Evaluation of the recrystallization kinetics of hot-melt extruded polymeric solid dispersions using an improved Avrami equation

Xin FengDepartment of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Mississippi, MS, USA,

Xingyou YeDepartment of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Mississippi, MS, USA,

Jun-Bom ParkDepartment of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Mississippi, MS, USA,

Wenli LuDepartment of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Mississippi, MS, USA,

Joe MorottDepartment of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Mississippi, MS, USA,

Brad BeissnerAshland Specialty Ingredients, Global Pharma R&D, Wilmington, DE, USA, and

Zhuoyang John LianAshland Specialty Ingredients, Global Pharma R&D, Wilmington, DE, USA, and

Elanor PintoAshland Specialty Ingredients, Global Pharma R&D, Wilmington, DE, USA, and

Vivian BiAshland Specialty Ingredients, Global Pharma R&D, Wilmington, DE, USA, and

Stu PorterAshland Specialty Ingredients, Global Pharma R&D, Wilmington, DE, USA, and

Tom DurigAshland Specialty Ingredients, Global Pharma R&D, Wilmington, DE, USA, and

Soumyajit MajumdarDepartment of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Mississippi, MS, USA,

Michael A. RepkaDepartment of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Mississippi, MS, USA, ;Pii Center for Pharmaceutical Technology, The University of Mississippi, University, Mississippi, MS, USACorrespondence[email protected]

show all

Abstract

The recrystallization of an amorphous drug in a solid dispersion system could lead to a loss in the drug solubility and bioavailability. The primary objective of the current research was to use an improved kinetic model to evaluate the recrystallization kinetics of amorphous structures and to further understand the factors influencing the physical stability of amorphous solid dispersions. Amorphous solid dispersions of fenofibrate with different molecular weights of hydroxypropylcellulose, HPC (Klucel™ LF, EF, ELF) were prepared utilizing hot-melt extrusion technology. Differential scanning calorimetry was utilized to quantitatively analyze the extent of recrystallization in the samples stored at different temperatures and relative humidity (RH) conditions. The experimental data were fitted into the improved kinetics model of a modified Avrami equation to calculate the recrystallization rate constants. Klucel LF, the largest molecular weight among the HPCs used, demonstrated the greatest inhibition of fenofibrate recrystallization. Additionally, the recrystallization rate (k) decreased with increasing polymer content, however exponentially increased with higher temperature. Also k increased linearly rather than exponentially over the range of RH studied.

Keywords

Declaration of interest

This project was partially supported by Grant Number P20GM104932 from the National Institute of General Medical Sciences (NIGMS), a component of NIH. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Evaluation of the recrystallization kinetics of hot-melt extruded polymeric solid dispersions using an improved Avrami equation

Information for

Open access

Opportunities

Help and information

Evaluation of the recrystallization kinetics of hot-melt extruded polymeric solid dispersions using an improved Avrami equation

Abstract

Declaration of interest

Reprints and Corporate Permissions

Academic Permissions

Related research

To cite this article:

Download citation

Information for

Open access

Opportunities

Help and information

Keep up to date

Your download is now in progress and you may close this window

Login or register to access this feature