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DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER

Review, Continuous Processing

 PROCESS, spectroscopy, SYNTHESIS, Uncategorized  Comments Off on Review, Continuous Processing
Jun 272016
 

Continuous Processing

 

Continuous production is a flow production method used to manufacture, produce, or process materials without interruption. Continuous production is called a continuous process or a continuous flow process because the materials, either dry bulk or fluids that are being processed are continuously in motion, undergoing chemical reactions or subject to mechanical or heat treatment. Continuous processing is contrasted with batch production.

Continuous usually means operating 24 hours per day, seven days per week with infrequent maintenance shutdowns, such as semi-annual or annual. Some chemical plants can operate for more than one or two years without a shutdown. Blast furnaces can run four to ten years without stopping.[1]

Production workers in continuous production commonly work in rotating shifts.

Processes are operated continuously for practical as well as economic reasons. Most of these industries are very capital intensive and the management is therefore very concerned about lost operating time.

Shutting down and starting up many continuous processes typically results in off quality product that must be reprocessed or disposed of. Many tanks, vessels and pipes cannot be left full of materials because of unwanted chemical reactions, settling of suspended materials or crystallization or hardening of materials. Also, cycling temperatures and pressures from starting up and shutting down certain processes (line kilns, boilers, blast furnaces, pressure vessels, etc.) may cause metal fatigue or other wear from pressure or thermal cycling.

In the more complex operations there are sequential shut down and start up procedures that must be carefully followed in order to protect personnel and equipment. Typically a start up or shut down will take several hours.

Continuous processes use process control to automate and control operational variables such as flow rates, tank levels, pressures, temperatures and machine speeds.[2]

Semi-continuous processes

Many processes such as assembly lines and light manufacturing that can be easily shut down and restarted are today considered semi-continuous. These can be operated for one or two shifts if necessary.

History

The oldest continuous flow processes is the blast furnace for producing pig iron. The blast furnace is intermittently charged with ore, fuel and flux and intermittently tapped for molten pig iron and slag; however, the chemical reaction of reducing the iron and silicon and later oxidizing the silicon is continuous.

Semi-continuous processes, such as machine manufacturing of cigarettes, were called “continuous” when they appeared.

Many truly continuous processes of today were originally batch operations.

The Fourdrinier paper machine, patented in 1799, was one of the earliest of the industrial revolution era continuous manufacturing processes. It produced a continuous web of paper that was formed, pressed, dried and reeled up in a roll. Previously paper had been made in individual sheets.

Another early continuous processes was Oliver Evans‘es flour mill (ca. 1785), which was fully automated.

Early chemical production and oil refining was done in batches until process control was sufficiently developed to allow remote control and automation for continuous processing. Processes began to operate continuously during the 19th century. By the early 20th century continuous processes were common.

Shut-downs

In addition to performing maintenance, shut downs are also when process modifications are performed. These include installing new equipment in the main process flow or tying-in or making provisions to tie-in sub-processes or equipment that can be installed while the process is operating.

Shut-downs of complicated processes may take weeks or months of planning. Typically a series of meetings takes place for co-ordination and planning. These typically involve the various departments such as maintenance, power, engineering, safety and operating units.

All work is done according to a carefully sequenced schedule that incorporates the various trades involved, such as pipe-fitters, millwrights, mechanics, laborers, etc., and the necessary equipment (cranes, mobile equipment, air compressors, welding machines, scaffolding, etc.) and all supplies (spare parts, steel, pipe, wiring, nuts and bolts) and provisions for power in case power will also be off as part of the outage. Often one or more outside contractors perform some of the work, especially if new equipment is installed.

Safety

Safety meetings are typically held before and during shutdowns. Other safety measures include providing adequate ventilation to hot areas or areas where oxygen may become depleted or toxic gases may be present and checking vessels and other enclosed areas for adequate levels of oxygen and insure absence of toxic or explosive gases. Any machines that are going to be worked on must be electrically disconnected, usually through the motor starter, so that it cannot operate. It is common practice to put a padlock on the motor starter, which can only be unlocked by the person or persons who is or are endangered by performing the work. Other disconnect means include removing couplings between the motor and the equipment or by using mechanical means to keep the equipment from moving. Valves on pipes connected to vessels that workers will enter are chained and locked closed, unless some other means is taken to insure that nothing will come through the pipes.

Continuous processor (equipment)

Continuous Production can be supplemented using a Continuous Processor. Continuous Processors are designed to mix viscous products on a continuous basis by utilizing a combination of mixing and conveying action. The Paddles within the mixing chamber (barrel) are mounted on two co-rotating shafts that are responsible for mixing the material. The barrels and paddles are contoured in such a way that the paddles create a self-wiping action between themselves minimizing buildup of product except for the normal operating clearances of the moving parts. Barrels may also be heated or cooled to optimize the mixing cycle. Unlike an extruder, the Continuous Processor void volume mixing area is consistent the entire length of the barrel ensuring better mixing and little to no pressure build up. The Continuous Processor works by metering powders, granules, liquids, etc. into the mixing chamber of the machine. Several variables allow the Continuous Processor to be versatile for a wide variety of mixing operations:[3]

  1. Barrel Temperature
  2. Agitator speed
  3. Fed rate, accuracy of feed
  4. Retention time (function of feed rate and volume of product within mixing chamber)

Continuous Processors are used in the following processes:

  • Compounding
  • Mixing
  • Kneading
  • Shearing
  • Crystallizing
  • Encapsulating

The Continuous Processor has an unlimited material mixing capabilities but, it has proven its ability to mix:

  • Plastics
  • Adhesives
  • Pigments
  • Composites
  • Candy
  • Gum
  • Paste
  • Toners
  • Peanut Butter
  • Waste Products

EXAMPLE…………….

 

 

Abstract Image

In the development of a new route to bendamustine hydrochloride, the API in Treanda, the key benzimidazole intermediate 5 was generated via catalytic heterogeneous hydrogenation of an aromatic nitro compound using a batch reactor. Because of safety concerns and a site limitation on hydrogenation at scale, a continuous flow hydrogenation for the reaction was investigated at lab scale using the commercially available H-Cube. The process was then scaled successfully, generating kilogram quantities on the H-Cube Midi. This flow process eliminated the safety concerns about the use of hydrogen gas and pyrophoric catalysts and also showed 1200-fold increase in space–time yield versus the batch processing.

Improved Continuous Flow Processing: Benzimidazole Ring Formation via Catalytic Hydrogenation of an Aromatic Nitro Compound

Org. Process Res. Dev., 2014, 18 (11), pp 1427–1433
Figure

EXAMPLE…………….


Correia et al. have published a three-step flow synthesis of rac-Effavirenz. This short synthetic route begins with cryogenic trifluoroacetylation of 1,4-dichlorobenzene. After quench and removal of morpholine using silica gel, this intermediate could either be isolated, or the product stream could be used directly in the next alkynylation step. Nucleophilic addition of lithium cyclopropylacetylide to the trifluoroacetate gave the propargyl alcohol intermediate in 90% yield in under 2 min residence time. This reaction was temperature-sensitive, and low temperatures were required to minimize decomposition. Again silica gel proved effective in the quench of the reaction. However, residual alkyne and other byproducts were difficult to remove. Thus, isolation of this intermediate was performed to minimize the impact of impurities on the final copper catalyzed cyanate installation/cyclization step to afford Effavirenz. Optimization of this step in batch mode for both copper source and ligand identified Cu(NO3)2 and CyDMEDA in a 1:4 molar ratio (20 mol % and 80 mol %, respectively) produced the product in 60% yield. Adaptation of this procedure to flow conditions resulted in poor conversion due to slow in situ reduction of the Cu(II) to Cu(I). Thus, a packed bed reactor of NaOCN and Cu(0) was used. Under these conditions, the ligand and catalyst loading could be reduced without compromising yield. Due to solubility limitations of Cu(NO3)2, Cu(OTf)2 was used with CyDMEDA in 1:2 molar ratio (5 mol % and 10 mol % loading, respectively). Under these optimized conditions, rac-Effavirenz was obtained in 62% isolated yield in reaction time of 1 h. This three-step process provides 45% overall yield of rac-Effavirenz and represents the shortest synthesis of this HIV drug reported to date
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1H NMR (400 MHz, CDCl3, ppm) δ9.45 (s, 1H), 7.49 (s, 1H), 7.35 (dd, J = 8.5, 1.5 Hz, 1H), 6.86 (d, J = 8.5 Hz, 1H), 1.43-1.36 (m, 1H); 0.93-0.85 (m, 4H);
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13C NMR (100 MHz, CDCl3, ppm) δ 149.2, 133.2, 131.7, 129.2, 127.8, 122.1 (q, JC-F = 286 Hz), 116.3, 115.1, 95.9, 79.6 (q, JC-F = 35 Hz), 66.1, 8.8, 0.6;
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19F NMR (376 MHz, CDCl3, ppm) δ -80.98.
1 T. J. Connolly; A. W.-Y Chan; Z. Ding; M. R. Ghosh; X. Shi; J. Ren, E. Hansen; R. Farr; M. MacEwan; A. Alimardanov; et al, PCT Int. Appl. WO 2009012201 A2 20090122, 2009.
2 (a) Z. Dai, X. Long, B. Luo, A. Kulesza, J. Reichwagen, Y. Guo, (Lonza Ltd), PCT Int. Appl. WO2012097510, 2012; (b) D. D. Christ; J. A. Markwalder; J. M. Fortunak; S. S. Ko; A. E. Mutlib; R. L. Parsons; M. Patel; S. P. Seitz, PCT Int. Appl. WO 9814436 A1 19980409, 1998 (c) C. A. Correia; D. T. McQuade; P. H. Seeberger, Adv. Synth. Catal. 2013, 355, 3517−3521.

A Concise Flow Synthesis of Efavirenz

  • DOI: 10.1002/anie.201411728
SUPP INFO
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 NEXT EXAMPLE…………….

 

Wang et al. developed a flow process that uses metal catalyzed hydrogenation of NAB (2-nitro-2′-hydroxy-5′-methylazobenzene) to BTA (2-(2′-hydroxy-5′-methylphenyl)benzotriazole), a commonly used ultraviolet absorber. The major challenge in this process was to optimize the reduction of the diazo functionality over the nitro group and control formation of over reduction side products. The initial screen of metals adsorbed onto a γ-Al2O3 support indicated Pd to be superior to the other metals and also confirmed that catalyst preparation plays an important role in selectivity. To better understand the characteristics of the supported metal catalyst systems, the best performing were analyzed by TEM, XRD, H2-TPR, and N2 adsorption–desorption. Finally, solvents and bases were screened ultimately arriving at the optimized conditions using toluene, 2 equiv n-butylamine over 1% Pd/Al2O3, which provided 90% yield BTA in process with 98% conversion. The process can run over 200 h without a decrease in performance
( ACS Sustainable Chem. Eng. 2015, 3,1890−1896)
.
Abstract Image

The synthesis of 2-(2′-hydroxy-5′-methylphenyl)benzotriazole from 2-nitro-2′-hydroxy-5′-methylazobenzene over Pd/γ-Al2O3 in a fixed-bed reactor was investigated. Pd/γ-Al2O3 catalysts were prepared by two methods and characterized by XRD, TEM, H2-TPR, and N2 adsorption–desorption. Employed in the above reaction, the palladium catalyst impregnated in hydrochloric acid exhibited much better catalytic performance than that impregnated in ammonia–water, which was possibly attributed to the better dispersion of palladium crystals on γ-Al2O3. This result demonstrated that the preparation process of the catalyst was very important. Furthermore, the reaction parameters were optimized. Under the optimized conditions (toluene, NAB/triethylamine molar ratio 1:2, 60 °C, 2.5 MPa hydrogen pressure, 0.23 h–1 liquid hourly space velocity), about 90% yield of 2-(2′-hydroxy-5′-methylphenyl)benzotriazole was obtained. Finally, the time on stream performance of the catalyst was evaluated, and the reaction could proceed effectively over 200 h without deactivation of the catalyst.

Construction of 2-(2′-Hydroxy-5′-methylphenyl)benzotriazole over Pd/γ-Al2O3 by a Continuous Process

ACS Sustainable Chem. Eng., 2015, 3 (8), pp 1890–1896
DOI: 10.1021/acssuschemeng.5b00507
Publication Date (Web): July 06, 2015

NEXT EXAMPLE…………….

 

Continuous Flow-Processing of Organometallic Reagents Using an Advanced Peristaltic Pumping System and the Telescoped Flow Synthesis of (E/Z)-Tamoxifen

continuous flow processing of organometallic reagents

A new enabling technology for the pumping of organometallic reagents such as n-butyllithium, Grignard reagents, and DIBAL-H is reported, which utilises a newly developed, chemically resistant, peristaltic pumping system. Several representative examples of its use in common transformations using these reagents, including metal–halogen exchange, addition, addition–elimination, conjugate addition, and partial reduction, are reported along with examples of telescoping of the anionic reaction products. This platform allows for truly continuous pumping of these highly reactive substances (and examples are demonstrated over periods of several hours) to generate multigram quantities of products. This work culminates in an approach to the telescoped synthesis of (E/Z)-tamoxifen using continuous-flow organometallic reagent-mediated transformations.

https://www.vapourtec.com/flow-chemistry-resource-centre/publications-citing-vapourtec/continuous-flow-processing-of-organometallic-reagents-using-an-advanced-peristaltic-pumping-system-and-the-telescoped-flow-synthesis-of-ez-tamoxifen/

 

NEXT EXAMPLE…………….

 

Multi-step Continuous Flow Pyrazole Synthesis via a Metal-free Amine-redox Process

A versatile multi-step continuous flow synthesis for the preparation of substituted pyrazoles is presented.

The automated synthesis utilises a metal-free ascorbic acid mediated reduction of diazonium salts prepared from aniline starting materials followed by hydrolysis of the intermediate hydazide and cyclo-condensation with various 1,3-dicarbonyl equivalents to afford good yields of isolated functionalised pyrazole products.

The synthesis of the COX-2 selective NSAID was demonstrated using this approach.

NEXT EXAMPLE…………….

 

Synthesis of a Precursor to Sacubitril Using Enabling Technologies

Continuous flow methodologyhas been used to enhance several steps in the synthesis of a precursor to Sacubitril.

In particular, a key carboethoxyallylation benefited from a reducedprocessing time and improved reproducibility, the latter attributable toavoiding the use of a slurry as in the batch procedure. Moreover, in batchexothermic formation of the organozinc species resulted in the formation ofside products, whereas this could be avoided in flow because heat dissipationfrom a narrow packed column of zinc was more efficient

NEXT EXAMPLE…………….

 

RAFT RAFT (Reversible Addition Fragmentation chain Transfer), a type of controlled radical polymerization, was invented by CSIRO in 1998 but developed in partnership with DuPont over a long term collaboration. Conventional polymerisation is fast but gives a wide distribution of polymer chain lengths. (known as a high polydispersity index ). RAFT is more versatile than other living polymerization techniques, such as atom transfer radical polymerization (ATRP) or nitroxide-mediated polymerization (NMP), it not only leads to polymers with a low polydispersity index and a predetermined molecular weight, but it permits the creation of complex architectures, such as linear block copolymers, comblike, star, brush polymers and dendrimers. Monomers capable of polymerizing by RAFT include styrenes, acrylates, acrylamides, and many vinyl monomers. CSIRO is the owner of the RAFT patents and is actively commercialising the technology. There are 12 licences in force and CSIRO is pursuing interest in a number of fields including human health, agriculture, animal health and personal care. RAFT is the dominant polymerization technique for the creation of polymer-protein or polymer-drug conjugates, permitting (for example) the combination of a polymer exhibiting high solubility with a drug molecule with poor solubility.. Though RAFT can be carried out in batch, it also lends itself to continuous flow processing, as this processing method offers an easy and reproducible scale-up route of the oxygen sensitive RAFT process. The possibility to effectively exclude oxygen using continuous flow reactors in combination with inline degassing methods offers advantages over batch processing at scales beyond the laboratory environment. Challenges associated with the high viscosity of the polymer product solution can be controlled using pressuriseable continuous flow reactor systems. http://www.csiro.au/products/RAFT.html
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Examples………..

Cyclohexaneperoxycarboxylic acid (6,  has been developed as a safe, inexpensive oxidant, with demonstrated utility in a Baeyer−Villiger rearrangement.34 Solutions of cyclohexanecarboxylic acid in hexane and 50% aqueous H2O2 were continuously added to 45% H2SO4 at 50−70 °C and slightly reduced pressure. The byproduct H2O was removed azeotropically, and the residence time in the reactor was 3 h. Processing was adjusted to maintain a concentration of 6 at 17−19%, below the detonable level, and the product was kept as a stable solution in hexane. These operations enhanced the safety margin in preparing 6.

figure

Scheme .  Generation of cyclohexaneperoxycarboxylic acid

Examples………..

Abstract Image

The conversion of a batch process to continuous (flow) operation has been investigated. The manufacture of 4,d-erythronolactone at kilogram scale was used as an example. Fully continuousprocessing was found to be impracticable with the available plant because of the difficulty in carrying out a multiphase isolation step continuously, so hybrid batch–continuous options were explored. It was found that very little additional laboratory or process safety work other than that required for the batch process was required to develop the hybrid process. A hybrid process was chosen because of the difficulty caused by the precipitation of solid byproduct during the isolation stage. While the project was a technical success, the performance benefits of the hybrid process over the batch were not seen as commercially significant for this system.

Multikilogram Synthesis of 4-d-Erythronolactone via Batch andContinuous Processing

Org. Process Res. Dev., 2012, 16 (5), pp 1003–1012

 

Examples………..

Abstract Image

Continuous Biocatalytic Processes

Org. Process Res. Dev., 2009, 13 (3), pp 607–616
Figure
Scheme . Biotransformation of sodium l-glutamate to γ-aminobutyric acid (GABA) by single-step α-decarboxylation with glutamate decarboxylase

PICS…………..

References

  1.  American Iron and Steel Institute
  2.  Benett, Stuart (1986). A History of Control Engineering 1800-1930. Institution of Engineering and Technology. ISBN 978-0-86341-047-5.
  3.  Ziegler, Gregory R.; Aguilar, Carlos A. (2003). “Residence Time Distribution in a Co-rotating, Twin-screw Continuous Mixer by the Step Change Method”. Journal of Food Engineering(Elsevier) 59 (2-3): 1–7.

Sources and further reading

  • R H Perry, C H Chilton, C W Green (Ed), Perry’s Chemical Engineers’ Handbook (7th Ed), McGraw-Hill (1997), ISBN 978-0-07-049841-9
  • Major industries typically each have one or more trade magazines that constantly feature articles about plant operations, new equipment and processes and operating and maintenance tips. Trade magazines are one of the best ways to keep informed of state of the art developments.
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ARAB MEDICINE- REVIEW

 Arab medicine review  Comments Off on ARAB MEDICINE- REVIEW
Jan 212014
 

ARAB MEDICINE- REVIEW

In the history of medicine, Islamic medicineArabic medicineGreco-Arabic and Greco-Islamic refer to medicine developed in the Islamic Golden Age, and written in Arabic, the lingua franca of Islamic civilization. The emergence of Islamic medicine came about through the interactions of the indigenous Arab tradition with foreign influences.Translation of earlier texts was a fundamental building block in the formation of Islamic medicine and the tradition that has been passed down.

Latin translations of Arabic medical works had a significant influence on the development of medicine in the high Middle Ages and early Renaissance, as did Arabic texts which translated the medical works of earlier cultures.

In the early Islamic and Mack’s period (661–750 AD), Muslims believed that Allah provided a treatment for every illness.Around the ninth century, the Islamic medical community began to develop and utilize a system of medicine based on scientific analysis. The importance of the health sciences to society was emphasized, and the early Muslim medical community strived to find ways to care for the health of the human body. Medieval Islam developed hospitals, expanded the practice of surgery.

Important medical thinkers and physicians of Islam were Al-Razi and Ibn Sina. Their knowledge on medicine was recorded in books that were influential in medical schools throughout Muslim history, and Ibn Sina in particular (under his Latinized name Avicenna) was also influential on the physicians of later medieval Europe. Throughout the medieval Islamic world, medicine was included under the umbrella of natural philosophy, due to the continued influence of the Hippocratic Corpus and the ideas of Aristotle and Galen. The Hippocratic Corpus was a collection of medical treatises attributed to the famous Greek physician Hippocrates of Cos (although it was actually composed by different generations of authors). The Corpus included a number of treatises which greatly influenced medieval Islamic medical literature

The first encyclopedia of medicine in Arabic language] was Persian scientist Ali ibn Sahl Rabban al-Tabari‘s Firdous al-Hikmah(“Paradise of Wisdom”), written in seven parts, c. 860. Al-Tabari, a pioneer in the field of child development, emphasized strong ties between psychology and medicine, and the need for psychotherapy and counseling in the therapeutic treatment of patients. His encyclopedia also discussed the influence of Sushruta and Chanakya on medicine, including psychotherapy

Medical contributions made by Medieval Islam not only involved the development and expansion of the human anatomy, but also included the use of plants as a type of remedy or medicine. Medieval Islamic physicians used natural substances as a source of medicinal drugs—including Papaver somniferum Linnaeus, poppy, and Cannabis sativa Linnaeus, hemp. In pre-Islamic Arabia, neither poppy nor hemp was known. Hemp was introduced into the Islamic countries in the ninth century from India through Persia and Greek culture and medical literature. Dioscorides, who according to the Arabs is the greatest botanist of antiquity, recommended hemp’s seeds to “quench geniture” and its juice for earaches.[27] Beginning in 800 and lasting for over two centuries, poppy use was restricted to the therapeutic realm. However, the dosages often exceeded medical need and was used repeatedly despite what was originally recommended. Poppy was prescribed by Yuhanna b. Masawayh to relieve pain from attacks of gallbladder stones, for fevers,indigestion, eye, head and tooth aches, pleurisy, and to induce sleep. Although poppy had medicinal benefits, Ali al-Tabari explained that the extract of poppy leaves was lethal, and that the extracts and opium should be considered poisons

The way early Arab medicine developed should be contrasted to how medicine evolved in Christianity up until the Renaissance. While Christian Rome and Byzantium inherited the rich Graeco-Roman medical legacy of thinkers like Hippocrates and Galen, after the fall of Rome in 476, Dark Age Europe increasingly tended towards a fatalistic view of suffering and disease, further tempered by superstition about curses and God’s punishment for man’s sins sent down in the form of disease and affliction.

Many historians point to the explicit tradition of fact-based, scientific medicine as articulated by the Prophet himself (pbuh). First, the concept of ‘sinful’ mankind seems not as strong in Islam as in early Christianity. Disease was seen by Arabs and other Muslims as one more problem to be solved, not a curse from God or a trial to be endured so one would be assured of entering Paradise.

Consider these statements on health and medicine attributed to the Prophet (pbuh):

“There is no disease that Allah has created, except that He also has created its treatment.”

“Make use of medical treatment, for Allah has not made a disease without appointing a remedy for it, with the exception of one disease, namely old age.”

The Prophet (pbuh) was also credited with articulating several specific medical treatments, including the use of honey, cupping, and cauterisation. He spoke about the contagious nature of leprosy, sexually transmitted disease, and the animal disease known as the mange. But most importantly, whereas other societies usually stigmatised and feared the sick and afflicted, at best isolating them and at worst leaving them somewhere to die, the Prophet (pbuh) and early Islam had a very compassionate and forgiving view of the sick.

As in other fields, the earliest Arab-Muslim medical efforts were devoted to translating the medical wisdom of older civilisations, beginning in the late 700s in Baghdad with the works of the Roman physician Galen as well as advanced medical writings from Persia, including the great pre-Islamic medical centre at Gundishapur.

Gundishapur is credited with having developed the first truly modern hospital, where patients actually went to be healed and cured, rather than prayed over as they suffered a slow and inevitable death as in Dark Age Europe.

The first major Arab-Muslim healer was the chemist Al Razi, who turned to medicine at about age 30, perhaps to find cures for his injuries suffered during alchemical experiments, especially eye ailments. His first inspiration was the Roman physician Galen.

Galen had pushed Roman medical knowledge as far as it could go in that time, undertaking innumerable vivisections of live animals to see how their organs functioned, as well as dissections of human cadavers.

Al Razi was especially troubled by Galen’s theory of the humours, which just didn’t hold up to examination. There seemed a lot more going on inside the human body than those four humours. And so he would write around 865:

“I prayed to God to direct and lead me to the truth in writing this book. It grieves me to oppose and criticise the man Galen from whose sea of knowledge I have drawn much. Indeed, he is the Master and I am the disciple. Although this reverence and appreciation will and should not prevent me from doubting, as I did, what is erroneous in his theories. I imagine and feel deeply in my heart that Galen has chosen me to undertake this task, and if he were alive, he would have congratulated me on what I am doing. I say this because Galen’s aim was to seek and find the truth and bring light out of darkness. I wish indeed he were alive to read what I have published.”

Al Razi would write as many as 184 papers and articles on subjects ranging from his doubts about Galen to the first known distinction between smallpox and measles, the discovery of allergic asthma, the discovery of fever as the body’s defence mechanism, medical ethics, using opium as a treatment for depression, the first medical handbook for common people, and paediatrics.

Al Razi would also theorise about the connection of the soul and state of mind to the physical health of the body, suggesting that someone with mental and emotional disturbances would be more vulnerable to infection and chronic ailments.

Al Razi’s medical insights would be translated into Latin several centuries after his death. By the late 1200s, mediaeval Europeans were beginning to stir out of their long Dark Age sleep and for a century were captivated by the writings of Al Razi – who by then had been given the Latin name Rhazes.

About eight decades after Al Razi, a brilliant healer named Al Zahrawi laid the foundation of modern surgery while working in the Umayyad imperial compound outside Cordoba.

Because all records were destroyed in the civil wars that marked the end of the Umayyad reign in Spain, hardly any facts about Al Zahrawi’s personal life remain. What does survive is his 30-chapter Kitab al Tasrif, a compendium of this man’s medical knowledge and genius. A century and a half after his death, it would be translated into Latin and have even more impact than the work of Rhazes. Al Zahrawi’s Latin name was Albucasis.

His discoveries would continue to resonate into the 21st century, first for his invention of about 200 medical instruments, many of which are still in use – such as the obstetrical forceps, scalpel, surgical needle, surgical retractor, specula, and the use of catgut for internal suturing. But he was also exceptional for innovating surgical procedures like mastectomies, orthodontia, repairing fractures, and using ligature for suturing arteries instead of cauterising them.

Another Muslim healer would follow in the Arabic tradition and even eclipse the great Al Zahrawi, this one a Persian working exclusively in Persia. This man was Ibn Sina. Europe and the Arab world would come to know him as Avicenna, the Prince of Medicine, and the single most important influence on Islamic and Western medicine for about 500 years.

Ibn Sina was consummately gifted. He is reputed to have memorised the Qur’an by age 10, Aristotle’s Metaphysics several years later (he claimed to have read it 40 times), and had become a practising physician by age 16.

Ibn Sina’s greatest motivation was his burning intellectual curiosity for the world, and the world beyond, not social status or financial security. By the age of 20, he had turned down his ruler’s offer to become court physician, preferring only the right to study as much as he wanted in the ruler’s royal library.

A political upheaval overthrew the ruler and Ibn Sina began a long life of wandering Persia in search of a secure patron who would allow him to indulge in his medical and scientific research. Unfortunately, political instability and Ibn Sina’s harshly arrogant manner meant he was constantly changing jobs.

But despite his unending struggle, he was able to gradually systemise Islamic understanding of the medical sciences in such a way that not only was the Arab and Islamic world forever indebted, so also was Europe and the West.

Although Ibn Sina is credited with writing as many as 450 papers and books in a dozen fields, the work that continued to resonate most powerfully was his Canon of Medicine written around 1025, a 14-volume work that was for 500 years Europe’s most influential medical source book. The Canon was a combination both of the collected medical wisdom of other writers as well as his own observations and research. Although it provided a window into forgotten Greek medicine, its greatest value was in the modernistic approach it took to a field riddled with false theory and ignorance.

It could be argued that Ibn Sina was the first to formally explain the experimental method in medicine, the spread of contagious diseases, the use of quarantine, clinical trials, psychiatry, and psychotherapy. He also seems to be the first to show that tuberculosis was a contagious disease, as well as to identify diabetes.

According to some sources, the Canon was the first documented explanation of modern medical methods like the randomised clinical trial, and the first modern set of comprehensive rules for testing new drugs.

His deeper research into the mind-body connection, and the mental or spiritual source of physical ailments, was built on the first intuitive work of men like Al Razi. But Ibn Sina went further, beginning the first documented forays into what we today would call psychotherapy, 900 years before Sigmund Freud.

One account says that a young man had come to him with a condition that looked very much like consumption. He was literally wasting away. But Ibn Sina could find no signs of a cancer or other disease that would indicate some physical explanation.

He conducted a series of interviews or conversations with the young man. As Ibn Sina spoke certain key words and phrases, he was also checking the man’s pulse and found it became elevated around certain terms. Thus it gradually emerged that the patient was in love with a woman back in his home village. For whatever reason he had never expressed this to her, and the unfulfilled desire was sapping him of his energy.

Ibn Sina gradually concluded that the source of the young man’s physical condition was his unexpressed love. He suggested that the patient go to the object of his affections and profess his love to her. The young man did this, the girl agreed to marry him, and the patient swiftly recovered his vitality.

As far as we know this was the earliest documented account of the use of word association in psychoanalysis, which modern medicine credits to Carl Jung 900 years later.

While medical thinkers like Al Razi, Al Zahrawi and Ibn Sina are closely tied to their innovations through their writings, many of the great breakthroughs of Arab medicine were collective undertakings and are difficult to identify with any single author or inventor.

This is particularly true with key Arab-Muslim institutions like the modern insane asylum, the public hospital, free medical care, and the pharmacy. The modern hospital itself was not an Arab invention, but Arabs and their partners made it a public institution and spread it around the world.

Isolated healing temples and places for the sick had existed in many older cultures including around the Mediterranean and across Asia. But with few exceptions they were unable to offer real cures in the modern sense. Often their method was a mixture of magic or religion with means of making one feel better, if only briefly.

But in 6th century pre-Islamic Persia, a true hospital called a bimaristan or ‘sick place’ was built in the city of Gundishapur, complete with surgery, pharmacy, and outpatient treatments. This came to the attention of the Arabs, in particular Caliphs Harun Al Rashid and his half-Persian son Al Mamun, and they set about replicating these institutions across their realm.

Harun invited a doctor from the bimaristan in Gundishapur to open the first bimaristan in Baghdad. Al Razi was later commissioned with overseeing the Audidi Hospital in Baghdad, in the mid 800s. He applied his evolving understanding of sanitation and infection to find the best location possible. He hung raw meat in various parts of the city to see comparative rates of decay, and where the meat lasted longest, there he put the hospital.

Audidi had more than two dozen doctors including surgeons, eye specialists, and physiologists.

By the year 1000, Baghdad alone would number five public hospitals when there were none in all of Europe. Hospitals would also be found in Cairo, Damascus, Aleppo, North Africa, and Al Andalus. These centres would offer surgery, outpatient clinics, mental wards, convalescent centres, and even nursing homes.

One of the greatest hospitals would be Al Mansuri in Cairo, which was reported to have as many as 8,000 beds and annual revenues of one million dirhams. Al Mansuri was a true public hospital because it was charged with offering treatment to anyone, rich or poor, including the indigent who could not pay at all.

The Arab establishment of humane mental wards and insane asylums was especially futuristic and important. The Arab world, in line with the teachings of the Prophet (pbuh) and others, never stigmatised the mentally afflicted, seeing mental illness as one more disease that might be cured. Europe and the West did not develop a modern non-judgmental view of mental illness until the 19th and 20th centuries.

Arab pharmacies were another important invention. Although other cultures offered various potions and herbs for sale, it was rare to find cures that really worked. People were just as inclined to faith healing and magic as to ‘healing’ substances, because they were all equally ineffective. But the evolution of modern evidence-based pharmacology under thinkers like Al Razi, Al Kindi and Ibn Sina created a new class of substances that really worked.

Arab pharmacies were known as saydala, and the first one seems to have been at Harun al Rashid’s hospital in Baghdad built in the late 700s. Within half a century saydala were spreading throughout the caliphate. These remedies were often fabricated right on the spot at in-house laboratories. More importantly, they were overseen by government inspectors to make sure they were pure, not out of date, measured in verified scales, and correctly identified.

Al Razi would even introduce the concept of generic drugs for the poor, while Al Kindi would also seek to identify cheaper alternative treatments for those who could not afford expensive drugs.

The same kind of modern pharmacies selling remedies that really worked would only begin to appear in Italy in about the 12th century, fuelled largely by the growing trade between Arabs and Europeans.

READ A GREAT ARTICLE AT

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1297506/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1475945/

Aqrabadhin of Al-Kindi. Translated by Martin Levey. Madison: The University of Wisconsin Press, 1966.

Kamal, Hassan. Encyclopedia of Islamic Medicine. Cairo: General Egyptian Book Organization, 1975.

Levey, Martin. Early Arabic Pharmacology. Leiden, Netherlands: E. J. Brill, 1973.

Savage-Smith, Emilie. Islamic Culture and the Medical Arts. Bethesda, Md.: National Library of Medicine, 1994.

Siddiqi, Muhammad Zubayr. Studies in Arabic and Persian Medical Literature. Calcutta: Calcutta University Press, 1959.

Usama, Ibn Shuraik. Sunna Abu-Dawud, Book 28, No. 3846 (part of the hadith, a narrative record of the sayings of Mohammed and his companions).

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