| Relative bioavailability of three different solid forms of PNU-141659 as determined with the artificial stomach-duodenum model. | |
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MedLine Citation:
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PMID: 20564336 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The artificial stomach-duodenum (ASD) apparatus was designed and constructed to assess the in vitro performance of bulk drugs and their formulations in a device which is able to simulate different species and physiological conditions. As a continued demonstration of its application to a pharmaceutical problem, screening experiments were performed on three different solid forms of a drug candidate, PNU-141659. This compound exhibited poor solubility and permeability, and presented a significant problem in the development of a successful dosage form. Simple formulations of an anhydrous form, a hydrated form and an amorphous form of the drug were all assessed with the ASD set up to simulate dog physiology. The solubility ordering of these three forms was anhydrate < hemihydrate < amorphous and this is the first ASD study to directly compare amorphous and crystalline solid forms. However, the results of the ASD studies showed that the hydrated form, with the intermediate solubility should provide the highest bioavailability, not the more soluble amorphous form. This occurred because the more soluble amorphous form underwent a phase conversion to Form I during the ASD experiment. The results from the ASD compared favorably with those later obtained from in vivo dog studies. |
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Authors:
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Stephen R Carino; David C Sperry; Michael Hawley |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: 99 ISSN: 1520-6017 ISO Abbreviation: J Pharm Sci Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-07-28 Completed Date: 2010-11-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: United States |
Other Details:
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Languages: eng Pagination: 3923-30 Citation Subset: IM |
Affiliation:
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Pfizer R&D, Eastern Point Road, Groton, Connecticut 06340, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Biological Availability* Chemistry, Pharmaceutical / instrumentation* Crystallization Duodenum / metabolism* Models, Biological Pharmaceutical Preparations / chemistry* Solubility Stomach / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Pharmaceutical Preparations |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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