title: Spray-dried nanocrystals for a highly hydrophobic drug: Increased drug loading, enhanced redispersity, and improved oral bioavailability.
abstract: For a highly hydrophobic and drug, it is difficult to formulate and solidify its nanocrystals with high drug loading and good redispersity. In this study, Allisartan Isoproxil was used as a model drug, and SDS was tested in combination with sugar alcohols to improve the drug loading and redispersity for its spray-dried nanocrystals, simultaneously. These spray-dried nanocrystals had high drug loading of 61.7% and good redispersity, which was mainly attributed to the addition of SDS. In addition, the nanocrystals were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray power diffraction analysis, Fourier transform infrared spectroscopy and Raman spectroscopy. The results showed that Allisartan Isoproxil was unchanged in chemical structure, but was partially amorphous. Regarding the in vitro dissolution, the optimism formulation shown an increased dissolution compared with the bulk drug and aggregated nanocrystals. Importantly, the optimum formulation increased the oral bioavailability of crude ALS-3 for 4.73 times. In conclusion, we developed a method to solidify aqueous nanocrystals with increased drug loading, good redispersity and improved bioavailability for high hydrophobic drugs.
authors.affiliation: School of Pharmacy and School of Wuya, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Yanxian
authors.initials: Y
authors.lastname: Hou
authors.affiliation: School of Pharmacy and School of Wuya, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Shao
authors.affiliation: School of Pharmacy and School of Wuya, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address: graham_pharm@aliyun.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: School of Pharmacy and School of Wuya, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy and School of Wuya, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China. Electronic address: sunjin0529@aliyun.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of Pharmacy and School of Wuya, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding / Q000379:methods; D057927:Hydrophobic and Hydrophilic Interactions; D007093:Imidazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D053758:Nanoparticles; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; C587132:allisartan isoproxil
keywords: Characterization; Drug loading; Nanocrystals; Oral bioavailability; Redispersity; Spray-drying