(W1030-09-61) Study on Solid Dispersion by High Shear Granulation Using HPMC and HPMCAS as Carrier

Purpose: Due to the increase in poorly water-soluble drugs, solid dispersion which one of the methods for improving dissolution is being investigated. The main methods for manufacturing solid dispersions are spray drying, hot melt extrusion, and fluidized bed granulation. However, a part of the method requires specialized equipment, and the resulting powders are bulky and have poor flowability. In this study, we introduce an example of solid dispersion production using a high shear granulator to solve these problems and compare its physical properties with those of fluidized bed granulation.

Methods: We used microcrystalline cellulose as a filler and low-substituted hydroxypropyl cellulose (L-HPC, LH-B1) as a disintegrant. HSG-1,3,4-9 was prepared with MCC/LH-B1 = 8/2 (w/w), and HSG-2 was prepared with MCC/LH-B1 = 9/1 (w/w). Two types of granulation liquid were prepared: a dissolution system in which the nifedipine(NIF)/ Hypromellose (HPMC, Pharmacoat^® 603) or HPMCAS (Shin-Etsu AQOAT^Ⓡ AS-LG, -MG, -HG) = 3/1(w/w) were dissolved in EtOH/water mixture (80/20 wt%) (HSG-1,2,4～6), and a dispersion system in which LH-B1 was dispersed in the above dissolution system (HSG-3,7-9). Wet stirring granulation was carried out with the composition HSG-1-9, and granulated powder was dried in a fluidized bed dryer. The dried product was evaluated for XRD, bulk density, angle of repose, and dissolution profiles in a larger than solubility of NIF.

Results: In all samples, the crystalline peak derived from NIF disappeared, confirming that NIF was amorphous. In addition, it was suggested that HSG-1-9(production by high shear granulator) results in a lower angle of repose and a larger bulk density than sample FBG-1-2 (production by fluidized bed granulation), resulting in better flowability. The dissolution rate of HSG-1-9 was improved compared to physical mixture and maintained a state of supersaturation. On the other hand, the dissolution rate of HSG-1-9 was lower than that of FBG-1-2.

Conclusion: By using Pharmacoat 603^® and HPMCAS, it was possible to produce solid dispersion with excellent flowability by the high shear granulation. In addition, the dissolution profiles of HSG-1-9 was improved compared to physical mixture and maintained a state of supersaturation.