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.
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Authors | Apurva R Patel, Chandraiah Godugu, Heather Wilson, Stephen Safe, Mandip Singh |
Journal | Pharmaceutical research
(Pharm Res)
Vol. 32
Issue 7
Pg. 2292-300
(Jul 2015)
ISSN: 1573-904X [Electronic] United States |
PMID | 25576245
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Emulsions
- Indoles
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Topics |
- Administration, Oral
- Animals
- Antineoplastic Agents
(administration & dosage, chemistry, pharmacokinetics, therapeutic use)
- Biological Availability
- Cell Line, Tumor
- Chemistry, Pharmaceutical
- Dogs
- Emulsions
- Humans
- Indoles
(administration & dosage, chemistry, pharmacokinetics, therapeutic use)
- Injections, Intravenous
- Lung Neoplasms
(drug therapy, metabolism, pathology)
- Male
- Mice, Nude
- Neoplasm Metastasis
- Rats, Sprague-Dawley
- Xenograft Model Antitumor Assays
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