Conversion into the amorphous form enhances the dissolution of poorly soluble drugs, however\nthe barrier to market for medicines containing an amorphous drug is poor stability. The aim was to\nproduce the amorphous form of a drug within a capsule, without thermal or mechanical stress during\nmanufacture. To facilitate this aim, the mechanism for drug-polymer interaction was explored.\nNifedipine and polyvinylpyrrolidone were dissolved in tert-butanol at different drug/polymer ratios.\nThese solutions were dispensed into gelatin capsules and freeze-dried. Differential scanning calorimetry\n(DSC) & novel FT-IR analysis based on peak symmetry measurements confirmed the absence of\ncrystallinity when polyvinylpyrrolidone exceeded 50%w/w. Capsules containing 10 mg of nifedipine\nwere amorphous and stable for over 3 months at ââ?°Ë?40 Ã?°C. Evidence of hydrogen bonding between\nthe N-H group of nifedipine and the C=O group of PVP was observed and this interaction inhibited\nnifedipine crystallisation. PVPââ?¬â?¢s high affinity for water and the nifedipine-polymer interaction lead to\na significant dissolution rate enhancement. The freeze-dried capsule, 10%w/w nifedipine/PVP, had the\nhighest dissolution rate constant of 0.37 Ã?± 0.05 minâË?â??1, and the lowest time to achieve 50% dissolution\nor t1/2 of 1.88 Ã?± 0.05 min. This formulation reached 80% dissolved in less than 6 min whereas the\nequivalent marketed liquid filled nifedipine capsule took 3 times longer to reach 80% dissolution.
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