In-vitro crystallization of indinavir in the presence of ritonavir and as a function of pH
The aim of this study was to investigate the in-vitro crystallization of indinavir as a function of pH alteration and in the presence of another protease inhibitor, ritonavir. Crystallization processes were studied for indinavir sulfate, indinavir free base and a commercial indinavir capsule dosage form, respectively. Crystallization induction times were determined with varying initial concentration of supersaturated solution, and in the presence or absence of seed material. In-vitro induction times were found to be significantly shorter for the indinavir capsule dosage form compared with that of indinavir sulfate and indinavir free base. Induction times were inversely proportional to the final concentration in pH 7 buffer for all materials, and were significantly shortened in the presence of seeds. The crystal morphology of indinavir varied under different crystallization conditions. This study demonstrated the potential for precipitation of indinavir upon pH elevation, while also suggesting that the presence of impurities or seeding material significantly shortens the induction time for indinavir crystal formation. This induction time period falls well within the gastric emptying time following the intake of a high-caloric meal, and within small intestinal transit time. The results of this study are in agreement with the clinical observation that a high-calorie protein meal significantly reduces the oral bioavailability of indinavir in man, accompanying a pH elevation in the stomach.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2003 |
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| Erschienen: |
2003 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:55 |
|---|---|
| Enthalten in: |
The Journal of pharmacy and pharmacology - 55(2003), 5 vom: 29. Mai, Seite 707-11 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Lilian Y [VerfasserIn] |
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| Themen: |
5W6YA9PKKH |
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| Anmerkungen: |
Date Completed 12.08.2003 Date Revised 21.11.2013 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM125939876 |
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| 100 | 1 | |a Li, Lilian Y |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a In-vitro crystallization of indinavir in the presence of ritonavir and as a function of pH |
| 264 | 1 | |c 2003 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 500 | |a Date Completed 12.08.2003 | ||
| 500 | |a Date Revised 21.11.2013 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The aim of this study was to investigate the in-vitro crystallization of indinavir as a function of pH alteration and in the presence of another protease inhibitor, ritonavir. Crystallization processes were studied for indinavir sulfate, indinavir free base and a commercial indinavir capsule dosage form, respectively. Crystallization induction times were determined with varying initial concentration of supersaturated solution, and in the presence or absence of seed material. In-vitro induction times were found to be significantly shorter for the indinavir capsule dosage form compared with that of indinavir sulfate and indinavir free base. Induction times were inversely proportional to the final concentration in pH 7 buffer for all materials, and were significantly shortened in the presence of seeds. The crystal morphology of indinavir varied under different crystallization conditions. This study demonstrated the potential for precipitation of indinavir upon pH elevation, while also suggesting that the presence of impurities or seeding material significantly shortens the induction time for indinavir crystal formation. This induction time period falls well within the gastric emptying time following the intake of a high-caloric meal, and within small intestinal transit time. The results of this study are in agreement with the clinical observation that a high-calorie protein meal significantly reduces the oral bioavailability of indinavir in man, accompanying a pH elevation in the stomach | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Capsules |2 NLM | |
| 650 | 7 | |a Dietary Proteins |2 NLM | |
| 650 | 7 | |a Indinavir |2 NLM | |
| 650 | 7 | |a 5W6YA9PKKH |2 NLM | |
| 650 | 7 | |a Ritonavir |2 NLM | |
| 650 | 7 | |a O3J8G9O825 |2 NLM | |
| 700 | 1 | |a Rodríguez-Hornedo, Naír |e verfasserin |4 aut | |
| 700 | 1 | |a Heimbach, Tycho |e verfasserin |4 aut | |
| 700 | 1 | |a Fleisher, David |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of pharmacy and pharmacology |d 1949 |g 55(2003), 5 vom: 29. Mai, Seite 707-11 |w (DE-627)NLM000019046 |x 2042-7158 |7 nnns |
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