Development of hot-melt extrusion as a novel technique for the ...
Development of hot-melt extrusion as a novel technique for the ...
Development of hot-melt extrusion as a novel technique for the ...
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Where, W 0 is <strong>the</strong> initial amount <strong>of</strong> drug in <strong>the</strong> pharmaceutical dosage <strong>for</strong>m, Wt is <strong>the</strong>remaining amount <strong>of</strong> drug in <strong>the</strong> pharmaceutical dosage <strong>for</strong>m at time t and Ks is a constantincorporating <strong>the</strong> surface volume relation.3Dividing Eq. (8.4) by W and simplifying: 1F )1/ 3 1 K t (8.5)1/0(3Where F=1− (W t /W 0 ) and F represents <strong>the</strong> drug dissolved fraction at time t and K 3 is <strong>the</strong>rele<strong>as</strong>e constant). When this model is used, it is <strong>as</strong>sumed that <strong>the</strong> rele<strong>as</strong>e rate is limited by <strong>the</strong>drug particle dissolution rate and not by <strong>the</strong> diffusion that might occur through <strong>the</strong> polymericmatrix.nKorsmeyer–Pepp<strong>as</strong> model: F K t (8.6)4Where K 4 is a constant incorporating <strong>the</strong> structural and geometric characteristics <strong>of</strong> <strong>the</strong> drugdosage <strong>for</strong>m, n is <strong>the</strong> rele<strong>as</strong>e exponent (e.g. zero order rele<strong>as</strong>e when n = 1, <strong>for</strong> tablets n =0.89), indicative <strong>of</strong> <strong>the</strong> drug rele<strong>as</strong>e mechanism and F represents <strong>the</strong> drug dissolved fractionat time t. This model is generally used to analyze <strong>the</strong> rele<strong>as</strong>e <strong>of</strong> which mechanism is not wellknown or when more than one type <strong>of</strong> rele<strong>as</strong>e phenomena is involved.3.0 Results and discussion3.1 Solubility parameters and <strong>extrusion</strong> processThe calculated solubility parameter <strong>of</strong> HCS, EC N10 and EC P7 were 22.60, 25.61and 25.27 MPa 1/2 , respectively. The difference between <strong>the</strong> calculated solubility parameters<strong>of</strong> <strong>the</strong> polymers and <strong>the</strong> drug indicates that HCS is likely to <strong>for</strong>m solid dispersions with bothpolymers EC N10 and EC P7. By using <strong>the</strong> Van Krevelen/H<strong>of</strong>tyzer equation, <strong>the</strong> values<strong>for</strong> HCS/EC N10 and HCS/EC P7 were 3.01 and 2.67 MPa 1/2 , respectively.3.2 Scanning electron microscopy (SEM)Surface morphology w<strong>as</strong> examined by SEM <strong>for</strong> both <strong>the</strong> drug and extrudates. Theextrudates containing both polymers exhibited no drug crystals on <strong>the</strong> extrudate surface withHCS (Fig. 8.1). Similarly, <strong>the</strong> absence <strong>of</strong> HCS crystals on <strong>the</strong> surface in all drug/ polymerextrudates indicates <strong>the</strong> presence <strong>of</strong> amorphous solid dispersions <strong>of</strong> <strong>the</strong> API into <strong>the</strong> polymermatrices [13] . Thus, <strong>the</strong> SEM observations were quite sensitive to elucidate <strong>the</strong> presence <strong>of</strong>drug/polymers amorphous solid dispersions by complementing <strong>the</strong> <strong>the</strong>rmal investigations(DSC, XRD).156 | P a g e