Preparation and bioavailability in healthy volunteers of cefaclor modified-release capsules

Abstract

Abstract:

Aim To investigate whether modified-release cefaclor capsules could lead to a more suitable pharmacokinetic profile in the plasma. Methods Cefaclor pellets were prepared by extrusion/spheronization and coated by Eudragit L30D-55 or Eudragit NE30D, then the two sorts of pellets were filled to capsules in a 35:65 ratio to made a modified-release(MR) capsules. The bioavailability of the MR capsules was studied in 24 healthy volunteers after oral administration in a fast state using a commercially available immediate release(IR) capsule as a reference. Results The results showed that the MR formulation had a relatively good bioavailability compared with the commercial capsules, as well as a longer time keeping drug level above MIC than immediate release capsule. The relative bioavailability of the MR capsules was 97.4 ± 12.1%. Conclusion The data of the present study indicate that time of cefaclor plasma concentration above MIC can be substantially prolonged if cefaclor is administered as a modified-release product.

Key words: Cefaclor, Cefaclor, Modified-release, Modified-release, Pellets, Pellets, Capsules, Capsules, Bioavailability, Bioavailability

CLC Number:

Supporting:

Lian-Dong Hu^*, Cheng-Wei Wang

. Preparation and bioavailability in healthy volunteers of cefaclor modified-release capsules[J]. .

References

[1] Barbhaiya RH, ShuklaVA, Gleason CR, et al. Phase I study of multiple-dose cefprozil and comparison with cefaclor [J]. Antimicrob Agents Chemother, 1990, 34 (6): 1198–1203.
[2] Barbhaiya RH, Shukla VA, Gleason CR, et al. Comparison of cefprozil and cefaclor pharmacokinetics and tissue penetration [J]. Antimicrob Agents Chemother, 1990, 34 (6): 1204–1249.
[3] James NC, Donn KH, Collins JJ, et al. Pharmacokinetics of cefuroxime axetil and cefaclor: relationship of concentrations in serum to MICs for common respiratory pathogens [J]. Antimicrob Agents Chemother, 1991, 35, 1860–1863.
[4] Satterwhite JH,CerimeleBJ,ColemanDL, et al. Pharmacokinetics of cefaclor AF: effects of age, antacids and H2-receptor antagonists [J]. Postgrad Med J, 1992, 68, S3–9.
[5] Sides GD, Franson TR, DeSante KA, et al. A comprehensive review of the clinical pharmacology and pharmacokinetics of cefaclor [J]. Clin Ther, 1988, 11 Suppl A: 5–19.
[6] Sourgen H, Derendorf H, Schifferen H. Pharmacokinetic profile of cefaclor [J]. Int J Clin Pharmacol Ther, 1997, 35 (9): 374–380.
[7] Alanis A, Longest KA, Senetar JE, et al. A multicentre trial of cefaclor advanced formulation versus cefaclor in the treatment of acute bronchitis [J]. Postgrad Med J, 1992, 68, S24–28.
[8] Craig WA, Ebert SC. Continuous infusion of beta-lactam antibiotics [J]. Antimicrob Agents Chemother, 1992, 36 (12): 2577–2583.
[9] Craig WA. Antibiotic selection factors and description of a hospital-based outpatient antibiotic therapy program in the USA [J]. Eur J Clin Microbiol Infect Dis, 1995, 14 (7), 636–642.
[10] Cramer J, Vachon L, Desforges C, et al. Dose frequency and dose interval compliance with multiple antiepileptic medications during a controlled clinical trial [J]. Epilepsia, 1995, 36 (11), 1111–1117.
[11] Eisen SA, Miller DK, Woodwards RS, et al. The effect of prescribed daily dose frequency on patient medication compliance[J]. Arch Intern Med, 1990, 150 (9), 1881–1884.

[1]	Xiuwei Yang, Youbo Zhang, Wei Xu. Determination and pharmacokinetic study of p-hydroxyphenethyl anisate following intravenous and oral administration in rats by RP-HPLC method [J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(11): 804-812.
[2]	Yajie Yin, Xiaofei Zhang, Zheng Cui, Wei Qu, Bing He, Wenbing Dai, Hua Zhang, Xueqing Wang, Qiang Zhang. In vitro dissolution and oral bioavailability study of fenofibrate nanomatrix system prepared by hot-melt extrusion [J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(5): 329-338.
[3]	Zhengsheng Liu, Haijun Hao, Mingsong Fan. Quercetin-phospholipids complex solid dispersion and quercetin solid dispersion: preparation and evaluation [J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(12): 868-877.
[4]	Jinfeng Zhang, Fan Wu, Jiayi Han, Jinghong Rong, Yi Li, Yu Liu, Xiao Liang, Xin Wang, Hao Pan, Hongsheng Liu, Lijiang Chen. Preparation, characterization and pharmacokinetic studies of total paeony glycoside nanocrystals [J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(2): 99-108.
[5]	Xinguo Zhang, Jinweng Liu, Fei Kou, Qianglin Wang, Ziyu Liu, Jianyong Li. Bioavailability and pharmacokinetics of alantolactone from Inula helenium in rats following intravenous and oral administrations [J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(4): 284-290.
[6]	Zhou Wen, Shan Ji, Feifan Xie, Gaoyun Hu, Zeneng Cheng. Determination of mefunidone, a novel anti-fibrotic agent analogue of pirfenidone, in plasma by HPLC-UV and its pharmacokinetic application in rats [J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(1): 45-52.
[7]	Xianchuang Wu, Haijun Hao, Yuxin Liu, Xiaoyong Song, Yongzhou Zhang, Hongqin Zhang. Bioavailability of 10-hydroxycamptothecin-phospholipid complex loaded by solid dispersion and lipid-based formulations [J]. Journal of Chinese Pharmaceutical Sciences, 2015, 24(12): 780-788.
[8]	Zhiyan Lin, Rongfu Yang, Yuenian Tang, Huaiping Tian, Jian Zhang. Application of UHPLC-MS/MS method in determining the content of multi-ingredient in hospital preparations [J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(4): 233-240.
[9]	Pallavi M. Chaudhari, Pravin D. Chaudhari. Formulation and characterization of extruded and spheronized pellets using pectin and crosslinking agents [J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(11): 790-798.
[10]	Haijun Hao^*, Youzhi Jia, Ru Han. Phytosomes: an effective approach to enhance the oral bioavailability of active constituents extracted from plants [J]. , 2013, 22(5): 385-392.
[11]	Yan-Jiao Li, Hui-Min Liu, Xiao-Fang Dang, Shuo-Feng Zhang, Jin-Ying Wu, Zhan-Hong Jia, Li-Wei Han^*. A pharmacokinetic study of puerarin formulated in mixed micelles in Beagle dogs by HPLC [J]. , 2012, 21(4): 327-332.
[12]	Ya-Ou Liu, Jie-Ming Fan, Xue-Qing Wang^*, Qiang Zhang. Preparation of sorafenib self-microemulsifying drug delivery system and its relative bioavailability in rats [J]. , 2011, 20(2): 164-170.
[13]	Yan-Li Zhang, Xing-Xin Yang, Xiao-Ni Li^*. Quantitative analysis of astragaloside IV in traditional Chinese medicine 'Huang-Qi-Si-Wu' Capsules by HPLC/UV [J]. , 2010, 19(3): 223-228.
[14]	Xin-Ru Li, Yu-Sheng Pei, Yan-Qing Huang, Yan-Xia Zhou, Yu-Chen Zhang, Yan Liu^. In vitro* and in vivo evaluation of a self-microemulsifying drug delivery system for silybin [J]. , 2009, 18(4): 342-347.
[15]	Ning Tang, Jie Lai, Ya-Pin Chen, Yi Lu^, Wei Wu^. Fenofibrate solid dispersion pellets prepared by fluid-bed coating: physical characterization, improved dissolution and oral bioavailability in beagle dogs [J]. , 2009, 18(2): 156-161.