(USAN) , also known as metamfetamine
, clouds crystal
, and desoxyephedrine
, is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs.
Methamphetamine occurs in two enantiomers, dextrorotary and levorotary. Dextromethamphetamine is a stronger psychostimulant, but levomethamphetamine has a longer half-life and is CNS-active with weaker (approx. one-tenth) effects on striatal dopamine and shorter psychodynamic effects. At high doses, both enantiomers of methamphetamine can induce stereotypy and psychosis, but levomethamphetamine is less desired by drug abusers because of its weaker pharmacodynamic profile. Although rarely prescribed, methamphetamine hydrochloride is approved by the U.S. Food and Drug Administration (FDA) for the treatment of attention deficit hyperactivity disorder and obesity under the trade name Desoxyn
Illicitly, methamphetamine may be sold either as pure dextromethamphetamine or in a racemic mixture. Both dextromethamphetamine and racemic methamphetamine are Schedule II controlled substances in the United States, and similarly the production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions. Internationally, methamphetamine has been placed in Schedule II of the United Nations Convention on Psychotropic Substances treaty.
Contrary to popular misconception, methamphetamine in both powder and crystal form is a hydrochloride salt. The freebase form of methamphetamine (as well as amphetamine) is an oily liquid. The misconception started with the fact that heroin and cocaine are injected or snorted as salts, but they are smoked in freebase form. See also: crack cocaine.
In low dosages, methamphetamine can increase alertness, concentration, and energy in fatigued individuals. In higher doses, it can induce mania with accompanying euphoria, feelings of self-esteem and increased libido. Methamphetamine has a high potential for abuse and addiction, activating the psychological reward system by triggering a cascading release of dopamine in the brain characterized as Amphetamine/Stimulant psychosis.
Chronic abuse may also lead to post-withdrawal syndrome, a result of methamphetamine-induced neurotoxicity to dopaminergic neurons. Post-withdrawal syndrome can persist beyond the withdrawal period for months, and sometimes up to a year. In addition to psychological harm, physical harm – primarily consisting of cardiovascular damage – may occur with chronic use or acute overdose.
Methamphetamine has found use as both a medicinal and recreational drug.
In United States, Methamphetamine has been approved by the Food and Drug Administration (FDA) in treating ADHD and exogenous obesity (obesity originating from factors outside of the patient's control) in both adults and children.
Methamphetamine is a drug that is under the Controlled Substances Act which is listed under Schedule II in the United States and is sold under the name Desoxyn
trademarked by the Danish pharmaceutical company Lundbeck.
Because methamphetamine is highly abused for negative purposes such as selling the prescription to others, or overdosing (which contributes to very dangerous side effects) than using the medication medically, it is a tightly controlled substance under federal law. The minimum dosage prescribed is 5 milligrams.
may be prescribed off-label for the treatment of narcolepsy and treatment-resistant depression.
Methamphetamine's levorotary form is available in many over-the-counter nasal decongestant products.
Methamphetamine is used as a recreational drug for its euphoric and stimulant properties.
Physical effects can include anorexia, hyperactivity, dilated pupils, flushed skin, excessive sweating, restlessness, dry mouth and bruxism (leading to "meth mouth"), headache, accelerated heartbeat, slowed heartbeat, irregular heartbeat, rapid breathing, high blood pressure, low blood pressure, high body temperature, diarrhea, constipation, blurred vision, dizziness, twitching, insomnia, numbness, palpitations, tremors, dry and/or itchy skin, acne, pallor, and – with chronic and/or high doses – convulsions, heart attack, stroke, and death.
Psychological effects can include euphoria, anxiety, increased libido, alertness, concentration, increased energy, increased self-esteem, self-confidence, sociability, irritability, aggressiveness, psychosomatic disorders, psychomotor agitation, dermatillomania (compulsive skin picking), hair pulling, delusions of grandiosity, hallucinations, excessive feelings of power and invincibility, repetitive and obsessive behaviors, paranoia, and – with chronic use and/or high doses – amphetamine psychosis.
Withdrawal symptoms of methamphetamine primarily consist of fatigue, depression, and increased appetite. Symptoms may last for days with occasional use and weeks or months with chronic use, with severity dependent on the length of time and the amount of methamphetamine used. Withdrawal symptoms may also include anxiety, irritability, headaches, agitation, restlessness, excessive sleeping, vivid or lucid dreams, deep REM sleep, and suicidal ideation.
Methamphetamine use has a high association with depression and suicide as well as serious heart disease, amphetamine psychosis, anxiety, and violent behaviors. Methamphetamine also has a very high addiction risk.
Methamphetamine is not directly neurotoxic but long-term use can have neurotoxic side-effects. Its use is associated with an increased risk of Parkinson's disease due to the fact that uncontrolled dopamine release is neurotoxic. Long-term dopamine upregulation occurring as a result of Methamphetamine abuse can cause neurotoxicity, which is believed to be responsible for causing persisting cognitive deficits, such as memory loss, impaired attention, and decreased executive function. Similar to the neurotoxic effects on the dopamine system, methamphetamine can also result in neurotoxicity to the serotonin system.
As a result of methamphetamine-induced neurotoxicity to dopaminergic neurons, chronic abuse may also lead to post acute withdrawals which persist beyond the withdrawal period for months, and even up to a year. A study performed on female Japanese prison inmates suffering from methamphetamine addiction showed that 49% experienced "flashbacks" afterward and 21% experienced a psychosis resembling schizophrenia which persisted for longer than six months post-methamphetamine use; this amphetamine psychosis could be resistant to traditional treatment. Other studies in Japan show that those who experience methamphetamine-induced psychosis are much more likely to experience psychotic symptoms again if they use methamphetamine.]
[ In addition to psychological harm, physical harm – primarily consisting of cardiovascular damage – may occur with chronic use or acute overdose.
As with other amphetamines, tolerance to methamphetamine is not completely understood but is known to be sufficiently complex that it cannot be explained by any single mechanism. The extent of tolerance and the rate at which it develops vary widely between individuals, and even within one person. It is highly dependent on dosage, duration of use, and frequency of administration. Tolerance to the awakening effect of amphetamines does not readily develop, making them suitable for the treatment of narcolepsy.
Short-term tolerance can be caused by depleted levels of neurotransmitters within the synaptic vesicles available for release into the synaptic cleft following subsequent reuse (tachyphylaxis). Short-term tolerance typically lasts until neurotransmitter levels are fully replenished; because of the toxic effects on dopaminergic neurons, this can be greater than 2–3 days. Prolonged overstimulation of dopamine receptors caused by methamphetamine may eventually cause the receptors to downregulate in order to compensate for increased levels of dopamine within the synaptic cleft. To compensate, larger quantities of the drug are needed in order to achieve the same level of effects.
Reverse tolerance or sensitization can also occur. The effect is well established, but the mechanism is not well understood.
Methamphetamine is highly addictive. While the withdrawal itself may not be dangerous, withdrawal symptoms are common with heavy use and relapse is common.
Methamphetamine-induced hyperstimulation of pleasure pathways can lead to anhedonia months after use has been discontinued. Investigation of treatments targeting dopamine signalling such as bupropion, or psychological treatments that raise hedonic tone, such as behavioral activation therapy, have been suggested. It is possible that daily administration of the amino acids L
-tyrosine and -5HTPL
/tryptophan can aid in the recovery process by making it easier for the body to reverse the depletion of dopamine, norepinephrine, and serotonin.]
[ Although studies involving the use of these amino acids have shown some success, this method of recovery has not been shown to be consistently effective.]
It is shown that taking ascorbic acid prior to using methamphetamine may help reduce acute toxicity to the brain, as rats given the human equivalent of 5–10 grams of ascorbic acid 30 minutes prior to methamphetamine dosage had toxicity mediated, yet this will likely be of little avail in solving the other serious behavioral problems associated with methamphetamine use and addiction that many users experience. Large doses of ascorbic acid also lower urinary pH, reducing methamphetamine's elimination half-life and thus decreasing the duration of its actions.
To combat addiction, doctors are beginning to use other forms of stimulants such as dextroamphetamine, the dextrorotatory (right-handed) isomer of the amphetamine molecule, to break the addiction cycle in a method similar to the use of methadone in the treatment of heroin addicts. There are no publicly available drugs comparable to naloxone, which blocks opiate receptors and is therefore used in treating opiate dependence, for use with methamphetamine problems. However, experiments with some monoamine reuptake inhibitors such as indatraline have been successful in blocking the action of methamphetamine. There are studies indicating that fluoxetine, bupropion and imipramine may reduce craving and improve adherence to treatment. Research has also suggested that modafinil can help addicts quit methamphetamine use, as can Topiramate.
Methamphetamine addiction is one of the most difficult forms of addictions to treat. Bupropion, aripiprazole, and baclofen have been employed to treat post-withdrawal cravings, although the success rate is low. Modafinil is somewhat more successful, but this is a Class IV scheduled drug. Adrafinil is the prodrug of Modafinil, being metabolized by the body to Modafinil in 45–60 minutes, and is not a controlled substance.]
[ Ibogaine has been used with success in Europe, where it is a Class I drug and available only for scientific research. Mirtazapine has been reported useful in some small-population studies.
As the phenethylamine phentermine is a constitutional isomer of methamphetamine, it has been suggested that it may be effective in treating methamphetamine addiction. Phentermine is a central nervous system stimulant that acts on dopamine and norepinephrine. When comparing (+)-amphetamine, (+/-)-ephedrine, and phentermine, one key difference among the three drugs is their selectivity for norepinephrine (NE) release vs. dopamine (DA) release. The NE/DA selectivity ratios for these drugs as determined in vitro
[(EC(50) NE(-1))/(EC(50) DA(-1))] are (+/-)-ephedrine (18.6) > phentermine (6.7) > (+)-amphetamine (3.5).
Abrupt interruption of chronic methamphetamine use results in the withdrawal syndrome in almost 90% of the cases.]
The mental depression associated with methamphetamine withdrawal lasts longer and is more severe than that of cocaine withdrawal.
Methamphetamine users and addicts may lose their teeth abnormally quickly, a condition informally known as meth mouth. According to the American Dental Association, meth mouth "is probably caused by a combination of drug-induced psychological and physiological changes resulting in xerostomia (dry mouth), extended periods of poor oral hygiene, frequent consumption of high-calorie, carbonated beverages and bruxism (teeth grinding and clenching)". Some reports have also speculated that the caustic nature of the drug is a contributing factor. Methamphetamine also has the potential to cause excessive cigarette smoking for users already smoking. This combined with the methamphetamine can perpetuate the "meth mouth". Similar, though far less severe, symptoms have been reported in clinical use of regular amphetamine, where effects are not exacerbated by extended periods of poor oral hygiene.
Short-term exposure to high concentrations of chemical vapors that may exist in black market methamphetamine laboratories can cause severe health problems or even result in death. Exposure to these substances can occur from volatile air emissions, spills, fires, and explosions. Such methamphetamine labs are often discovered when fire fighters respond to a blaze. Methamphetamine cooks, their families, and first responders are at highest risk of acute health effects from chemical exposure, including lung damage and chemical burns to the body. Following a seizure of a methamphetamine lab, there is often a low exposure risk to chemical residues, however this contamination should be sanitized. Chemical residues and lab wastes that are left behind at a former methamphetamine lab can result in severe health problems for people who use the property, therefore local health departments should thoroughly assess the property for hazards prior to allowing it to be reinhabited, especially by children. Those seeking home ownership in heavy meth use areas should be especially careful while house hunting and be sure to have properties inspected before purchasing.
Methamphetamine present in a mother's bloodstream passes through the placenta to a fetus, and is also secreted into breast milk. Infants born to methamphetamine-abusing mothers were found to have a significantly smaller gestational age-adjusted head circumference and birth weight measurements. Methamphetamine exposure was also associated with neonatal withdrawal symptoms of agitation, vomiting and tachypnea. This withdrawal syndrome is relatively mild and only requires medical intervention in approximately 4% of cases.
Men who use methamphetamine, cocaine, MDMA, and ketamine, are twice as likely to have unprotected sex than those who do not use such drugs, according to British research. American psychologist Perry N. Halkitis performed an analysis using data collected from community-based participants among gay and bisexual men to examine the associations between their methamphetamine use and sexual risk taking behaviors. Methamphetamine use was found to be related to higher frequencies of unprotected sexual intercourse in both HIV-positive and unknown casual partners in the study population. The association between methamphetamine use and unprotected acts were also more pronounced in HIV-positive participants. These findings suggested that methamphetamine use and engagement in unprotected anal intercourse are co-occurring risk behaviors that potentially heighten the risk of HIV transmission among gay and bisexual men. Methamphetamine allows users of both sexes to engage in prolonged sexual activity, which may cause genital sores and abrasions. Methamphetamine can also cause sores and abrasions in the mouth via bruxism (teeth clenching and grinding), which can turn typically low-risk sex acts, such as oral sex, into high-risk sexual activity. As with the injection of any drug, if a group of users share a common needle, blood-borne diseases, such as HIV or hepatitis, can be transmitted. The level of needle sharing among methamphetamine users is similar to that among other drug injection users.
Following oral administration, methamphetamine is readily absorbed into the bloodstream, with peak plasma concentrations achieved in approximately 3.13 to 6.3 hours post ingestion. The amphetamine metabolite peaks at 10 to 24 hours. Methamphetamine is also well absorbed following inhalation and following intranasal administration. It is distributed to most parts of the body. Methamphetamine is known to produce central effects similar to the other stimulants, but at smaller doses, with fewer peripheral effects. Methamphetamine's high lipophilicity also allows it to cross the blood brain barrier faster than other stimulants, where it is more stable against degradation by monoamine oxidase (MAO).
Methamphetamine is metabolized in the liver with the main metabolites being amphetamine (active) and 4-hydroxymethamphetamine (pholedrine); other minor metabolites include 4-hydroxyamphetamine, norephedrine, and 4-hydroxynorephedrine. Other drugs metabolized to amphetamine and methamphetamine include benzphetamine, furfenorex, and famprofazone. Selegiline (marketed as Deprenyl, EMSAM, and others) is metabolized into levomethamphetamine which in turn is metabolized into levoamphetamine. Although only the D-Isomer of selegiline will metabolize into active metabolites, both isomers may cause a positive result for methamphetamine and amphetamine on a drug test, in certain cases.
It is excreted by the kidneys, with the rate of excretion into the urine heavily influenced by urinary pH. Between 30-54% of an oral dose is excreted in urine as unchanged methamphetamine and 10-23% as unchanged amphetamine. Following an intravenous dose, 45% is excreted as unchanged parent drug and 7% amphetamine. The half-life of methamphetamine is variable with a mean value of between 9 and 12 hours.
Methamphetamine and amphetamine are often measured in urine, sweat or saliva as part of a drug-abuse testing program, in plasma or serum to confirm a diagnosis of poisoning in hospitalized victims, or in whole blood to assist in a forensic investigation of a traffic or other criminal violation or a case of sudden death. Chiral techniques may be employed to help distinguish the source of the drug, whether obtained legally (via prescription) or illicitly, or possibly as a result of formation from a prodrug such as famprofazone or selegiline. Chiral separation is needed to assess the possible contribution of l-methamphetamine (Vicks Inhaler) toward a positive test result. In 2011, researchers at John Jay College of Criminal Justice reported that dietary zinc supplements can mask the presence of methamphetamine and other drugs in urine.]
[ Similar claims have been made in web forums on that topic.
A member of the family of phenethylamines, methamphetamine is chiral, with two isomers, levorotatory and dextrorotatory. The levorotatory form, called levomethamphetamine, is an over-the-counter drug used in inhalers for nasal decongestion.
Methamphetamine is a potent central nervous system stimulant that affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and emotional responses associated with alertness or alarming conditions. The acute physical effects of the drug closely resemble the physiological and psychological effects of an epinephrine-provoked fight-or-flight response, including increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), bronchodilation, and hyperglycemia (increased blood sugar). Users experience an increase in focus, increased mental alertness, and the elimination of fatigue, as well as a decrease in appetite. It is known to produce central effects similar to the other stimulants, but at smaller doses, with fewer peripheral effects. Methamphetamine's fat solubility also allows it to enter the brain faster than other stimulants, where it is more stable against degradation by monoamine oxidase (MAO).
The methyl group is responsible for the potentiation of effects as compared to the related compound amphetamine, rendering the substance more lipid-soluble, enhancing transport across the blood–brain barrier, and more stable against enzymatic degradation by monoamine oxidase (MAO). Methamphetamine causes the norepinephrine, dopamine, and serotonin (5HT) transporters to reverse their direction of flow. This inversion leads to a release of these transmitters from the vesicles to the cytoplasm and from the cytoplasm to the synapse (releasing monoamines in rats with ratios of about NE:DA = 1:2, NE: 5HT = 1:60), causing increased stimulation of post-synaptic receptors. Methamphetamine also indirectly prevents the reuptake of these neurotransmitters, causing them to remain in the synaptic cleft for a prolonged period (inhibiting monoamine reuptake in rats with ratios of about: NE:DA = 1:2.35, NE:5HT = 1:44.5). Methamphetamine also interacts with TAAR1 to trigger phosphorylation of PKA and PKC, ultimately resulting in the internalization of dopamine transporters. The presynaptic cell is less able to effectively remove dopamine from the synapse. The binding of methamphetamine to TAAR1 also activates adenylyl cyclase, which allows for increased intracellular cAMP. Taken together, the binding of methamphetamine to TAAR1 results in a massive efflux of neurogenic monoamines with a sustained synaptic presence.
Methamphetamine is a potent neurotoxin, shown to cause dopaminergic degeneration. High doses of methamphetamine produce losses in several markers of brain dopamine and serotonin neurons. Dopamine and serotonin concentrations, dopamine and 5HT uptake sites, and tyrosine and tryptophan hydroxylase activities are reduced after the administration of methamphetamine. It has been proposed that dopamine plays a role in methamphetamine-induced neurotoxicity, because experiments that reduce dopamine production or block the release of dopamine decrease the toxic effects of methamphetamine administration. When dopamine breaks down, it produces reactive oxygen species such as hydrogen peroxide. It is likely that the approximate twelvefold increase in dopamine levels and subsequent oxidative stress that occurs after taking methamphetamine mediates its neurotoxicity. The lab of David Sulzer and colleagues at Columbia University developed a technique known as "intracellular patch electrochemistry" to measure concentrations of dopamine in the cytosol, and found massive increases following methamphetamine, leading to the "cytosolic dopamine hypothesis" of neurotoxicity, in which dopamine oxidation, particularly close to synaptic vesicles, produce oxidative stress that in turn leads to exacerbation of autophagy that can destroy axons and dendrites.
Recent research published in the Journal of Pharmacology And Experimental Therapeutics
(2007) indicates that methamphetamine binds to and activates a G protein-coupled receptor called TAAR1. TAARs are a newly discovered receptor family whose members are activated by a number of amphetamine-like molecules called trace amines, thyronamines, and certain volatile odorants.
It has been demonstrated that a high core temperature is correlated with an increase in the neurotoxic effects of methamphetamine.
Methamphetamine has been reported to occur naturally in Acacia berlandieri
, and possibly Acacia rigidula
, trees that grow in West Texas. Methamphetamine and amphetamine were long thought to be strictly human-synthesized, but Acacia
trees contain these and numerous other psychoactive compounds (e. g., mescaline, nicotine, dimethyltryptamine), and the related compound β-phenethylamine is known to occur from numerous Acacia
species. The findings, however, have never been confirmed or repeated, leading some researchers to believe the results were the result of cross-contamination.]
Studies have shown that the subjective pleasure of drug use (the reinforcing component of addiction) is proportional to the rate at which the blood level of the drug increases. These findings suggest the route of administration used affects the potential risk for psychological addiction independently of other risk factors, such as dosage and frequency of use. Intravenous injection is the fastest route of drug administration, causing blood concentrations to rise the most quickly, followed by smoking, suppository (anal or vaginal insertion), insufflation (snorting), and ingestion (swallowing). Ingestion does not produce a rush, an acute transcendent state of euphoria as forerunner to the high experienced with the use of methamphetamine, which is most pronounced with the intravenous route of administration. While the onset of the rush induced by injection can occur in as little as a few seconds, the oral route of administration requires approximately half an hour before the high sets in.
Injection carries relatively greater risks than other methods of administration. The hydrochloride salt of methamphetamine is soluble in water. Intravenous users may use any dose range, from less than 100 milligrams to over one gram, using a hypodermic needle, although it should be noted that typically street methamphetamine is “cut,” or diluted, with a water-soluble cutting material, which constitutes a significant portion of a given street methamphetamine dose. Intravenous users risk developing pulmonary embolism (PE), a blockage of the main artery of the lung or one of its branches, and commonly develop skin rashes (also known as "speed bumps") or infections at the site of injection. As with the injection of any drug, if a group of users share a common needle without sterilization procedures, blood-borne diseases, such as HIV or hepatitis, can be transmitted.
Smoking amphetamines refers to vaporizing it to inhale the resulting fumes, not burning it to inhale the resulting smoke. It is commonly smoked in glass pipes made from glassblown Pyrex tubes and light bulbs. It can also be smoked off aluminium foil, which is heated underneath by a flame. This method is also known as "chasing the white
dragon" (whereas smoking heroin is known as "chasing the dragon"). There is little evidence that methamphetamine inhalation results in greater toxicity than any other route of administration. Lung damage has been reported with long-term use, but manifests in forms independent of route (pulmonary hypertension (PH)), or limited to injection users (pulmonary embolism (PE)).
Another popular route of administration to intake methamphetamine is insufflation (snorting). This method allows methamphetamine to be absorbed through the soft tissue of the mucous membrane in the sinus cavity, and then directly into the bloodstream, bypassing first-pass metabolism.
Suppository (anal or vaginal insertion) is a less popular method of administration used in the community with comparatively little research into its effects. Information on its use is largely anecdotal with reports of increased sexual pleasure and the effects of the drug lasting longer, though as methamphetamine is centrally active in the brain, these effects are likely experienced through the higher bioavailability of the drug in the bloodstream (second to injection) and the faster onset of action (than insufflation). Nicknames for the route of administration within some methamphetamine communities include a "butt rocket", a "booty bump", "potato thumping", "turkey basting", "plugging", "boofing", "suitcasing", "hooping", "keistering", "shafting", "bumming", and "shelving" (vaginal).
Shortly after the first synthesis of amphetamine in 1887, methamphetamine was synthesized from ephedrine in 1893 by Japanese chemist Nagai Nagayoshi. The term "methamphetamine" was derived from elements of the chemical structure of this new compound: ylmeth
. In 1919, crystallized methamphetamine was synthesized by pharmacologist Akira Ogata via reduction of ephedrine using red phosphorus and iodine.
One of the earliest uses of methamphetamine was during World War II, when it was used by Axis and Allied forces. The company Temmler produced methamphetamine under the trademark Pervitin
and so did the German and Finnish militaries. It was also dubbed "Pilot's chocolate" or "Pilot's salt". It was widely distributed across rank and division, from elite forces to tank crews and aircraft personnel, with many millions of tablets being distributed throughout the war. Its use by German Panzer crews also led to it being known as "Panzerschokolade" ("Panzer chocolate" or "tankers' chocolate"). More than 35 million three-milligram doses of Pervitin were manufactured for the German army and air force between April and July 1940. From 1942 until his death in 1945, Adolf Hitler was given intravenous injections of methamphetamine by his personal physician Theodor Morell. It is possible that it was used to treat Hitler's speculated Parkinson's disease, or that his Parkinson-like symptoms that developed from 1940 onwards resulted from using methamphetamine. In Japan, methamphetamine was sold under the registered trademark of Philopon (ヒロポン hiropon) by Dainippon Pharmaceuticals (present-day Dainippon Sumitomo Pharma [DSP]) for civilian and military use. As with the rest of the world at the time, the side effects of methamphetamine were not well studied, and regulation was not seen as necessary. In the 1940s and 1950s the drug was widely administered to Japanese industrial workers to increase their productivity.
Methamphetamine and amphetamine were given to Allied bomber pilots during World War II to sustain them by fighting off fatigue and enhancing focus during long flights. The experiment failed because soldiers became agitated, could not channel their aggression and showed impaired judgment. Rather, dextroamphetamine (Dexedrine) became the drug of choice for American bomber pilots, being used on a voluntary basis by roughly half of the U.S. Air Force pilots during the Persian Gulf War, a practice which came under some media scrutiny in 2003 after a mistaken attack on Canadian troops.
Following the use of amphetamine (such as Benzedrine, introduced 1932) in the 1930s for asthma, narcolepsy, and symptoms of the common cold, in 1943, Abbott Laboratories requested U.S. FDA approval of methamphetamine for treatment of narcolepsy, mild depression, postencephalitic parkinsonism, chronic alcoholism, cerebral arteriosclerosis, and hay fever, which was granted in December 1944.]
Sale of the massive postwar surplus of methamphetamine in Europe, North America, and Japan stimulated civilian demand. After World War II, a large Japanese military stockpile of methamphetamine, known by its trademark Philopon, flooded the market. Post-war Japan experienced the first methamphetamine epidemic, which later spread to Guam, the U. S. Marshall Islands, and to the U. S. West Coast.
In 1948, the Philopon trademark came under a well-publicized lawsuit by Philips Corporation. Philips, under its Koninklijke division, filed suit against Dainippon Pharmaceuticals to cease using Philipon as the commercial name for methamphetamine. Philips claimed the exclusive right to use the trademark as a portmanteau of Philips and Nippon, the Japanese name of the country. DSP's attorneys challenged Philips' standing to sue as a foreign (Dutch) corporation. The matter was ultimately settled out of court in 1952, with Dainippon Pharmaceuticals agreeing to pay Philips a 5% royalty on worldwide sales of methamphetamines sold by DSP under the Philopon label. The Japanese Ministry of Health banned production less than a year later.
In the 1950s, there was a rise in the legal prescription of methamphetamine to the American public. In the 1954 edition of Pharmacology and Therapeutics
, conditions treatable by methamphetamine included "narcolepsy, postencephalitic parkinsonism, alcoholism, certain depressive states, and in the treatment of obesity." Methamphetamine constituted half of the amphetamine salts for the original formulation for the diet drug Obetrol, which later became the ADHD drug Adderall. Methamphetamine was also marketed for sinus inflammation or for non-medicinal purposes as "pep pills" or "bennies".
In 1950 the Japanese Ministry of Health banned stimulant production, but drug companies continued to produce stimulants and they wound up on the black market. From 1951 to 1954 a series of acts were passed by the Japanese government to try to stop production and sale of stimulants; however, the production and sale of stimulant drugs continued through criminal syndicates such as Yakuza criminal organizations. On the streets, it is also known as S, Shabu, and Speed, in addition to its old trademarked name.
The 1960s saw the start of significant use of clandestinely manufactured methamphetamine, most of which was produced by motorcycle gangs. It was also prescribed by San Franciscan drug clinics to treat heroin addiction. Beginning in the 1990s, the production of methamphetamine in users' own homes for personal and recreational use became popular.
In 1970, methamphetamine was regulated in the Controlled Substances Act in the U. S., and a public education campaign was mounted against it.
By the 2000s, the only two FDA approved marketing indications remaining for methamphetamine were for attention-deficit hyperactivity disorder (ADHD) and the short-term management of exogenous obesity, although the drug is clinically established as effective in the treatment of narcolepsy.
The production, distribution, sale, and possession of methamphetamine is restricted or illegal in many jurisdictions. Methamphetamine has been placed in Schedule II of the United Nations Convention on Psychotropic Substances treaty.
North Korea might be facing one of the world's worst meth epidemics. Although the secrecy of the North Korean government means that any report may be only approximate, there have been an increasing number of signs that meth is very widespread throughout the country, used both recreationally and as medicine. Methamphetamine is called Bingdu
(Hangul: ; Hanja: ; "ice poison") in the Korean language.
In 1983, laws were passed in the United States prohibiting possession of precursors and equipment for methamphetamine production. This was followed a month later by a bill passed in Canada enacting similar laws. In 1986, the U.S. government passed the Federal Controlled Substance Analogue Enforcement Act in an attempt to curb the growing use of designer drugs. Despite this, use of methamphetamine expanded from its initial base in California throughout the rural United States, especially through the Midwest and South. Government officials in many U.S. counties now report that meth is their most serious drug problem. Meth use is said to be particularly common in the American western states, where the substance is in high demand. States like Montana, South Dakota, Idaho, Colorado and Arizona have all launched extensive efforts – both private and public – to stop meth use.
Methamphetamine is most structurally similar to methcathinone and amphetamine. Synthesis is relatively simple, but entails risk with flammable and corrosive chemicals, particularly the solvents used in extraction and purification; therefore, illicit production is often discovered by fires and explosions caused by the improper handling of volatile or flammable solvents. The six major routes of production begin with either phenyl-2-propanone (P2P) or with one of the isomeric compounds pseudoephedrine and ephedrine.
One procedure uses the reductive amination of phenyl-2-propanone (phenylacetone) with methylamine, P2P was usually obtained from phenylacetic acid and acetic anhydride, though many other methods have been considered, and phenylacetic acid might arise from benzaldehyde, benzylcyanide, or benzylchloride. Methylamine is crucial to all such methods, and is produced from the model airplane fuel nitromethane, or formaldehyde and ammonium chloride, or methyl iodide with hexamine. This was once the preferred method of production by motorcycle gangs in California, until DEA restrictions on the chemicals made the process difficult. Pseudoephedrine, ephedrine, phenylacetone, and phenylacetic acid are currently DEA list I and acetic anhydride is list II on the DEA list of chemicals subject to regulation and control measures. This method can involve the use of mercuric chloride and leaves behind mercury and lead environmental wastes. The methamphetamine produced by this method is racemic, consisting partly of the less-desired levomethamphetamine isomer.
The alternative Leuckart route also relies on P2P to produce a racemic product, but proceeds via methylformamide in formic acid to an intermediate N-formyl-methamphetamine, which is then decarboxylated with hydrochloric acid.
Two infrequently used reductive amination routes have also been reported. The "nitropropene route", in which benzaldehyde is condensed with nitroethane to produce 1-phenyl-2-nitropropene, which is subsequently reduced by hydrogenation of the double bond and reduction of the nitro group using hydrogen over a palladium catalyst or lithium aluminum hydride. The "oxime route" reacts phenyl-2-propanol with hydroxylamine to produce an oxime intermediate which likewise is hydrogenated using hydrogen over a palladium catalyst or lithium aluminum hydride.
Illicit methamphetamine is more commonly made by the reduction of ephedrine or pseudoephedrine, which produces the more active d-methamphetamine isomer. The maximum conversion rate for ephedrine and pseudoephedrine is 92%, although typically, illicit methamphetamine laboratories convert at a rate of 50% to 75%. Most methods of illicit production involve protonation of the hydroxyl group on the ephedrine or pseudoephedrine molecule.
Though dating back to the discovery of the drug, the Nagai route did not become popular among illicit manufacturers until ca. 1982, and comprised 20% of production in Michigan in 2002 It involves red phosphorus and hydrogen iodide (also known as hydroiodic acid or iohydroic acid). (The hydrogen iodide is replaced by iodine and water in the "Moscow route") The hydrogen iodide is used to reduce either ephedrine or pseudoephedrine to methamphetamine. On heating the precursor is rapidly iodinated by the hydrogen iodide to form iodoephedrine. The phosphorus assists in the second step, by consuming iodine to form phosphorus triiodide (which decomposes in water to phosphorous acid, regenerating hydrogen iodide). Because hydrogen iodide exists in a chemical equilibrium with iodine and hydrogen, the phosphorus reaction shifts the balance toward hydrogen production when iodine is consumed. In Australia, criminal groups have been known to substitute "red" phosphorus with either hypophosphorous acid or phosphorous acid (the "Hypo route"). This is a hazardous process for amateur chemists because phosphine gas, a side-product from in situ hydrogen iodide production, is extremely toxic to inhale. The reaction can also create toxic, flammable white phosphorus waste. Methamphetamine produced in this way is usually more than 95% pure.
The conceptually similar Emde route involves reduction of ephedrine to chloroephedrine using thionyl chloride (SOCl2
), followed by catalytic hydrogenation. The catalysts for this reaction are palladium or platinum. The Rosenmund route also uses hydrogen gas and a palladium catalyst poisoned with barium sulfate (Rosenmund reduction), but uses perchloric acid instead of thionyl chloride.
The Birch reduction, also called the "Nazi method", became popular in the mid-to-late 1990s and comprised the bulk of methamphetamine production in Michigan in 2002. It reacts pseudoephedrine with liquid anhydrous ammonia and an alkali metal such as sodium or lithium. The reaction is allowed to stand until the ammonia evaporates. However, the Birch reduction is dangerous because the alkali metal and ammonia are both extremely reactive, and the temperature of liquid ammonia makes it susceptible to explosive boiling when reactants are added. It has been the most popular method in Midwestern states of the U. S. because of the ready availability of liquid ammonia fertilizer in farming regions.
In recent years, a simplified "Shake 'n Bake" one-pot synthesis has become more popular. The method is suitable for such small batches that pseudoephedrine restrictions are less effective, it uses chemicals that are easier to obtain (though no less dangerous than traditional methods), and it is so easy to carry out that some addicts have made the drug while driving. It involves placing crushed pseudoephedrine tablets into a nonpressurized container containing ammonium nitrate, water, and a hydrophobic solvent such as Coleman fuel or automotive starting fluid, to which lye and lithium (from lithium batteries) is added. Hydrogen chloride gas produced by a reaction of salt with sulfuric acid is then used to recover crystals for purification. The container needs to be "burped" periodically to prevent failure under accumulating pressure, as exposure of the lithium to the air can spark a flash fire; thus an abandoned reaction becomes a severe hazard to firefighters. The battery lithium can react with water to shatter a container and potentially start a fire or explosion.
Producing methamphetamine in this fashion can be extremely dangerous and has been linked to several fatalities. Because users frequently carry out the reaction in a two-liter bottle held close to their bodies, which can explode if the cap is removed too soon or if it accidentally perforates, the procedure has led to a large number of severe burns — for example, approximately 70 in Indiana during 2010 and 2011. As 90% of these cases in the United States lack health insurance, and the average cost for their treatment is $130,000 (60% more than the average), which is only partially compensated by Medicaid, this method of synthesis has been blamed for the closure of hospital burn units and a cost to taxpayers of tens or hundreds of millions of dollars.
Until the early 1990s, methamphetamine for the U.S. market was made mostly in labs run by drug traffickers in Mexico and California. Indiana state police found 1,260 labs in 2003, compared to just 6 in 1995, although this may be partly a result of increased police activity. As of 2007, drug and lab seizure data suggests that approximately 80 percent of the methamphetamine used in the United States originates from larger laboratories operated by Mexican-based syndicates on both sides of the border and that approximately 20 percent comes from small toxic labs (STLs) in the United States.
Mobile and motel-based methamphetamine labs have caught the attention of both the U.S. news media and the police. Such labs can cause explosions and fires and expose the public to hazardous chemicals. Those who manufacture methamphetamine are often harmed by toxic gases. Many police departments have specialized task forces with training to respond to cases of methamphetamine production. The National Drug Threat Assessment 2006, produced by the Department of Justice, found "decreased domestic methamphetamine production in both small and large-scale laboratories", but also that "decreases in domestic methamphetamine production have been offset by increased production in Mexico." The report concluded that "methamphetamine availability is not likely to decline in the near term. "
Methamphetamine labs can give off noxious fumes, such as phosphine gas, methylamine gas, solvent vapors, acetone or chloroform, iodine vapors, white phosphorus, anhydrous ammonia, hydrogen chloride/muriatic acid, hydrogen iodide, lithium and sodium gases, ether, or methamphetamine vapors. If performed by amateurs, manufacturing methamphetamine can be extremely dangerous. If the red phosphorus overheats, because of a lack of ventilation, phosphine gas can be produced. This gas is highly toxic and, if present in large quantities, is likely to explode upon autoignition from diphosphine, which is formed by overheating phosphorus.]
In July 2007, Mexican officials at the port of Lázaro Cárdenas seized a ship carrying 19 tons of pseudoephedrine, a raw material needed for methamphetamine. The shipment originated in Hong Kong and passed through the United States at the port of Long Beach prior to its arrival in Mexico.
The Australian Crime Commission's illicit drug data report for 2011–2012 was released in western Sydney, Australia on 20 May 2013 and revealed that the average strength of crystal methamphetamine doubled in most Australian jurisdictions within a 12-month period and the majority of domestic laboratory closures involved small "addict-based" operations.
In Japan, methamphetamine seizures are usually white crystals of high purity, but contain impurities that vary according to the means of production, and are sometimes adulterated.
Diagnostic impurities are the naphthalenes 1-benzyl-methylnaphthalene and 1,3-dimethyl-2-phenylnaphthalene, arising in the Nagai and Leuckart routes, and cis-
1,2-dimethyl-3-phenylaziridine, ephedrine, or erythro-3,4-dimethyl- 5-phenyloxazolidine, arising in the Nagai and Emde routes; these are absent in the reductive amination route. Characteristic impurities of the Birch route include N-methyl-1-(1-(1,4-cyclohexadienyl))-2-propanamine. Methamphetamine produced by the Birch route contains phenyl-2-propanone, the precursor for the reductive amination route, as a degradation product. However, specific diagnostic impurities are not very reliable in practice, and it is generally preferable for forensic technicians to evaluate a larger profile of trace compounds.
A common adulterant is dimethyl sulfone, a solvent and cosmetic base without known effect on the nervous system; other adulterants include dimethylamphetamine HCl, ephedrine HCl, sodium thiosulfate, sodium chloride, sodium glutamate, and a mixture of caffeine with sodium benzoate.
In the United States, illicit methamphetamine comes in a variety of forms with prices varying widely over time. Most commonly, it is found as a colorless crystalline solid. Impurities may result in a brownish or tan color. Colorful flavored pills containing methamphetamine and caffeine are known as yaa baa (Thai for "crazy medicine").
An impure form of methamphetamine is sold as a crumbly brown or off-white rock, commonly referred to as "peanut butter crank". It may be diluted or cut with non-psychoactive substances like inositol, isopropylbenzylamine or dimethylsulfone. Another popular method is to combine methamphetamine with other stimulant substances, such as caffeine or cathine, into a pill known as a "Kamikaze", which can be particularly dangerous due to the synergistic effects of multiple stimulants. Reports in 2007 of the appearance of flavored "Strawberry Quik meth" circulated in the media and local law enforcement, but were debunked in 2010 by the DEA, although meth of varying colors
has been seized.
Rarely, the impure reaction mixture from the hydrogen iodide/red phosphorus route is used without further modification, usually by injection; it is called "ox blood". "Meth oil" refers to the crude methamphetamine base produced by several synthesis procedures. Ordinarily it is purified by exposure to hydrogen chloride, as a solution or as a bubbled gas, and extraction of the resulting salt occurs by precipitation and/or recrystallization with ether/acetone.
Slang terms for methamphetamine, especially common among illicit users, are numerous and vary from region to region. Some names are "crystal meth", "meth", "speed", "crystal", "clavo", "ice", "shards", "shabu/shaboo", "glass", "jib", "crank", "batu/batunas", "scanté", "schizznit", "gack", "tweak", "rizz", "rock", "tina" and "cold". Some terms vary by region or subculture.
Some regional terms are based on the original trade names; thus "필로폰" ("Pilopon") in South Korea, "Пико" for pure methamphetamine in Bulgaria or "piko" in the Czech Republic, Slovakia, and Poland after the trade name "Pervitin". Also "peří" ("feathers", phonetically similar to "Pervitin") and "perník" ("gingerbread", phonetically similar to "Pervitin" in the Czech Republic. In New Zealand it is called "P
Other local names include “冰毒” (Bīng Dú
, Chinese for "Ice drug") in China, "ya ba" (Thai for "Crazy Medicine", Thailand), "ya ice" (Thai for "Ice drug", Thailand), "đá" (Vietnamese for "ice", Vietnam), "batu kilat" (Malaysian for "shining rocks", Malaysia), "bato" (Filipino for "rock" or "stone", Philippines) "شیشه" (in translation "Glass", transliterate to "Shishe", Iran), "tik" (South Africa), "dimineata speciala aurie" ("Special golden morning", Romania), "bala" in Brazilian Portuguese, "tjäck" in Swedish, "ספיד" in Israel and "Teeft" United Kingdom.
"Vint", Russian for "a screw", specifically refers to a very impure homemade form of methamphetamine in Russia. The name originally comes from "Pervitin," a pharmaceutical trademark.
The DSM IV has amphetamine defined in two ways: Amphetamine dependence (304.40) and Amphetamine abuse (305.70)
dsrd (o, p, m, p, a, d, s), sysi/epon, spvo
proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)
cof, enz, met
noco, nuvi, sysi/epon, met
is the (natural or artificial) process of formation of solid crystals precipitating from a solution, melt or more rarely deposited directly from a gas. Crystallization is also a chemical solid–liquid separation technique, in which mass transfer of a solute from the liquid solution to a pure solid crystalline phase occurs. In chemical engineering crystallization occurs in a crystallizer. Crystallization is therefore an aspect of precipitation, obtained through a variation of the solubility conditions of the solute in the solvent, as compared to precipitation due to chemical reaction.
The crystallization process consists of two major events, nucleation
and crystal growth
is the step where the solute molecules dispersed in the solvent start to gather into clusters, on the nanometer scale (elevating solute concentration in a small region), that become stable under the current operating conditions. These stable clusters constitute the nuclei. However, when the clusters are not stable, they redissolve. Therefore, the clusters need to reach a critical size in order to become stable nuclei. Such critical size is dictated by the operating conditions (temperature, supersaturation, etc.). It is at the stage of nucleation that the atoms arrange in a defined and periodic manner that defines the crystal structure — note that "crystal structure" is a special term that refers to the relative arrangement of the atoms, not the macroscopic properties of the crystal (size and shape), although those are a result of the internal crystal structure.
The crystal growth
is the subsequent growth of the nuclei that succeed in achieving the critical cluster size. Nucleation and growth continue to occur simultaneously while the supersaturation exists. Supersaturation is the driving force of the crystallization, hence the rate of nucleation and growth is driven by the existing supersaturation in the solution. Depending upon the conditions, either nucleation or growth may be predominant over the other, and as a result, crystals with different sizes and shapes are obtained (control of crystal size and shape constitutes one of the main challenges in industrial manufacturing, such as for pharmaceuticals). Once the supersaturation is exhausted, the solid–liquid system reaches equilibrium and the crystallization is complete, unless the operating conditions are modified from equilibrium so as to supersaturate the solution again.
Many compounds have the ability to crystallize with different crystal structures, a phenomenon called polymorphism. Each polymorph is in fact a different thermodynamic solid state and crystal polymorphs of the same compound exhibit different physical properties, such as dissolution rate, shape (angles between facets and facet growth rates), melting point, etc. For this reason, polymorphism is of major importance in industrial manufacture of crystalline products.
There are many examples of natural process that involve crystallization.
Geological time scale process examples include:
Usual time scale process examples include:
For crystallization (see also recrystallization) to occur from a solution it must be supersaturated. This means that the solution has to contain more solute entities (molecules or ions) dissolved than it would contain under the equilibrium (saturated solution). This can be achieved by various methods, with (1) solution cooling, (2) addition of a second solvent to reduce the solubility of the solute (technique known as antisolvent or drown-out), (3) chemical reaction and (4) change in pH being the most common methods used in industrial practice. Other methods, such as solvent evaporation, can also be used. The spherical crystallization has some advantages (flowability and bioavailability) for the formulation of pharmaceutical drugs (see ref Nocent & al., 2001)
From a material industry perspective:
Used to improve (obtaining very pure substance) and/or verify their purity.
Crystallization separates a product from a liquid feedstream, often in extremely pure form, by cooling the feedstream or adding precipitants which lower the solubility of the desired product so that it forms crystals.
Well formed crystals are expected to be pure because each molecule or ion must fit perfectly into the lattice as it leaves the solution. Impurities would normally not fit as well in the lattice, and thus remain in solution preferentially. Hence, molecular recognition is the principle of purification in crystallization. However, there are instances when impurities incorporate into the lattice, hence, decreasing the level of purity of the final crystal product. Also, in some cases, the solvent may incorporate into the lattice forming a solvate
. In addition, the solvent may be 'trapped' (in liquid state) within the crystal formed, and this phenomenon is known as "inclusion".
Equipment for the main industrial processes for crystallization.
The nature of a crystallization process is governed by both thermodynamic and kinetic factors, which can make it highly variable and difficult to control. Factors such as impurity level, mixing regime, vessel design, and cooling profile can have a major impact on the size, number, and shape of crystals produced.
Now put yourself in the place of a molecule within a pure and perfect crystal
, being heated by an external source. At some sharply defined temperature, a bell rings, you must leave your neighbours, and the complicated architecture of the crystal collapses to that of a liquid. Textbook thermodynamics says that melting occurs because the entropy, S, gain in your system by spatial randomization of the molecules has overcome the enthalpy, H, loss due to breaking the crystal packing forces:
This rule suffers no exceptions when the temperature is rising. By the same token, on cooling the melt, at the very same temperature the bell should ring again, and molecules should click back into the very same crystalline form. The entropy decrease due to the ordering of molecules within the system is overcompensated by the thermal randomization of the surroundings, due to the release of the heat of fusion; the entropy of the universe increases.
But liquids that behave in this way on cooling are the exception rather than the rule; in spite of the second principle of thermodynamics, crystallization usually occurs at lower temperatures (supercooling). This can only mean that a crystal is more easily destroyed than it is formed. Similarly, it is usually much easier to dissolve a perfect crystal in a solvent than to grow again a good crystal from the resulting solution. The nucleation and growth of a crystal are under kinetic, rather than thermodynamic, control.
As mentioned above, a crystal is formed following a well-defined pattern, or structure, dictated by forces acting at the molecular level. As a consequence, during its formation process the crystal is in an environment where the solute concentration reaches a certain critical value, before changing status. Solid formation, impossible below the solubility threshold at the given temperature and pressure conditions, may then take place at a concentration higher than the theoretical solubility level. The difference between the actual value of the solute concentration at the crystallization limit and the theoretical (static) solubility threshold is called supersaturation and is a fundamental factor in crystallization dynamics. Supersaturation is the driving force for both the initial nucleation step and the following crystal growth, both of which could not occur in saturated or undersaturated conditions.
Nucleation is the initiation of a phase change in a small region, such as the formation of a solid crystal from a liquid solution. It is a consequence of rapid local fluctuations on a molecular scale in a homogeneous phase that is in a state of metastable equilibrium. Total nucleation is the sum effect of two categories of nucleation – primary and secondary.
Primary nucleation is the initial formation of a crystal where there are no other crystals present or where, if there are crystals present in the system, they do not have any influence on the process. This can occur in two conditions. The first is homogeneous nucleation, which is nucleation that is not influenced in any way by solids. These solids include the walls of the crystallizer vessel and particles of any foreign substance. The second category, then, is heterogeneous nucleation. This occurs when solid particles of foreign substances cause an increase in the rate of nucleation that would otherwise not be seen without the existence of these foreign particles. Homogeneous nucleation rarely occurs in practice due to the high energy necessary to begin nucleation without a solid surface to catalyse the nucleation.
Primary nucleation (both homogeneous and heterogeneous) has been modelled with the following:
Secondary nucleation is the formation of nuclei attributable to the influence of the existing microscopic crystals in the magma. The first type of known secondary crystallization is attributable to fluid shear, the other due to collisions between already existing crystals with either a solid surface of the crystallizer or with other crystals themselves. Fluid shear nucleation occurs when liquid travels across a Crystal at a high speed, sweeping away nuclei that would otherwise be incorporated into a Crystal, causing the swept-away nuclei to become new crystals. Contact nucleation has been found to be the most effective and common method for nucleation. The benefits include the following
The following model, although somewhat simplified, is often used to model secondary nucleation:
Once the first small crystal, the nucleus, forms it acts as a convergence point (if unstable due to supersaturation) for molecules of solute touching – or adjacent to – the crystal so that it increases its own dimension in successive layers. The pattern of growth resembles the rings of an onion, as shown in the picture, where each colour indicates the same mass of solute; this mass creates increasingly thin layers due to the increasing surface area of the growing crystal. The supersaturated solute mass the original nucleus may capture
in a time unit is called the growth rate
expressed in kg/(m2*h), and is a constant specific to the process. Growth rate is influenced by several physical factors, such as surface tension of solution, pressure, temperature, relative crystal velocity in the solution, Reynolds number, and so forth.
The main values to control are therefore:
The first value is a consequence of the physical characteristics of the solution, while the others define a difference between a well- and poorly designed crystallizer.
The appearance and size range of a crystalline product is extremely important in crystallization. If further processing of the crystals is desired, large crystals with uniform size are important for washing, filtering, transportation, and storage. The importance lies in the fact that large crystals are easier to filter out of a solution than small crystals. Also, larger crystals have a smaller surface area to volume ratio, leading to a higher purity. This higher purity is due to less retention of mother liquor which contains impurities, and a smaller loss of yield when the crystals are washed to remove the mother liquor. The theoretical crystal size distribution can be estimated as a function of operating conditions with a fairly complicated mathematical process called population balance theory (using population balance equations).
The main factors influencing solubility are, as we saw above:
So we may identify two main families of crystallization processes:
This division is not really clear-cut, since hybrid systems exist, where cooling is performed through evaporation, thus obtaining at the same time a concentration of the solution.
A crystallization process often referred to in chemical engineering is the fractional crystallization. This is not a different process, rather a special application of one (or both) of the above.
Most chemical compounds, dissolved in most solvents, show the so-called direct
solubility that is, the solubility threshold increases with temperature.
So, whenever the conditions are favourable, crystal formation results from simply cooling the solution. Here cooling
is a relative term: austenite crystals in a steel form well above 1000 °C. An example of this crystallization process is the production of Glauber's salt, a crystalline form of sodium sulphate. In the picture, where equilibrium temperature is on the x-axis and equilibrium concentration (as mass percent of solute in saturated solution) in y-axis, it is clear that sulphate solubility quickly decreases below 32.5 °C. Assuming a saturated solution at 30 °C, by cooling it to 0 °C (note that this is possible thanks to the freezing-point depression), the precipitation of a mass of sulphate occurs corresponding to the change in solubility from 29% (equilibrium value at 30 °C) to approximately 4.5% (at 0 °C) – actually a larger crystal mass is precipitated, since sulphate entrains hydration water, and this has the side effect of increasing the final concentration.
There are of course limitation in the use of cooling crystallization:
The simplest cooling crystallizers are tanks provided with a mixer for internal circulation, where temperature decrease is obtained by heat exchange with an intermediate fluid circulating in a jacket. These simple machines are used in batch processes, as in processing of pharmaceuticals and are prone to scaling. Batch processes normally provide a relatively variable quality of product along the batch.
crystallizer is a model, specifically conceived by Swenson Co. around 1920, having a semicylindric horizontal hollow trough in which a hollow screw conveyor or some hollow discs, in which a refrigerating fluid is circulated, plunge during rotation on a longitudinal axis. The refrigerating fluid is sometimes also circulated in a jacket around the trough. Crystals precipitate on the cold surfaces of the screw/discs, from which they are removed by scrapers and settle on the bottom of the trough. The screw, if provided, pushes the slurry towards a discharge port.
A common practice is to cool the solutions by flash evaporation: when a liquid at a given T0
temperature is transferred in a chamber at a pressure P1
such that the liquid saturation temperature T1
is lower than T0
, the liquid will release heat according to the temperature difference and a quantity of solvent, whose total latent heat of vaporization equals the difference in enthalpy. In simple words, the liquid is cooled by evaporating a part of it.
In the sugar industry vertical cooling crystallizers are used to exhaust the molasses in the last crystallization stage downstream of vacuum pans, prior to centrifugation. The massecuite enters the crystallizers at the top, and cooling water is pumped through pipes in counterflow.
Another option is to obtain, at an approximately constant temperature, the precipitation of the crystals by increasing the solute concentration above the solubility threshold. To obtain this, the solute/solvent mass ratio is increased using the technique of evaporation. This process is of course insensitive to change in temperature (as long as hydration state remains unchanged).
All considerations on control of crystallization parameters are the same as for the cooling models.
Most industrial crystallizers are of the evaporative type, such as the very large sodium chloride and sucrose units, whose production accounts for more than 50% of the total world production of crystals. The most common type is the forced circulation
(FC) model (see evaporator). A pumping device (a pump or an axial flow mixer) keeps the crystal slurry in homogeneous suspension throughout the tank, including the exchange surfaces; by controlling pump flow, control of the contact time of the crystal mass with the supersaturated solution is achieved, together with reasonable velocities at the exchange surfaces. The Oslo, mentioned above, is a refining of the evaporative forced circulation crystallizer, now equipped with a large crystals settling zone to increase the retention time (usually low in the FC) and to roughly separate heavy slurry zones from clear liquid.
Whichever the form of the crystallizer, to achieve an effective process control it is important to control the retention time and the crystal mass, to obtain the optimum conditions in terms of crystal specific surface and the fastest possible growth. This is achieved by a separation – to put it simply – of the crystals from the liquid mass, in order to manage the two flows in a different way. The practical way is to perform a gravity settling to be able to extract (and possibly recycle separately) the (almost) clear liquid, while managing the mass flow around the crystallizer to obtain a precise slurry density elsewhere. A typical example is the DTB (Draft Tube and Baffle
) crystallizer, an idea of Richard Chisum Bennett (a Swenson engineer and later President of Swenson) at the end of the 1950s. The DTB crystallizer (see images) has an internal circulator, typically an axial flow mixer – yellow – pushing upwards in a draft tube while outside the crystallizer there is a settling area in an annulus; in it the exhaust solution moves upwards at a very low velocity, so that large crystals settle – and return to the main circulation – while only the fines, below a given grain size are extracted and eventually destroyed by increasing or decreasing temperature, thus creating additional supersaturation. A quasi-perfect control of all parameters is achieved. This crystallizer, and the derivative models (Krystal, CSC, etc.) could be the ultimate solution if not for a major limitation in the evaporative capacity, due to the limited diameter of the vapour head and the relatively low external circulation not allowing large amounts of energy to be supplied to the system.
Hot-filtration, 1 solvent
2 solvent, with evaporation
slow evaporation 1 solvent
slow evaporation 2 solvent
slow gas diffusion 2 solvent
slow liquid diffusion
slow liquid diffusion – H Tube