is below the resolution of the instrument, it is easy to distinguish between the coated and un-coated MCC surfaces. The main observation is that the characteristically rough MCC surface becomes smoother after being coated; imperfections and cracks on the surface are filled. It should be noted that TEM analysis was not possible due to curvature of the surface and desorption of the active from the surface as a result of the increased partial vapour pressure of the active under vacuum of the TEM. Microtomes were also not possible due to the fragile nature of MCC.
3.1.2.3. EDX. As noted earlier, ferrocene was chosen as the active for EDX studies because it contains iron, which is easily distinguishable from the MCC background. An 85 × 425 m rectangular area was selected and the scan detected there was 0.07 wt% iron on the surface. The loading of ferrocene on MCC was found to be 179 mg/g and the iron content in ferrocene is 30.12 wt%. The calculated iron content (0.054 wt%) therefore agrees reasonably well with the EDX scan result. Furthermore, a point scan on the surface detected a relatively abundant source of ferrocene (0.57 wt%), which was a consequence of the undulated MCC surface preferentially collecting a higher loading of the precipitated ferrocene particles.
3.2. Coating
using
Two actives,
RESS-BFB
benzoic
acid and ferrocene were used in these tests. The RESS process conditions were the same as for the RESS-Wurster tests
except: the nozzle was heated to around 60
C, there was no air flow in to the fluidised bed and 40 and 60 g MCC were used. Quantitative analyses
of
◦
coated MCC are shown in Table 2. The results indicate that the RESS-BFB was able to achieve higher loadings
depending on the mass of MCC used and consequently the bed depth. Particles of nano-size will be collected by diffusional mechanisms which are more effective in a deeper bed. Surface analyses of the sample were carried out using the same methods as those used on RESS-WTS samples (SEM, EDX, Confocal Raman) and similar results were obtained. These results indicate the possibility of using the same coating principles but different equipment to achieve similar outcomes, therefore giving more flexibility in the facility design when considering this process.
3.3. Process yield
The intention of this work is to present a coating process that allows the production of nanoparticles and their capture onto larger carriers. At this stage, the results of process yield are not given; however, the process yield depends on the properties of the active and the operation parameters and for the tests presented it ranged from 14% to 74%. It is our intention to report fully the effect of operation parameters on process yield in forthcoming work.
4. Conclusion
The novel RESS-fluidized bed coating process developed in this work combines the principles of supercritical fluid precipitation with those of fluidized bed coating to achieve coatings of nanoparticles onto a micron-sized excipient, for a range of nanoparticle actives. Typically, active loadings in the order of1–10 mg/g of excipient can be achieved in 10 min. The process avoids the use of liquids and the whole procedure is simpler, faster and easier than conventional coating processes in a Wurster coater. It combines the advantages of both the RESS and fluidized bed processes, by generating nano-particles of organic based compounds by RESS and coating them onto excipient micro-particles. The limitations of this process lie in the solubilities of actives in carbon dioxide.
Acknowledgements
The authors thank the EPSRC (EP/F037228/1) for funding this research and Dr J Bowen for help using the Confocal Raman microscope. The Confocal Raman microscope used in this research was obtained, through Birmingham Science City: Innovative Uses for Advanced Materials in the Modern World (West Midlands Centre for Advanced Materials Project 2), with support from Advantage West Midlands (AWM) and part funded by the European Regional Development Fund (ERDF).
จะต่ำกว่าความละเอียดของเครื่องมือ ซึ่งง่ายต่อการแยกระหว่างเคลือบ และไม่เคลือบผิว MCC สังเกตหลักคือ ว่า ผิว MCC characteristically หยาบจะนุ่มหลังจากการเคลือบ ข้อบกพร่องและรอยแตกบนพื้นผิว filled มันควรจดบันทึกว่า ยการวิเคราะห์ไม่ได้เนื่องจากขนาดของพื้นผิวและ desorption ใช้งานอยู่จากพื้นผิวเนื่องจากความดันไอเพิ่มขึ้นบางส่วนของการใช้งานภายใต้สุญญากาศยการ Microtomes ได้ยังไม่ได้เนื่องจากลักษณะเปราะบางของ MCC3.1.2.3. เรื่อง ตามที่ระบุไว้ก่อนหน้านี้ เฟอร์โรซีนถูกเลือกเป็นใช้งานอยู่สำหรับศึกษาเรื่องเนื่องจากประกอบด้วยเหล็ก ซึ่งไม่ได้แตกต่างจากพื้นหลัง MCC มี 85 × 425 เมตรสี่เหลี่ยมมีเลือกตั้ง และการสแกนตรวจพบมี 0.07 wt %เหล็กบนพื้นผิว โหลดของเฟอร์โรซีนใน MCC พบเป็น 179 mg/g และเนื้อหาเหล็กในเฟอร์โรซีนเป็น 30.12 wt % เนื้อหาเหล็กคำนวณ (0.054 wt %) จึงตกลงด้วยดีกับผลการสแกนเรื่อง นอกจากนี้ สแกนจุดบนพื้นผิวตรวจพบแหล่งค่อนข้างอุดมสมบูรณ์ของเฟอร์โรซีน (0.57 wt %), ซึ่งเป็นเวรผิว MCC undulated โน้ตรวบรวมการโหลดสูงของอนุภาคตะกอนเฟอร์โรซีน3.2 การเคลือบ โดยใช้ Actives สอง RESS BFBbenzoic เฟอร์โรซีนและกรดที่ใช้ในการทดสอบเหล่านี้ RESS การประมวลผลเงื่อนไขได้เหมือนกันสำหรับการทดสอบ RESS Wurster except: the nozzle was heated to around 60C, there was no air flow in to the fluidised bed and 40 and 60 g MCC were used. Quantitative analyses of ◦coated MCC are shown in Table 2. The results indicate that the RESS-BFB was able to achieve higher loadings depending on the mass of MCC used and consequently the bed depth. Particles of nano-size will be collected by diffusional mechanisms which are more effective in a deeper bed. Surface analyses of the sample were carried out using the same methods as those used on RESS-WTS samples (SEM, EDX, Confocal Raman) and similar results were obtained. These results indicate the possibility of using the same coating principles but different equipment to achieve similar outcomes, therefore giving more flexibility in the facility design when considering this process.3.3. Process yieldThe intention of this work is to present a coating process that allows the production of nanoparticles and their capture onto larger carriers. At this stage, the results of process yield are not given; however, the process yield depends on the properties of the active and the operation parameters and for the tests presented it ranged from 14% to 74%. It is our intention to report fully the effect of operation parameters on process yield in forthcoming work.4. ConclusionThe novel RESS-fluidized bed coating process developed in this work combines the principles of supercritical fluid precipitation with those of fluidized bed coating to achieve coatings of nanoparticles onto a micron-sized excipient, for a range of nanoparticle actives. Typically, active loadings in the order of1–10 mg/g of excipient can be achieved in 10 min. The process avoids the use of liquids and the whole procedure is simpler, faster and easier than conventional coating processes in a Wurster coater. It combines the advantages of both the RESS and fluidized bed processes, by generating nano-particles of organic based compounds by RESS and coating them onto excipient micro-particles. The limitations of this process lie in the solubilities of actives in carbon dioxide.AcknowledgementsThe authors thank the EPSRC (EP/F037228/1) for funding this research and Dr J Bowen for help using the Confocal Raman microscope. The Confocal Raman microscope used in this research was obtained, through Birmingham Science City: Innovative Uses for Advanced Materials in the Modern World (West Midlands Centre for Advanced Materials Project 2), with support from Advantage West Midlands (AWM) and part funded by the European Regional Development Fund (ERDF).
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