TY - JOUR

T1 - Synthesis of poly(sebacic anhydride)-indomethacin controlled release composites via supercritical carbon dioxide assisted impregnation

AU - Gong, K.

AU - Rehman, I.U.

AU - Darr, J.A.

PY - 2007/6/29

Y1 - 2007/6/29

N2 - Poly(sebacic anhydride), PSA and indomethacin drug composite (DC) formulations were prepared using supercritical CO2 (sc-CO2) aided mixing. The effect of the experimental temperature and sebacic acid purity on the physical properties of PSA-indomethacin DCs was investigated using a range of analytical techniques. The nature of the PSA-indomethacin interaction in composites after processing in sc-CO2 under various conditions was investigated using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and powder X-ray diffraction (XRD) methods, respectively. The results indicate that processing at 130 °C of a 4:1 (w/w) ratio PSA-indomethacin mixture, renders the indomethacin amorphous and dispersed within the polymer matrix. The primary interaction between PSA and indomethacin appears to be hydrogen bonding between the carboxylic acid OH of indomethacin and the carbonyl group of PSA. In vitro dissolution studies revealed that the processed composites exhibit a substantially enhanced dissolution rate compared to the physical mixtures. Also, through the control of experimental conditions, the initial burst effect of the drug release was largely alleviated. Instead, the erosion of PSA (zero order degradation) became the dominant factor in controlling the drug release rate. © 2007 Elsevier B.V. All rights reserved.

AB - Poly(sebacic anhydride), PSA and indomethacin drug composite (DC) formulations were prepared using supercritical CO2 (sc-CO2) aided mixing. The effect of the experimental temperature and sebacic acid purity on the physical properties of PSA-indomethacin DCs was investigated using a range of analytical techniques. The nature of the PSA-indomethacin interaction in composites after processing in sc-CO2 under various conditions was investigated using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and powder X-ray diffraction (XRD) methods, respectively. The results indicate that processing at 130 °C of a 4:1 (w/w) ratio PSA-indomethacin mixture, renders the indomethacin amorphous and dispersed within the polymer matrix. The primary interaction between PSA and indomethacin appears to be hydrogen bonding between the carboxylic acid OH of indomethacin and the carbonyl group of PSA. In vitro dissolution studies revealed that the processed composites exhibit a substantially enhanced dissolution rate compared to the physical mixtures. Also, through the control of experimental conditions, the initial burst effect of the drug release was largely alleviated. Instead, the erosion of PSA (zero order degradation) became the dominant factor in controlling the drug release rate. © 2007 Elsevier B.V. All rights reserved.

KW - Amorphous

KW - Impregnation

KW - Indomethacin

KW - Poly(sebacic anhydride)

KW - Sc-CO2

KW - Supercritical fluid

KW - acid anhydride

KW - carbon dioxide

KW - indometacin

KW - poly(sebacic anhydride)

KW - unclassified drug

KW - analytic method

KW - article

KW - controlled drug release

KW - differential scanning calorimetry

KW - drug formulation

KW - drug solubility

KW - drug synthesis

KW - hydrogen bond

KW - infrared spectroscopy

KW - priority journal

KW - X ray diffraction

KW - Calorimetry, Differential Scanning

KW - Carbon Dioxide

KW - Decanoic Acids

KW - Delayed-Action Preparations

KW - Dicarboxylic Acids

KW - Polymers

KW - Solubility

KW - Spectroscopy, Fourier Transform Infrared

KW - X-Ray Diffraction

U2 - 10.1016/j.ijpharm.2007.02.009

DO - 10.1016/j.ijpharm.2007.02.009

M3 - Journal article

VL - 338

SP - 191

EP - 197

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -