title: Application of spray granulation for conversion of mixed phospholipid-bile salt micelles to dry powder form: influence of drug hydrophobicity on nanoparticle reagglomeration.
abstract: The aim of this study was to investigate the feasibility of using spray granulation as a drying method to convert phospholipid (PL)-sodium deoxycholate (SDC)-mixed micelles (MMs) containing a water-insoluble drug to a solid dosage form and to evaluate how drugs with significantly different physicochemical properties affect the spray granulation process and subsequent in vitro and in vivo processes. Cucurbitacin B (Cu B) and glycyrrhizin (GL) were used as the model drugs. After spray granulation, the dried Cu B-PL/SDC-MM powder was completely redispersible within 15 minutes in vitro. Meanwhile, the area under the curve during 24 hours (AUC0-24) and peak serum concentration from the dried powder were significantly (P<0.05) lower than the values from Cu B-PL/SDC-MMs in vivo. However, a better result was obtained for GL, ie, the drug was redispersed completely within 5 minutes in vitro. Further, absorption from the dried GL-PL/SDC-MM powder was increased to the same level as that for GL-PL/SDC-MMs in vivo compared with the control group. The difference in these results can be found in Cu B and GL. Cu B nanoparticles reagglomerated when released, resulting in slower redispersibility and less absorption compared with the original PL-SDC-MMs. However, no agglomeration or delay was observed for GL. A possible explanation is the difference in surface hydrophobicity between Cu B and GL. The results of this study not only show that spray granulation is an effective drying technique that can complement spray-drying and freeze-drying, but also confirm that the physicochemical properties of a drug have a significant influence on the in vitro and in vivo performance of the dried powder obtained after spray granulation.
authors: Department of Pharmacy, 302 Military Hospital, Beijing, People's Republic of China.
authors: Qingyuan
authors: Q
authors: Lv
authors: Institute for Drug and Instrument Control, Health Department, General Logistics Department of People's Liberation Army, Beijing, People's Republic of China.
authors: Xianyi
authors: X
authors: Li
authors: Department of Pharmacy, 302 Military Hospital, Beijing, People's Republic of China.
authors: Baode
authors: B
authors: Shen
authors: Department of Pharmacy, 302 Military Hospital, Beijing, People's Republic of China.
authors: He
authors: H
authors: Xu
authors: Department of Pharmacy, 302 Military Hospital, Beijing, People's Republic of China.
authors: Chengying
authors: C
authors: Shen
authors: Department of Pharmacy, 302 Military Hospital, Beijing, People's Republic of China.
authors: Ling
authors: L
authors: Dai
authors: Department of Pharmacy, 302 Military Hospital, Beijing, People's Republic of China.
authors: Jinxia
authors: J
authors: Bai
authors: Department of Pharmacy, 302 Military Hospital, Beijing, People's Republic of China.
authors: Hailong
authors: H
authors: Yuan
authors: Department of Pharmacy, 302 Military Hospital, Beijing, People's Republic of China.
authors: Jin
authors: J
authors: Han
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003890:Desiccation / Q000379:methods; D004285:Dogs; D004355:Drug Stability; D019695:Glycyrrhizic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008823:Micelles; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D012995:Solubility; D014315:Triterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D001647:Bile Acids and Salts; D008823:Micelles; D010743:Phospholipids; D011208:Powders; D014315:Triterpenes; C041246:cucurbitacin B; D019695:Glycyrrhizic Acid
keywords: cucurbitacin B; fluid bed granulation; glycyrrhizin; mixed phospholipid-bile salt micelles; poorly water soluble drugs