Tags

Type your tag names separated by a space and hit enter

Effect of HM30181 mesylate salt-loaded microcapsules on the oral absorption of paclitaxel as a novel P-glycoprotein inhibitor.
Int J Pharm. 2016 Jun 15; 506(1-2):93-101.IJ

Abstract

The purpose of this study was to develop HM30181 mesylate salt (HM30181M)-loaded microcapsules as a novel P-glycoprotein inhibitor for enhancing the oral absorption of paclitaxel. The effect of various carriers including hydrophilic polymers and solvents on the solubility of HM30181M were evaluated. Among the hydrophilic polymers and solvents tested, HPMC and methylene chloride (and ethanol) provided the highest HM30181M solubility. Numerous HM30181M-loaded microcapsules were prepared with HPMC, silicon dioxide and acidifying agents using a spray-drying technique, and their solubility, dissolution and physicochemical properties were evaluated. Furthermore, a pharmacokinetic study was performed after oral administration of paclitaxel alone, simultaneously with HM30181M powder or HM30181M-loaded microcapsules to rats. Among the acidifying agents investigated, phosphoric acid provided the best improvement in the solubility and dissolution of HM30181M. Moreover, the microcapsule composed of HM30181M, HPMC, silicon dioxide and phosphoric acid at a weight ratio of 3:6:3:2 remarkably enhanced the solubility and dissolution of HM30181M compared with the HM30181M powder alone. The microcapsules were spherical in shape, had a reduced particle size of about 7μm, and contained HM30181M in an amorphous state. Furthermore, this microcapsule significantly enhanced HM30181M absorption, making it about 1.7-fold faster and 1.6-fold greater after simultaneous administration, leading to about 70- and 2-fold improved oral bioavailability of paclitaxel compared with paclitaxel alone and the simultaneous administration with HM30181M powder, respectively. Thus, this novel microcapsule could be a potential candidate for effective P-glycoprotein inhibition during oral administration of paclitaxel.

Authors+Show Affiliations

College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea; Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-myeon, 893-5 Hwaseong, Gyeonggi-Do 445-913, South Korea.College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea; Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-myeon, 893-5 Hwaseong, Gyeonggi-Do 445-913, South Korea.College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-myeon, 893-5 Hwaseong, Gyeonggi-Do 445-913, South Korea.Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-myeon, 893-5 Hwaseong, Gyeonggi-Do 445-913, South Korea.College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, South Korea.Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-myeon, 893-5 Hwaseong, Gyeonggi-Do 445-913, South Korea. Electronic address: jswoo@hanmi.co.kr.College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea. Electronic address: hangon@hanyang.ac.kr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27106527

Citation

Kim, Jin Cheul, et al. "Effect of HM30181 Mesylate Salt-loaded Microcapsules On the Oral Absorption of Paclitaxel as a Novel P-glycoprotein Inhibitor." International Journal of Pharmaceutics, vol. 506, no. 1-2, 2016, pp. 93-101.
Kim JC, Kim KS, Kim DS, et al. Effect of HM30181 mesylate salt-loaded microcapsules on the oral absorption of paclitaxel as a novel P-glycoprotein inhibitor. Int J Pharm. 2016;506(1-2):93-101.
Kim, J. C., Kim, K. S., Kim, D. S., Jin, S. G., Kim, D. W., Kim, Y. I., Park, J. H., Kim, J. O., Yong, C. S., Youn, Y. S., Woo, J. S., & Choi, H. G. (2016). Effect of HM30181 mesylate salt-loaded microcapsules on the oral absorption of paclitaxel as a novel P-glycoprotein inhibitor. International Journal of Pharmaceutics, 506(1-2), 93-101. https://doi.org/10.1016/j.ijpharm.2016.04.034
Kim JC, et al. Effect of HM30181 Mesylate Salt-loaded Microcapsules On the Oral Absorption of Paclitaxel as a Novel P-glycoprotein Inhibitor. Int J Pharm. 2016 Jun 15;506(1-2):93-101. PubMed PMID: 27106527.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of HM30181 mesylate salt-loaded microcapsules on the oral absorption of paclitaxel as a novel P-glycoprotein inhibitor. AU - Kim,Jin Cheul, AU - Kim,Kyeong Soo, AU - Kim,Dong Shik, AU - Jin,Sung Giu, AU - Kim,Dong Wuk, AU - Kim,Yong Il, AU - Park,Jae-Hyun, AU - Kim,Jong Oh, AU - Yong,Chul Soon, AU - Youn,Yu Seok, AU - Woo,Jong Soo, AU - Choi,Han-Gon, Y1 - 2016/04/19/ PY - 2016/03/09/received PY - 2016/03/31/revised PY - 2016/04/14/accepted PY - 2016/4/24/entrez PY - 2016/4/24/pubmed PY - 2017/4/13/medline KW - Bioavailability KW - HM30181 mesylate salt KW - Microcapsule KW - P-glycoprotein inhibitor KW - Paclitaxel KW - Solubility SP - 93 EP - 101 JF - International journal of pharmaceutics JO - Int J Pharm VL - 506 IS - 1-2 N2 - The purpose of this study was to develop HM30181 mesylate salt (HM30181M)-loaded microcapsules as a novel P-glycoprotein inhibitor for enhancing the oral absorption of paclitaxel. The effect of various carriers including hydrophilic polymers and solvents on the solubility of HM30181M were evaluated. Among the hydrophilic polymers and solvents tested, HPMC and methylene chloride (and ethanol) provided the highest HM30181M solubility. Numerous HM30181M-loaded microcapsules were prepared with HPMC, silicon dioxide and acidifying agents using a spray-drying technique, and their solubility, dissolution and physicochemical properties were evaluated. Furthermore, a pharmacokinetic study was performed after oral administration of paclitaxel alone, simultaneously with HM30181M powder or HM30181M-loaded microcapsules to rats. Among the acidifying agents investigated, phosphoric acid provided the best improvement in the solubility and dissolution of HM30181M. Moreover, the microcapsule composed of HM30181M, HPMC, silicon dioxide and phosphoric acid at a weight ratio of 3:6:3:2 remarkably enhanced the solubility and dissolution of HM30181M compared with the HM30181M powder alone. The microcapsules were spherical in shape, had a reduced particle size of about 7μm, and contained HM30181M in an amorphous state. Furthermore, this microcapsule significantly enhanced HM30181M absorption, making it about 1.7-fold faster and 1.6-fold greater after simultaneous administration, leading to about 70- and 2-fold improved oral bioavailability of paclitaxel compared with paclitaxel alone and the simultaneous administration with HM30181M powder, respectively. Thus, this novel microcapsule could be a potential candidate for effective P-glycoprotein inhibition during oral administration of paclitaxel. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/27106527/Effect_of_HM30181_mesylate_salt_loaded_microcapsules_on_the_oral_absorption_of_paclitaxel_as_a_novel_P_glycoprotein_inhibitor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(16)30318-0 DB - PRIME DP - Unbound Medicine ER -