Development of a bio-relevant pH gradient dissolution method for a high-dose, weakly acidic drug, its optimization and IVIVC in Wistar rats: a case study of magnesium orotate dihydrate (notice n° 755759)
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| fixed length control field | 02489cam a2200277 4500500 |
| 005 - DATE AND TIME OF LATEST TRANSACTION | |
| control field | 20250123100204.0 |
| 041 ## - LANGUAGE CODE | |
| Language code of text/sound track or separate title | fre |
| 042 ## - AUTHENTICATION CODE | |
| Authentication code | dc |
| 100 10 - MAIN ENTRY--PERSONAL NAME | |
| Personal name | Verma, Hitesh |
| Relator term | author |
| 245 00 - TITLE STATEMENT | |
| Title | Development of a bio-relevant pH gradient dissolution method for a high-dose, weakly acidic drug, its optimization and IVIVC in Wistar rats: a case study of magnesium orotate dihydrate |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. | |
| Date of publication, distribution, etc. | 2022.<br/> |
| 500 ## - GENERAL NOTE | |
| General note | 12 |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | Magnesium orotate dihydrate (MOD) is a weakly acidic drug (pKa 2.83) which belongs to Biopharmaceutical Classification System (BCS) Class I at a dose of 500 mg and to BCS Class II at a dose of 1,000 mg. It is clinically prescribed at a dose of 3,000 mg (in two to three divided doses). The aim of the present study was to develop a bio-relevant pH gradient dissolution method for MOD in order to evaluate whether its clinically practiced therapeutic dose may be absorbed or not. The developed method revealed that MOD undergoes slow, but complete dissolution within 180 minutes, corresponding to the time to achieve maximum serum concentration (Tmax) in vivo. Optimization studies revealed that a rotational speed of 75 rpm provided reliable results (relative standard deviation of less than 20% up to a 10-minute time point, and less than 10% for the other time points), and MOD underwent complete dissolution within the testing timeframe at this rotational speed. Based on a pharmacokinetics study and the Wagner Nelson method, the relative extent of MOD absorption, when administered at a high dose equivalent to a human dose of 1,524 mg in Wistar rats in comparison to its oral suspension, was greater than 90%. In vitro – in vivo correlation, established through a deconvolution method, showed excellent correlation between percent of drug dissolved and percent of drug absorbed ( R2 = 0.9303). Therefore, even when MOD is administered at a single high dose, it can undergo slow but complete dissolution and absorption in vivo. |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | in vitro |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | correlation (IVIVC) |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | high-dose weakly acidic drug |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | – |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | magnesium orotate |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | dissolution |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | in vivo |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | pharmacokinetics |
| 690 ## - LOCAL SUBJECT ADDED ENTRY--TOPICAL TERM (OCLC, RLIN) | |
| Topical term or geographic name as entry element | bio-relevant pH gradient dissolution |
| 700 10 - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Garg, Rajeev |
| Relator term | author |
| 786 0# - DATA SOURCE ENTRY | |
| Note | Magnesium Research | 35 | 3 | 2022-07-01 | p. 88-95 | 0953-1424 |
| 856 41 - ELECTRONIC LOCATION AND ACCESS | |
| Uniform Resource Identifier | <a href="https://shs.cairn.info/revue-magnesium-research-2022-3-page-88?lang=en&redirect-ssocas=7080">https://shs.cairn.info/revue-magnesium-research-2022-3-page-88?lang=en&redirect-ssocas=7080</a> |
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