Study on Mechanism for Amorphous Drug Stabilization Using Gelucire 50/13

• Shimpi Shamkant Laxman

  Formulation Research Division, APL Research Centre, Aurobindo Pharma Ltd.

• Mahadik Kakasaheb Ramoo

  Department of Pharmaceutics, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy

• Paradkar Anant Raghunath

  Institute of Pharmaceutical Innovation, and IRC in Polymer Science and Technology, University of Bradford

抄録

Methods of preparation and application of amorphous form are well established but it is equally important to note that devitrification of amorphous drugs has limited their applications. Present study was performed to investigate mechanism for amorphous drug stabilization using Gelucire in comparison with polyvinylpyrrolidone (PVP). Etoricoxib and celecoxib were taken as model drugs for this study, as etoricoxib has only proton accepting site for hydrogen bonding in comparison with celecoxib, which has both proton accepting and donating site. Solid dispersion of celecoxib with polyvinylpyrrolidone and Gelucire was prepared by spray drying and melt-granulation technique respectively. X-ray powder diffractometry and differential scanning calorimetry were used to study the physical state of the drug. Dissolution studies were performed to differentiate dissolution performance. Stability study samples were evaluated for physical state of the drug and dissolution performance. An IR study in correlation with molecular modeling was carried out to study the mechanism for stabilization. Dissolution of melt-granulation of amorphous celecoxib was improved significantly as compared to amorphous celecoxib and Celecoxib-PVP solid dispersion. Melt-granulation with lipid seemed to be more dominant than amorphization of drug for improving dissolution. Stability data revealed that PVP was significantly advantageous for amorphous form stabilization whereas Gelucire failed in case of Celecoxib. In contrast to this, our previous study revealed the stabilization ability of Gelucire for amorphous etoricoxib. Molecular modeling and IR studies revealed that H-bonding was predominant mechanism for stabilization. Out of two proposed mechanism for amorphous drug stabilization by lipids, H-bonding ability is more dominant than immobilization of molecule in lipid matrix.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 57 (9), 937-942, 2009

  公益社団法人 日本薬学会

キーワード

• amorphous state
• solid dispersion
• Gelucire
• mechanism
• stabilization
• molecular modeling

詳細情報

• CRID: 1390282679145204608
• NII論文ID: 130000124188
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.57.937
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 10332557
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10332557
• Web Site: http://www.jstage.jst.go.jp/article/cpb/57/9/57_9_937/_pdf
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • CiNii Articles
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