微生态活菌片剂生产中干法制粒粒度分布对产品质量的影响

目的探讨干法制粒工艺中粒度分布对微生态活菌片剂质量的影响。方法应用干法制粒工艺制造粉料,通过对不同粒径的片重、硬度和脆碎度进行测定,确定出压制素片的颗粒最佳粒径范围,然后对工艺参数压辊压力、加料速度和压辊转速进行正交试验,选择所制颗粒的粒径与最佳粒径一致的工艺为最优工艺,再通过对最佳工艺压制出的片剂进行稳定性研究,从而验证粒径对产品质量的影响。结果粒径分布在20~80目时,片剂重量、硬度和脆碎度的结果不仅符合标准还较稳定。工艺参数中压辊压力为110KN、加料转速为70rpm、压辊转速为9.0rpm时所压制片剂的粒径范围在20~80目时所占最大,约97.82%。对产品中长双歧杆菌、保加利亚乳杆菌和嗜热链球菌的6个月稳定性检测再次确定粒径分布在20~80目时,产品质量最优。结论干法制粒工艺粉料粒径分布在20~80目时,微生态活菌片剂质量为最优。     

我国微生态制剂的现状和发展设想

通过人外文献和市场的调查,并结合科研实践,指出了当前我国微生态制剂发展中存在的一些严峻问题,在介绍了人体肠道微生态规律、微生态制剂应有的质量标准,以及比较了多种产品的活菌含量和“亿活菌价”的基础上,作者认为,提高我国微生态制剂质量的４个关键应该是：选育优良菌种,提高活菌含量,延长保质期和添加有益菌的生长促进剂。为促进我国微生态制剂事业更快、更稳健地发展,作者提出了７项具体建议。     

我院微生态制剂临床使用情况分析

微生态制剂又称益生菌、生态制剂或活菌制剂。其定义是：含活菌和（或）死菌包括组分和产物的微生物制剂,供口服或经由其它粘膜径投入,指在粘膜表面处改善微生物和酶的平衡,或刺激特异性和非特异性免疫机制。感染的微生物制剂在５０年代就已问世,医用微生态制剂多采用...     

产花生四烯酸油脂高山被孢霉干法造粒提油及菌粕的重复利用

对高产花生四烯酸油脂高山被孢霉干法造粒提油工艺中3个参数及菌粕重复利用进行研究。设计三因素四水平L16(43)正交试验,考察造粒直径、正己烷与菌粕的比例、萃取时间对提油效率及正己烷回收率的影响。结果表明:当含水率20%~25%、造粒直径1.2mm、正己烷的体积与颗粒的质量比20∶1L/g、萃取时间5h时,每克干菌体油脂得率0.5594g,正己烷的回收率达90%。与均质湿法提油相比,分别提高了17.35%和83.67%。用碱性蛋白酶及复合酶(纤维素酶、果胶酶和碱性蛋白酶)处理菌粕,以50%替代氮源(酵母膏)添加到培养基中,发酵周期分别为10d和7d。此时,生物量、油脂产量、花生四烯酸产量都达到了最大值,分别为30.33g/L、16.25g/L、8.59g/L(碱性蛋白酶处理);29.77g/L、16.89g/L、7.12g/L(复合酶处理)。其中,复合酶处理菌粕的生产强度可达4.253g/(L·d)、2.413g/(L·d)和1.017g/(L·d),与碱性蛋白酶处理相比,其生产强度分别提高了40.22%、48.49%和18.39%。干法造粒提油是有效的,且酶法处理菌粕的方法有应用前景。     

微生态活菌制剂的临床研究及应用

人与其寄居的微生物群构成人体的微生态环境 ,这些微生物群对人体有着极其重要的生理作用 ,人体的健康依赖于二者之间的平衡 ,如果平衡失调将导致疾病发生。自 192 8年Alexander Flem ing发现青霉素以来 ,抗生素已广泛应用于临床 ,人们认识到了其对恢复健康的重要价值 ,同时也逐渐认识到了滥用抗生素或治疗措施不当 ,已经导致菌群失调和耐药菌株产生 ,造成或加重了微生态失衡 ,使得人们越来越重视研究用于调节微生态失衡的微生态疗法。微生态活菌制剂的临床研究及应用就是其中一个重要方面。1　微生态活菌制剂1.1　概念　微生态活菌制剂指…     

枯草芽孢杆菌微生态制剂发酵研究进展

微生态制剂是饲用抗生素的绿色有效替代品。枯草芽孢杆菌在逆境中可形成抗逆性强的芽孢,在生产和应用过程中保持高活性,是一种高效的微生态制剂菌种。提高枯草芽孢杆菌活菌数及芽孢率是保证微生态制剂产品质量的关键。本文综述了枯草芽孢杆菌芽孢形成的分子生物学机制及影响芽孢形成的重要因素,进一步比较枯草芽孢杆菌微生态制剂不同发酵方式的特点,重点阐述了提高枯草芽孢杆菌有效生物量的工艺优化,最后介绍了枯草芽孢杆菌微生态制剂的应用,并对将来研究思路进行了讨论。     

动物微生态制剂研究应用进展

动物微生态制剂是在动物微生态理论指导下,采用已知有益的微生物所制成的生物制品或活菌制剂。综述了动物微生态制剂的产生起源、益生菌和微生态制剂的概念、微生态制剂所用菌株、作用机制、国内外应用现状及发展前景。     

仪器法测定口服酪酸梭菌散剂活菌数的研究与应用

目的利用BD FACSMicroCount~(TM)全自动微生物计数分析系统测定口服酪酸梭菌活菌散剂中的活菌数,以探索BD FACSMicroCount~(TM)全自动微生物计数分析系统测定微生态制剂活菌数的可行性。方法按照《BD FACSMicroCount~(TM)全自动微生物计数分析系统使用说明书》对该药品的活菌数进行测定。结果仪器所测得数据与药品包装上理论活菌数基本相符。结论可使用BD FACSMicroCount~(TM)全自动微生物计数分析系统测定微生态制剂活菌数。     

动物微生态制剂在宠物领域的应用现状及研究进展

动物微生态制剂是在动物微生态理论指导下,采用益生菌制成的活菌制剂。本文主要结合国内外的研究资料,对动物微生态制剂在宠物领域的应用现状、研究进展及存在的问题进行综述。     

微生态调节剂及细菌类生物反应调节剂抗肿瘤作用的研究进展

微生态调节剂是指含活菌和死菌包括组分和产物或者是仅含活菌体和死菌体和微生物制剂,供口服或经由其它粘膜途径投入,其目的主要是在粘膜表面处改善微生物和酶的平衡,并在一定程度上刺激特异性和非特异性免疫机制。微生态调节剂抗肿瘤作用分为二个方向,一是通过口服控...     

Roll Compaction and Tableting of High Loaded Metformin Formulations Using Efficient Binders

Metformin has a poor tabletability and flowability. Therefore, metformin is typically wet granulated with a binder before tableting. To save production costs, it would be desirable to implement a roll compaction/dry granulation (RCDG) process for metformin instead of using wet granulation. In order to implement RCDG, the efficiency of dry binders is crucial to ensure a high drug load and suitable properties of dry granules and tablets. This study evaluates dry granules manufactured by RCDG and subsequently tableting of high metformin content formulations (≥?87.5%). Based on previous results, fine particle grades of hydroxypropylcellulose and copovidone in different fractions were compared as dry binders. The formulations are suitable for RCDG and tableting. Furthermore, results can be connected to in-die and out-of-die compressibility analysis. The addition of 7% of dry binder is a good compromise to generate sufficient mechanical properties on the one hand, but also to save resources and ensure a high metformin content on the other hand. Hydroxypropylcellulose was more efficient in terms of granule size, tensile strength and friability. Three percent croscarmellose was added to reach the specifications of the US Pharmacopeia regarding dissolution. The final formulation has a metformin content of 87.5%. A loss in tabletability does not occur for granules compressed at different specific compaction forces, which displays a robust tensile strength of tablets independent of the granulation process.     

Dry granulation and compression of spray-dried plant extracts

The purpose of this research was to evaluate the influence of dry granulation parameters on granule and tablet properties of spray-dried extract (SDE) fromMaytenus ilicifolia, which is widely used in Brazil in the treatment of gastric disorders. The compressional behavior of the SDE and granules of the SDE was characterized by Heckel plots. The tablet properties of powders, granules, and formulations containing a high extract dose were compared. The SDE was blended with 2% magnesium stearate and 1% colloidal silicon dioxide and compacted to produce granules after slugging or roll compaction. The influences of the granulation process and the roll compaction force on the technological properties of the granules were studied. The flowability and density of spray-dried particles were improved after granulation. Tablets produced by direct compression of granules showed lower crushing strength than the ones obtained from nongranulated material. The compressional analysis by Heckel plots revealed that the SDE undergoes plastic deformation with a very low tendency to rearrangement at an early stage of compression. On the other hand, the granules showed an intensive rearrangement as a consequence of fragmentation and rebounding. However, when the compaction pressure was increased, the granules showed plastic deformation. The mean yield pressure values showed that both granulation techniques and the roll compaction force were able to reduce the material's ability to undergo plastic deformation. Finally, the tablet containing a high dose of granules showed a close dependence between crushing strength and the densification degree of the granules (ie, roll compaction force). Published: October 14, 2005     

Physicochemical properties of extracellular matrix proteins in post-burn human granulation tissue

Wound healing is a finely controlled biological process involving a series of complex cellular interactions. Following inflammation, the wound bed matrix is gradually replaced by granulation tissue followed by the long slow process where collagen accumulates and restores tensile strength. The studies revealed that human granulation tissue varied in many aspects in comparison with normal skin. In granulation tissue the molecular organization of collagen showed an increased amount of type III collagen resembling embryonic tissue. The presence of type V collagen with three distinct chains was the characteristic feature of granulation tissue. The physicochemical properties of collagen extracted from granulation tissue showed the influence of proteoglycans during collagen aggregation and these proteoglycans from the major non-collagenous proteins during the proliferative phase of healing.     

Monitoring the fluidized bed granulation process based on<Emphasis Type="Italic">S</Emphasis>-statistic analysis of a pressure time series

Pressure fluctuation measurements collected during the fluidized bed granulation of pharmaceutical granule have been analyzed using the attractor comparison technique denoted as theS-statistic. Divergence of the bed state from the reference during granulation is followed by a return to a condition statistically similar to the original state of the dry fluidized ingredients on drying. This suggests insensitivity of theS-statistic technique to the changes in particle size distribution occurring during the granulation process. Consequently, the monitoring of pressure fluctuations alone may provide an easily implemented technique for the tracking of granule moisture and process end-point determination. Published: September 30, 2005     

Evaluation of the Physicochemical Properties and Compaction Behavior of Melt Granules Produced in Microwave-Induced and Conventional Melt Granulation in a Single Pot High Shear Processor

Recently, microwave-induced melt granulation was shown to be a promising alternative to conventional melt granulation with improved process monitoring capabilities. This study aimed to compare the physicochemical and compaction properties of granules produced from microwave-induced and conventional melt granulation. Powder admixtures comprising equivalent proportions by weight of lactose 200 M and anhydrous dicalcium phosphate were granulated with polyethylene glycol 3350 under the influence of microwave-induced and conventional heating in a 10-L single pot high shear processor. The properties of the granules and compacts produced from the two processes were compared. Relative to conventional melt granulation, the rates at which the irradiated powders heated up in microwave-induced melt granulation were lower. Agglomerate growth proceeded at a slower rate, and this necessitated longer massing durations for growth induction. These factors prompted greater evaporative moisture losses from the melt granules. Additionally, nonuniform heating of the powders under the influence of microwaves led to increased inter-batch variations in the binder contents of resultant melt granules and a reliance of content homogeneity on massing duration. Agglomerate growth proceeded more rapidly under the influence of conventional heating due to the enhanced heating capabilities of the powders. Melt granules produced using the conventional method possessed higher moisture contents and improved content homogeneity. The compaction behavior of melt granules were affected by their mean sizes, porosities, flow properties, binder, and moisture contents. The last two factors were responsible for the disparities in compaction behavior of melt granules produced from microwave-induced and conventional melt granulation.     

Successful treatment for perinephric abscess with recombinant human granulocyte colony-stimulating factor following nephrectomy in a patient of myelodysplastic syndrome: A case report

The 35-year-old man with myelodysplastic syndrome (MDS) and granulocytopenia with dry cough and high fever was eventually found to have a left perinephric abscess ofStaphylococcus aureus. He underwent left nephrectomy and drainage of perinephric space in conjunction with appropriate antibiotics. However, because of persistent granulocytopenia,Staph. aureus never cleared up with formation of only poor granulation. Recombinant human granulocyte colony-stimulating factor (G-CSF) was added to the above treatment leading to prompt improvement in granulocytopenia and emergence of the good granulation tissue. G-CSF will probably become one of the important agents in treating MDS with granulocytopenia.     

Preparation and Characterization of a Novel Co-processed Excipient of Chitin and Crystalline Mannitol

A co-processed excipient was prepared from commercially available crystalline mannitol and α-chitin using direct compression as well as spray, wet, and dry granulation. The effect of the ratio of the two components, percentage of lubricant and particle size, on the properties of the prepared co-processed excipient has been investigated. α-Chitin forms non-hygroscopic, highly compactable, disintegrable compacts when co-processed with crystalline mannitol. The compaction properties of the co-processed mannitol–chitin mixture were found to be dependent upon the quantity of mannitol added to chitin, in addition to the granulation procedure used. Optimal physicochemical properties of the excipient, from a manufacturing perspective, were obtained using a co-processed mannitol–chitin (2:8, w/w) mixture prepared by wet granulation (Cop-MC). Disintegration time, crushing strength, and friability of tablets, produced from Cop-MC using magnesium stearate as a lubricant, were found to be independent of the particle size of the prepared granules. The inherent binding and disintegration properties of the compressed Cop-MC are useful for the formulation of poorly compressible, high-strength, and low-strength active pharmaceutical ingredients. The ability to co-process α-chitin with crystalline mannitol allows chitin to be used as a valuable industrial pharmaceutical excipient.     

Formulation of controlled-release baclofen matrix tablets: Influence of some hydrophilic polymers on the release rate and in vitro evaluation

This work aims at investigating different types and levels of hydrophilic matrixing agents, including methylcellulose (MC), sodium alginate (Alg), and sodium carboxymethylcellulose (CMC), in an attempt to formulate controlled-release matrix tablets containing 25 mg baclofen. The tablets were prepared by wet granulation. Prior to compression, the prepared granules were evaluated for flow and compression characteristics. In vitro, newly formulated controlled-release tablets were compared with standard commercial tablets (Lioresal and baclofen). The excipients used in this study did not alter physicochemical properties of the drug, as tested by the thermal analysis using differential scanning calorimetry. The flow and compression characteristics of the prepared granules significantly improved by virtue of granulation process. Also, the prepared matrix tablets showed good mechanical properties (hardness and friability). MC- and Alg-based tablet formulations showed high release-retarding efficiency, and good reproducibility and stability of the drug release profiles when stored for 6 months in ambient room conditions, suggesting that MC and Alg are good candidates for preparing modified-release baclofen tablet formulations.     

In-Line Monitoring of a High-Shear Granulation Process Using the Baseline Shift of Near Infrared Spectra

Although near infrared (NIR) spectra are primarily influenced by undesired variations, i.e., baseline shifts and non-linearity, and many applications of NIR spectroscopy to the real-time monitoring of wet granulation processes have been reported, the granulation mechanisms behind these variations have not been fully discussed. These variations of NIR spectra can be canceled out using appropriate pre-processing techniques prior to spectral analysis. The present study assessed the feasibility of directly using baseline shifts in NIR spectra to monitor granulation processes, because such shifts can reflect changes in the physical properties of the granular material, including particle size, shape, density, and refractive index. Specifically, OPUSGRAN^®, a novel granulation technology, was investigated by in-line NIR monitoring. NIR spectra were collected using a NIR diffuse reflectance fiber optic probe immersed in a high-shear granulator while simultaneously examining the morphology, particle size, density, strength, and Raman images of the mixture during granulation. The NIR baseline shift pattern was found to be characteristic of the OPUSGRAN^® technology and was attributed to variations in the light transmittance, reflection, and scattering resulting from changes in the physicochemical properties of the samples during granulation. The baseline shift also exhibited an inflection point around the completion of granulation, and therefore may be used to determine the endpoint of the process. These results suggest that a specific pattern of NIR baseline shifts are associated with the unique OPUSGRAN^® granulation mechanism and can be applied to monitor the manufacturing process and determine the endpoint.