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

Apurva R. Patel, Chandraiah Godugu, Heather Wilson, Stephen Safe, Mandip Singh

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Purpose: 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.

Original languageEnglish (US)
Pages (from-to)2292-2300
Number of pages9
JournalPharmaceutical Research
Volume32
Issue number7
DOIs
StatePublished - Jul 30 2015

Keywords

  • DIM
  • anti-cancer activity
  • dual channel spray drying
  • enteric coating
  • self-emulsifying drug delivery

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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