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RISS 인기검색어
- 검색키워드
- 저자 : Alhalaweh, Amjad (검색결과 2 건)
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Bioavailability of indomethacin-saccharin cocrystals.
Jung, Min-Sook,Kim, Jeong-Soo,Kim, Min-Soo,Alhalaweh, Amjad,Cho, Wonkyung,Hwang, Sung-Joo,Velaga, Sitaram P Pharmaceutical Society of Great Britain 2010 Journal of pharmacy and pharmacology Vol.62 No.11
<P>Objectives??Pharmaceutical cocrystals are new solid forms with physicochemical properties that appear promising for drug product development. However, the in-vivo bioavailability of cocrystals has rarely been addressed. The cocrystal of indomethacin (IND), a Biopharmaceutical Classification System class II drug, with saccharin (SAC) has been shown to have higher solubility than IND at all pH. In this study, we aimed to evaluate the in-vitro dissolution and in-vivo bioavailability of IND-SAC cocrystals in comparison with IND in a physical mixture and the marketed product Indomee®. Methods??Scale-up of the cocrystals was undertaken using cooling batch crystallisation without seeding. The chemical and physical purity of the up-scaled material was verified using high-performance liquid chromatography, differential scanning calorimetry and powder X-ray diffraction. The IND-SAC cocrystals and IND plus SAC were mixed with lactose and the formulations were placed into gelatin capsules. In-vitro dissolution studies were then performed using the rotating basket dissolution method. The intrinsic dissolution rate of IND and IND-SAC cocrystals was also determined. Finally, a bioavailability study for the formulations was conducted in beagle dogs. The plasma samples were analysed using high-performance liquid chromatography and the pharmacokinetic data were analysed using standard methodologies. Key findings??The bulk cocrystals (i.e. scaled-up material) were chemically and physically pure. The in-vitro dissolution rate of the cocrystals was higher than that of IND and similar to that of Indomee® at pH 7.4 and pH 1.2. The in-vivo bioavailability of the IND-SAC cocrystals in dogs was significantly higher (ANOVA, P??lt;??.05) than that of IND but not significantly different from Indomee® (ANOVA, P??gt;??.05). Conclusions??The study indicates that the improved aqueous solubility of the cocrystals leads to improved bioavailability of IND. Thus, the cocrystals are a viable alternative solid form that can improve the dissolution rate and bioavailability of poorly soluble drugs.</P>
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Cho, Wonkyung,Kim, Min-Soo,Jung, Min-Sook,Park, Junsung,Cha, Kwang-Ho,Kim, Jeong-Soo,Park, Hee Jun,Alhalaweh, Amjad,Velaga, Sitaram P.,Hwang, Sung-Joo Elsevier 2015 International Journal of Pharmaceutics Vol.478 No.1
<P><B>Abstract</B></P> <P>The overall aim of this study was to prepare a nasal powder formulation of salmon calcitonin (sCT) using an absorption enhancer to improve its bioavailability. In this work, powder formulations for nasal delivery of sCT were studied using various absorption enhancers and stabilizers. Powders were prepared by two different methods: conventional spray-drying (SD) and novel supercritical fluid-assisted spray-drying (SASD) to investigate the role of CO<SUB>2</SUB> in the particle formation process. The prepared sCT powder formulations were characterized by several analyses; powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), and the Fourier transform infrared (FT-IR) spectroscopy method. The particle size distribution was also evaluated. <I>In vivo</I> absorption tests were carried out in Sprague-Dawley rat using the prepared powder formulations, and the results were compared to those of raw sCT. Quantitative analysis by high-performance liquid chromatography (HPLC) indicated that sCT was chemically stable after both the SD and SASD processes. Results of PXRD, SEM, and FT-IR did not indicate a strong interaction or defragmentation of sCT. The <I>in vivo</I> absorption test showed that SD- and SASD-processed sCT powders increased the bioavailability of the drug when compared to the nasal administration of raw sCT. In addition, SASD-processed sCT exhibited higher nasal absorption when compared with SD-processed sCT in all formulations due to a reduction of particle size. The results from this study illustrate that the preparation of nasal powders using the SASD process could be a promising approach to improve nasal absorption of sCT.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
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