title: New investigation of distribution imaging and content uniformity of very low dose drugs using hot-melt extrusion method.
abstract: The content uniformity of low dose drugs in dosage forms is very important for quality assurance. The aim of this study was to prepare uniformly and homogeneously distributed dosage forms of very low-dose drugs using twin screw hot-melt extrusion (HME) and to investigate the distribution of drugs using instrumental analyses. For the feasibility of HME method, a very low amount of coumarin-6, a fluorescent dye, was used to visualize distribution images using confocal laser scanning microscope (CLSM). Limaprost, tamsulosin and glimepiride were then used as low-dose model drugs to study the applicability of HME for content uniformity and distribution behaviors. Hydrophilic thermosensitive polymers with low melting point, such as Poloxamer188 and polyethylene glycol (PEG) 6000, were chosen as carriers. The melt extrusion was carried out around 50°C, at which both carriers were easily dissolved but model drugs remained in solid form. The physicochemical properties of the hot-melt extrudates, including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR), were measured. Content uniformity of the drugs was also checked by HPLC. CLSM imaging showed that model drugs were well distributed throughout the hot-melt extrudate, giving better content uniformity with low batch-to-batch variations compared with simple physical mixtures. DSC, PXRD and FT-IR data showed that there was no interaction or interference between model drugs and thermosensitive polymers. The current HME methods could be used to prepare uniformly distributed and reproducible solid dosage forms containing very low dose drugs for further pharmaceutical applications.
authors.affiliation: College of Pharmacy, Ajou University, Suwon 443-749, Republic of Korea.
authors.forename: Jun-Bom
authors.initials: JB
authors.lastname: Park
authors.forename: Chin-Yang
authors.initials: CY
authors.lastname: Kang
authors.forename: Wie-Soo
authors.initials: WS
authors.lastname: Kang
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Han
authors.forename: Beom-Jin
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003374:Coumarins / Q000737:chemistry; D004304:Dosage Forms; D004337:Drug Carriers / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006358:Hot Temperature; D018613:Microscopy, Confocal / Q000379:methods; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013678:Technology, Pharmaceutical / Q000379:methods*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D003374:Coumarins; D004304:Dosage Forms; D004337:Drug Carriers; D005456:Fluorescent Dyes; D004364:Pharmaceutical Preparations; D011108:Polymers; D020442:Poloxamer; D011092:Polyethylene Glycols
keywords: Content uniformity; Coumarin-6; Distribution imaging; Hot-melt extrusion; Low dose drugs; Thermosensitive polymers