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  • Title: Solid state and dissolution rate characterization of co-ground mixtures of nifedipine and hydrophilic carriers.
    Author: Friedrich H, Nada A, Bodmeier R.
    Journal: Drug Dev Ind Pharm; 2005 Sep; 31(8):719-28. PubMed ID: 16221606.
    Abstract:
    Co-ground powders of the poorly water-soluble drug nifedipine and a hydrophilic carrier, [partially hydrolyzed gelatin (PHG), polyvinylpyrrolidone (PVP), sodium dodecyl sulfate (SDS), hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), urea or Pluronic F108] were prepared in order to improve the dissolution rate of nifedipine. The effects of type of grinding equipment, grinding time, and type of hydrophilic carrier on the crystallinity of nifedipine (x-ray diffraction and differential scanning calorimetry) on the interaction between drug and carriers (differential scanning calorimetry), on the particle size and appearance (scanning electron microscopy), on the wettability (contact angle measurements), and on the drug release were investigated. Grinding nifedipine together with these carriers improved the dissolution rate. PHG-ground mixtures resulted in the fastest dissolution rate followed by PVP, SDS, HPMC, Pluronic, urea, and PEG. This effect was not only due to particle size reduction, which increased in the order PHG<PEG=SDS<Pluronic<drug<urea<HPMC<PVP, but also resulted from the ability of some carriers (PVP and HPMC) to prevent reaggregation of the finely divided drug particles. PVP, HPMC, and PHG formed a powder with amorphous drug. The carriers improved the wettability of the ground products in the order HPMC<drug<urea<PVP<SDS<PHG<PEG<Pluronic. Differential scanning calorimetry (DSC) measurements gave valuable information about the nature of drug crystallinity and the interactions with the carriers within the ground mixtures.
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