Influence of processing methods on physico-mechanical properties of Ibuprofen/HPC-SSL formulation

Abstract

The objective of the present study was to investigate the influence of processing methods on the physical and mechanical properties of formulations containing Ibuprofen and HPC-SSL. The powder blends, containing Ibuprofen and HPC-SSL in ratio of 9:0.5, were processed using melt granulation (MG) by hot melt extrusion (HME) and wet granulation (WG) by high shear mixer. Formulated granules and powder blends were compressed into round flat faced tablets using Riva Piccola tablet press. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) studies proved that granulation process did not significantly alter the crystallinity of Ibuprofen, however, particle density and flow properties were significantly improved. Scanning electron microscopy (SEM) and particle size analysis corroborate with the findings that the flow characteristics of granules from MG were relatively superior to other formulations. Formulations were investigated for out-of-die compaction behaviour using Heckel, Kawakita, and CTC profile analysis. Detailed examination revealed that all three formulations differed in particle size due to the granulation, thus conferring to different compaction behaviour. In WG and MG, granulation offered an increase in particle size resulting in high compressibility along with deformation at low compression pressure. This results into low yield pressure, low yield strength, and higher densification, as compared with dry blend. The current work provides an insight into factors affecting physical and mechanical properties tablets, which can facilitate the rational selection of suitable change in processing method instead of changing excipients.     

The pig as a model system for investigating the recruitment and contribution of myofibroblasts in skin healing

In the skin-healing field, porcine models are regarded as a useful analogue for human skin due to their numerous anatomical and physiological similarities. Despite the widespread use of porcine models in skin healing studies, the initial origin, recruitment and transition of fibroblasts to matrix-secreting contractile myofibroblasts are not well defined for this model. In this review, we discuss the merit of the pig as an animal for studying myofibroblast origin, as well as the challenges associated with assessing their contributions to skin healing. Although a variety of wound types (incisional, partial thickness, full thickness, burns) have been investigated in pigs in attempts to mimic diverse injuries in humans, direct comparison of human healing profiles with regards to myofibroblasts shows evident differences. Following injury in porcine models, which often employ juvenile animals, myofibroblasts are described in the developing granulation tissue at 4 days, peaking at Days 7–14, and persisting at 60 days post-wounding, although variations are evident depending on the specific pig breed. In human wounds, the presence of myofibroblasts is variable and does not correlate with the age of the wound or clinical contraction. Our comparison of porcine myofibroblast-mediated healing processes with those in humans suggests that further validation of the pig model is essential. Moreover, we identify several limitations evident in experimental design that need to be better controlled, and standardisation of methodologies would be beneficial for the comparison and interpretation of results. In particular, we discuss anatomical location of the wounds, their size and depth, as well as the healing microenvironment (wet vs. moist vs. dry) in pigs and how this could influence myofibroblast recruitment. In summary, although a widespread model used in the skin healing field, further research is required to validate pigs as a useful analogue for human healing with regards to myofibroblasts.     

基于LF-NMR/MRI的维C银翘片制粒中润湿剂评价方法研究

目的应用低场核磁共振时域技术(low field nuclear magnetic resonance time domain technique,LF-NMR)、低场核磁成像技术(low field nuclear magnetic resonance imaging,LF-MRI)对高剪切制粒中润湿剂(乙醇)进行定性、定量分析。方法以维C银翘片高剪切湿法制粒为研究对象,采用LF-NMR建立润湿剂用量测定方法,结合横向弛豫时间(T2)和LFMRI测得的二位影像图对润湿剂分布与变化进行定性分析,探讨峰面积(A₂)与颗粒得率的关系。结果润湿剂用量与A₂呈现良好的相关性(R²=0.9575)。随着润湿剂用量增加,T2向右移动,A₂逐渐增加,质子在增加;LF-MRI表明随着润湿剂用量增加,影像图逐渐清晰,即非结合态质子(束缚态质子及自由态质子)在颗粒中逐渐增加。当润湿剂用量增加至20%~25%时,结合态质子含量不再增加,此时颗粒得率最高。结论LF-NMR和LF-MRI能快速、准确检测制粒中润湿剂用量变化和分布状态,为阐明润湿剂对颗粒性质的影响和成型机制提供评价方法。     

Effect of binders on the release rates of direct molded verapamil tablets using twin-screw extruder in melt granulation

Conventional manufacturing of pharmaceutical tablets often involves single processes such as blending, granulation, milling and direct compression. A process that minimizes and incorporates all these in a single continuous step is desirable. The concept of omitting milling step followed by direct-molding of tablets utilizing a twin-screw extruder in a melt granulation process using thermoplastic binders was explored. The objective of this study was to investigate the effect of combining hydrophilic binder (HPMC K4M, PEO 1M), and hydrophobic binder (Compritol^® ATO 888, Precirol^® ATO 5) on the release profiles of direct-molded tablets and direct-compressed tablets from milled extrudates using a quality-by-design approach. It was identified that hydrophilic binder type and process significantly affects (p = 0.005) the release profiles of verapamil. Moreover, two-way interaction analysis demonstrated that the combination of process with type of hydrophilic polymer (p = 0.028) and the type of hydrophilic polymer with polymer ratio (p = 0.033) significantly affected the release profiles. The formulation release kinetics correlated to Higuchi release model and the mechanism correlated to a non-Fickian release mechanism. The results of the present study indicated that direct-molded tablets with different release profiles can be manufactured without milling process and through a continuous melt granulation using twin-screw extruder with appropriate thermoplastic binder ratio.     

An Investigation on Spray-Granulated,Macroporous, Bioactive Glass Microspheres for a Controlled Drug Delivery System

Bioactive glass (BG) has been regarded as an excellent candidate for biomedical applications due to its superior properties of bioactivity, biocompatibility, osteoconductivity and biodegradability. Thus, in this study, we aimed to fabricate drug carriers that were capable of loading therapeutic antibiotics while promoting bone regeneration using macroporous BG microspheres, prepared by a spray drying method. Characterizations of particle morphology and specific surface area were carried out via scanning electron microscopy and nitrogen adsorption/desorption isotherm. Evaluations of in vitro bioactivity were performed based on Kokubo’s simulated body fluid to confirm the formation of the hydroxyapatite (HA) layer after immersion. In addition, the in vitro drug release behaviors were examined, using tetracycline as the therapeutic antibiotic in pH 7.4 and 5.0 environments. Finally, the results showed that BG microspheres of up to 33 μm could be mass-produced, targeting various therapeutic situations and their resulting bioactivities and drug release behaviors, and related properties were discussed.     

不同药用辅料流化床制粒的物性质量分析研究

目的研究5种药用辅料制粒后颗粒的物性指标,分析探讨颗粒物性指标的相关性及颗粒物性质量。方法采用Pearson相关性分析法分析颗粒的7项评价指标相关性,采用主成分分析法对颗粒物性指标进行主成分分析和综合评价。结果粒径分布宽度与松密度及振实密度呈极显著正相关,松密度与振实密度呈极显著正相关,振实密度与压缩度呈显著正相关。对第一主成分产生正向影响较大的物性指标是粒径分布宽度和振实密度。乳糖+水制成的颗粒及甘露醇+水制成的颗粒综合评价得分较高,可溶性淀粉+HPMC制成的颗粒综合评价得分最低。结论不同药用辅料制成的颗粒物性质量存在差异,乳糖和甘露醇分别以水为粘合剂制成的颗粒物性质量较好,可溶性淀粉以HPMC为粘合剂制成的颗粒物性质量较差。     

碱性成纤维细胞生长因子对大鼠真皮下血管网皮片愈合的影响

目的:探讨碱性成纤维细胞因子(bFGF)对大鼠真皮下血管网皮片愈合的影响。方法:Wistar大白鼠30只,每只背部切取2个真皮下血管网皮片并原位移植缝合,上部皮片下注入bFGF为实验组。下部皮片为对照组,术后大体肉眼观察皮片成后情况,并于2,4,6,8d取材镜下组织学观察CD34阳性细胞数、血管内皮细胞生长情况,微血管密度及肉芽组织生长情况。结果:实验组与对照组皮片成活率分别为93%及64%,经配对t检验差异显著(t=3.701,P<0.01)。其镜下观察CD34阳性细胞数、微血管数及肉芽组织厚度两组均有明显差异(P<0.01)。结论:bFGF具有广泛的细胞增殖效应,可通过多个环节促进小血管形成及肉芽组织增长,加速移植皮片与周围皮肤的愈合过程。     

不同提取工艺肠安颗粒的比较研究

目的:对不同提取工艺肠安颗粒的比较研究.方法:采用小鼠乙酸刺激法复制溃疡性结肠炎动物模型,将处方药材按3种提取方法制成不同的提取液,观察小鼠的整体状况、出现溃疡的动物数、溃疡点数和病理变化.结果:三种药液给药后,小鼠的整体状况、小鼠结肠出现溃疡的动物数、结肠溃疡点数、病理切片均与模型组有显著差异;工艺B组小鼠整体状况比其他2个中药工艺组好,结肠出现溃疡的动物数最少,结肠溃疡点数最少,病理切片显示:炎症细胞轻度浸润,基本形态与正常组相似.结论:各个中药工艺组的提取物都对实验溃疡性结肠炎模型有不同程度的疗效,工艺B组疗效显著.     

感冒退热泡腾片的干法制粒工艺研究

目的 研究感冒退热泡腾片干法制粒的工艺条件.方法 考察压轮压力、压轮转速和浸膏粉含水量对颗粒得率和颗粒脆碎度的影响.结果 压轮压力、压轮转速和浸膏粉含水量对颗粒得率和颗粒脆碎度有显著性影响.结论 感冒退热泡腾片干法制粒工艺的研究为感冒退热泡腾片研究与生产提供技术参考.