JPWO2007100028A1 - Method for inspecting or measuring the strength of a powder compression molding - Google Patents

Abstract

The present invention provides a method for non-destructively inspecting or measuring the properties of powder compression moldings (particularly tablets). More specifically, a method is provided for non-destructively inspecting or measuring the strength of an overall powder compression molding that leads to tablet breakage, breakage, abrasion, and the like. The present invention relates to a method for nondestructively measuring the surface hardness of a powder compression molded product, inspecting or measuring the physical strength of the powder compression molded product, and a method for evaluating the physical strength of the powder compression molded product. About. More specifically, the present invention includes a step of nondestructively measuring the surface hardness at a plurality of points on the surface of the powder compression molded product, and a step of comparing the measured surface hardness of the powder compression molded product. The present invention relates to a method for inspecting or measuring the strength of a powder compression molded product, a method for producing a powder compression molded product comprising the method, and a method for evaluating the fragility of a tablet by the method.

Description

  The present invention relates to a method for inspecting or measuring the physical strength of a powder compression molded product by a non-destructive method, and a method for evaluating the physical strength of a powder compression molded product. More specifically, the present invention includes a step of nondestructively measuring the surface hardness at a plurality of points on the surface of the powder compression molded product, and a step of comparing the measured surface hardness of the powder compression molded product. The present invention relates to a method for inspecting or measuring the strength of a powder compression molded product, a method for producing a powder compression molded product comprising the method, and a method for evaluating the fragility of the powder compression molded product by the method.

Tablets are a type of powder compression molding that is formed by compressing powders and granules, and because they are compact and can keep their weight constant, they can be used for pharmaceutical formulation, food molding, industrial materials and disposal. It is widely applied to make products compact. Tablets must maintain sufficient mechanical strength to maintain their shape until they are used, but quickly disintegrate into a uniform dispersion or solution when used, and each contained in the tablet The function and action of the ingredient must be easily expressed. For this reason, the tablet needs to be prepared so as to have an appropriate hardness and an appropriate disintegration property.
The process of compression-molding the raw material powder to produce tablets, that is, tableting, is carried out by a tableting machine having an upper punch and a lower punch. Usually, granules are often compression-molded. Sometimes. The success or failure of tableting depends on various parameters such as characteristic values such as adhesive force and volume compressibility of the raw material powder, pressure at the time of tableting, compression speed, coefficient of friction with the inner wall of the die, etc. If the parameters are not controlled properly, the moldability will be insufficient and various problems will occur such as clogging, lamination, chipping or coating, etc. It becomes difficult to form a tablet that can withstand. For example, capping where the tablet breaks sideways or lamination where the tablet splits into two or more layers occurs when the raw powder is excessively dried or compressed too quickly, and chipping where the edges of the tablet are missing is excessive. It is said to be generated by compression. In addition to the trouble in the molding process, the quality may be deteriorated due to tablet breakage in the next process due to insufficient molding. Examples of this include poor appearance due to tablet abrasion or surface rubbing in the coating process following the tableting process. These troubles are induced by various factors such as tableting conditions at the time of tableting and the characteristic values of the raw material powder. Therefore, in maintaining the quality as a tablet, the tableting conditions depend on the characteristics of the raw material powder. It is important to accurately set and check and measure whether or not the tablet is properly molded, and evaluate or predict whether or not there is any tableting failure and whether or not the appropriate strength is maintained. .

Various measures have been taken to prevent tableting troubles due to such a lack of moldability. For example, in order to prevent capping, sticking, binding, etc. during tableting, a method using a tableting lubricant containing a hardened oil and fat having an average particle size of less than 20 μm (see Patent Document 1), In order to prevent crushing troubles such as capping and sticking, a method using a lubricant for tablets made of a fatty acid metal salt having a melting point of 145 to 165 ° C. and an average particle diameter of 1 to 20 μm (Patent Document 2) The xylitol content is greater than 90% by weight and the content of one or more other polyols is less than 10% by weight to improve the hardness, impact resistance and capping properties of the resulting tablets. A method using a directly compressible tableting aid, characterized by being produced by spray drying or fluid bed granulation (see Patent Document 3), sticking, A method of incorporating the tablet for the preparation of granules in order to prevent the tableting trouble such as ping fats such as vitamin E with 30% less (see Patent Document 4) have been reported.
There have been many reports on measures for preventing tableting troubles and insufficient moldability. However, there has been no report on a method for accurately evaluating or predicting whether or not the tableting has been properly formed by inspecting and measuring the occurrence frequency of tableting failure, moldability and related tablet strength.

  In addition, the compression rupture method hardness measurement test and the friability test have been used to evaluate the physical strength of tablets. Since these tests are destructive measurements, tablets after measurement should be used. There was an inconvenience that it was not possible. For this reason, attempts have been made to measure the physical strength of tablets without breaking the tablets. For example, there is a certain correlation between the integrated value of the near-infrared absorption rate of a tablet and the hardness of the entire tablet, and a method for measuring the overall hardness of one tablet nondestructively by the absorption rate of near-infrared has been proposed ( (See Patent Document 5). In addition, there is a correlation between the Young's modulus measured by using an ultrasonic hardness meter (Young's modulus meter) and the hardness measured by using a Monsanto hardness meter. There is also a report that it can be measured (Non-Patent Document 1).

Japanese Patent Laid-Open No. 2005-126397 JP 2004-131398 A JP-T-2001-519378 Japanese Patent Laid-Open No. 11-178895 Japanese National Patent Publication No. 10-509796 22nd Symposium on Formulation and Particle Design Symposium 2005 p.74-76

  The present invention provides a method for non-destructively inspecting or measuring the properties of powder compression moldings (typically tablets). More specifically, a method is provided for non-destructively inspecting or measuring the overall tablet strength that leads to tablet breakage, breakage, wear and the like.

Conventionally, inspection and measurement of the physical strength of a tablet have been focused on the hardness and friability of the whole tablet, and a compression fracture hardness test and a friability test have been used. In the nondestructive test, only the surface hardness of the tablet has been measured.
The present inventors have measured the surface hardness of a tablet, but surprisingly found that the surface hardness is not constant depending on the tablet, and the surface hardness may vary depending on the measurement position of the tablet. As a result of further investigation, if there is a difference in surface hardness between the upper surface of the tablet and the lower surface on the opposite side, the tablet is likely to crack or break, and the tablet moldability is improved. It was found that capping is likely to occur during tableting.
Such measurement of surface hardness of two or more points can be achieved for the first time by nondestructive testing of tablets. Even if the hardness of the whole tablet can be measured by conventional destructive testing, It was not possible to measure the partial strength at a plurality of locations and compare the difference in hardness of each portion. Further, the reported nondestructive test only discloses that only the whole hardness of one tablet can be measured. Even if the overall hardness of a tablet is related to the resistance to the compression force and the friability, the index related to the frequency of occurrence of cracking / breakage against impact and the frequency of capping during tableting is not necessarily I couldn't.
That is, the present inventors have found an index of overall physical strength related to the presence or absence of cracking, rubbing, or breakage of a tablet, particularly the presence or absence of capping during tableting, and found an inspection method and a measurement method thereof. .
More specifically, the present inventors have conducted intensive research on a method for evaluating the occurrence of capping during tableting, and as a result, measured the surface hardness of two points on the tablet surface with an ultrasonic hardness meter, and the measurement It was found that the strength of the tablet can be more accurately evaluated based on the value, and the present invention was completed.
Furthermore, the present invention is not limited to tablets, but, for example, powders such as solid preparations such as bathing agents, slug tablets and pellets produced in an intermediate process in the pharmaceutical and food fields, and uncoated tablets that are the core of coated tablets It can be applied to molded products.

That is, the present invention relates to a step of nondestructively measuring the surface hardness at any of a plurality of points on the surface of the powder compression molded product, that is, two or more points, and the surface of the measured powder compression molded product. The present invention relates to a method for inspecting or measuring the strength of a powder compression molding including a step of comparing hardness.
The present invention also non-destructively measures the hardness at a plurality of points on the surface of the powder compression molding formed by compressing the powder, and the measured surface hardness of the powder compression molding And a method of inspecting or measuring the strength of the powder compression molded product.
Furthermore, the present invention includes a step of nondestructively measuring the surface hardness at a plurality of points on the surface of the powder compression molded product, and a step of comparing the measured surface hardness of the powder compression molded product. The present invention relates to a method for evaluating the fragility of a powder compression molded product by a method for inspecting or measuring the strength of a body compression molded product.

The present invention will be described in more detail as follows (1) to (18).
(1) Powder compression molding including a step of nondestructively measuring the surface hardness at a plurality of points on the surface of the powder compression molding, and a step of comparing the surface hardness of the measured powder compression molding A method for inspecting or measuring object strength.
(2) The method described in (1) above, wherein any plurality of points on the surface of the powder compression-molded product are selected from the opposite surfaces of the powder compression-molded product.
(3) The method described in (1) or (2) above, wherein any plurality of points on the surface of the powder compression molded product are two points.
(4) One of the two arbitrary points on the surface of the powder compression molding is one point near the center of the upper surface of the powder compression molding, and the other one is one point near the center of the opposite surface, The method described in (3).
(5) The step of comparing the surface hardness of the measured powder compression molding is a step of comparing the maximum value and the minimum value of the measured surface hardness of the powder compression molding. The method described in any one of (4).
(6) The method described in any one of (1) to (5) above, wherein the inspection or measurement of the strength of the powder compression molded product is for evaluating the moldability of the tablet.
(7) The method described in any one of (1) to (6) above, wherein the inspection or measurement of the strength of the powder compression molded product is for evaluating the capping property of the tablet.
(8) Any one of the above (1) to (7), wherein the nondestructive measurement of the surface hardness of the powder compression molded product is measured using an ultrasonic hardness meter (Young's modulus meter). The method described in one.
(9) The method according to any one of (1) to (8), wherein the powder compression-molded product is a tablet.
(10) The method described in (9) above, wherein the tablet is a pharmaceutical composition.
(11) Nondestructively measure the hardness at a plurality of points on the surface of the powder compression molding formed by compressing the powder, and compare the measured surface hardness of the powder compression molding A method for producing a powder compression molded product, comprising a step of inspecting or measuring the strength of the powder compression molded product.
(12) At least one point of a plurality of arbitrary points on the surface of the powder compression molded product is one point near the center of the upper surface of the powder compression molded product, and the other point is one point near the center of the opposite surface. The method described in (11) above.
(13) The nondestructive measurement of the surface hardness of the powder compression molded product is described in (11) or (12) above, which is measured using an ultrasonic hardness meter (Young's modulus meter). Method.
(14) The step (11) to (13), wherein the step of inspecting or measuring the strength of the powder compression molding is a step of inspecting or measuring the total number of powder compression moldings molded by compressing the powder. The method as described in any one of these.
(15) including the step of selecting only the powder compression molded product in which no abnormality is found in the step of inspecting or measuring the strength of the powder compression molded product and modifying the selected powder compression molded product (11) ) To (14).
(16) including the step of selecting only the powder compression molded product in which no abnormality is found in the step of inspecting or measuring the strength of the powder compression molded product and coating the selected powder compression molded product (11) ) To (15).
(17) The method according to any one of (11) to (16), wherein the powder compression molded product is a tablet.
(18) The method described in (17) above, wherein the tablet to be measured is a pharmaceutical composition.

The present invention focuses on a mechanical imbalance in a powder compression molded product (particularly a tablet) formed by compressing a powder and provides a new index for inspecting, measuring or evaluating the strength of the powder compression molded product. It is to provide.
Conventionally, as a method for measuring the strength of a tablet, a compression fracture hardness measurement test and a friability test have been used, but these test methods are methods in which a tablet is broken and examined, and as a whole tablet The strength was only measured, and the mechanical imbalance (bias) in one tablet could not be examined. In addition, methods for measuring the effective fracture envelope of raw materials have been devised for the purpose of preventing tablet breakage, rubbing, breakage, and obstruction at the time of tableting, but not only the measurement is complicated, but also several types of raw materials. The predictability when using a mixture of substances was extremely poor. For this reason, it has been considered difficult to measure the mechanical imbalance (bias) in a tablet that has been compressed by a conventional measurement method, and the mechanical imbalance in a tablet that has been compressed in the first place. There was no prediction that there was (bias). Furthermore, it has not been predicted that the strength of the tablet can be evaluated by the method provided by the present invention.
In addition, the physical properties (hardness and friability) obtained in the conventional compression rupture method hardness measurement test and friability test are not necessarily correlated with the frequency of capping, and the presence or absence of capping during tableting can be determined from these physical properties. It was extremely difficult to predict accurately.

Non-Patent Document 1 describes an ultrasonic hardness meter (Young's modulus meter). This ultrasonic hardness meter (Young's modulus meter) uses a piezoelectric ceramic element (PZT), and is a piezoelectric for vibration. By combining the element (vibrator) and the vibration sensing piezoelectric element (pickup), the output based on the vibration sensed by the pickup is returned to the vibrator by the feedback circuit, and the change is output to measure the Young's modulus of the subject. To do. According to Non-Patent Document 1, there is a correlation between the Monsanto hardness of the tablet and the Young's modulus measured by the ultrasonic hardness meter (Young's modulus meter) (correlation coefficient is 0.86 to 0.99). It is disclosed that the surface hardness of the tablet can be measured by the ultrasonic hardness meter (Young's modulus meter). The correlation coefficient described in Non-Patent Document 1 is quite high, and the surface hardness of the tablet can be measured with high reliability with the ultrasonic hardness meter (Young's modulus meter). In Non-Patent Document 1, the contact pressure of the ultrasonic hardness meter (Young's modulus meter) used for the measurement was 24 g, but by changing the contact pressure and contact depending on the type of tablet and the state of the surface. Further, it is described that the hardness of a wider range of tablets can be measured.

Therefore, the inventors made two types of tablets, tablet A and tablet B, and measured the hardness and Young's modulus of these tablets. The results are shown in Table 1 below.

Each measurement used 5 tablets. As for “convex surface 1” in Table 1, the larger measured value on the two convex surfaces of the tablet is “convex surface 1”.
As a result, there was a correlation as disclosed in Non-Patent Document 1 between the hardness of the tablet and the measured Young's modulus. Surprisingly, the value of the Young's modulus differs depending on the measurement position of the tablet. I understood it. For example, the difference in Young's modulus between convex surface 1 and convex surface 2 was 0.90 GPa for tablet A, and 0.86 GPa for tablet B. Further, the measurement on the side surface showed a value more than twice the value of the convex surface 1.

The inventors further examined what this difference is due to. Therefore, as a result of preparing and examining various tablets, it was found that these differences are related to the strength of the tablets. For this purpose, the present inventors made several tablets C that may be damaged by impact, and the time (minutes) required for the damage in the friability test on four tablets arbitrarily selected from the prepared tablets. ) And the measured Young's modulus. The results are shown in Table 2 below.

“> 60” in Table 2 indicates that no damage occurred even at 60 minutes. “Convex surface 1” has the same meaning as in Table 1 above.
As a result, the tablets C1 and C2 having a small difference between the measured values of the convex surface 1 and the convex surface 2 did not break even at 60 minutes, but the tablets C3 and 4 having a large difference caused lateral cracking at 30 minutes and capping. Damaged.
From these facts, a large difference in the measured values of the surface hardness at multiple points of the tablet indicates that the tablet strength is not sufficient, and the difference in the measured values of the surface hardness is useful for evaluating and predicting the presence or absence of breakage or capping of the tablet. It became clear that it became an indicator.

  The present invention is characterized in that, firstly, a powder compression molded product is measured nondestructively, and secondly, the measurement is performed at a plurality of two or more points. And thirdly, it is characterized by comparing the measured values at these points, and fourthly, the strength of the powder compression molding can be evaluated based on the measured values compared. It is characterized by clarifying what can be done.

The powder compression molded product in the present invention is not particularly limited as long as it is formed by compressing an amorphous solid such as a granule or a powder into a certain shape. The method for forming a powder compression molded product by compressing the powder may be any method such as a dry method, a wet method, a semi-dry method, an extrusion method, and a rolling method. Moreover, there is no restriction | limiting in particular in the shape shape | molded, Any shape, such as a disk shape, a lens shape, and an ellipse, may be sufficient. The powder compression molded product in the present invention is preferably a tablet, but is not limited thereto. For example, it may be a solid agent such as a bath agent, a slag tablet and a pellet produced in an intermediate process in the pharmaceutical and food fields, and an uncoated tablet that is the core of a coated tablet. As the tablet of the present invention, since the surface hardness of the tablet is nondestructively measured, a tablet in which the component to be measured is exposed on the surface is preferable. Although the uncoated tablet which compressed and shape | molded the granule and powder is preferable, it is not limited to this. For example, when measuring the coating state of a film-coated tablet or a sugar-coated tablet, it may be a film-coated tablet or a sugar-coated tablet.
Further, the method of the present invention measures, inspects and evaluates the strength of a powder compression molded product, and is not limited to the use as a control for use of tablets, but is used for pharmaceuticals, agricultural chemicals, foods, industrial materials. The present invention can be applied to powder compression moldings in all fields. Preferred applications include, but are not limited to, tablets that require strict specifications (especially tablets that are pharmaceutical compositions).

The strength of the powder compression molded product of the present invention is different from the hardness of a tablet measured by a conventional method, and means a physical strength capable of maintaining a constant shape of the tablet until use, It means a physical or mechanical strength that can prevent the tablet from being unable to maintain a certain shape due to rubbing, chipping or cracking. In addition, physical strength that can serve as an index of capping and lamination during tableting and tablet rubbing that occurs in the coating process is also included in the strength of the powder compression molded product of the present invention.
The surface hardness of the powder compression molded product in the present invention is the hardness of a local portion of a tablet measured by a nondestructive method such as ultrasonic waves, and may be expressed as “surface hardness”. “Hardness” in the expression “surface hardness” does not necessarily coincide with “hardness” such as hardness measured using a conventionally known Monsanto hardness tester. It may be a value derived from a measured value measured by a destructive method. Therefore, a measured value measured by a nondestructive method such as ultrasonic waves can be used as it is as the surface hardness or surface hardness of the present invention, or the measured value can be converted and used.
The plurality of points on the surface of the powder compression molded product in the method of the present invention is not particularly limited as long as it is 2 points or more, but the method of the present invention is a mechanical imbalance in one powder compression molded product. Since the purpose is to examine (bias), it is preferable to select a position as different as possible as the measurement point. Further, the number of measurement points is preferably as many as possible, but it is preferable to select a small number of efficient measurement points because of the complexity of measurement and the complexity of comparison of measurement values. Preferable measurement points include one point on each of the upper surface of the tablet and the lower surface on the opposite side. More preferably, there are one point near the center (convex surface) of the upper surface of the tablet and one point near the center (convex surface) of the lower surface of the opposite surface. In addition, when manufactured tablets are continuously manufactured by moving on a conveyor or the like, the surface of the tablets can be measured from above and below on a part of the conveyor, A part or all of the lower surface can be continuously measured simultaneously with part or all.

The non-destructive measurement in the present invention is not particularly limited as long as the physical properties of the surface of the powder compression molded product, preferably the surface hardness can be measured without destroying the powder compression molded product. Examples include irradiating the surface of a powder compression molded product with ultrasonic waves or near infrared rays, and measuring the absorption rate or reflected wave. The nondestructive measurement method may be either a non-contact method or a contact method. Examples of the nondestructive surface hardness measurement method based on the near-infrared absorptance include the method described in Patent Document 5, and the nondestructive surface hardness measurement method using ultrasonic waves is disclosed in Non-Patent Document 1. The methods described are mentioned. The descriptions of these documents are incorporated herein by reference.
A preferable non-destructive measurement in the method of the present invention includes an ultrasonic hardness meter (Young's modulus meter) described in Non-Patent Document 1. In this case, it is not necessary to convert the measured Young's modulus to hardness, and the measured Young's modulus value can be used as it is as the parameter value of the surface hardness in the present invention. This is because in the present invention, the absolute value of the measured value is also important for confirming the strength of the powder compression molded product, but at the same time, the relative relationship between these measured values is also important. is there.

The step of comparing the measured surface hardness of the tablet in the present invention can be performed by calculating a difference or quotient (ratio) of the measured values and comparing this value with a standard value. The allowable limit depends on the shape and composition of the powder compression molding to be measured and the position to be measured, so determine the measurement position for a specific powder compression molding. To produce powder compression moldings with appropriate strength and tablets that may break, determine their standard values (standard values), and determine acceptable limits from these standard values. is necessary. For example, according to the experimental results shown in Table 2 above, according to the difference between the convex surface 1 and the convex surface 2, when the difference is at least 2.5 or more, the tablet has insufficient tablet strength and is damaged. However, when the difference is 1.8, it is determined that the tablet does not break and has sufficient tablet strength (see tablet C1 in Table 2). In this way, the comparison can be made based on the difference between the measured values, and similarly, the determination can be made based on the ratio between the two. For example, in the example of Table 2, if the ratio of the convex surface 1 to the convex surface 2 is at least 0.36 or more, it is determined that the tablet has sufficient tablet strength without breakage (see tablet C1 in Table 2). However, if the ratio is 0.19 or less, the tablet has insufficient tablet strength and breaks (see tablet C3 in Table 2). It is also possible to determine by combining such difference and quotient (ratio). Which method is used to create the determination standard can be appropriately determined experimentally according to the type of powder compression molding and the measurement position.
Of course, it is also important that the surface hardness of the powder compression molded product has a certain value or more. This is because the moldability of the powder compression molded product may not be maintained unless the powder compression molded product has a surface hardness of a certain value or more. For example, as shown in Table 7 below, if the absolute value is small even if only the difference in surface hardness or quotient at the two measured points is in a preferable state, the moldability of the powder compression molded product It is because it becomes impossible to maintain. As described above, it is also important to evaluate the moldability of the powder compression molded article in consideration of not only the relative relationship of the measured values but also the absolute value of the measured values.
Furthermore, if a determination criterion can be obtained by experiment, it can be programmed, and the measured value can be input to compare the surface hardness of the powder compression molded product with a computer such as a personal computer.

The method of the present invention comprises nondestructively measuring the surface hardness at two or more points on the surface of the powder compression molding and evaluating the measured surface hardness of the powder compression molding and / or The strength of the powder compression molding is characterized by a non-destructive inspection or measurement method, and the fragility of the powder compression molding can be evaluated by this method. That is, the surface hardness at two or more points on the surface of the powder compression molded product is measured nondestructively, and the measured value is evaluated and / or the difference or quotient (ratio) as a result of comparison is determined by powder compression. It can be used as an index of the fragility of the molded product. Although the absolute hardness of the powder compression molding is necessary to maintain the moldability of the powder compression molding, the present invention is not limited to the overall physical strength of the powder compression molding. In addition, the present invention provides a novel concept on the formulation that a partial physical strength imbalance (bias) of a powder compression molded product can be used as a new index of tablet strength.
Furthermore, the method of the present invention is a non-destructive method, and the method of the present invention can be directly incorporated into the production process of a conventional powder compression molded product. Therefore, the present invention also provides a method for producing a powder compression molded product in which the method of the present invention is incorporated. The method for inspecting or measuring the strength of the powder molded product of the present invention can be provided during any step in the conventional tablet production method, but it is preferably incorporated after the step of tableting to obtain an uncoated tablet. By providing a step in which the inspection or measurement method of the present invention can be carried out on a part of the continuous flow of manufactured tablets, the tablet strength can be confirmed for all or a part of the manufactured tablets. . And if necessary, a step of removing a tablet with insufficient tablet strength from the production line based on the result of the inspection or measurement can be provided. Moreover, the method of this invention is not limited to a plain tablet, It can apply as a method of test | inspecting or measuring the deviation of the surface hardness of a film coat tablet or a sugar-coated tablet surface.
Furthermore, when manufacturing a film-coated tablet or a sugar-coated tablet, the uncoated tablet is modified by incorporating the step of carrying out the inspection or measuring method of the present invention after the step of obtaining the uncoated tablet (ie, film coating or Only tablets with no abnormalities (ie, tablets with sufficient tablet strength) can be selected.

The present invention is a novel formulation based on the fact that not only the overall physical strength of a tablet but also the partial physical strength imbalance (bias) of the tablet can be used as a new indicator of tablet strength. It provides a concept and can not only measure the surface hardness of the tablet non-destructively but also examine or measure the physical strength of the tablet. Therefore, the method of the present invention enables more thorough quality control as a tablet product. In addition, since the method of the present invention is a non-destructive method, it is possible to reduce the destruction of useless products, resulting in an economic merit.
Furthermore, the method of the present invention is not only simple, but also can quantify tablet strength, enables quality control by a computer, and provides a more objective index of tablet strength.

  EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, this invention is not limited at all by these Examples.

(1) Manufacture of test tablets A and B Using the components of the types and amounts shown in Table 3, the following tablets A and B were manufactured by the following method.
N- (1-octyl-5-carboxymethyl-4,6-dimethylindoline-7-yl) -2,2-dimethylpropanamide (US Pat. No. 6,063,806; hereinafter referred to as “Compound A”), lactose, crospovidone Then, ascorbic acid and tartaric acid were added and mixed with a high-speed stirring granulator, and the resulting mixture was sprayed with a hydroxypropylcellulose aqueous solution with a fluidized bed granulator. The resulting granulated product is dried using a fluidized bed dryer, and the dried granulated product is forced to pass through a screen using a granulator, and low-substituted hydroxypropylmethylcellulose, calcium silicate, stearic acid Magnesium was added and mixed with a diffusion mixer.

The obtained mixture was tableted using a rotary tableting machine equipped with an open feeder, and tablet B was tableted using a rotary tableting machine equipped with a stirring feeder under the conditions shown in Table 4, respectively. A double R punch having a diameter of 9.5 mm was used as the punch for tableting.

(2) Measurement of Young's modulus The Young's modulus of 5 tablets arbitrarily selected from each of the tablets A and B prepared in (1) above and the tablet B5 tablet prepared in (2) above were respectively measured by Axim Corp. It measured using the sonic hardness meter (Young's modulus meter).
To measure, fix the tablet to the measurement table so that the tablet measurement position is at the top, and place it so that it is directly under the probe tip of the ultrasonic hardness tester (Young's modulus meter) fixed to the stand. The tip was pressed vertically to measure. About each tablet, it measured about two places of the convex surface of the upper and lower sides of a tablet, and the side of a tablet.
(3) Measurement of tablet hardness The hardness of the tablet after measuring the Young's modulus of (2) above was measured by a usual method using a compression fracture hardness tester.
(5) Results About the hardness and Young's modulus of tablet A and tablet B, 5 tablets each were measured, and the average value thereof was calculated. The results were as shown in Table 1 above.

(1) Production of test tablet C Tablet C was produced by the following production method using the same formulation as tablet A shown in Table 3.
Lactose, crospovidone, ascorbic acid and tartaric acid were added and mixed with a high-speed stirring granulator, and the resulting mixture was sprayed with a hydroxypropylcellulose aqueous solution with a fluid bed granulator. The resulting granulated product is dried using a fluidized bed dryer, and the dried granulated product is forced to pass through a screen using a granulator, and low-substituted hydroxypropylmethylcellulose, calcium silicate, stearic acid Magnesium was added and mixed with a diffusion mixer.
The obtained mixture was tableted under the tableting conditions shown in Table 5 using a rotary tableting machine equipped with a stirring feeder and a double R punch having a diameter of 9.5 mm.

(2) Measurement of Young's modulus The Young's modulus of four tablets arbitrarily selected from the tablets C produced in the above (1) were measured using an ultrasonic hardness meter (Young's modulus meter) manufactured by Axim.
To measure, fix the tablet to the measurement table so that the tablet measurement position is at the top, and place it so that it is directly under the probe tip of the ultrasonic hardness tester (Young's modulus meter) fixed to the stand. The tip was pressed vertically to measure. For each tablet, two locations on the upper and lower convex surfaces of the tablet were measured.
(3) Measurement of time until breakage by friability test After the measurement of (2) above, each of tablets C1 to C4 is in accordance with the method described in the Japanese Pharmacopoeia (14th revision). The friability test was conducted by the method described above. The time to breakage was determined by observing whether or not the tablet was broken every 60 minutes until 60 minutes from the start of the test, and the time when the tablet breakage was confirmed was defined as “time to breakage due to friability test”.
(4) Results The Young's modulus of each of the tablets C1 to C4 and the time until breakage by the friability test were as shown in Table 2 above.

Experimental example 3

(1) Manufacture of trial tablet D Tablets D1-D4 were manufactured by the following manufacturing method using the formulation shown in the following Table 6.
After mixing crystalline cellulose, low-substituted hydroxypropylcellulose, light anhydrous silicic acid, magnesium stearate, and talc with a diffusion mixer, the tablet weight is about 1000 mg with a rotary tableting machine equipped with a stirring feeder. Tableted. The obtained tablets were crushed with a granulator to obtain granules for tableting. Next, after mixing the obtained granules for tableting with a diffusion mixer, using a rotary tableting machine equipped with a stirring feeder, a double R punch having a diameter of 8.5 mm is prepared so that the tablet mass becomes 250 mg. Used for tableting at various tableting pressures.

(2) Measurement of Young's modulus The Young's modulus of the tablet D produced in the above (1) was measured using an ultrasonic hardness meter (Young's modulus meter) manufactured by Axim.
To measure, fix the tablet to the measurement table so that the tablet measurement position is at the top, and place it so that it is directly under the probe tip of the ultrasonic hardness tester (Young's modulus meter) fixed to the stand. The tip was pressed vertically to measure. For each tablet, two locations on the upper and lower convex surfaces of the tablet were measured.
(3) Evaluation of worn ratio After the tablet whose mass was measured was shaken for 2 minutes at a speed of 250 times per minute in a plastic tube, the mass was measured again. The change in mass before and after the shaking was calculated as the ratio of wear.
(4) Evaluation of tablet rubbing Tablets were put into pan coating, and after rotating the pan for 20 minutes, the tablets were taken out and visually evaluated for the degree of tablet rubbing.

(4) Results The Young's modulus of each of the tablets D1 to D4, the ratio of abrasion, and the rubbing of the tablets are as shown in Table 7 above. The confirmed tablet rubbing was also found to be small. Therefore, when the surface hardness of both surfaces was measured and the difference between them was small and the value was high, it was found that troubles due to tablet formability in the coating of the process can be avoided, and tablets of good quality can be obtained.

  In the present invention, the partial physical strength imbalance (bias) of the powder compression molding is not the overall physical strength of the powder compression molding (particularly tablet), but the strength of the powder compression molding. It provides a new concept on the formulation that can be used as a new index of the product, and it is possible to perform more thorough quality control as a product of the powder compression molding product. In addition, since the method of the present invention is a non-destructive method, it is possible to reduce the destruction of useless products, such as the pharmaceutical industry, the agricultural chemical industry, the food industry, etc. that manufacture powder compression moldings (especially tablets) The present invention is extremely useful in a wide range of industrial fields, and the present invention has industrial applicability.

Claims (18)

  The strength of the powder compression molding comprising the steps of non-destructively measuring the surface hardness at a plurality of points on the surface of the powder compression molding and comparing the measured surface hardness of the powder compression molding. How to inspect or measure.   The method according to claim 1, wherein any of a plurality of points on the surface of the powder compression molding is selected from the opposite surfaces of the powder compression molding.   The method according to claim 1 or 2, wherein any plurality of points on the surface of the powder compression molding product are two points.   Any one of two points on the surface of the powder compression molding is one point near the center of the upper surface of the powder compression molding, and the other one is one point near the center of the opposite surface. The method described in item 3.   The step of comparing the surface hardness of the measured powder compression molding is a step of comparing the maximum value and the minimum value of the measured surface hardness of the powder compression molding. A method according to any one of the paragraphs.   The method according to any one of claims 1 to 5, wherein the test or measurement of the strength of the powder compression molded product is for evaluating the moldability of the tablet.   The method according to any one of claims 1 to 6, wherein the inspection or measurement of the strength of the powder compression molded product is for evaluating the capping property of the tablet.   The non-destructive measurement of the surface hardness of the powder compression molded product is measured using an ultrasonic hardness meter (Young's modulus meter), according to any one of claims 1 to 7. The described method.   The method according to any one of claims 1 to 8, wherein the powder compression molded product is a tablet.   The method according to claim 9, wherein the tablet is a pharmaceutical composition.   Nondestructive measurement of the hardness at any point on the surface of a powder compression molding formed by compressing the powder, and comparing the measured surface hardness of the powder compression molding A method for producing a powder compression-molded product, comprising a step of inspecting or measuring the strength of the compression-molded product.   At least one point of any of a plurality of points on the surface of the powder compression molding is one point near the center of the upper surface of the powder compression molding, and the other point is one point near the center of the opposite surface. A method as described in paragraph 10 of the above.   The method according to claim 11 or 12, wherein the nondestructive measurement of the surface hardness of the powder compression molded product is measured using an ultrasonic hardness meter (Young's modulus meter).   The step of inspecting or measuring the strength of the powder compression molded product is a step of inspecting or measuring all or part of the powder compression molded product formed by compressing the powder. A method according to any one of the paragraphs.   12. The method according to claim 11, comprising a step of selecting only a powder compression molded product in which no abnormality is found in the step of inspecting or measuring the strength of the powder compression molded product and modifying the selected powder compression molded product. 15. The method according to any one of items 14 to 14.   12. The method according to claim 11, further comprising: selecting only a powder compression molded product in which no abnormality is found in the step of inspecting or measuring the strength of the powder compression molded product, and coating the selected powder compression molded product. 16. The method according to any one of items 15 to 15.   The method according to any one of claims 11 to 16, wherein the powder compression molded product is a tablet.   The method according to claim 17, wherein the tablet to be measured is a pharmaceutical composition.