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Improving the Chemical Stability of Amorphous Solid Dispersion with Cocrystal Technique by Hot Melt Extrusion

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ABSTRACT

Purpose

To explore in-situ forming cocrystal as a single-step, efficient method to significantly depress the processing temperature and thus minimize the thermal degradation of heat-sensitive drug in preparation of solid dispersions by melting method (MM) and hot melt extrusion (HME).

Methods

Carbamazepine (CBZ)-nicotinamide (NIC) cocrystal solid dispersions were prepared with polymer carriers PVP/VA, SOLUPLUS and HPMC by MM and/or HME. The formation of cocrystal was investigated by differential scanning calorimetry and hot stage polarized optical microscopy. State of CBZ in solid dispersion was characterized by X-ray powder diffraction and optical microscopy. Interactions between CBZ, NIC and polymers were investigated by FTIR. Dissolution behaviors of solid dispersions were compared with that of pure CBZ.

Results

CBZ-NIC cocrystal with melting point of 160°C was formed in polymer carriers during heating process, and the preparation temperature of amorphous CBZ solid dispersion was therefore depressed to 160°C. The dissolution rate of CBZ-NIC cocrystal solid dispersion was significantly increased.

Conclusions

By in-situ forming cocrystal, chemically stable amorphous solid dispersions were prepared by MM and HME at a depressed processing temperature. This method provides an attractive opportunity for HME of heat-sensitive drugs.

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Abbreviations

CBZ:

carbamazepine

DSC:

differential scanning calorimetry

FTIR:

fourier transform infrared spectroscopy

HME:

hot melt extrusion

HPLC:

high performance liquid chromatography

HSPM:

hot stage polarized optical microscopy

MM:

melting method

NIC:

nicotinamide

T g :

glass transition temperature

T m :

melting point

TGA:

thermal gravimetric analysis

XRPD:

X-ray powder diffraction

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ACKNOWLEDGMENTS & DISCLOSURES

This work was supported by Guangdong Research Center for Drug Delivery Systems (No. GCZX-A0801). We are grateful to Mrs. Aiping Huang for the help of HSPM experiment. We are also acknowledging Thermo Fisher Scientific (China) Co., Ltd. for the help of HME experiment.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, Guangdong, People’s Republic of China

    Xu Liu, Ming Lu, Zhefei Guo, Lin Huang, Xin Feng & Chuanbin Wu

  2. Research & Development Center of Pharmaceutical Engineering, Sun Yat-Sen University, Guangzhou, 510006, People’s Republic of China

    Chuanbin Wu

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  1. Xu Liu
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  2. Ming Lu
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Correspondence to Ming Lu or Chuanbin Wu.

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Liu, X., Lu, M., Guo, Z. et al. Improving the Chemical Stability of Amorphous Solid Dispersion with Cocrystal Technique by Hot Melt Extrusion. Pharm Res 29, 806–817 (2012). https://doi.org/10.1007/s11095-011-0605-4

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  • DOI: https://doi.org/10.1007/s11095-011-0605-4

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