Preparation and characterization of hydroxypropyl methyl cellulose films containing stable BCS Class II drug nanoparticles for pharmaceutical applications

Published Date
International Journal of Pharmaceutics
28 February 2012, Vol.423(2):496–508, doi:10.1016/j.ijpharm.2011.12.001

Pharmaceutical nanotechnology

• Author 

• Lucas Sievens-Figueroa ^a
• Anagha Bhakay ^a
• Jackeline I. Jerez-Rozo ^b
• Natasha Pandya ^a
• Rodolfo J. Romañach ^b
• Bozena Michniak-Kohn ^d
• Zafar Iqbal ^c
• Ecevit Bilgili ^a
• Rajesh N. Davé ^a,,

• aDepartment of Chemical, Biochemical, and Pharmaceutical Engineering, New Jersey Institute of Technology, United States
• bDepartment of Chemistry, University of Puerto Rico, Mayagüez Campus, United States
• cDepartment of Chemistry and Environmental Science, New Jersey Institute of Technology, United States
• dDepartment of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, United States

Received 7 October 2011. Revised 29 November 2011. Accepted 1 December 2011. Available online 9 December 2011. 

Abstract

The design and feasibility of a simple process of incorporating stable nanoparticles into edible polymer films is demonstrated with the goal of enhancing the dissolution rate of poorly water soluble drugs. Nanosuspensions produced from wet stirred media milling (WSMM) were transformed into polymer films containing drug nanoparticles by mixing with a low molecular weight hydroxylpropyl methyl cellulose (HPMC E15LV) solution containing glycerin followed by film casting and drying. Three different BCS Class II drugs, naproxen (NPX), fenofibrate (FNB) and griseofulvin (GF) were studied. The influence of the drug molecule on the film properties was also investigated. It was shown that film processing methodology employed has no effect on the drug crystallinity according to X-ray diffraction (XRD) and Raman spectroscopy. Differences in aggregation behavior of APIs in films were observed through SEM and NIR chemical imaging analysis. NPX exhibited the strongest aggregation compared to the other drugs. The aggregation had a direct effect on drug content uniformity in the film. Mechanical properties of the film were also affected depending on the drug–polymer interaction. Due to strong hydrogen bonding with the polymer, NPX exhibited an increase in Young's Modulus (YM) of approximately 200%, among other mechanical properties, compared to GF films. A synergistic effect between surfactant/polymer and drug/polymer interactions in the FNB film resulted in an increase of more than 600% in YM compared to the GF film. The enhancement in drug dissolution rate of films due to the large surface area and smaller drug particle size was also demonstrated.

Graphical abstract

Keywords

• Nanosuspensions
• Media milling
• BCS Class II
• Pharmaceutical films
• Hydroxylpropyl methyl cellulose

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Copyright © 2011 Elsevier B.V. All rights reserved.

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