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KMID : 1146920230530040549
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Journal of Pharmaceutical Investigation
2023 Volume.53 No. 4 p.549 ~ p.561
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An economically advantageous amorphous solid dispersion of the fixed combination of lopinavir and ritonavir
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Yun Taek-Seon
Jung Min-Woo
Bang Ki-Hyun
Lee Hong-Ki
Jin Min-Ki
Yoo Hye-Lim
Won Jong-Hee
Song Bo-Min
Hwang Yu-Rim
Baek Jong-Suep
Cho Cheong-Weon
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Abstract
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Purpose : Solid dispersion strategies have recently been used to increase the solubility and bioavailability of poorly soluble drugs. Among these various strategies for solid dispersion, the method using polymers and adsorbents can improve the solubility and bioavailability of poorly soluble drugs and provide excellent powder fluidity. Therefore, the purpose of this study was to prepare and evaluate an amorphous solid dispersion (ASD) composed of LPV, RTV, polymer and adsorbent for oral administration.
Methods : The ASD powder was manufactured by dispersing LPV and RTV in a polymer solution and adsorbing the dispersion with an adsorbent. The ASD was characterized using physical characterization, differential scanning calorimetry, Fourier transform-infrared, powder X-ray diffractometer, in vitro release, and cytotoxicity tests. And ASD performed pharmacokinetic studies in rats.
Results : The ASD increased the solubility of raw LPV and RTV by 5.71 times and 4.38 times, respectively. When copovidone was used as the polymer in the ASD, the solubility was maintained for 10 days in the solubility kinetic test, whereas the solubility of LPV decreased from day 2 due to precipitation in an ASD without copovidone. The adsorbent, Florite PS-10, had a flowability suitable for the ASD powder, and the ASD did not increase cell cytotoxicity. In pharmacokinetic study, ASD showed 1186.51% relative bioavailability compared to raw LPV and about 2.1-fold increase than commercial products after oral administration.
Conclusion : Manufacture of an ASD powder using Florite PS-10 and copovidone as an oral administration formulation of LPV and RTV could be a new effective drug delivery system for human immunodeficiency virus treatment.
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KEYWORD
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Adsorbent, Amorphous solid dispersion, Lopinavir, Polymer, Ritonavir
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