Cefdinir Solid Dispersion Composed of Hydrophilic Polymers with Enhanced Solubility, Dissolution, and Bioavailability in Rats

Abstract: The aim of this work was to develop cefdinir solid dispersions (CSDs) prepared using hydrophilic polymers with enhanced dissolution/solubility and in vivo oral bioavailability. CSDs were prepared with hydrophilic polymers such as hydroxypropyl-methylcellulose (HPMC; CSD1), carboxymethylcellulose-Na (CMC-Na; CSD2), polyvinyl pyrrolidone K30 (PVP K30; CSD3) at the weight ratio of 1:1 (drug:polymer) using a spray-drying method. The prepared CSDs were characterized by aqueous solubility, differential scanning calorimetry (DSC), powder X-ray diffraction (p-XRD), scanning electron microscopy (SEM), aqueous viscosity, and dissolution test in various media. The oral bioavailability of CSDs was also evaluated in rats and compared with cefdinir powder suspension. The cefdinir in CSDs was amorphous form, as confirmed in the DSC and p-XRD measurements. The developed CSDs commonly resulted in about 9.0-fold higher solubility of cefdinir and a significantly improved dissolution profile in water and at pH 1.2, compared with cefdinir crystalline powder. Importantly, the in vivo oral absorption (represented as AUCinf) was markedly increased by 4.30-, 6.77- and 3.01-fold for CSD1, CSD2, and CSD3, respectively, compared with cefdinir suspension in rats. The CSD2 prepared with CMC-Na would provide a promising vehicle to enhance dissolution and bioavailability of cefdinir in vivo.

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Cefdinir Solid Dispersion Composed of Hydrophilic Polymers with Enhanced Solubility, Dissolution, and Bioavailability in Rats
Hyun-Jong Cho 1,†, Jun-Pil Jee 2,†, Ji-Ye Kang 3, Dong-Yeop Shin 4, Han-Gon Choi 5, Han-Joo Maeng 6,* and Kwan Hyung Cho 3,*
1 College of Pharmacy, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon 24341, Korea
2 College of Pharmacy, Chosun University, 309 Pilmun-daero, Gwangju 61452, Korea
3 College of Pharmacy, Inje University, 197 Inje-ro, Gimhae 50834, Korea
4 School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 16419, Korea
5 College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Ansan 15588, Korea
6 College of Pharmacy, Gachon University, 191 Hambakmoei-ro, Yeonsu-gu, Incheon 21936, Korea
* Correspondence: Tel.: +82-32-820-4935 (H.-J.M.); +82-55-320-3883 (K.H.C.)
Molecules 2017, 22(2), 280; doi:10.3390/molecules22020280
molecules-22-00280.pdf
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