Nitrendipine Solid Dispersions

In the present study, solid dispersions (SDs) of the poorly water-soluble drug nitrendipine (NTD) were prepared using the twin screw extruder method, the melt-mixing method and a pulse combustion dryer system, HYPULCON, in order to improve the dissolution property of NTD. The physicochemical properties of SD particles were investigated and the carriers and the method of preparation were compared.SDs of NTD were prepared using the twin screw extruder method with hydroxypropylmethylcellulosephthalate (HPMCP) and Carbopol as carriers. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) analysis showed that NTD was dispersed in the amorphous state in the NTD-HPMCP SD and existed in the form of crystallites in the NTD-Carbopol SD. Fourier transformation IR (FT-IR) spectroscopy indicated the presence of hydrogen bonding between NTD and HPMCP, while no interaction between NTD and Carbopol was showed by FT-IR and solid NMR analysis. NTD-Carbopol SD was found to give much higher dissolution than crystalline NTD and physical mixtures, while the dissolution of NTD-HPMCP SD was markedly decreased. However, the dissolution of NTD-Carbopol SD decreased with the Carbopol content increased. It was indicated that Carbopol has a greater ability to improve the dissolution of NTD than HPMCP when a twin screw extruder was employed to prepare the solid dispersions, and the polymer and its content had great effect on the dissolution of the drug.SDs of NTD were prepared using the melt-mixing method with hydrophilic silica particles (Aerosil and Sylysia) with different particle size and specific surface areas as carriers. PXRD and DSC analysis showed that NTD in the SDs was dispersed in the amorphous state. FT-IR spectroscopy obtained with the SDs indicated the presence of hydrogen bonding between the secondary amine groups of NTD and silanol groups of silica particles. After treated with the melt-mixing method, NTD was adsorbed on the surfaces of Aerosil or in the pore of Sylysia through the hydrogen bonding interaction. The specific surface area and the adsorbed water amount of the SDs were also significantly improved, hence dispersibility and wettability of NTD was improved by the carriers. The dissolution property of NTD in the SDs was remarkably improved regardless of the grade of silica with supersaturation observed. The properties of Aerosil (such as particle size, specific surface area and dispersibility) had a great effect on the dissolution of NTD. The drug supersaturation concentration tended to decreased with increase of specific surface area. However, the pore size and specific surface area of Sylysia showed little effect on the drug dissolution rate. The drug supersaturation concentration of NTD-Aerosil SD was higher than that of NTD-Sylysia SD. The stability test indicated that amorphous NTD in the SD with Aerosil 200 was stable for at least 1 month under the humid conditions (40℃/75% RH).A pulse combustion dryer system, HYPULCON, was used to prepare SDs of NTD with PVA, PVP and silica particles as carriers. When aqueous suspension was used for preparation, NTD-Aerosil systems exhibited higher dissolution than other carriers. The degree of drug crystallinity decreased when substituting Tween 80 solution for aqueous suspension. PXRD and DSC analysis showed that NTD in the NTD-Aerosil SD prepared with a 5% (v/v) Tween 80 solution was dispersed in the amorphous state. FT-IR Spectroscopy indicated the presence of hydrogen bonds between NTD and Aerosil. Aerosil had a greater ability to improve the dissolution of NTD than Sylysia and other polymers. The highest drug supersaturation concentration was maintained continuously during the dissolution test of the NTD-Aerosil SD prepared with the 5% (v/v) Tween 80 solution by HYPULCON. The NTD-Aerosil SD particles prepared with HYPULCON using Tween 80 solutions showed improved properties over those prepared with a conventional spray dryer, such as a smaller particle size, a tighter particle size distribution, and no agglomeration. The good hydrophilicity and dispersibility of Aerosil, lower the surfaces tension of Tween 80 solution, and the actions of shock waves and ultrasonic waves might account for the amorphization of NTD and improved dissolution rate of SDs.