A powder solid dispersion system (SD) of ketoprofen (KP) or ibuprofen (IP), which possess low melting points, plus crospovidone (CrosPVP), have good fluidity characteristics and can be used to formulate tablets. Tablets of KP or IP in the SD of adequate hardness within a narrow weight range can be prepared by direct compression. Addition of microcrystalline cellulose (MCC) resulted in greater hardness characteristics and less variation in tablet weight. Forces during the tableting process were measured with a tableting process analyzer (TabAll) equipped with a single-punch for determining capping and sticking properties during the tableting process. Pressure transmission ratio from the upper to the lower punch and die wall force were increased by adding 1% magnesium stearate (MS) to the SD. Ejection force decreased when MS was added to the SD. When tablets of the IP SD were prepared without excipient, scraper pressure (SP) was large, resulting in sticking. However, addition of 1% MS, lowered the SP value and eliminated sticking. Thus, an SD of compounds with a low melting point such as KP or IP is suitable for tablet manufacture by direct compression with the addition of 1% MS.
Solid dispersion systems (SD) improve the solubility and/or dissolution rate of poorly water-soluble drugs by dispersing a drug in a carrier to render it amorphous.1,2) However, the method possesses several disadvantages, including manufacturing difficulties due to materials that are soft, tacky, or have poor fluidity for SD, 3) and preparation of tablets using SD, which allow only slow dissolution of drugs.4) SD methods also require a variety of excipients and a complicated procedure for preparing tablets or capsules. 5)Thus, only a few marketed products utilize this system. Therefore, an SD method involving simple manufacturing and formulation processes for preparation of tablets or capsules that enhance drug dissolution would be a great advance.In this study, SD was applied to the preparation of tablets, because tablets can be manufactured inexpensively and in high quantity. Crospovidone (CrosPVP) was chosen as a carrier because it has two useful characteristics. First, it is a powder with good fluidity and it is used as a disintegration agent in tablet. Second, CrosPVP has the same chemical structure as povidon, which is commonly used as carrier of SD. We developed an SD of indomethacin (IM) with CrosPVP by mechanically mixing and heating and forming tablets by direct compression with only 1% magnesium stearate (MS) as a lubricant.6) However, to prevent capping and sticking during the tableting process, the compaction properties of the powders and the quality of the tablets need to be evaluated and optimized. We evaluated compaction properties of the SD of IM with CrosPVP using a singlepunch machine equipped with several force analysis elements. ExperimentalMaterials CrosPVP (Polyplasdone XL ® , USP grade, mean particle size, 75 mm (Ͻ75 mm; 22%, 75-150 mm; 42%, 150 mmϽ; 35%)) was a gift from ISP Japan (Tokyo). IM (JP grade, particle size, 1-2 mm) was obtained from Nippon Bulk Yakuhin (Osaka). MCC (Avicel ® PH-102, mean particle size, 90 mm (Ͻ75 mm; 26%, 75-150 mm; 32%, 150 mmϽ; 41%)) and MS were obtained from Asahi Kasei Chemicals (Tokyo) and Wako Pure Chemical Industries (Osaka), respectively. All other reagents were of analytical grade.Preparation of SD The SD was prepared according to a procedure published previously.6) Briefly, a weight ratio of IM : CrosPVPϭ1 : 3 or 2 : 3 was used. A physical mixture (Pmix) was obtained by blending IM and CrosPVP using a spatula. The Pmix then was mixed with a high-speed elliptical-rotor type mixer (Theta-Composer Lab ® type THC, Tokujyu Kousakusyo, Kanagawa) for 30 min, followed by heating in air at 125°C (IM : CrosPVPϭ1 : 3) or 145°C (IM : CrosPVPϭ2 : 3) for 30 min.Powder Fluidity of SD and Related Materials The angles of repose of the SD and related materials were measured with a turntable apparatus (Tsutsui Rikagaku Kikai, Tokyo).Compressibility index (CI) was calculated using the following equation:where V 0 is powder volume before tapping and V f is powder volume after tapping infinitely. V f was calculated by Kawakita's equation 7) using data from 200 tapping tim...
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