Your browser doesn't support javascript.
loading
Quality by design development of brivanib alaninate tablets: degradant and moisture control strategy.
Badawy, Sherif I F; Lin, Judy; Gokhale, Madhushree; Desai, Sachin; Nesarikar, Vishwas V; LaMarche, Keirnan R; Subramanian, Ganeshkumar A; Narang, Ajit S.
Afiliación
  • Badawy SI; Drug product Science and Technology, Bristol-Myers Squibb Research and Development, New Brunswick, NJ, USA. Electronic address: sherif.badawy@bms.com.
  • Lin J; Drug product Science and Technology, Bristol-Myers Squibb Research and Development, New Brunswick, NJ, USA.
  • Gokhale M; Drug product Science and Technology, Bristol-Myers Squibb Research and Development, New Brunswick, NJ, USA.
  • Desai S; Drug product Science and Technology, Bristol-Myers Squibb Research and Development, New Brunswick, NJ, USA.
  • Nesarikar VV; Drug product Science and Technology, Bristol-Myers Squibb Research and Development, New Brunswick, NJ, USA.
  • LaMarche KR; Drug product Science and Technology, Bristol-Myers Squibb Research and Development, New Brunswick, NJ, USA.
  • Subramanian GA; Drug product Science and Technology, Bristol-Myers Squibb Research and Development, New Brunswick, NJ, USA.
  • Narang AS; Drug product Science and Technology, Bristol-Myers Squibb Research and Development, New Brunswick, NJ, USA.
Int J Pharm ; 469(1): 111-20, 2014 Jul 20.
Article en En | MEDLINE | ID: mdl-24780101
A quality by design approach was applied to the development of brivanib alaninate tablets. Brivanib alaninate, an ester pro-drug, undergoes hydrolysis to its parent compound, BMS-540215. The shelf-life of the tablets is determined by the rate of the hydrolysis reaction. Hydrolysis kinetics in the tablets was studied to understand its dependence on temperature and humidity. The BMS-540215 amount versus time profile was simulated using a kinetic model for the formation of BMS-540215 as function of relative humidity in the environment and a sorption-desorptiom moisture transfer model for the relative humidity inside the package. The combined model was used to study the effect of initial tablet water content on the rate of degradation and to identify a limit for initial tablet water content that results in acceptable level of the degradant at the end of shelf-life. A strategy was established for the moisture and degradant control in the tablet based on the understanding of its stability behavior and mathematical models. The control strategy includes a specification limit on the tablet water content and manufacturing process controls that achieve this limit at the time of tablet release testing.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triazinas / Profármacos / Agua / Inhibidores de la Angiogénesis / Alanina Tipo de estudio: Prognostic_studies Idioma: En Revista: Int J Pharm Año: 2014 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triazinas / Profármacos / Agua / Inhibidores de la Angiogénesis / Alanina Tipo de estudio: Prognostic_studies Idioma: En Revista: Int J Pharm Año: 2014 Tipo del documento: Article Pais de publicación: Países Bajos