Application of membrane separation technology in the purification of pharmaceutical components.

Traditional Chinese medicine (TCM) is often composed of a variety of natural medicines. Its composition is complex, and many of its components can not be analyzed and identified. The first step in the rational application of TCM is to successfully separate the effective components which is also a great inspiration for the development of new drugs. Among the many separation technologies of TCM, the traditional heating concentration separation technology has high energy consumption and low efficiency. As a new separation technology, membrane separation technology has the characteristics of simple operation, high efficiency, environment-friendly and so on. The separation effect of high molecular weight difference solution is better. The applications of several main membrane separation technologies such as microfiltration, nanofiltration, ultrafiltration and reverse osmosis are reviewed, the methods of restoring membrane flux after membrane fouling are discussed, and their large-scale industrial applications in the future are prospected and summarized.

A quality by design approach for the qualification of automating compounding device for parenteral nutrition.

Automated compounding device (ACD) are increasingly used for parenteral nutrition (PN) bag production, and their acquisition must be sufficiently thought. The law requires the qualification of these ACD, but did not specify the tests to be performed. The quality by design (QbD) risk based approach allowed to define the quality target product profile in order to acquire the best ACD for each unit, and thanks a risk analysis permitted to define the critical quality attributes (CQA). These CQA will allowed to define tests performed during qualification. The ACD qualified was a 12 pump volumetric system. The CQA for PN bags consisted in sterile, precisely and accurately production with enough stability. During operational qualification volumetric accuracy test was performed, and during the performance qualification: flush volume, media fill, microbiological integrity of environment, sterility of control bag and production test were performed. At the end, all tests were conclusive (excepted for some results mostly due to analytical bias) and the ACD was considered to produce sterile bags in a control environment, precisely (relative standard deviation < 4%) and accurately (mean bias < 1% for weight and < 7% for other controls) with a sufficient stability. The QbD risk based approach allowed to acquire the best ACD for our need, and qualify relevant elements regarding the production process.

Developing patient-centric medicines for older people: Reflections from the draft EMA paper on the pharmaceutical development of medicines for use in the older population.

Increased global longevity requires a re-evaluation of current structures in society to adapt to the consequential demographic shift. As (very) old people are prone to impaired human organ and body functions resulting in, for example, multimorbidity, polypharmacy, hospitalisation and problems in medication management, it is increasingly acknowledged that re-evaluations should include the suitability of pharmaceutical patient care as one of the cornerstones of public health. Following the 2011 European Medicines Agency (EMA) Geriatric Strategy, in 2017 the EMA published the draft "Reflection paper on the pharmaceutical development of medicines for use in the older population". The draft paper was opened for public consultation and specific attention and feedback (either supportive or with a proposal for revision) was asked on three design aspects: tablet breaking, drug administration through enteral feeding tubes and medication management. Following publication, the draft paper was presented at two public conferences attended by participants from different disciplines. This manuscript is intended to draw the attention of different stakeholder parties to the urgent need to collaborate on the emerging issues arising from increasing longevity and multimorbidity, and especially those associated with pharmaceutical patient care and drug product design, including the need for collaborative research into existing or emerging knowledge gaps. The manuscript focuses on the three aforementioned aspects of pharmaceutical development (tablet breaking, drug administration through enteral feeding tubes and medication management) as these highly relate to medication safety and efficacy and constitute persistent and typical challenges for older people, caregivers and healthcare professionals in daily clinical practice.

[Future Perspective of Pharmacoepidemiology in the "Big Data Era" and the Growth of Information Sources]. / Perspectiva futura de la farmacoepidemiología en la era del "Big data" y la expansión de las fuentes de información.

The arrival of new drug into the market requires many years of previous research along with the need of continuous evaluation throughout the lifetime of the drug. This warrants pharmacoepidemiological research which may be defined as the study of the use and the effects of drugs in large populations. Nowadays this type of research seems more feasible thanks to the massive expansion of the information sources and data (e.g: clinical patient registries, electronic medical records). However there is a risk of information overload, fragmented evidence and given the enthusiasm aroused by the "Big Data", it must be emphasized that its nature is mainly observational, and therefore subject to bias and confusion. The application of epidemiological methods in this scenario seems essential for any analysis. In short, the management and use of these data sources to generate useful information expansion is the next challenge for the application of research methods in modern pharmacoepidemiology.

Preparation and process optimization of notoginsenoside R1 chitosan nanoparticles / 中国基层医药

Objective To prepare optimization of notoginsenoside R1 chitosan nanoparticles,to provide a theoretical basis for clinical application of the drug.Methods Notoginsenoside R1 chitosan nanoparticles were prepared,HPLC method was used to detect the content of notoginsenoside R1 chitosan nanoparticles,preparation technology of nanoparticles were optimized by orthogonal experiment,and the optimized preparation technology of nanoparticles was verified.Results HPLC standard curve equation was A =911.49C -1803.4(r =0.999 9),linear range was from 25 to 900 g/mL.The intra day precision were 1.520%,0.884% and 0.969%(n =6),and the inter day precision were 1.591%,1.447% and 1.269%(n =6).The recovery rates of low,medium and high concentra-tions were (98.11 ±1.16)%,(101.27 ±0.59)% and (100.97 ±0.82)%.4 factors of orthogonal experiment:the concentration of chitosan,the mass ratio of drug and carrier,temperature and rotational speed,and 3 levels of each factor were selected.The average particle size,encapsulation efficiency and drug loading were selected as control indexes.The test results were determined by the method of comprehensive weighted scoring.The orthogonal design was designed according to L9(34)orthogonal design.The optimization process was 2% of chitosan concentration,20% of the weight ratio of drug and carrier,35 ℃ of temperature,600 r/min of rotational speed.According to the optimized process,the average particle size was (123.40 ±7.68)nm,the encapsulation efficiency was (58.41 ±1.59)%,and the drug loading amount was (10.46 ±0.53)%.Conclusion The optimized preparation process of notoginsenoside R1 chitosan nanoparticles is simple and easy to operate,the entrapment efficiency and drug loading amount were high. As a new dosage form,it has a good clinical application prospect.

Process study of brain protein hydrolysate of inactivate and virus removal / 中国基层医药

Objective To study the process of brain protein hydrolysate of inactivate and virus removal.Methods The Parvoviridae parvovirus genera of porcine parvovirus (PPV),vesicular stomatitis virus rhabdovirus genera of vesicular stomatitis virus (VSV) were chosen as a model virus,wherein PPV represents no envelope deoxyribonucleic acid(DNA) virus,VSV represents the envelope ribonucleic acid(RNA) virus.Simulation of the production process of virus inactivation steps 100 ℃ × 30 min,ultrafiltration as inactivation/removal condition.The virus respectively according to 1 ∶ 9 into the brain protein hydrolysate,high temperature and ultra filtration virus inactivation/removal.In pig kidney cells (PK-15) in PPV cell culture,Africa green monkey kidney cells(Vero cells) cultured VSV,determination of virus titer.Results PPV and VSV through the sterilization,virus median tissue culture infective dose(TCID50) were 6.15log/0.1mL(logs),5.37 log/0.1mL(logs) ;removal processaverage virus reduction coefficient were 6.15log/0.1mL(logs),5.37 log/0.1mL(logs).Conclusion The high temperature and ultra filtration produces brain protein hydrolysate solution process are effective virus inactivation/removal process.

The preparation of cold -dampness medicine iron stick and treatment clinical observation of cold -dampness lumbago / 中国基层医药

Objective To investigate the preparation process of cold -dampness medicine iron stick and the curative effect of cold -dampness medicine iron stick,thus to provide reference for the clinical treatment of cold -dampness lumbago.Methods Using science and technology of preparation and the thermal effect of cold -dampness medicine iron stick was observed.1 20 cases with cold -dampness lumbago of dampness type with low back pain, according to the order of treatment were divided into the observation group and control group.63 cases of the treatment group were given cold -dampness medicine iron stick affixed to the surface of the skin,57 cases of the control group were given kanlisha affixed to the surface of the skin.The treatment effect after one course of treatment was observed. Results Cold -dampness medicine iron stick heat effect index of heat time was 1 2min,to thermal time was 1 0.8h, the highest temperature was 56.5℃,thermal equilibrium curve was gentle and lasting.The efficacy of the two groups of drugs within the observation time effect was obvious.The total effective rate of the observation group was 90.5%(57 /63),which was higher than 75.4%(43 /57)of the control group,the difference was statistically significant (χ2 =4.87,P <0.05).During the treatment,local skin blisters,rash,itching and other low temperature burns and other allergic reaction were not found.Conclusion Cold -dampness medicine iron stick process is stable and controllable in quality and heat balance curve slow long -lasting,determine the efficacy,innovative therapies,it is easily accepted by patients and worthy to be popularized in clinical practice.

Study in preparation of ofloxaxcin gelatin microspheres / 天津医药

Objective To study the optimum condition of preparing ofloxaxcin gelatin microspheres. Methods Oflox?axcin gelatin microspheres were manufactured using the emulsion chemical-cross linking method and gelatin was employed as carrier, liquid paraffin as oil phase, Span80 as emulsifier, . The loading capability and entrapment efficiency of the ofloxax?cin gelatin microspheres were determined by UV Spectrophotometry. The effect of gelatin concentration, oil/water volume ra?tio, gelatin/ofloxaxcin mass ratio and volume fraction of span80 on drug loading capability and entrapment efficiency were in?vestigated. The optimum proportions of each component was obtained by L9 (34) orthogonal test, based on the above 4 factors, using sum of drug loading capability and entrapment efficiency as evaluation index. Results The optimum condition for manufacturing high quality ofloxaxcin gelatin microspheres used 20%of gelatin concentration,water/oil volume ratio at 3.5∶1, gelatin/ofloxaxcin mass ratio at 1∶1, the span 80 volume fraction of 2.5%. Conclusion Drug loading capability and entrap?ment efficiency of the ofloxaxcin gelatin microspheres reached 80%using this manufacture technology therefore the prepara?tion was stable and feasible.

Study on process for the spray drying of shengmaisan prescription granule / 中国基层医药

Objective To define the optimal process for spray drying of shengrnaisan prescription granule.Methods The optimal process for spray drying was investigate by single factor experiment.Results The optimal process for spray drying of shengmaisan prescription granule involved temperature of liquid feedstock of 30 ～ 40℃,relative density of extract of 1.10,the rate of liquid feedstock of 50 ～ 60 ml/min,inlet temperature of 175 ～ 180℃,and outlet temperature of 85 ～ 90℃.Conclusion The optimized process is rational and feasible.

Optimization of riboflavin sodium phosphate loading to calcium alginate floating microspheres by response surface methodology / 北京大学学报(医学版)

Objective:To investigate the preparation, optimization and in vitro properties of riboflavin sodium phosphate floating microspheres. Methods: The floating microspheres composed of riboflavin sodium phosphate and calcium alginate were prepared using ion gelatin-oven drying method. Results: The properties of the microspheres were investigated, including the buoyancy, release, appearance and entrapment efficiency. The formulation was optimized by response surface methodology (RSM). Conclusion: The optimized microspheres were round. The entrapment efficiency was 57.49%. All the microspheres could float on the artificial gastric juice over 8 hours. The release of the drug from the microspheres complied with Fick' s diffusion.

Studies on Extracting Process of Hujin Granules / 广州中医药大学学报

[Objective] To optimize the conditions of the extracting process of Hujin Granules. [Methods] The orthogonal design was applied. With the total emodin and the total anthraquinone (TA) content as the parameters for the alcohol-extraction, the concentration of alcohol, the volume of solvent and the extracting time were used for optimization of alcohol-extraction. With the total polysaccharide (TP) as the parameters for water-extraction, the soaking time, the volume of water and the extracting time were used for optimization of water-extraction. [Results] The optimum conditions of alcohol-extraction were: extracting with 70% alcohol 245 mL for 2 hours and extracting twice. The optimum conditions of water-extraction were: extracting with 80 mL water (not for soaking) for 1.5 hours, extracting 3 times. [Conclusion] The results indicate that the extracting process is rational and feasible, and can provide evidence for the extracting process of Hujin Granules.

Escalado por modelación en la producción farmacéutica

Se estudia el escalado de los procesos de mezclado y secado según el flujo tecnológico instalado en un laboratorio de producción farmacéutica, haciendo uso del principio de semejanza (rigurosa para el mezclado y extrapolada para el secado), fundamento de la teoría de los modelos. A partir de las metodologías aplicadas, se obtienen ecuaciones de escala convenientemente validadas, que permiten predecir a partir del laboratorio el comportamiento de los procesos considerados.

The scale-up of the mixing and drying processes in studies according to the technological flow installed in a pharmaceutical production laboratory, making use of the resemblance principle (rigorous for mixing and extrapolated for drying), which is the basis of the theory of models. Conveniently validated scale ecuations are obtained from the applied methodologies, allowing to predict, starting from the laboratory, the behaviour of the processes under consideration.

Protocolo de validación de métodos analíticos para la cuantificación de fármacos

Se presenta un resumen de las consideraciones generales para la confección del protocolo de validación de métodos analíticos utilizados en la determinación cuantitativa de fármacos en forma de materia prima o en formulaciones y en estudios de estabilidad. Se describe detalladamente el proceso de validación que incluye los requisitos exigidos para la utilización de las materias primas, materiales de referencia, equipamiento, personal y determinación de los parámetros de linealidad, precisión, exactitud y selectividad (con el procesamiento estadístico de los resultados experimentales y criterios de aceptación), así como la presentación de los resultados en el informe final de la validación.

A summary of the general considerations fot the formulation of a validation protocol of the analytical methods used in drug quantitative determination in a raw material form, or in formulations and firmness studies. The validation process is fully described; it includes the necessary requirements for the usage of raw materials, reference materials, supplying, personnel, and determination of linearity, preciseness, exactness, and selectiveness (with the statistical processing of experimental results, and acceptance criteria), as well as the presentation of outcomes in the validation final report.

Effect of Different Extration Methods on Pharmacological Action of Chuanping Prescription / 中药新药与临床药理

Objective To select the optimal exacting process for Chuanping prescription (CP).Methods The anti- and the anti- asthma ticanti effects of extracts obtained by different extracting processes from CP were observed.Results The anti- asthmatic effect of extract obtained by ion exchange resin(IER) method was better than that by acid- liquid- extraction alcohol- precipitate method (ALEAP) (P