共处理技术制备直接压片高功能辅料的方法及应用进展

片剂因剂量准确、服用方便、质量稳定被广泛应用.粉末直接压片工艺是制备片剂较为简便的方法.然而,受粉体流动性、可压性、稀释潜力等性质的影响,目前只有不到20％的活性药物成分(API)可通过粉末直接压片工艺制备成片剂.应用颗粒工程学,通过共处理技术将两种或多种辅料在颗粒水平上相结合,可改善辅料的性能,进而满足直接压片法对粉体性质的要求.本文讨论了共处理技术制备直接压片高功能辅料的优势、共处理技术常规方法并例举了已经上市的直接压片高功能辅料及其应用前景,为共处理技术制备高功能辅料应用于粉末直接压片工艺提供思路.     

乳糖-纤维素复合辅料的制备及其性能评价

目的制备乳糖-纤维素复合辅料,用于直接压片技术。方法通过乳糖结晶工艺制备质量比为75∶25的乳糖-纤维素复合辅料。比较复合辅料与简单混合物的粉体学性质以及片剂质量。结果复合辅料显示出较好的流动性、填充性和可压性,对可压性差的药物具有很好的稀释作用。结论乳糖-纤维素复合辅料通过对乳糖及粉状纤维素物理性能的改变,更加适用于直接压片工艺。     

球晶造粒技术制备可直压乙基纤维素及适应性研究

目的 评价进口、国产乙基纤维素(EC)及球晶技术自制EC聚集体对药物的适应性.方法 分别以阿司匹林含量为10%～90%与进口、国产乙基纤维素(EC)及自制EC聚集体混合后直接压片,测定混合物粉体学性质如休止角,流出速度,卡氏指数及压片后的片重差异、脆碎度、硬度,以考察聚集体对药物的稀释潜力.结果 与国产及进口乙基纤...     

乳糖-淀粉复合辅料的制备及其性能评价

目的制备乳糖-淀粉复合辅料,用于直接压片技术。方法通过乳糖结晶工艺制备质量比为85∶15的乳糖-淀粉复合辅料。比较复合辅料与简单混合物的粉体学性质以及片剂质量。结果复合辅料显示出较好的流动性、填充性、可压性和崩解性,低剂量片剂的含量均匀度符合要求。结论乳糖-淀粉复合辅料通过对简单混合物物理性能的改变,适用于直接压片技术。     

乳糖-淀粉复合辅料的制备及其性能评价

目的 制备乳糖-淀粉复合辅料,用于直接压片技术.方法 通过乳糖结晶工艺制备质量比为85:15的乳糖-淀粉复合辅料.比较复合辅料与简单混合物的粉体学性质以及片剂质量.结果 复合辅料显示出较好的流动性、填充性、可压性和崩解性,低剂量片剂的含量均匀度符合要求.结论 乳糖-淀粉复合辅料通过对简单混合物物理性能的改变,适用于直接压片技术.     

乳糖粉体学性质的初步探讨

测定 5种型号乳糖产品的粒度分布、松密度、摇实密度、休止角、流速及成形性 ,确定何种乳糖适合用作直接压片辅料。以双氯芬酸钾为模型药物 ,用各型号乳糖为填充剂直接压片 ,制得双氯芬酸钾片 ,测定所得片子的硬度、脆碎度和片重差异。结果显示 :粒度以GranuLac 2 0 0最细 ,其他几种差不多 ;流动性以GranuLac 2 0 0最差 ,GranuLac 70次之 ,其他三种相差不大 ,成形性以Cellactosc 80最好 ,Tablettose70次之 ,CapsuLac 80最差。综合各项粉体学性质 ,Cellactose80和Tablettose 70较适合用作直接压片的辅料。用以上各型号乳糖作填充剂直接压片制得双氯芬酸钾片 ,其压片结果与上述测定结果基本相符 ,显示粉体学指标的测定对辅料的选择确有一定的指导作用     

乳糖粉体学性质的初步探讨

测定5种型号乳糖产品的粒度分布、松密度、摇实密度、休止角、流速及成形性,确定何种乳糖适合用作直接压片辅料.以双氯芬酸钾为模型药物,用各型号乳糖为填充剂直接压片,制得双氯芬酸钾片,测定所得片子的硬度、脆碎度和片重差异.结果显示:粒度以GranuLac 200最细,其他几种差不多;流动性以GranuLac 200最差,GranuLac 70次之,其他三种相差不大,成形性以Cellactosc 80最好,Tablettose 70次之,CapsuLac 80最差.综合各项粉体学性质,Cellactose 80和Tablettose 70较适合用作直接压片的辅料.用以上各型号乳糖作填充剂直接压片制得双氯芬酸钾片,其压片结果与上述测定结果基本相符,显示粉体学指标的测定对辅料的选择确有一定的指导作用.     

预混辅料直接压片的性质考察

目的考察几种预混辅料的性质。方法以粒度分布、休止角、堆密度为指标,考察预混辅料的粉体学性质,并将预混辅料应用于粉末直接压片工艺中。结果与普通辅料淀粉、微晶纤维素相比,预混辅料直压淀粉、直压微晶纤维素的休止角、压缩度小,流动性好。结论预混辅料的粉体学性质优于普通辅料,且粉末直接压片法所得片剂质量良好。     

乳糖粉体学性质的初步探讨

测定5种型号乳糖产品的粒度分布、松密度、摇实密度、休止角、流速及成形性，确定何种乳糖适合用作直接压片辅料。以双氯芬酸钾为模型药物，用各型号乳糖为填充剂直接压片，制得双氯芬酸钾片，测定所得片子的硬度、脆碎度和片重差异。结果显示：粒度以GranuLac200最细，其他几种差不多；流动性以GranuLac200最差，GranuLac70次之，其他三种相关不大，成形性以Cellactosc 80最好，Tablettose70次之，CapsuLac80最差。综合各项粉体学性质，Cellactose80和Tablettose70较适合用作直接压片的辅料。用以上各型号乳糖作填充剂直接压片制得双氯芬酸钾片，其压片结果与上述测定结果基本相符，显示粉体学指标的测定对辅料的选择确有一定的指导作用。     

不同型号甘露醇对吲达帕胺直接压片的影响研究

目的对比Parteck M200、M100直压甘露醇和直压甘露醇C、D 4种不同型号甘露醇对吲达帕胺直接压片的影响,为直接压片选择辅料提供参考。方法以吲达帕胺为模型药物考察粉体学,采用直压工艺与4种甘露醇压片后,进行片剂质量分析比较。结果 4种型号甘露醇对模型药物均有很好的容纳性,Parteck M200、M100直压甘露醇与吲达帕胺的相容性及混合压片后的溶出度较好。结论甘露醇是良好的直压工艺的填充剂,不同型号的甘露醇与模型药物混合有一定的差异。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.