title: Inclusion complex of aprepitant with cyclodextrin: evaluation of physico-chemical and pharmacokinetic properties.
abstract: OBJECTIVE
  Aprepitant (APR) is a water insoluble drug approved for the treatment of chemotherapy induced nausea and vomiting (CINV) and post-operative nausea and vomiting (PONV). The innovator Emend® is a formulation incorporating drug nanoparticles with good bioavailability (~67%). The objective of the current work was to evaluate the feasibility of formulating a cyclodextrin complex of APR with enhanced solubility/dissolution rate and concomitantly bioavailability.
  
  
  METHODS
  The complex was prepared using two approaches: kneading and slurry method. The formulated complex was evaluated using DSC, XRPD and FT-IR studies.
  
  
  RESULTS
  DSC, XRPD and FT-IR studies confirmed the interaction of β-cyclodextrin with APR indicating formation of a true complex wherein the drug was encapsulated in the cyclodextrin cavity (inclusion phenomenon). In addition to inclusion complexation, non inclusion phenomenon viz., interaction among hydroxyl groups of cyclodextrin and APR was also observed. The saturation solubility and dissolution rate of drug complex was higher than that of aprepitant API. The rate (C(max)) and extent of absorption (AUC) of APR from the complex were found to be comparable to that of Emend® (Reference product).
  
  
  CONCLUSIONS
  These studies established that cyclodextrin complexation may provide another viable and cost effective option for enhancing solubility and bioavailability of APR.
authors.affiliation: CoE Formulation Technology, Integrated Product Development Organization, Dr. Reddy's Laboratories Limited , Hyderabad , India.
authors.forename: Devendra N
authors.initials: DN
authors.lastname: Ridhurkar
authors.forename: Khalid Akhter
authors.initials: KA
authors.lastname: Ansari
authors.forename: Deepak
authors.initials: D
authors.lastname: Kumar
authors.forename: Neeraj S
authors.initials: NS
authors.lastname: Kaul
authors.forename: T
authors.initials: T
authors.lastname: Krishnamurthy
authors.forename: Sanju
authors.initials: S
authors.lastname: Dhawan
authors.forename: Raviraj
authors.initials: R
authors.lastname: Pillai
mesh_terms: D000328:Adult; D000932:Antiemetics / Q000032:analysis / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D000077608:Aprepitant; D001682:Biological Availability; D055598:Chemical Phenomena; D018592:Cross-Over Studies; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D005240:Feasibility Studies; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D055595:Mechanical Phenomena; D009025:Morpholines / Q000032:analysis / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D053758:Nanoparticles / Q000737:chemistry*; D064729:Neurokinin-1 Receptor Antagonists / Q000032:analysis / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D064449:Sequestering Agents / Q000737:chemistry; D012995:Solubility
chemical_list: D000932:Antiemetics; D003505:Cyclodextrins; D004337:Drug Carriers; D005079:Excipients; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D064449:Sequestering Agents; D000077608:Aprepitant