Editorial Note
CONTINUOUS PRODUCTION OF PHARMACEUTICALS
Dr. Kal Renganathan Sharma
Department of Physics, College of Science and Technology
Rm 228 Spearman Technology
Bldg.Texas Southern University
3100 Cleburne Street
Houston, TX 77004
Chemical engineering principles can be applied to scale-up formulations of drugs into large production in continuous manner. There are number of advantages for preferring continuous processes over batch modes. The quality will be higher, process cost will be lower. Capital investment and plant costs can be depreciated over reasonable periods of time. Centralized control is possible in continuous processes. The raw materials can be procured in whole sale prices. The finishing operations for the product such as formation of capsules, coating, coloring etc can be sewn into the process flow with benefit. Productivity will be higher and product uniformity will be more. The residence time in the reactors can be lowered and the throughput can be increased. Less manual labor is required. Inventory costs will be on the lower side. Enviromental impact is more benign in the case of continuous process compared with batch mode. Depending on the demand optimal strategies can be devised. Some times space can be minimized for the same throughput. [Read More]
Editor's note
$1000 Genome is within reach
The quest is on to map every known function of every test organism in the universe to the protein signals. Protein signals are linked then to genes in eukoryotes. According to M. Schena who along with his professor Davis pioneered the microarray analysis method in order to obtain sequencing information from gene expression studies, “human disease is going to be eradicated as we know it by the year 2050”.The HGP, human genome project was completed ahead of time. ..................Read more,click on HTML .
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Review articleSystemic sclerosis (SSc) is a highly heterogeneous disease which would benefit from the adoption of a stratified medicine approach, to improve outcomes for patients and reduce costs to the healthcare system. SSc is orphan of disease activity biomarkers, as the current gold standard prognostic test: the modified Rodnan skin score (MRSS) is flawed. The MRSS has been shown to be unreliable, insensitive to change and not specific in measuring skin fibrosis. Physical measurements of skin thickness, genetic risk factors and autoantibodies may all allow patient stratification, however as proteins are the mediators of biological function; proteomics may offer the best approach .................Read more ,click on HTML.
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Upcoming Artcle
Takotsubo Cardiomyopathy precipitated by positive emotion, recurrence in same patient. Understanding the facts and review of literature.
1.Dr Lakshmi Kant Pathak, MD, MRCP, FACP
Sanford Medical Center
University Of North Dakota, Fargo, USA
2.Dr Chirag Chavda, MD
Methodist Health system, Dallas, USA
3.Dr Mohamed Mohamed, MD
Sanford Medical Center
University Of North Dakota, Fargo, USA
4. Dr Vimala Vijayaraghavan, MD
Caribbean Medical University, Chicago. USA.
The Impact of Operator Education Level on the Safety and Tolerability of Transcranial Magnetic Stimulation.
Svensson, Travis K. RN, MD, PhD
Associate Professor, School of Nursing and Health Professions
University of San Francisco
Adjunct Clinical Professor, Department of Family Medicine
Sanford Medical Center
Assistant Clinical Professor, Department of Psychiatry
University of California San Francisco.
Gene Silencing of IL-13 by siRNA Aerosol Inhalation Inhibits Asthma Phenotype in the Murine Model of Asthma.
Objectives: This study was intended to investigate whether aerosol inhalation of IL-13 siRNA was effective in reduce IL-13 expression and thus attenuated asthma phenotype.
Methods: The ovalbumin (OVA)-challenged mouse model of asthma was used to assess the effect of IL-13 interference. Airway inflammation in lung tissue was assessed using hematoxylin and eosin (H&E). The mRNA expression of IL-13 gene was determined using real-time PCR.
Results: Aerosol inhalation of the IL-13 siRNA was shown to reduce the expression of IL-13 and reduced airway inflammation in lung tissues compared with control group.
Conclusion: Our results demonstrated the effectiveness of aerosol inhalation of IL-13 siRNA in preventing airway inflammation in vivo and suggested potential therapeutic applications.
Guo Chen1, Zhenghua Nib2, Qingge Chen1, Xiongbiao Wang1,*
Affiliation:
1 Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, PR China
2 Central lab, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, PR China
Acute Toxicity, Analgesic Activity of Nepetagranatensis Essential Oil.
Gastroprotective Activity of Hericium erinaceus on Gastric Injury Rat Model Induced by Glacial Acetic Acid and Pyloric Ligation
Fu Wen-Juan1, Chen Ju2, Ke Jian1, Yu Wen-Hui1, Wang Lan-Ying2, Wu Ding-Tao2, Xiong Ai-Hua1, Nie Hong1* and Zhao Jing2*
1.Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
Sexual Harassment: University Stigmata
Kanda, Raquel, G*.,(Junior Fellow),França, Bianca, M.,(Junior Fellow),Cerino, Elizabelle, G.,(Junior Fellow),Baima, Eduardo, F.,(Junior Fellow), Lima,Jobson, N.F.,(Junior Fellow),Feitosa,Uilna, N. S,Dr.Lima, Nádia Nara, R.,Dr.Damasceno, Kécia, S.,Dr. Kanda, Paulo, M.,(PhD), Rolim-Neto, Modesto, L.(PhD).
1.Federal University of Cariri, Divine Savior Street, 284, Center, Barbalha, Ceara, Brazil.
2.Institutional Program for Scientific Initiation (PIBIC) / National Council for Scientific and Technological Development (CNPq) fellow at Faculty of Medicine
3.Federal University of Cariri, Barbalha, Ceara, Brazil. Postgraduate Program in Health Sciences - Faculty of Medicine of ABC, Santo André, São Paulo, Brazil
4.Neurovale. The electroencephalograph (EEG) laboratory. Taubaté. São Paulo, Brazil
Disseminated histoplasmosis in the child with diabetes mellitus: Case Report
Background: Diabetes and HIV infection are common co-morbid conditions of disseminated Histoplasmosis.
Case report: This study reports a case of disseminated histoplasmosis in a 4 year old boy with type 1 diabetes mellitus history diagnosed a year before. He was admitted with high fever and cough in pediatric emergency. The child evaluated with more productive cough, hepatosplenomegaly, generalized painful lymph node, whitish plaques in the oral cavity, angular cheilitis and ocular disease (erythema in the sclera and bilateral conjunctiva, leftmost). Diagnosis was based on histopathological examination, culture, bacterioscopy and PCR. Despites the adequate treatment, patient developed blinds in the left eye.
Conclusion: After all, we conclude that histoplasmosis became an important public health problem due to the high number of immunocompromised patients, what makes it important the attention on differential diagnosis
Claudio Gleidiston Lima da Silva, Raquel Melo Vieira, Eudes Alves Simões Neto, José Mauricio Pereira Lopes, Raul Rodrigues Barros, Bernardo Nogueira Faé, Jucier Gonçalves Junior, Modesto Leite Rolim Neto, Maria do Socorro Vieira dos Santos*
Faculty of Medicine, Federal University of Cariri, UFCA, Barbalha, Ceará, Brazil
Editorial Note
CONTINUOUS PRODUCTION OF PHARMACEUTICALS
Dr. Kal Renganathan Sharma
Department of Physics, College of Science and Technology
Rm 228 Spearman Technology
Bldg.Texas Southern University
3100 Cleburne Street
Houston, TX 77004
Chemical engineering principles can be applied to scale-up formulations of drugs into large production in continuous manner. There are number of advantages for preferring continuous processes over batch modes. The quality will be higher, process cost will be lower. Capital investment and plant costs can be depreciated over reasonable periods of time. Centralized control is possible in continuous processes. The raw materials can be procured in whole sale prices. The finishing operations for the product such as formation of capsules, coating, coloring etc can be sewn into the process flow with benefit. Productivity will be higher and product uniformity will be more. The residence time in the reactors can be lowered and the throughput can be increased. Less manual labor is required. Inventory costs will be on the lower side. Enviromental impact is more benign in the case of continuous process compared with batch mode. Depending on the demand optimal strategies can be devised. Some times space can be minimized for the same throughput.
Some of the hurdles that needs to be overcome in order to have widespread use of continuous processes for pharmaceutical production is the misperceptions of higher risk. A paradigm shift and outside the box thinking is needed for continuous production of drugs. Investors who are happy with current methods need be better informed. They may be used to the conventional pharma units with stepwise reactions, purifications and final product formulations were performed in the batch mode. Change to continuous does not mean that there is need for more engineering and operating skill. Chemical engineers are trained in order to accomplish some of the goals such as crystallization, purification, reaction, separation and heat transfer steps needed in pharmaceutical production. Handling solids need expertise in powder technology, continuous crystallization and particulate processing. Use of continuous crystallization can result in cost savings of about 50%. Start-up and shut down procedures in the continuous processes can be optimized using transient models tested on the computer. FDA approvals for the drug can be used effectively using quality inspections in process implementation. FDA encourage continuous production. Optimization of the total cost of operation with tradeoffs of operating costs and capital costs can result in arrival of certain number of stages for each unit operation used. Expertise in separation, purification and integration of biocatalysis are needed for continuous pharmaceutical production.
The industrial controls market size is expected to reach ~ 150 billion dollars world wide. Process dynamics can be studied using desktop computers and proactive process solutions can be sought. Stability analysis using a pencil and paper can lead to a better perspective on the range of operation of the process variables. Control and automation have grown tremendously with the advent of computers and programmable logic controllers, PLCs. Plant start-up, Plant Shut-down operations gets more attention of the lead engineer compared with those during steady-state operation of the plant. Transient analysis is not well studied.. Transient behavior of chemical reactors, distillation columns, absorption towers, adsorption beds, extraction units and other unit operations needs to be better studied.
Collegiate education methods have to keep pace with the developments in the field of industrial controls. Moore’s law states that computing speed of microprocessors double every 18 months. Biological databanks double in size every 10 months. Mathematical methods for model development have been refined over centuries. The methods and means available to the engineer need be better utilized.
Computer simulation and model development can be an integral part of an engineer’s endeavors. The days when the effect of professionals who do mathematical modeling and computer simulation on the bottom line of the enterprise is only indirect are over. The coming era is when the PW, Present Worth of chemical plants are better for having an army of engineers and Ph.D scholars who perform process dynamics studies, develop process control block diagrams, instrument the chemical plant with sensors hooked with data acquisition to the desktop computer.
GlaxoSmithKline, Novartis, DSM, Lonza are developing continuous process technogies for pharmaceutical production. Over $ 1 billion has been invested in continuous process for pharmaceutical production. Glaxo is building a $ 50 million plant in Singapore in order to manufacture asthma and allergy drug fluticasone propionate. Contract manufacturing can be used in order to perform flow hydrogenations that are catalyzed in packed bed configuration, distillation, extraction, crystallization from the tube to manufacturing. SK Life Sciences sill run 60-70% of the chemistries in batch mode. The operators need to be trained in the PFD, process flow diagram. This can also be shown to the customers. Material and Energy balance can lead to cost savings for the enterprise. Spreadsheets can be used for this purpose. It does not come as a surprise that the high attrition rate in pharmaceutical industry can be decreased when continuous process is adopted. Several unit operations have to be made to work in consonance with each other. It is hard to miss the efficient conversion of raw materials to product using continuous process in large scale. Scale-up principles such as L/D, length over diameter ratio of the reactors, distillation columns, adsorption towers, agitator speed and power draw used, pre-treatment of raw materials can be augmented using reliable mathematical models for mixing, heat transfer, mass transfer for a given pharmaceutical chemistry.Waste heat recovery and energy audit can lead to a more optimcal operation. For new products the continuous processes are readily adapted. The cost of over the counter drugs may decrease. Value addition during development of pharmaceutical products are high. It is not hard to break down the value addition along the sequence of unit operations used from raw material pre-treatment to post-treatment of the drug capsule steps.
Industrial scale flow processes can be developed for a step identified in the bench scale. One example here is the nitation step developed by DSM. DSM manufactured API, active pharmaceutical ingredient at a capacity of few hundreds of tons per year. They ran hundreds of microscale reactors in parallel. Usually PFR, plug flow reactor is more efficient. Utility costs will be high in the parallel configuration. The cost of recovery of the unreacted materials and recycling back to the reactors will consume the money budgeted. This is because of the low conversion in the microreactors and high conversion in the case of the PFR. In cases where the yield of the reaction is low in the bench scale attempts have to made in order to improve the yield. Advances have been made in the downstream processing methods used in pharmaceutical industry. Implementation of these changes can result in higher overall yield of the product. Research in continuous manufacturing has lead to the development of a pilot effort to make the API in Tekturna a cardiovascular drug, i.e., AliskirneHemifumarate. The number of operations in the batch mode was 21. The unit operations used in the continuous process is 14. Novartis is spending $ 65 million for more R & D over a 10 year period. Some steps used in continuous manufacturing of pharmaceuticals are reactions, separations, purification, crystallization, drying, formulation, tableting. 3 million tablets a year can be made at a reactor output of 41 g/hr. Portable units are possible.
Nutritional supplement, NBMI was developed by University of Kentucky in 6 years with the help of contract manufacturing. The drug is intended for use as antioxidant and can be used for reversing ageing. Clinical trials are being conducted. It works by mercury chelation. PCI the contract manufacturer eliminated chloroform used as solvent, increased the yield to 98%, isolated the material in powder form and made into capsules.
Last Updated (Friday, 25 July 2014 02:29)