Effect of substitution of plasticizer dibutyl phthalate with dibutyl sebacate on Eudragit® RS30D drug release rate control.

In the current study, the influence of type of plasticizer used with Eudragit® RS 30D on the drug release was investigated in solid dosage form extrusion/spheronization, and film coating. The drug pellets were coated for controlling drug release with Eudragit® RS 30D containing dibutyl phthalate and compared with dibutyl sebacate as an alternative plasticizer. To study the influence of pH of the dissolution medium on the drug release profile, capsules are tested for drug release profile at pH 1.2, 4.4, and 6.3. Additionally, the aging effect on the curing of Eudragit® RS 30D is evaluated by exposing the capsules dosage form to room temperature (25 °C ± 2 °C/60% ± 5% RH) for time 0, 3, 6, and 9 months, accelerated temperature (40 °C ± 2 °C/75% ± 5% RH) for time 0, 3, and 6 months, and intermediate temperature (30 °C ± 2 °C/65% ± 5% RH) for time 0, 6, and 9 months. The replacement of dibutyl phthalate, with dibutyl sebacate for polymer coating system in similar concentration is comparable with respect to plasticization effect. The coalescence of the polymer particles is not changed and requires no additional processing parameter control or additional curing time.

Application of a hot-melt granulation process to enhance fenofibrate solid dose manufacturing.

Evaluation of hot-melt granulation of fenofibrate and croscarmellose sodium and its cooling time for the molten mass in a ratio of 55:45 was conducted to assess the manufacturing process capability to produce an acceptable granulation which flows well on Korsch PH300 tablet compression machine. The formation of the drug-polymer eutectic mixture was investigated by differential scanning calorimetry, scanning electron microscopy and X-ray powder diffraction. The physical properties of the hot-melt was determined by examining the milled blocks after solidification and milling after cooling periods of 10, 20 and 30 d. The milled material was assessed for the effect of hold time of the blend on the solid dose compression characteristics. The impact of cooling on the processing of the blocks was assessed after 10, 20 and 30 d of cooling. The study suggests that after the hot-melt formed the fenofibrate crystallized independently and a solid solution with croscarmellose sodium was not formed. The age of the blocks determined the hardness of the crystals, changing the processing nature of the granules with respect to compression and powder flow characteristics. The blocks processed after 20 d and beyond produced granules with a characteristic suitable for holding the blend for 14 d in the bin with no impact on flow properties and compressibility of the blend. There was no chipping, capping, sticking or picking observed and a higher compression speed was achieved.