as tablet type 11) and / or for another combination of drop counts and drop heights (e.g., 5 drops from a height of 1.5 meters, or 4 drops from a height of 2 meters). In some cases, such steps may be performed by personnel at the manufacturing facility and / or by the computing system 1200.

[0099] In some cases, determining such a prediction may include performing an impact test on the 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, assessing the physical strength or robustness of the additional tablet or set of tablets. For example, this step may include performing an impact test on an additional tablet or set of tablets associated with, for example, tablet type 11, and measuring a peak impact force value that indicates the peak amount of impact force received by the additional tablet or set of tablets from the impactor component during the impact test, or more specifically, the maximum force that the additional tablet experiences before breaking during the impact test. In this example, this step may be based on the model discussed above and on the peak impact force value to determine the predicted physical defect rate of tablet type 11. Figure 11A The predicted physical defect rates for various tablet types are depicted, where the prediction can be based on the average peak impact force obtained from performing impact tests on tablets belonging to that tablet type. In some cases, the predicted physical defect rate can be targeted at specific tablet drop scenarios, such as a tablet being dropped five times from a height of two meters. In this case, the prediction may include using curves associated with this scenario, such as... Figure 9E curve 905 or Figure 11B The curve 1105. For example, Figure 11A The prediction may include determining values ​​for the physical defect rates corresponding to, for example, 508N, 234N, and 128N on curve 1105.

[0100] As another example, step 6010 above may include determining a predicted physical defect rate for additional scenarios, such as those different from the tablet drop test scenario described in step 6006. For example, this step may include determining a predicted physical defect rate for tablet type 1, tablet type 2, tablet type 11, tablet type 12, or some other tablet type, for a scenario where tablets of that tablet type are dropped four times from a height of 2 meters. This scenario may differ from... Figures 9A-9F As shown, Figures 9A-9FThis indicates the case where a tablet drop test is performed in step 6006. In such an example, this step may include determining one or more intermediate physical defect rates, which may be physical defect rates associated with the case directly represented by the model in step 6010, and which are closest to the additional cases discussed above. For example, as Figure 9D and 9E As shown, if the additional case refers to the tablet being dropped four times from a height of two meters, the intermediate physical defect rate can include a first physical defect rate associated with the case where the tablet is dropped once from a height of two meters, and a second physical defect rate associated with the case where the tablet is dropped five times from a height of two meters. In this example, the prediction steps discussed above can infer the physical defect rate for the additional case (dropped four times from a height of two meters) based on the intermediate physical defect rate discussed above.

[0101] As discussed above, one aspect of this disclosure relates to using a measurement of the peak impact force involved in causing a tablet to break to assess the physical strength or robustness of a tablet or a batch of tablets, or more specifically, to predict the rate of physical defects in a batch of tablets (or some other parameter indicating the likelihood that the tablets will experience physical defects). More particularly, the peak impact force value can provide a strong indicator or strong predictor of the rate of physical defects that a batch of tablets is likely to experience. For example, Figure 12A The p-value and R-value associated with the peak impact force are depicted. 2 Values ​​and p-values ​​and R-values ​​associated with tensile strength 2 The values ​​are compared using data. The p-value of a parameter can indicate how useful that parameter is for explaining variations in the physical defect rate, or more specifically, whether the parameter supports the hypothesis that the physical defect rate is affected by that parameter. Figure 12A As shown, peak impact force values ​​can have low p-values. Low p-values ​​(e.g., p-values ​​less than 0.05) can indicate a high probability that the null hypothesis is false, such as the null hypothesis that the physical defect rate is unaffected by changes in peak impact force. In other words, a low p-value for the peak impact force can indicate, or at least satisfy, the assumption that the physical defect rate is affected by or related to changes in the peak impact force. Figure 12A Furthermore, the p-value for tensile strength may be much higher than the p-value for peak impact force. A high p-value for a parameter, such as a p-value greater than 0.05, may indicate that the parameter has only a limited effect or no effect on the physical defect rate. Figure 12B Additional data were provided that showed a lack of correlation between tensile strength and physical defect rate in the tablets. Figure 12A Further indications suggest that the fitted curve or equation describing the relationship between peak impact force and physical defect rate has a higher R-value compared to the curve or equation describing the relationship between tensile strength and physical defect rate. 2 A higher R-value is a better value compared to the data points used to perform curve fitting.2 The value can indicate that the fitted curve has a low error level. Figure 12C The figure shows the R-squared value of the fitted curve. 2 The fitted curve is used to attempt to correlate tensile strength with the rate of physical defects. For example... Figure 12C As shown, the R of this curve 2 Values ​​relative to similar Figure 11B The curve of R 2 Lower, Figure 11B The peak impact force is correlated with the physical defect rate. Therefore, Figure 11B , 12A Data from 12C indicates that, compared to other parameters such as tensile strength, peak impact force has a greater impact on the physical defect rate and a greater ability to accurately predict it. More generally, peak impact force can provide a greater ability than other parameters to assess the physical strength or robustness of tablets. Figure 15 This further demonstrates the limited ability of other parameters, such as fragility, to predict physical defect rates. The fragility test is a qualitative test that provides a pass / fail standard for the mechanical strength of a tablet (e.g., pass: no tablets break and weight loss less than 1%, or fail: any single tablet breaks and / or weight loss greater than 1%). This test only provides data under test conditions (fixed drop height and fixed number of drops) and may have little or no ability to infer (more or less the impact) beyond the test conditions. Furthermore, the fragility test may lack the ability to measure the energy absorbed by a broken tablet and therefore may not be able to explain the cause of a particular tablet breaking or fracturing.

[0102] Figure 13 The illustration shows method 13000, which can be performed to predict the physical defect rate using peak impact force values. As discussed in more detail below, method 13000 can be performed based on a model, such as the model determined above using impact tests and tablet drop tests. In some embodiments, method 13000 can be performed by a computing system, such as computing system 1200.

[0103] In one embodiment, method 13000 may include step 13002, wherein computing system 1200 receives a peak impact force value measured by sensors (e.g., 1100, 2100, 3100) of a tablet testing apparatus during an impact test in which an impactor component of the tablet testing apparatus impacts and causes a tablet or a group of tablets to break. The tablet or group of tablets may belong to a specific tablet type, such as tablet type 11. The peak impact force value may indicate the peak amount of impact force received by the tablet or group of tablets from an impactor component (e.g., 1120, 2120, 3120) during the impact test. If the impact test is performed on a group of tablets, the peak impact force value may be the average of the peak values ​​of the amounts of force received by each tablet in that group. In some cases, the peak impact force may be the maximum amount of force a tablet experiences before breaking during the impact test, or the average of the maximum amounts of the maximum forces each tablet in that group experiences before breaking.

[0104] In one embodiment, method 13000 may include step 13004, wherein the calculation system 1200 determines at least one predicted physical defect rate for a tablet type (e.g., tablet type 11) associated with the tablet or a set of tablets used in the impact test, based on the peak impact force value. As discussed above, tablet type is associated with physical properties or a set of physical properties 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 can predict the likelihood that a tablet belonging to that tablet type will break when dropped onto a solid surface.

[0105] In one embodiment, at least one physical defect rate can be determined based on a stored model that describes the relationship between the peak impact force value and the physical defect rate, such as the models discussed above. For example, the model may include, or may be described by, a curve or equation describing the relationship between the peak impact force value and the physical defect rate, such as... Figure 14 The curve shown above illustrates this. As discussed above, peak impact force can describe the peak amount of force imparted to a single tablet, or the average of the peak amounts of force imparted to a group of tablets. Figure 14 In the example, the at least one physical defect rate can be determined as a value on a curve that corresponds to the peak impact force determined in step 13002.

[0106] In one embodiment, the at least one predicted physical defect rate may include a first predicted physical defect rate associated with a specific scenario in which the tablet falls or may fall onto a solid surface, such as when the tablet falls five times and / or from a height of two meters. In some cases, method 13000 may determine multiple predicted physical defect rates for multiple scenarios in which the tablet falls or may fall onto a solid surface. For example, multiple predicted physical defect rates of the tablet may be associated with multiple different drop heights, multiple different drop counts, and / or multiple different combinations of drop heights and drop counts from which the tablet may fall onto a solid surface. As described above, in some cases, making such a prediction may include inferring a predicted physical defect rate based on an intermediate physical defect rate.

[0107] In one embodiment, method 13000 may include determining, based on peak impact force values, the predicted maximum height from which a tablet of a tablet type can be dropped without breaking or the predicted maximum number of times the at least one predicted physical defect rate does not exceed a predetermined defect rate threshold, and / or the predicted maximum number of times a tablet of a tablet type can be dropped without breaking or the predicted maximum number of times the at least one predicted physical defect rate does not exceed a predetermined defect rate threshold. Such determination can be used to evaluate the physical strength or robustness of a tablet or tablet formulation, and / or whether the formulation needs to be adjusted to increase its physical strength.

[0108] While various embodiments have been described above, it should be understood that they are presented merely as illustrations and examples of the art and not as limitations. It will be apparent to those skilled in the art that various changes in form and detail may be made without departing from the spirit and scope of the art. Therefore, the breadth and scope of the art should not be limited by any of the foregoing embodiments, but should be defined solely by the appended claims and their equivalents. It will also be understood that each feature of each embodiment discussed herein and each reference cited herein can be used in conjunction with features of any other embodiment. All patents and disclosures discussed herein are incorporated herein by reference in their entirety.

Claims

1. A computer-aided method for a solid drug dosage form testing device, comprising: An impact test is performed on a first plurality of tablets or a first plurality of groups of tablets, wherein the impact test comprises an impactor component of a solid drug dosage form testing device impacting the first plurality of tablets or the first plurality of groups of tablets and causing them to break, and wherein each of the first plurality of tablets or each of the first plurality of groups of tablets is associated with a corresponding tablet type among a plurality of tablet types having different corresponding physical properties. During the impact test, multiple peak impact force values ​​are measured, which indicate the corresponding peak amount of impact force received by the first plurality of tablets or the first plurality of groups of tablets from the impactor component during the impact test, wherein the multiple peak impact force values ​​are associated with the plurality of tablet types; A tablet drop test is performed on a second set of tablets, wherein the tablet drop test includes dropping the second set of tablets onto a solid surface, wherein each of the second set of tablets is associated with a corresponding tablet type among the multiple tablet types; Based on the tablet drop test, multiple physical defect rates associated with the various tablet types were measured; Based on the multiple peak impact force values ​​and multiple physical defect rates, a model describing the relationship between the peak impact force values ​​and the physical defect rates is determined; and Based on the model, the predicted physical defect rate of one tablet type or additional tablet type among multiple tablet types is determined.

2. The computer-aided method for a solid drug dosage form testing device according to claim 1, wherein, The different physical properties associated with the various tablet types include, for each of the multiple tablet types, at least one of the following: (i) the corresponding formulation of the tablet type, or (ii) the corresponding porosity of the tablet type.

3. The computer-aided method for a solid drug dosage form testing device according to claim 1 or 2, wherein, The plurality of physical defect rates are a first plurality of physical defect rates associated with a first drop height, and the method further includes measuring a second plurality of physical defect rates associated with a second drop height.

4. The computer-aided method for a solid drug dosage form testing device according to claim 1, wherein, The plurality of physical defect rates are a first plurality of physical defect rates associated with a first drop count, the first drop count indicating the number of times a tablet in the second plurality of tablets falls onto the solid surface during a tablet drop test, and wherein the method further includes measuring a second plurality of physical defect rates associated with a second drop count.

5. The computer-aided method for a solid drug dosage form testing device according to claim 1, wherein, Determining the predicted physical defect rate for additional tablet types includes: An impact test is performed on the additional tablets associated with the additional tablet type, wherein the impact test includes an impactor component impacting the additional tablets and causing them to rupture; and An additional peak impact force value is measured, which indicates the peak amount of the fracture impact force received by the additional tablet from the impactor component during the impact test. The predicted physical defect rate of the additional tablet type is determined based on the model and the additional peak impact force value.

6. The computer-aided method for a solid drug dosage form testing device according to claim 1, wherein, The impact test is performed using a solid drug dosage form testing device, which includes: Impactor components; An impact platform, which is configured to provide an impact point; The housing, the impactor component and the impact platform are disposed within the housing, the housing including a mechanism configured to releasably suspend the impactor component above the impact portion within the housing; A sensor data acquisition system comprising one or more sensors, configured to acquire sensor data indicating the velocity or kinetic energy of the impactor component as it is released to fall toward the impact site; and A solid dosage form dispensing mechanism has a first pushing component and a second pushing component connected to the impact platform, wherein the first pushing component has a first recessed portion, the second pushing component has a second recessed portion, and the impact point is located between the first recessed portion of the first pushing component and the second recessed portion of the second pushing component. Wherein, the recessed portion of the first recessed part of the first pushing member extends inward toward the interior of the first pushing member away from the impact portion. Wherein, the recess of the second recessed portion of the second pushing member extends inward toward the interior of the second pushing member away from the impact portion, and The first and second pushing components are configured to move toward each other to position a solid drug dosage form disposed between the first and second recessed portions at the impact site.

7. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The first recessed portion forms a first concave corner, wherein the second recessed portion forms a second concave corner. Furthermore, the first and second pushing components are configured to surround the solid drug dosage form when it is disposed at the impact site.

8. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The first recessed portion forms a groove adapted to receive the second recessed portion when the first pushing member and the second pushing member move toward each other.

9. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The outer casing forms an impact chamber that surrounds the impact region to contain debris generated during impact testing. Furthermore, the solid drug dosage form testing device further includes at least one of the following: (i) an airflow generator configured to generate an airflow that applies pressure to the impact chamber, or (ii) a vacuum configured to generate a negative pressure to prevent debris from leaving the impact chamber.

10. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The impactor component has a rounded end facing the impact site.

11. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The impactor component has a mass of less than or equal to 1 kg.

12. The computer-aided method for a solid drug dosage form testing device according to claim 11, wherein, The impactor component has a mass of less than or equal to 0.5 kg.

13. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to be releasably suspended above the impact site to less than or equal to 120 cm.

14. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to be releasably suspended above the impact site to a height of less than or equal to 110 cm.

15. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to be releasably suspended above the impact site to a height of less than or equal to 100 cm.

16. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to a height of less than or equal to 90 cm, allowing it to be releasably suspended above the impact site.

17. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to a height of less than or equal to 80 cm, allowing it to be releasably suspended above the impact site.

18. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to a height of less than or equal to 70 cm, allowing it to be releasably suspended above the impact site.

19. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to a height of less than or equal to 60 cm, allowing it to be releasably suspended above the impact site.

20. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to a height of less than or equal to 50 cm, allowing it to be releasably suspended above the impact site.

21. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to a height of less than or equal to 40 cm, allowing it to be releasably suspended above the impact site.

22. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to a height of less than or equal to 30 cm, allowing it to be releasably suspended above the impact site.

23. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to a height of less than or equal to 20 cm, allowing it to be releasably suspended above the impact site.

24. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to be releasably suspended above the impact site to a height of less than or equal to 10 cm.

25. The computer-aided method for a solid drug dosage form testing device according to claim 6, wherein, The housing has a maximum distance that limits the impactor component to a height of less than or equal to 5 cm, allowing it to be releasably suspended above the impact site.

26. A computer-implemented method for a solid drug dosage form testing apparatus, comprising: During an impact test, a peak impact force value is received by a sensor of a solid drug dosage form testing device, in which an impactor component of the device impacts and breaks a set of tablets, wherein the peak impact force value indicates the average peak amount of impact force received by the set of tablets from the impactor component during the impact test; and Based on the peak impact force value, at least one predicted physical defect rate is determined for a tablet type associated with a set of tablets used in the impact test, wherein the tablet type is associated with physical properties or a set of physical properties of the set of tablets, and wherein the at least one predicted physical defect rate predicts the likelihood that a set of tablets belonging to the tablet type will break when dropped onto a solid surface.

27. The computer-implemented method for a solid drug dosage form testing apparatus according to claim 26, wherein, Determining the at least one predicted physical defect rate includes determining multiple predicted physical defect rates for the set of tablets, wherein the multiple predicted physical defect rates are associated with multiple different drop heights from which the set of tablets can fall onto the solid surface.

28. The computer-implemented method for a solid drug dosage form testing apparatus according to claim 26 or 27, wherein, Determining the at least one predicted physical defect rate includes determining multiple predicted physical defect rates for the set of tablets, wherein the multiple predicted physical defect rates are associated with multiple different drop counts of the set of tablets, wherein each of the multiple different drop counts indicates the number of times one or more tablets in the set of tablets have fallen onto the solid surface.

29. The computer-implemented method for a solid drug dosage form testing apparatus according to claim 26, further comprising determining, based on the peak impact force value, a predicted maximum height from which a group of tablets of the tablet type can fall without breaking or where the at least one predicted physical defect rate does not exceed a predetermined defect rate threshold.

30. The computer-implemented method for a solid drug dosage form testing apparatus according to claim 26, wherein, The at least one predicted physical defect rate is determined based on a stored model describing the relationship between the peak impact force value and the physical defect rate.

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