Thermodynamics of Drug Nanoencapsulation: Case Study of Phenytoin- Poly (D, L-lactide) Nanocarrier

Author(s): Nisha Vijay, James B. Murowchick, Bi-Botti C. Youan

Journal Name: Current Drug Delivery

Volume 7 , Issue 5 , 2010

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In order to rationalize the nanoencapsulation process, a thermodynamic analysis allowed to predict the limit of a model drug (phenytoin, PHT) loading into poly (d, l-lactic acid) nanocarrier (PLA NC) prepared by solvent displacement method. The NC were characterized for size, morphology, thermal behavior and crystallography by dynamic light scattering, electron microscopies, differential scanning calorimetry, and powder X-ray diffraction, respectively. The drug loading, encapsulation efficiency (EE) and in vitro drug release profile were determined using high performance liquid chromatography. There was a logarithmic correlation between the partial molar free energy change based on the molecular descriptors and the drug / polymer weight (D/P) ratio predicting an equilibrium state at ratio=0.29. This was consistent with experimental data as PHT appeared to be loaded either in crystalline or molecular/amorphous state within the PLA matrix with an average EE coefficient of 91.5%. Overall, the smallest PHT NC had a mean diameter of 231 nm and was produced at the limiting D/P ratio of 0.33, using PHT: 18mg, PLA: 60mg and surfactant: 0.3% w/v. The drug release occurred by diffusion following Higuchi model within 24 hours. These data suggested that thermodynamic analysis allows elucidating PHT encapsulation within PLA NC and may be useful in the rationale design of other macromolecular basednanocarriers.

Keywords: Drug loading, nanocarrier, phenytoin, poly (d, l-lactide), thermodynamics

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Article Details

Year: 2010
Page: [343 - 354]
Pages: 12
DOI: 10.2174/156720110793566254
Price: $65

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