title: Liquid and solid self-microemulsifying drug delivery systems for improving the oral bioavailability of andrographolide from a crude extract of Andrographis paniculata.
abstract: The purpose of this study was to develop self-microemulsifying formulations of an Andrographis paniculata extract in liquid and pellet forms for an improved oral delivery of andrographolide. The optimized liquid self-microemulsifying drug delivery system (SMEDDS) was composed of A. paniculata extract (11.1%), Capryol 90 (40%), Cremophor RH 40 (40%) and Labrasol (8.9%). This liquid SMEDDS was further adsorbed onto colloidal silicon dioxide and microcrystalline cellulose, and converted to SMEDDS pellets by the extrusion/spheronization technique. The microemulsion droplet sizes of the liquid and pellet formulations after dilution with water were in the range of 23.4 and 30.3 nm. The in vitro release of andrographolide from the liquid SMEDDS and SMEDDS pellets was 97.64% (SD 1.97%) and 97.74% (SD 3.36%) within 15 min, respectively while the release from the initial extract was only 10%. The oral absorption of andrographolide was determined in rabbits. The C(max) value of andrographolide from the A. paniculata extract liquid SMEDDS and SMEDDS pellet formulations (equivalent to 17.5mg/kg of andrographolide) was 6-fold and 5-fold greater than the value from the initial extract in aqueous suspension (equivalent to 35 mg/kg of andrographolide), respectively. In addition, the AUC(0-12h) was increased 15-fold by the liquid SMEDDS and 13-fold by the SMEDDS pellets compared to the extract in aqueous suspension, respectively. The results clearly indicated that the liquid and solid SMEDDS could be effectively used to improve the dissolution and oral bioavailability that would also enable a reduction in the dose of the poorly water soluble A. paniculata extract.
authors: Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
authors: Namfa
authors: N
authors: Sermkaew
authors: Wichan
authors: W
authors: Ketjinda
authors: Prapaporn
authors: P
authors: Boonme
authors: Narubodee
authors: N
authors: Phadoongsombut
authors: Ruedeekorn
authors: R
authors: Wiwattanapatapee
mesh_terms: D035685:Andrographis; D000818:Animals; D001682:Biological Availability; D004224:Diterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D005750:Gastric Juice / Q000737:chemistry; D005989:Glycerides; D008297:Male; D009930:Organic Chemicals / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D011817:Rabbits; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D004224:Diterpenes; D005989:Glycerides; D009930:Organic Chemicals; D010936:Plant Extracts; D011409:Propylene Glycols; D013501:Surface-Active Agents; C440220:Labrasol; C022131:cremophor; D011092:Polyethylene Glycols; C030419:andrographolide
keywords: Andrographis paniculata; Andrographolide; Oral absorption; SMEDDS; Self-microemulsifying drug delivery systems