Journal of Pharmaceutics & Drug Delivery ResearchISSN: 2325-9604

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From preclinical to IND formulation development: Using a QbD risk based approach


Alphonso Higuera

Aztech Sciences Inc., USA

: J Pharm Drug Deliv Res

Abstract


Statement of the Problem: Preclinical formulations development leading to IND enabling studies present a unique platform opportunity whether it is in support for ADME & toxicity studies, preliminary safety / efficacy assessment, patent exclusivity, or life-cycle-management product endeavors. The work presented here describes a systematic pathway using a risk management based approach during formulation platform screening. This includes the use of simples solvent to cosolvent, nano suspension and spraydried amorphous solid dispersions intended for parenteral, oral systems, among others. FMEA and Quality-by-Design elements are implemented with the aim of providing high drug load and stable formulations in efforts to achieve a desired in-vivo exposure. Case studies using a low solubility/low permeability drug candidate is presented using various cosolvent systems as well as HPMC/HPMCAS and surfactants for spray-dried amorphous solid platforms. Structure-based relationships with solubilization characterisitics are also presented. Results from the case study demonstrate high solubilization using pyrrolidone based solvents suggesting a strong structure-solubility relationship at the N--H and C=O bond level producing over 100x solubility increase when compared to water and significant in vivo exposure. The outcome of this work is supported by comparing in-vivo animal plasma data for further bridging studies and IND enabling studies during product development.

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