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 language | English (US) |
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Pages (from-to) | 2292-2300 |
Number of pages | 9 |
Journal | Pharmaceutical Research |
Volume | 32 |
Issue number | 7 |
DOIs | |
State | Published - 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)