title: Evaluation of Spray BIO-Max DIM-P in Dogs for Oral Bioavailability and in Nu/nu Mice Bearing Orthotopic/Metastatic Lung Tumor Models for Anticancer Activity.
abstract: OBJECTIVE
  In an effort to prepare an oral dosage form for poorly bioavailable anti-cancer agents, we have incorporated spray drying using a customized spray gun generating enteric coated Self-emulsifying drug delivery systems. The objective of this study was to design and evaluate pharmacokinetics and pharmacodynamic characteristics of Spray BIO-Max DIM-P (SB DIM-P).
  
  
  METHODS
  SB DIM-P was prepared and optimized based on physico-chemical characteristics using design of experiment (DOE-Vr 8.0) software. Pharmacokinetic parameters in dogs and rats were evaluated and analyzed using Winonlin. Anti-tumor activity was carried out in orthotopic and metastatic lung tumor models using size M capsules in mice.
  
  
  RESULTS
  Based on the optimization using DOE analysis of SB DIM-P characteristics, formulations were selected for further investigation. Pharmacokinetic studies showed a 30% increase in oral bioavailability in rats and ~2.9 times more bioavailability of SB DIM-P compare to solution in dogs. SB DIM-P showed ~20-25% more tumor volume/weight reduction in H1650 metastatic tumor model and ~25-30% tumor volume/weight reduction in A549 orthotopic tumor model compared to DIM-P solution.
  
  
  CONCLUSIONS
  Our studies demonstrate the potential application of spray dried enteric coated self-emulsifying delivery system (SB DIM-P) to enhances oral absorption and efficacy of DIM-P in lung tumor models.
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, 32307, USA.
authors.forename: Apurva R
authors.initials: AR
authors.lastname: Patel
authors.forename: Chandraiah
authors.initials: C
authors.lastname: Godugu
authors.forename: Heather
authors.initials: H
authors.lastname: Wilson
authors.forename: Stephen
authors.initials: S
authors.lastname: Safe
authors.forename: Mandip
authors.initials: M
authors.lastname: Singh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004285:Dogs; D004655:Emulsions; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D017207:Rats, Sprague-Dawley; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D007211:Indoles