An innovative method for the preparation of high API-loaded hollow spherical granules for use in controlled-release formulation.
The aim of this study was to prepare controlled-release (CR) granules with suitable particle strength, flowability, particle size distribution (PSD) and density characteristics for blending with other excipients. We also wanted these CR granules to contain large quantities of active pharmaceutical ingredient (API). A high shear mixer was used to mix an API with various polymers at various feed ratios, and the resulting granulated materials were sprayed with solvent. The wet granules were dried using a fluidized bed dryer to give CR granules. The API content of the granules was determined to be 95wt%. The granules were found to be spherical in shape with smooth surfaces by scanning electron microscopy. The inner structure of each granule was determined to be hollow by X-ray computed tomography, highlighting the unusual mechanism of this granulation process. The PSD of the granules was found to be dependent on that of the constituent polymer, and a narrow PSD was obtained by adjusting the PSD of the polymer. The dissolution profile of the granules was also dependent on the constituent polymer. Taken together, these results show that we have successfully developed a new manufacturing technology for the simple and low-cost preparation of ideal CR granules.
Sumitomo Dainippon Pharma Co., Ltd., 3-45 Kurakakiuchi 1-chome, Ibaraki-shi, Osaka 567-0878, Japan. Electronic address: takumi-asada@ds-pharma.co.jp.
Takumi
T
Asada
Sumitomo Dainippon Pharma Co., Ltd., 3-45 Kurakakiuchi 1-chome, Ibaraki-shi, Osaka 567-0878, Japan.
Mitsuaki
M
Kobiki
Sumitomo Dainippon Pharma Co., Ltd., 3-45 Kurakakiuchi 1-chome, Ibaraki-shi, Osaka 567-0878, Japan.
Yasushi
Y
Ochiai
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Yasunori
Y
Iwao
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Shigeru
S
Itai
D003692:Delayed-Action Preparations / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D007213:Indomethacin / Q000737:chemistry; D007555:Isoxazoles / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D000078305:Zonisamide
D003692:Delayed-Action Preparations; D005079:Excipients; D007555:Isoxazoles; D011108:Polymers; D013607:Tablets; D000078305:Zonisamide; D007213:Indomethacin
Controlled release; Granulation; High active pharmaceutical ingredient-loaded granule; High shear mixer; Hollow spherical particle; Low cost