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  • Title: Application of rotatable central composite design in the preparation and optimization of poly(lactic-co-glycolic acid) nanoparticles for controlled delivery of paclitaxel.
    Author: Kollipara S, Bende G, Movva S, Saha R.
    Journal: Drug Dev Ind Pharm; 2010 Nov; 36(11):1377-87. PubMed ID: 20545520.
    Abstract:
    CONTEXT: Polymeric carrier systems of paclitaxel (PCT) offer advantages over only available formulation Taxol® in terms of enhancing therapeutic efficacy and eliminating adverse effects. OBJECTIVE: The objective of the present study was to prepare poly (lactic-co-glycolic acid) nanoparticles containing PCT using emulsion solvent evaporation technique. METHODS: Critical factors involved in the processing method were identified and optimized by scientific, efficient rotatable central composite design aiming at low mean particle size and high entrapment efficiency. Twenty different experiments were designed and each formulation was evaluated for mean particle size and entrapment efficiency. The optimized formulation was evaluated for in vitro drug release, and absorption characteristics were studied using in situ rat intestinal permeability study. RESULTS: Amount of polymer and duration of ultrasonication were found to have significant effect on mean particle size and entrapment efficiency. First-order interactions of amount of miglyol with amount of polymer were significant in case of mean particle size, whereas second-order interactions of polymer were significant in mean particle size and entrapment efficiency. The developed quadratic model showed high correlation (R(2) > 0.85) between predicted response and studied factors. The optimized formulation had low mean particle size (231.68 nm) and high entrapment efficiency (95.18%) with 4.88% drug content. The optimized formulation showed controlled release of PCT for more than 72 hours. In situ absorption study showed faster and enhanced extent of absorption of PCT from nanoparticles compared to pure drug. CONCLUSION: The poly (lactic-co-glycolic acid) nanoparticles containing PCT may be of clinical importance in enhancing its oral bioavailability.
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