<>/Border[0 0 0]>>
0000014078 00000 n Gaster D Tablets 20mg, 11. 0000014687 00000 n
This study shows that all the tested products, which are clinically available in Japan, showed good disintegration and that the disintegration time varied according to the product. 0000007844 00000 n
Improved disintegration of ODTs has been achieved by increasing the porosity to let the liquid penetrate the tablet easily, and by using disintegrants that have excellent water absorption and wetting capacities.12) Thus, the hardness, diameter, thickness, and weight of ODTs are not likely to be major factors that influence disintegration time. 0000008554 00000 n
(2) Orally disintegrating tablets have appropriate disintegration properties. All volunteers who provided written informed consent participated in the study. 0000001691 00000 n
0000003323 00000 n
www.plosone.org 8*qTEYZccld".Y)&:.Ye1Kt'ra,'r.0%)EH}`EYd$q`\ hQr"*K0Xi/$ 7> gq$ersOdAbl(1C_7 '2a cfL3}bFQ8 ':,@Lb} [-b (O@4r EQ Randale S, Dabhi C, Tekada A, Belgamwar V, Gattani S, Surana S. Rapidly disintegrating tablets containing taste masked metoclopramide hydrochloride prepared by extrusion-precipitation method. endobj 
0000077986 00000 n
<>/Border[0 0 0]>> On the other hand, the compendial disintegration test does not seem to accurately reproduce the disintegration behavior of ODTs in the oral cavity as the test is carried out in a large volume of test solution (i.e., 900mL). Similarly, the in vitro disintegration times of the 26 clinically used ODT products ranged between 4.4 and 30.4s. Currently, there are couples of apparatus for measuring disintegration time of ODTs. Promac D tablets 75 (Zeria Pharmaceutical Co., Ltd.), Magmitt Tab 330mg (Kyowa Chemical Industry Co., Ltd.), Magmitt Tab. H\j0z 2020-12-31 Bi Y, Sunada H, Yonezawa Y, Danjo K, Otsuka A, Iida K. Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity. 10.1371/journal.pone.0244646 endobj ODTs, which can be taken without water, can be taken even when water is not readily available at work, or when the patient does not want his/her disease known to people in the workplace. Each point represents a value for each ODT product listed in Table 1. 
www.plosone.org The same applies to ODT disintegration time. The clinical disintegration time of each ODT was measured. 25 0 obj 0000021297 00000 n
0000003226 00000 n
Clinical Disintegration Times of Clinically Available ODTs, 2013 The Pharmaceutical Society of Japan, Edited and published by The Pharmaceutical Society of Japan, Validation of the Method for the Measurement of Clinical Disintegration Time, Measurement of Clinical Disintegration Time in Clinically Available ODTs. endstream 0000004627 00000 n
17 0 obj In these patients, medication is often controlled and administered by nurses and caregivers, and a greater burden of medication assistance is placed on health care providers and the patients families. 2 0 obj
Each point represents a value for the volunteers, while the horizontal line indicates the mean value of the group. Here, ODTs are described as follows: (1) Orally disintegrating tablets are tablets that are administered by rapidly dissolving or disintegrating in the mouth. endobj The placebo ODTs were prepared by direct compression method using a single-station tableting machine (HANDTAB-100; Ichihashi-seiki Co., Ltd., Kyoto, Japan). ). endobj x\YFr~"Z&C I#owXpD7 H?/++ In addition, the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity. 0000017151 00000 n In other words, wetting by liquid is the first requisite for tablet disintegration, even though swelling, wetting, liquid surface tension, viscosity, and capillary action may all be involved. 5 0 obj endobj Liquid penetrates through pores deep into the tablet, and the disintegrant exerts its disintegrating function by absorbing the water that reached into the tablet.
Sastry SV, Nyshadham JR, Fix JA. 3 to 5s) indicated that 7 to 17 subjects are required to detect a 5-s difference in the disintegration time of 2 ODTs, with 5% alpha error and 80% power at a two-sided 5% significance level. These include the following: a method using a compendial disintegration test device equipped with an adaptation of the JP dissolution test method for use with ODTs,12,13) dissolution test measurement of disintegration time using CCD camera imaging,10) utilization of a tablet compaction analysis system,14) application of a texture analyzer from the field of food science,11) tablet disintegration with upward water penetration from beneath the tablet and applying spindle rotation from above,15) and the Kyoto-model disintegration test.16) Although each of these test methods has been reported to show a correlation with disintegration time in the mouth as for the tested ODTs in this study, ODT products are currently manufactured and marketed by many manufacturers in various sizes using various formulation technologies.12,17) Therefore, the oral disintegration behavior may vary by product; some ODTs are designed to disintegrate while leaving the core intact and others are formulated to quickly disintegrate and spread in the mouth. 3 0 obj Even that orodispersible tablets (ODTs) have been successfully used in therapy for more than 20years, there is still no compendial method of their disintegration time evaluation other than the pharmacopoeial disintegration test conducted in 800900mL of distilled water. Therefore, it is likely that the easier water penetrates the tablet, the faster the tablet disintegrates. endobj Orally disintegrating tablets (ODTs) have the superior physical property of excellent disintegration that allows them to be taken with little or no water, and are well proven to be easily taken.13) The biggest benefit of ODTs is their use in rescuing patients who are incapable of taking oral medication, but there may be other benefits depending on the patient. <>/Border[0 0 0]>>
<>/Border[0 0 0]>> Basen OD Tablets 0.2mg, 15. The mean in vitro disintegration times of the 26 clinically used ODT products, measured using Tricorptester, ranged from 4.40 to 30.4s (Table 1). endobj 4). The use of ODTs will not only improve compliance but also ease the burden of medication assistance, because ODTs can address issues such as the patient spitting out the medication or taking a long time to swallow it. 0000001116 00000 n Gaslon NOD Tablets 2mg, and 17. endobj
Pages 1488-1493, (compatible with EndNote, Reference Manager, ProCite, RefWorks). Tamslon-OD Tablets 0.2mg, 14. 1).
Promac D tablets 75, 2. Shahinaze A. Fouad, Fady A. Malaak, Mohamed A. El-Nabarawi, Khalid Abu Zeid Copyright 2022 Elsevier B.V. or its licensors or contributors. [16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R 34 0 R 35 0 R 36 0 R] endobj Copyright 2015 The Authors. <> endobj Participants took a 15-min interval between tests of ODT-A and ODT-B. endobj In this study, a significant positive correlation was observed between the measured and clinical disintegration times, demonstrating that ODT disintegration time measured by Tricorptester is a good reflection of the oral disintegration time, regardless of manufacturer, formulation technology, and size of tablet. <>/Border[0 0 0]>> 33 0 obj 0000013805 00000 n Amlodipine 2.5mg, 6. When the relationships of the measured in vitro disintegration time with tablet hardness, diameter, weight, and thickness were evaluated for each ODT product, there was no significant correlation between the in vitro disintegration time and any of the parameters (Fig. This measurement was performed on 10 tablets of each type of ODT and the mean disintegration time was calculated. <> <>/Border[0 0 0]>> <>/Border[0 0 0]>> The wetting time of each ODT product was measured as described previously with minor modification.8,9) In brief, a piece of paper tissue folded twice was placed in a culture dish containing 6mL of the test solution (NaCl, 1.44g/L; KCl, 1.47g/L; and Tween 80, 0.3%) at 37C. Khan S, Kataria P, Nkhat P, Yeole P. Taste masking of ondansetron hydrochloride by polymer carrier system and formulation of rapid-disintegrating tablets. 0000016644 00000 n endobj 1 0 obj Before the test, the oral cavity of participants was rinsed with a cup of water (120mL). Magmitt Tab. 2. Interestingly, a significant correlation was observed between the in vitro disintegration times of the tested ODTs and the wetting times of the corresponding tablet. Suzuki H, Onishi H, Takahashi Y, Iwata M, Machida Y. By continuing you agree to the use of cookies. In addition, we attempted to evaluate the correlation between the clinical disintegration time and the in vitro disintegration time of ODTs which was measured using Tricorptester, a newly developed disintegration testing apparatus. Six series of ODTs were prepared by direct compression. endobj 0000002807 00000 n 21 0 obj 19 0 obj Clinical Disintegration Time of Orally Disintegrating Tablets Clinically Available in Japan in Healthy Volunteers, Fig. In this study, we have selected Tricorptes, which is a newly developed disintegration testing apparatus, because it has not been reported the relationship of the in vitro disintegration time measured of ODTs by this apparatus with the clinical disintegration time which were evaluated from a validated clinical trial. 0000010052 00000 n <>/Border[0 0 0]>> However, when ODT disintegration time is to be evaluated in humans, ethical issues arise because tablets containing active pharmaceutical ingredients are administered to humans. Shibata Y, Yamamoto Y, Fujii M, Kondoh M, Watanabe Y. 30 0 obj A description of the handling of ODTs has been added in the general guidelines for the preparation of Japanese Pharmacopoeia (JP) upon the 16th revision. endobj Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Guidance for Industry: Orally Disintegrating Tablets, U.S. Department of Health and Human Services, U.S.A., December, 2008. doi:10.1371/journal.pone.0244646 Harada T, Narazaki R, Nagira S, Ohwaki T, Aoki S, Iwamoto K. Evaluation of the disintegration properties of commercial famotidine 20mg orally disintegrating tablets using a simple new test and human sensory test. <>/Border[0 0 0]>> On the other hand, guidance regarding ODTs has been issued by the United States Food and Drug Administration (FDA) in 2008.4) The guidance provides a definition of ODTs, stating that ODTs should rapidly disintegrate in saliva without the need for chewing or liquids. endobj Therefore, an appropriate method is required to evaluate the disintegration time of ODTs. Department of Pharmacy Practice and Science, School of Pharmaceutical Sciences University of Shizuoka, 2013
<>/Border[0 0 0]>> A novel method for predicting disintegration time in the mouth of rapidly disintegrating tablet by compaction analysis using TabAll. They were allowed to move the tablet gently against the upper palate of the mouth with their tongue without biting. Magmitt Tab. 4e). 0000004167 00000 n A significant positive correlation was observed between in vitro and clinical disintegration times of 17 ODT products (r=0.79; p<0.001, Fig. <>stream 117). Development of orally disintegrating tablets containing solid dispersion of a poorly soluble drug for enhanced dissolution: In-vitro optimization/in-vivo evaluation All other chemicals were of reagent grade. 35 0 obj endobj endobj Several methods have been reported for the measurement of ODT disintegration. ScienceDirect is a registered trademark of Elsevier B.V. ScienceDirect is a registered trademark of Elsevier B.V. Gaslon NOD Tablets 4mg, 16. 0000069958 00000 n In addition, the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity. 20 0 obj 34 0 obj %PDF-1.6 hb```b`` * @QcSZ47(Z00<5_ $.Q C)qYbEGD9y(.liek2NFE"$9LYaq nKGGc fqE8P L*@Z5!Nd`LgctjOddfdbRe4qg?X6010dRa8b@oRp)101443*5 : ?C endstream endobj 279 0 obj <>/Filter/FlateDecode/Index[39 201]/Length 30/Size 240/Type/XRef/W[1 1 1]>>stream Morita Y, Tsushima Y, Yasui M, Termoz R, Ajioka J, Takayama K. Evaluation of the disintegration time of rapidly disintegrating tablets, Abdelbary G, Eouani C, Prinderre P, Joachim J, Reynier J, Piccerelle P. Reynier Jp., Piccerelle Ph. 2) for each ODT product (Nos. Recent trend of fast dissolving tabletAn overveiw of fomulation technology. 0000005628 00000 n To date, no studies have described validation of the method for measuring the clinical disintegration time of ODTs although a few studies have reported the disintegration time in the oral cavity.7,10,11) Thus, we first validated the method for measuring the clinical disintegration time of ODTs in healthy volunteers who were randomly assigned to 3 groups. 32 0 obj 0000006291 00000 n Healthy volunteers (n, 910; age range, 2128 years) participated in this randomized crossover trial. 330mg, 3. <>/Border[0 0 0]>> The test solution (NaCl, 1.44g/L; KCl, 1.47g/L; and Tween 80, 0.3%) was warmed to 37C and dripped from a height of 80mm at a flow rate of 6.0mL/min. The clinical disintegration time was measured for 17 ODT products (Nos. ODT-A contained Ludiflash (BASF, Ludwigshafen, Germany), and ODT-B contained Ludiflash and cocoa powder (NF-15, Morinaga Shoji Co., Ltd., Yokohama, Japan). Recent technological advances in oral drug deliveryA review. The clinical disintegration time of each ODT was measured by an investigator with a stopwatch. No significant difference was observed in the clinical disintegration time of ODT-A and ODT-B among the 3 groups. Takepron OD Tablets 30mg. Each point represents the mean value of the in vitro or clinical disintegrating times (Table 1, Fig. 0000057569 00000 n 18 0 obj 0000016110 00000 n In this study, we aimed to evaluate the clinical disintegration time of 17 ODTs that are currently available for clinical use in Japan. To validate the method for measuring the clinical disintegration time of ODTs, the subjects were randomly assigned to 3 groups, and the clinical disintegration time was measured. 0000006711 00000 n false
Determination of the. 0000006193 00000 n The result of this study showed that a significant positive correlation was found between in vitro and clinical disintegration times, which showed that the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity. The clinical disintegration time of 17 ODT products, measured as the time required for oral disintegration in a clinical trial, was between 17.6 and 33.8s (Fig. <>/Border[0 0 0]>> To evaluate the intra-assay precision, we randomly divided 18 healthy volunteers (age range, 2128 years) into 3 groups and performed a randomized crossover trial to determine the clinical disintegration time for placebo ODT-A and ODT-B. 0000011971 00000 n 37 0 obj On the other hand, wetting time of ODTs correlated significantly with in vitro disintegrating time (r=0.718; p<0.001, Fig. The tablet diameter was between 6.0 and 11.5mm, weight was between 80 and 570mg, and thickness was between 2.4 and 4.9mm. endobj The clinical disintegration time of ODT-A in the 3 groups was 13.83.8s, 16.63.4s, and 16.62.5s, and that for ODT-B was 30.83.6s, 31.52.6s, and 28.45.6s (Fig. These results have shown that development of novel biorelevant methods of ODTs disintegration time determination is eligible and scientifically justified. However, there is no specific description of the disintegration time or method for measuring disintegration time. Development of oral acetaminophen chewable tablets with inhibited bitter taste. endobj The authors thank Mr. Ryouichi Takenaka and Mr. Kenjirou Yamada for their excellent technical assistance. We use cookies to help provide and enhance our service and tailor content and ads. In vitro disintegration time of 26 ODT products (Nos. All compressed conventional and ODTs weighed 250mg and had a diameter of 9.0mm. FDA guidelines indicate that the disintegration time of ODTs should be approximately within 30s.4) Our result indicated that ODT products, which are clinically used in Japan, have good disintegration (within approximately 30s) and that the disintegration time varies according to the product. 27 0 obj trailer <<9CB92B2296E64E8D9AF47ED9F6041774>]/Prev 353306/XRefStm 1511>> startxref 0 %%EOF 280 0 obj <>stream Clinical Disintegration Times of ODT-A (A) and ODT-B (B) in 3 Groups of Healthy Volunteers, Fig. Their mechanical properties and disintegration times were measured with pharmacopoeial and alternative methods and compared with the in vivo results. Harnal D Tablets 0.2mg, 7. Disintegration time is an important quality attribute of ODTs, and the evaluation of disintegration time is positioned as a key step in formulation development, manufacturing, and clinical practice. <>/Border[0 0 0]>> In contrast, there were no relationship between in vitro disintegration time and tablet hardness, diameter, weight, and thickness.
<>/Border[0 0 0]>> 0000015465 00000 n The clinical disintegration time was measured for 17 ODT products (Nos. Amlodipine 5mg, 8. We added other 9 ODT products (Nos. No significant difference was observed in the clinical disintegration time of each ODT among the 3 groups to which the subjects were randomly assigned. 2). Narazaki R, Harada T, Takami N, Kato Y, Ohwaki T. A new method for disintegration studies of rapid disintegrating tablet. The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs). Issue 9 Disintegration time is an important characteristic of orally disintegrating tablets (ODTs), and evaluation of disintegration time is a key step in formulation development, manufacturing, and clinical practice. Tricorptester is a test device composed of 2 meshes; a lower mesh, on which an ODT is placed, and an upper mesh, which is attached to holders and is in contact with the ODT, on which artificial saliva is dripped from above. The hardness of ODT was determined by a load cell-type hardness tester, PC-30 (Okada Seiko Co., Ltd., Tokyo, Japan) using 10 tablets for each product. Therefore, several alternative tests more relevant to in vivo conditions were described by different researchers. A similar issue seems to be present with children who are not good at swallowing and require caregivers for controlling and administering their medication. 0000010648 00000 n Kakutani R, Muro H, Makino T. Development of a new disintegration method for orally disintegrating tablets. Each point represents a value for the volunteers, while the horizontal line indicates the mean value of the group. The pharmacopoeial method correlated with the in vivo data much worse (r=0.8925, p<0.05). Therefore, the actual disintegration time of ODTs in the oral cavity does not often correlate with the in vitro disintegration time measured by disintegration tests of USP or JP.58). calculated from results of our study (ca. 117). The aim of this study was to compare these methods and correlate them with in vivo results. <>/Border[0 0 0]>> V )H(Od]|.!KA \)_Q mta2]\},fbN$pA/-/.wfe}{E,T};o7]^W~x"X=I?^oHO[Tf~ssq~0WvY-vbL{i~ _O';f_M]5slF/=tn~Ehjn@*Po[+/d, Shahinaze A. Fouad, Fady A. Malaak, Mohamed A. El-Nabarawi, Khalid Abu Zeid, Development of orally disintegrating tablets containing solid dispersion of a poorly soluble drug for enhanced dissolution: In-vitro optimization/in-vivo evaluation. <>/Border[0 0 0]>> 117) listed as follows: 1. Mizumoto T, Tamura T, Kawai H, Kajiyama A, Itai S. Formulation design of taste-masked particles, including famotidine, for an oral fast-disintegrating dosage form. hbbg`b``3 endstream endobj 241 0 obj <>/Metadata 37 0 R/PageLabels 34 0 R/Pages 36 0 R/StructTreeRoot 39 0 R/Type/Catalog/ViewerPreferences<>>> endobj 242 0 obj <>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/StructParents 0/TrimBox[0.0 0.0 552.756 793.701]/Type/Page>> endobj 243 0 obj <>stream $8fB_Yr,x,D`"MEPDqxR,$'QR.Je9F"R}b1f 2020-12-31 Amlodipine-OD Tablets 5mg TOWA, 10. Patients with dementia or schizophrenia have difficulty in managing their medication by themselves due to cognitive impairment and psychiatric disorders, and sometimes refuse medication.
0000014078 00000 n Gaster D Tablets 20mg, 11. 0000014687 00000 n
This study shows that all the tested products, which are clinically available in Japan, showed good disintegration and that the disintegration time varied according to the product. 0000007844 00000 n
Improved disintegration of ODTs has been achieved by increasing the porosity to let the liquid penetrate the tablet easily, and by using disintegrants that have excellent water absorption and wetting capacities.12) Thus, the hardness, diameter, thickness, and weight of ODTs are not likely to be major factors that influence disintegration time. 0000008554 00000 n
(2) Orally disintegrating tablets have appropriate disintegration properties. All volunteers who provided written informed consent participated in the study. 0000001691 00000 n
0000003323 00000 n
www.plosone.org 8*qTEYZccld".Y)&:.Ye1Kt'ra,'r.0%)EH}`EYd$q`\ hQr"*K0Xi/$ 7> gq$ersOdAbl(1C_7 '2a cfL3}bFQ8 ':,@Lb} [-b (O@4r EQ Randale S, Dabhi C, Tekada A, Belgamwar V, Gattani S, Surana S. Rapidly disintegrating tablets containing taste masked metoclopramide hydrochloride prepared by extrusion-precipitation method. endobj 0000077986 00000 n
<>/Border[0 0 0]>> On the other hand, the compendial disintegration test does not seem to accurately reproduce the disintegration behavior of ODTs in the oral cavity as the test is carried out in a large volume of test solution (i.e., 900mL). Similarly, the in vitro disintegration times of the 26 clinically used ODT products ranged between 4.4 and 30.4s. Currently, there are couples of apparatus for measuring disintegration time of ODTs. Promac D tablets 75 (Zeria Pharmaceutical Co., Ltd.), Magmitt Tab 330mg (Kyowa Chemical Industry Co., Ltd.), Magmitt Tab. H\j0z 2020-12-31 Bi Y, Sunada H, Yonezawa Y, Danjo K, Otsuka A, Iida K. Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity. 10.1371/journal.pone.0244646 endobj ODTs, which can be taken without water, can be taken even when water is not readily available at work, or when the patient does not want his/her disease known to people in the workplace. Each point represents a value for each ODT product listed in Table 1. www.plosone.org The same applies to ODT disintegration time. The clinical disintegration time of each ODT was measured. 25 0 obj 0000021297 00000 n
0000003226 00000 n
Clinical Disintegration Times of Clinically Available ODTs, 2013 The Pharmaceutical Society of Japan, Edited and published by The Pharmaceutical Society of Japan, Validation of the Method for the Measurement of Clinical Disintegration Time, Measurement of Clinical Disintegration Time in Clinically Available ODTs. endstream 0000004627 00000 n
17 0 obj In these patients, medication is often controlled and administered by nurses and caregivers, and a greater burden of medication assistance is placed on health care providers and the patients families. 2 0 obj Each point represents a value for the volunteers, while the horizontal line indicates the mean value of the group. Here, ODTs are described as follows: (1) Orally disintegrating tablets are tablets that are administered by rapidly dissolving or disintegrating in the mouth. endobj The placebo ODTs were prepared by direct compression method using a single-station tableting machine (HANDTAB-100; Ichihashi-seiki Co., Ltd., Kyoto, Japan). ). endobj x\YFr~"Z&C I#owXpD7 H?/++ In addition, the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity. 0000017151 00000 n In other words, wetting by liquid is the first requisite for tablet disintegration, even though swelling, wetting, liquid surface tension, viscosity, and capillary action may all be involved. 5 0 obj endobj Liquid penetrates through pores deep into the tablet, and the disintegrant exerts its disintegrating function by absorbing the water that reached into the tablet.
Sastry SV, Nyshadham JR, Fix JA. 3 to 5s) indicated that 7 to 17 subjects are required to detect a 5-s difference in the disintegration time of 2 ODTs, with 5% alpha error and 80% power at a two-sided 5% significance level. These include the following: a method using a compendial disintegration test device equipped with an adaptation of the JP dissolution test method for use with ODTs,12,13) dissolution test measurement of disintegration time using CCD camera imaging,10) utilization of a tablet compaction analysis system,14) application of a texture analyzer from the field of food science,11) tablet disintegration with upward water penetration from beneath the tablet and applying spindle rotation from above,15) and the Kyoto-model disintegration test.16) Although each of these test methods has been reported to show a correlation with disintegration time in the mouth as for the tested ODTs in this study, ODT products are currently manufactured and marketed by many manufacturers in various sizes using various formulation technologies.12,17) Therefore, the oral disintegration behavior may vary by product; some ODTs are designed to disintegrate while leaving the core intact and others are formulated to quickly disintegrate and spread in the mouth. 3 0 obj Even that orodispersible tablets (ODTs) have been successfully used in therapy for more than 20years, there is still no compendial method of their disintegration time evaluation other than the pharmacopoeial disintegration test conducted in 800900mL of distilled water. Therefore, it is likely that the easier water penetrates the tablet, the faster the tablet disintegrates. endobj Orally disintegrating tablets (ODTs) have the superior physical property of excellent disintegration that allows them to be taken with little or no water, and are well proven to be easily taken.13) The biggest benefit of ODTs is their use in rescuing patients who are incapable of taking oral medication, but there may be other benefits depending on the patient. <>/Border[0 0 0]>>
<>/Border[0 0 0]>> Basen OD Tablets 0.2mg, 15. The mean in vitro disintegration times of the 26 clinically used ODT products, measured using Tricorptester, ranged from 4.40 to 30.4s (Table 1). endobj 4). The use of ODTs will not only improve compliance but also ease the burden of medication assistance, because ODTs can address issues such as the patient spitting out the medication or taking a long time to swallow it. 0000001116 00000 n Gaslon NOD Tablets 2mg, and 17. endobj
Pages 1488-1493, (compatible with EndNote, Reference Manager, ProCite, RefWorks). Tamslon-OD Tablets 0.2mg, 14. 1).
Promac D tablets 75, 2. Shahinaze A. Fouad, Fady A. Malaak, Mohamed A. El-Nabarawi, Khalid Abu Zeid Copyright 2022 Elsevier B.V. or its licensors or contributors. [16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R 34 0 R 35 0 R 36 0 R] endobj Copyright 2015 The Authors. <> endobj Participants took a 15-min interval between tests of ODT-A and ODT-B. endobj In this study, a significant positive correlation was observed between the measured and clinical disintegration times, demonstrating that ODT disintegration time measured by Tricorptester is a good reflection of the oral disintegration time, regardless of manufacturer, formulation technology, and size of tablet. <>/Border[0 0 0]>> 33 0 obj 0000013805 00000 n Amlodipine 2.5mg, 6. When the relationships of the measured in vitro disintegration time with tablet hardness, diameter, weight, and thickness were evaluated for each ODT product, there was no significant correlation between the in vitro disintegration time and any of the parameters (Fig. This measurement was performed on 10 tablets of each type of ODT and the mean disintegration time was calculated. <> <>/Border[0 0 0]>> <>/Border[0 0 0]>> The wetting time of each ODT product was measured as described previously with minor modification.8,9) In brief, a piece of paper tissue folded twice was placed in a culture dish containing 6mL of the test solution (NaCl, 1.44g/L; KCl, 1.47g/L; and Tween 80, 0.3%) at 37C. Khan S, Kataria P, Nkhat P, Yeole P. Taste masking of ondansetron hydrochloride by polymer carrier system and formulation of rapid-disintegrating tablets. 0000016644 00000 n endobj 1 0 obj Before the test, the oral cavity of participants was rinsed with a cup of water (120mL). Magmitt Tab. 2. Interestingly, a significant correlation was observed between the in vitro disintegration times of the tested ODTs and the wetting times of the corresponding tablet. Suzuki H, Onishi H, Takahashi Y, Iwata M, Machida Y. By continuing you agree to the use of cookies. In addition, we attempted to evaluate the correlation between the clinical disintegration time and the in vitro disintegration time of ODTs which was measured using Tricorptester, a newly developed disintegration testing apparatus. Six series of ODTs were prepared by direct compression. endobj 0000002807 00000 n 21 0 obj 19 0 obj Clinical Disintegration Time of Orally Disintegrating Tablets Clinically Available in Japan in Healthy Volunteers, Fig. In this study, we have selected Tricorptes, which is a newly developed disintegration testing apparatus, because it has not been reported the relationship of the in vitro disintegration time measured of ODTs by this apparatus with the clinical disintegration time which were evaluated from a validated clinical trial. 0000010052 00000 n <>/Border[0 0 0]>> However, when ODT disintegration time is to be evaluated in humans, ethical issues arise because tablets containing active pharmaceutical ingredients are administered to humans. Shibata Y, Yamamoto Y, Fujii M, Kondoh M, Watanabe Y. 30 0 obj A description of the handling of ODTs has been added in the general guidelines for the preparation of Japanese Pharmacopoeia (JP) upon the 16th revision. endobj Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Guidance for Industry: Orally Disintegrating Tablets, U.S. Department of Health and Human Services, U.S.A., December, 2008. doi:10.1371/journal.pone.0244646 Harada T, Narazaki R, Nagira S, Ohwaki T, Aoki S, Iwamoto K. Evaluation of the disintegration properties of commercial famotidine 20mg orally disintegrating tablets using a simple new test and human sensory test. <>/Border[0 0 0]>> On the other hand, guidance regarding ODTs has been issued by the United States Food and Drug Administration (FDA) in 2008.4) The guidance provides a definition of ODTs, stating that ODTs should rapidly disintegrate in saliva without the need for chewing or liquids. endobj Therefore, an appropriate method is required to evaluate the disintegration time of ODTs. Department of Pharmacy Practice and Science, School of Pharmaceutical Sciences University of Shizuoka, 2013
<>/Border[0 0 0]>> A novel method for predicting disintegration time in the mouth of rapidly disintegrating tablet by compaction analysis using TabAll. They were allowed to move the tablet gently against the upper palate of the mouth with their tongue without biting. Magmitt Tab. 4e). 0000004167 00000 n A significant positive correlation was observed between in vitro and clinical disintegration times of 17 ODT products (r=0.79; p<0.001, Fig. <>stream 117). Development of orally disintegrating tablets containing solid dispersion of a poorly soluble drug for enhanced dissolution: In-vitro optimization/in-vivo evaluation All other chemicals were of reagent grade. 35 0 obj endobj endobj Several methods have been reported for the measurement of ODT disintegration. ScienceDirect is a registered trademark of Elsevier B.V. ScienceDirect is a registered trademark of Elsevier B.V. Gaslon NOD Tablets 4mg, 16. 0000069958 00000 n In addition, the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity. 20 0 obj 34 0 obj %PDF-1.6 hb```b`` * @QcSZ47(Z00<5_ $.Q C)qYbEGD9y(.liek2NFE"$9LYaq nKGGc fqE8P L*@Z5!Nd`LgctjOddfdbRe4qg?X6010dRa8b@oRp)101443*5 : ?C endstream endobj 279 0 obj <>/Filter/FlateDecode/Index[39 201]/Length 30/Size 240/Type/XRef/W[1 1 1]>>stream Morita Y, Tsushima Y, Yasui M, Termoz R, Ajioka J, Takayama K. Evaluation of the disintegration time of rapidly disintegrating tablets, Abdelbary G, Eouani C, Prinderre P, Joachim J, Reynier J, Piccerelle P. Reynier Jp., Piccerelle Ph. 2) for each ODT product (Nos. Recent trend of fast dissolving tabletAn overveiw of fomulation technology. 0000005628 00000 n To date, no studies have described validation of the method for measuring the clinical disintegration time of ODTs although a few studies have reported the disintegration time in the oral cavity.7,10,11) Thus, we first validated the method for measuring the clinical disintegration time of ODTs in healthy volunteers who were randomly assigned to 3 groups. 32 0 obj 0000006291 00000 n Healthy volunteers (n, 910; age range, 2128 years) participated in this randomized crossover trial. 330mg, 3. <>/Border[0 0 0]>> The test solution (NaCl, 1.44g/L; KCl, 1.47g/L; and Tween 80, 0.3%) was warmed to 37C and dripped from a height of 80mm at a flow rate of 6.0mL/min. The clinical disintegration time was measured for 17 ODT products (Nos. ODT-A contained Ludiflash (BASF, Ludwigshafen, Germany), and ODT-B contained Ludiflash and cocoa powder (NF-15, Morinaga Shoji Co., Ltd., Yokohama, Japan). Recent technological advances in oral drug deliveryA review. The clinical disintegration time of each ODT was measured by an investigator with a stopwatch. No significant difference was observed in the clinical disintegration time of ODT-A and ODT-B among the 3 groups. Takepron OD Tablets 30mg. Each point represents the mean value of the in vitro or clinical disintegrating times (Table 1, Fig. 0000057569 00000 n 18 0 obj 0000016110 00000 n In this study, we aimed to evaluate the clinical disintegration time of 17 ODTs that are currently available for clinical use in Japan. To validate the method for measuring the clinical disintegration time of ODTs, the subjects were randomly assigned to 3 groups, and the clinical disintegration time was measured. 0000006711 00000 n false
Determination of the. 0000006193 00000 n The result of this study showed that a significant positive correlation was found between in vitro and clinical disintegration times, which showed that the in vitro disintegration time of ODTs measured using Tricorptester is a good reflection of the disintegration time in the oral cavity. The clinical disintegration time of 17 ODT products, measured as the time required for oral disintegration in a clinical trial, was between 17.6 and 33.8s (Fig. <>/Border[0 0 0]>> To evaluate the intra-assay precision, we randomly divided 18 healthy volunteers (age range, 2128 years) into 3 groups and performed a randomized crossover trial to determine the clinical disintegration time for placebo ODT-A and ODT-B. 0000011971 00000 n 37 0 obj On the other hand, wetting time of ODTs correlated significantly with in vitro disintegrating time (r=0.718; p<0.001, Fig. The tablet diameter was between 6.0 and 11.5mm, weight was between 80 and 570mg, and thickness was between 2.4 and 4.9mm. endobj The clinical disintegration time of ODT-A in the 3 groups was 13.83.8s, 16.63.4s, and 16.62.5s, and that for ODT-B was 30.83.6s, 31.52.6s, and 28.45.6s (Fig. These results have shown that development of novel biorelevant methods of ODTs disintegration time determination is eligible and scientifically justified. However, there is no specific description of the disintegration time or method for measuring disintegration time. Development of oral acetaminophen chewable tablets with inhibited bitter taste. endobj The authors thank Mr. Ryouichi Takenaka and Mr. Kenjirou Yamada for their excellent technical assistance. We use cookies to help provide and enhance our service and tailor content and ads. In vitro disintegration time of 26 ODT products (Nos. All compressed conventional and ODTs weighed 250mg and had a diameter of 9.0mm. FDA guidelines indicate that the disintegration time of ODTs should be approximately within 30s.4) Our result indicated that ODT products, which are clinically used in Japan, have good disintegration (within approximately 30s) and that the disintegration time varies according to the product. 27 0 obj trailer <<9CB92B2296E64E8D9AF47ED9F6041774>]/Prev 353306/XRefStm 1511>> startxref 0 %%EOF 280 0 obj <>stream Clinical Disintegration Times of ODT-A (A) and ODT-B (B) in 3 Groups of Healthy Volunteers, Fig. Their mechanical properties and disintegration times were measured with pharmacopoeial and alternative methods and compared with the in vivo results. Harnal D Tablets 0.2mg, 7. Disintegration time is an important quality attribute of ODTs, and the evaluation of disintegration time is positioned as a key step in formulation development, manufacturing, and clinical practice. <>/Border[0 0 0]>> In contrast, there were no relationship between in vitro disintegration time and tablet hardness, diameter, weight, and thickness.
<>/Border[0 0 0]>> 0000015465 00000 n The clinical disintegration time was measured for 17 ODT products (Nos. Amlodipine 5mg, 8. We added other 9 ODT products (Nos. No significant difference was observed in the clinical disintegration time of each ODT among the 3 groups to which the subjects were randomly assigned. 2). Narazaki R, Harada T, Takami N, Kato Y, Ohwaki T. A new method for disintegration studies of rapid disintegrating tablet. The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs). Issue 9 Disintegration time is an important characteristic of orally disintegrating tablets (ODTs), and evaluation of disintegration time is a key step in formulation development, manufacturing, and clinical practice. Tricorptester is a test device composed of 2 meshes; a lower mesh, on which an ODT is placed, and an upper mesh, which is attached to holders and is in contact with the ODT, on which artificial saliva is dripped from above. The hardness of ODT was determined by a load cell-type hardness tester, PC-30 (Okada Seiko Co., Ltd., Tokyo, Japan) using 10 tablets for each product. Therefore, several alternative tests more relevant to in vivo conditions were described by different researchers. A similar issue seems to be present with children who are not good at swallowing and require caregivers for controlling and administering their medication. 0000010648 00000 n Kakutani R, Muro H, Makino T. Development of a new disintegration method for orally disintegrating tablets. Each point represents a value for the volunteers, while the horizontal line indicates the mean value of the group. The pharmacopoeial method correlated with the in vivo data much worse (r=0.8925, p<0.05). Therefore, the actual disintegration time of ODTs in the oral cavity does not often correlate with the in vitro disintegration time measured by disintegration tests of USP or JP.58). calculated from results of our study (ca. 117). The aim of this study was to compare these methods and correlate them with in vivo results. <>/Border[0 0 0]>> V )H(Od]|.!KA \)_Q mta2]\},fbN$pA/-/.wfe}{E,T};o7]^W~x"X=I?^oHO[Tf~ssq~0WvY-vbL{i~ _O';f_M]5slF/=tn~Ehjn@*Po[+/d, Shahinaze A. Fouad, Fady A. Malaak, Mohamed A. El-Nabarawi, Khalid Abu Zeid, Development of orally disintegrating tablets containing solid dispersion of a poorly soluble drug for enhanced dissolution: In-vitro optimization/in-vivo evaluation. <>/Border[0 0 0]>> 117) listed as follows: 1. Mizumoto T, Tamura T, Kawai H, Kajiyama A, Itai S. Formulation design of taste-masked particles, including famotidine, for an oral fast-disintegrating dosage form. hbbg`b``3 endstream endobj 241 0 obj <>/Metadata 37 0 R/PageLabels 34 0 R/Pages 36 0 R/StructTreeRoot 39 0 R/Type/Catalog/ViewerPreferences<>>> endobj 242 0 obj <>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/StructParents 0/TrimBox[0.0 0.0 552.756 793.701]/Type/Page>> endobj 243 0 obj <>stream $8fB_Yr,x,D`"MEPDqxR,$'QR.Je9F"R}b1f 2020-12-31 Amlodipine-OD Tablets 5mg TOWA, 10. Patients with dementia or schizophrenia have difficulty in managing their medication by themselves due to cognitive impairment and psychiatric disorders, and sometimes refuse medication.