Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct Compression
Hydrochlorothiazide (HCTZ)/losartan potassium (LOS-K) was used as a model drug to prepare compound tablets through the investigation of the compression and mechanical properties of mixed powders to determine the formulation and preparation factors, followed by D-optimal mixture experimental design t...
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MDPI AG
2022-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/8/1741 |
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| author | Qiuhua Luo Qianying Zhang Puxiu Wang |
| author_facet | Qiuhua Luo Qianying Zhang Puxiu Wang |
| author_sort | Qiuhua Luo |
| collection | DOAJ |
| description | Hydrochlorothiazide (HCTZ)/losartan potassium (LOS-K) was used as a model drug to prepare compound tablets through the investigation of the compression and mechanical properties of mixed powders to determine the formulation and preparation factors, followed by D-optimal mixture experimental design to optimize the final parameters. The type and amount of lactose monohydrate (SuperTab<sup>®</sup>14SD, 19.53–26.91%), microcrystalline cellulose (MCC PH102, 32.86–43.31%), pre-gelatinized starch (Starch-1500, 10.96–15.91%), and magnesium stearate (0.7%) were determined according to the compressive work, stress relaxation curves, and Py value. Then, the compression mechanism of the mixed powder was investigated by the Kawakita equation, Shapiro equation, and Heckel analysis, and the mixed powder was classified as a Class-II powder. The compaction pressure (150–300 MPa) and tableting speed (1200–2400 Tab/h) were recommended. A D-optimal mixture experimental design was utilized to select the optimal formulation (No 1, 26.027% lactose monohydrate, 32.811% MCC PH102, and 15.462% pregelatinized starch) according to the drug dissolution rate, using Hyzaar<sup>®</sup> tablets as a control. Following oral administration in beagle dogs, there were no significant differences in bioavailability between the No. 1 tablet and the Hyzaar<sup>®</sup> tablet in HCTZ, losartan carboxylic acid (E-3174), and LOS-K (F < F<sub>0.05</sub>). Thus, formulation and preparation factors were determined according to the combination of the compression and mechanical properties of the mixed powder and quality of tablets, which was demonstrated to be a feasible method in direct powder compression. |
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| id | doaj.art-0b34578fb45549ce86dd7cf0e716f7ae |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T09:50:34Z |
| publishDate | 2022-08-01 |
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| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-0b34578fb45549ce86dd7cf0e716f7ae2023-12-02T00:10:19ZengMDPI AGPharmaceutics1999-49232022-08-01148174110.3390/pharmaceutics14081741Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct CompressionQiuhua Luo0Qianying Zhang1Puxiu Wang2Department of Pharmacy, The First Affiliated Hospital of China Medical University, Shenyang 110001, ChinaDepartment of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Pharmacy, The First Affiliated Hospital of China Medical University, Shenyang 110001, ChinaHydrochlorothiazide (HCTZ)/losartan potassium (LOS-K) was used as a model drug to prepare compound tablets through the investigation of the compression and mechanical properties of mixed powders to determine the formulation and preparation factors, followed by D-optimal mixture experimental design to optimize the final parameters. The type and amount of lactose monohydrate (SuperTab<sup>®</sup>14SD, 19.53–26.91%), microcrystalline cellulose (MCC PH102, 32.86–43.31%), pre-gelatinized starch (Starch-1500, 10.96–15.91%), and magnesium stearate (0.7%) were determined according to the compressive work, stress relaxation curves, and Py value. Then, the compression mechanism of the mixed powder was investigated by the Kawakita equation, Shapiro equation, and Heckel analysis, and the mixed powder was classified as a Class-II powder. The compaction pressure (150–300 MPa) and tableting speed (1200–2400 Tab/h) were recommended. A D-optimal mixture experimental design was utilized to select the optimal formulation (No 1, 26.027% lactose monohydrate, 32.811% MCC PH102, and 15.462% pregelatinized starch) according to the drug dissolution rate, using Hyzaar<sup>®</sup> tablets as a control. Following oral administration in beagle dogs, there were no significant differences in bioavailability between the No. 1 tablet and the Hyzaar<sup>®</sup> tablet in HCTZ, losartan carboxylic acid (E-3174), and LOS-K (F < F<sub>0.05</sub>). Thus, formulation and preparation factors were determined according to the combination of the compression and mechanical properties of the mixed powder and quality of tablets, which was demonstrated to be a feasible method in direct powder compression.https://www.mdpi.com/1999-4923/14/8/1741direct compressioncompression and mechanical propertiesD-optimal mixture experimental designdissolution ratebioavailibility |
| spellingShingle | Qiuhua Luo Qianying Zhang Puxiu Wang Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct Compression Pharmaceutics direct compression compression and mechanical properties D-optimal mixture experimental design dissolution rate bioavailibility |
| title | Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct Compression |
| title_full | Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct Compression |
| title_fullStr | Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct Compression |
| title_full_unstemmed | Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct Compression |
| title_short | Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct Compression |
| title_sort | hydrochlorothiazide losartan potassium tablet prepared by direct compression |
| topic | direct compression compression and mechanical properties D-optimal mixture experimental design dissolution rate bioavailibility |
| url | https://www.mdpi.com/1999-4923/14/8/1741 |
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