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Tadalafil-malonic a...
Tadalafil-malonic acid cocrystal : Physicochemical characterization, pH-solubility and supersaturation studies
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- Shimpi, Manishkumar R. (författare)
- Luleå tekniska universitet,Medicinsk vetenskap,Kemiteknik
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- Al-Hayali, Amani (författare)
- Luleå tekniska universitet,Medicinsk vetenskap
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- Cavanagh, Katie L. (författare)
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor
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- Rodríguez- Hornedo, Nair (författare)
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor
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- Velaga, Sitaram P. (författare)
- Luleå tekniska universitet,Medicinsk vetenskap
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visa färre...
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(creator_code:org_t)
- 2018-06-18
- 2018
- Engelska.
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 18:8, s. 4378-4387
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The purpose of this study was to enhance the solubility and dissolution of a poorly water-soluble drug, tadalafil (TDF), by cocrystal formation with malonic acid (MOA), to characterize the cocrystal structure, and to quantify the cocrystal solution behavior. The crystal structure revealed a 1:1 stoichiometry wherein the TDF molecules form a double layered structure through N–H…O=C interactions linked to a catemeric chain of MOA molecules via O-H…O hydrogen bonds. Cocrystal solubility advantage (SA defined as Scocrystal/Sdrug) or supersaturation index was determined from eutectic point measurements to be 102 to 129 in the pH range of 1 to 3. Cocrystal dissolution generated supersaturation levels (Cmax/Sdrug) of 30 in buffer and 120 in the presence of a nucleation inhibitor, HPMC. The amorphous form of TDF generated supersaturation 3 times lower than cocrystal in buffer, and not significantly different from cocrystal in the presence of HPMC. Thus, supersaturation index is a valuable metric for assessing the risk of cocrystal conversion during kinetic studies and for predicting conditions when the usage of a precipitation inhibitor may significantly increase cocrystal exposure levels.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Annan hälsovetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Other Health Sciences (hsv//eng)
- NATURVETENSKAP -- Kemi -- Fysikalisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Physical Chemistry (hsv//eng)
Nyckelord
- Health Science
- Hälsovetenskap
- Chemistry of Interfaces
- Gränsytors kemi
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- art (ämneskategori)
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