The API Industry at a Glance
Active Pharmaceutical Ingredients Explained

The API Industry at a Glance


The Active Pharmaceutical Ingredient Industry is the organ by which active pharmaceutical ingredients are manufactured from raw materials through both chemical and physical means. Depending on the complexity of the molecule required, synthesis of APIs might need multi-step complex chemistry utilizing a range of processing technologies.

Top API Manufacturers

The leading manufacturer of APIs today is TAPI (Teva Active Pharmaceutical Ingredients). Specializing in range of API-related fields, TAPI works in areas such as chemical synthesis, fermentation, chromatography and plant extraction and now has the industry’s largest portfolio of over 300 API products.  In 2011 alone they achieved third-party sales of around $750 million.

Dr. Reddy’s is another leading manufacturer with 60 APIs for drug use, diagnostic kits and biotechnology products. Aurobindo and Cipla manufacture 200 APIs each, exporting their products to well over 200 countries worldwide. Other notable manufacturers are Sandoz-Lek-Biochemie, Ranbaxy, Matrix and Sun.

API Outsourcing

APIs are commonly referred to as ‘bulk pharmaceuticals’ and are in fact usually made in places at quite a distance to where tablets, suspensions and liquids are manufactured. Today, the greatest concentrations of API manufacturers are located around Asia, specifically in India and China. This has led to more and more companies to outsource API manufacturing to such places, which has the main benefit of eliminating the need to invest in highly expensive equipment and infrastructure – which on top of everything can also be complicated to install and maintain. A good example can be found with AstraZeneca, who manufacture 85% of its APIs but are currently in the process of withdrawing from all API production in favor of outsourcing.


Regardless of where the active pharmaceutical ingredient is made, companies must adhere to strict safety and quality standards set by the country where it will be used. So those APIs manufactured in China or India for use in the United States must still be inspected and licensed by the FDA. Similarly, if the API is intended for use in Europe, they would need to meet regulations set by the European Medicines Agency. Regular inspection outside the country of use however can prove difficult with counterfeiting and contamination being high on the list of various agencies’ concerns. For instance, since 2008, the FDA has considerably increased its overseas staff as a way of attempting to eliminate these problems. As a result, countries such as India have gained their foothold in the global market and now have around 75 FDA-approved manufacturing facilities for API synthesis.

Going Green

Today there are more and more calls for API manufacturers to go green – that is to say, to reduce the waste they produce. Every year, large pharmaceutical manufacturers can produce anywhere from 3000 to 5000 tons of hazardous waste each.  If one were to ask any reputable API manufacturer how they would like to improve the process, they’d likely say to make the reactions faster, or to make them cheaper. Ironically the first steps in reducing waste from API synthesis would be to reduce the number of reactions required to produce a given molecule.  Therefore though the goal may be different, the means turn out to be the same as fewer reactions mean less solvent to dispose of. Another step in going green is to find different solvents and catalysts that are not only more efficient, but are also better for the environment.

To the Future

Major API manufacturers such as Merck, AstraZeneca and GlaxoSmithKline are also moving away from multifunctional plants and instead opting for specific activities at specific sites. In this way, there are serious concerns as to how any centralized control could function as after all an API manufactured by one company, in one country, with the excipient manufactured in another by a different company, then packaged and distributed by another company altogether makes the route rather difficult to monitor or control.

The current growth in new medical technologies is spurring the demand for APIs worldwide today especially with the increased importation of raw pharmaceutical ingredients from emerging markets. According to Boehringer Ingelheim, countries such as India and China, which now supply over 40% of APIs used in the U.S. will double that figure to a whopping 80% in just the next 10 years.

Venlafaxine – Manufacturers & Genaral Information

Venlafaxine is an anti-depressant of the SNRI (serotonin-norepinephrine reuptake inhibitor) class. It works primarily by altering chemical levels in the brain that may become unbalanced thereby causing depression.
Marketed under the brand name Effexor it is administered as an extended-release capsule containing venlafaxine hydrochloride. As well as being prescribed for depression it is also used to treat anxiety and panic disorders.
In 2007, it was the sixth most commonly prescribed drug for depressive problems. According to Wolters Kluwer Health, sales of venlafaxine hydrochloride reached roughly US$880 million in the period 2011-2012.


Venlafaxine has the empirical formula C17H27NO2. It is either a white or off-white crystalline sold that is structurally and pharmacologically similar to the opioid analgesic tramadol.


Today numerous pharmaceutical companies manufacture Venlafaxine as a generic drug. It has been available generically in the U.S. since August 2006, and in Canada since December 2006 because of patent expiry. Studies have highlighted that the extended release version results in fewer patients suffering from nausea and therefore fewer discontinuing the drug. Wyeth sells venlafaxine XR under the trade name Efexor-XR in Australia, New Zealand and Switzerland.
Other manufacturers of the extended release venlafaxine include: TAPI, Cobalt Pharmaceuticals Inc., Genpharm, Medley, Osmotica Pharmaceuticals, Laboratoire Riva Inc., Novopharm Limited, Pharmascience Inc., Ratiopharm, Sandoz, Cipla Medpro, Pharmadynamics and IntelliPharmaCeutics.

For those of you that want to learn more about the drug itself, we recommend reading the Venlafaxine page on Mayo Clinic’s Website.

Carbidopa API

Carbidopa is a peripheral dopa-decarboxylase inhibitor that results in significant pharmacological activity only when given in combination with levodopa. Carbidoba inhibits the peripheral decarboxylation of levodopa to dopamine preventing its breakdown before reaching the brain and so increasing its effectiveness. When used with levodopa it allows for a lower dosage of levodopa to be used, a faster response time and a mitigation of adverse reactions. Marketed individual under the name Atamet, caribidopa is also available as a combination drug with levodopa under the brand name Sinemet.

Parkinson’s disease is thought to be strong linked with low levels of dopamine in the key areas of the brain. When levodopa is taken orally, it crosses through this ‘blood-brain barrier’ and then converted into dopamine. The resulting effect is an increase in brain dopamine levels that is thought to improve nerve conduction and mitigate movement disorders in Parkinson’s disease.

There is also some evidence to suggest that carbidopa when used in conjunction with 5-HTP may be useful in the treatment of myoclonus, a neuromuscular disorder.

Diltiazem in Today’s Medicine

Diltiazem hydrochloride is a medication used for treating high blood pressure or chest pain known as angina. It is a calcium channel blocker that is also used to effectively treat migraines. Diltiazem is an inhibitor of the CYP3A4 enzyme and is also a potent vasodilator, increasing blood flow whilst decreasing blood pressure.

In Depth

Diltiazem is part of the benzothiazepine class of calcium channel blockers used in the treatment of hypertension, angina pectoris and superventricular tachyarrhythmias.  Like various other calcium channel blockers, diltiazem works by inhibiting the transmembrance influx of calcium ions into muscle cells. This inhibition results in arterial vasodilation and decreases oxygen use in the myocardium.

Several million prescriptions for diltiazem are written each year. It is currently available orally under numerous generic formulations as well as commercial brand names such as Cardizem and Tiazac. Extended release formulations are too availalble and are widely used. These come under the names Cardizem CD, Cadizem LA, Cartia XT, Dilacor XR, Dilt-XR, Diltia XT and Taztia XT. Dosages vary from 60 to 420mg daily.

Other Treatments

Recent studies have demonstrated that diltiazem is able to reduce cocaine cravings in drug-addicted rats. It is thought it works by affecting dopaminergic and gluatmatergic signaling in the brain. Diltiazem has also shown to enhance the pain relieving effects of morphine in animal tests.

Research regarding the use of diltiazem for prophylaxis of cluster migraines is ongoing as it has shown some efficacy. Currently doctors in the US prescribe it off-label for such use.

As well as the aforementioned conditions, Diltiazem is also used in the treatment of anal fissures. If taken topically in a cream it has shown increased effectiveness. Like all non-surgical treatments of anal fissure it has demonstrated good overall short-term efficacy.


Diltiazem should be taken with caution by patients with liver and/or kidney impairment, ventricular dysfunction, congestive heart failure, sinoatrial nodal dysfunction and severe bradycardia. Cirrhosis patients ought to consider decreasing the dosage of calcium channel blockers. Diltiazem should also not be used in those with acute myocardial infarction. Since it is classified as pregnancy category C, it should be taken with caution during pregnancy and only when the benefits outweight the potential risk to the fetus.

Gemfibrozil API

Gemfibrozil is the generic name for a drug used for lowering lipid levels. Belonging to the class of drugs known as fibrates it is administered to effectively treat hyperlipidemia (Type III) and hypertriglyceridemia (type IV). It is marketed under the brand name Lopid, with other names being Jezil and Gen-Fibro. It has the chemical formula C24H34N4O5S.

Therapeutic Effects

Gemfibrozil is an activator or Peroxisome proliferator-activated receptor-alpha or PPARα, a nuclear receptor involved in the metabolism of carbohydrates and fat. It is also involved in adipose tissue differentiation.

The resulting effect is a reduction of triglyceride levels, reduction of very low density lipoprotein (VLDL) levels and a minor reduction of LDL levels. It also results in a small increase in high density lipoprotein (HDL) levels. The recommended dosage of gemfibrozil is 600 mg half-an-hour before breakfast and dinner.

Precautions and Toxicities

Gemfibrozil should not be given to those suffering from hepatic or renal dysfunction. It should also be used with caution in individuals with biliary tract disease, obese patients, native Americans and pregnant women.

Gemfibrozil increases levels of repaglinide in people with diabetes therefore increasing the chances of developing hypoglycaemia. In this way this combination should be avoided.

Use of gemfibrozil can also cause GI distress, musculoskeletal pain, increased incidence of gallstones, hypokalemia as well as an increased risk of cancer.

Drug Interactions

When used together with statins such such as simvastatin or pravastatin, this increases the chances of developing a condition known as rhabdomyloysis or muscle injury. This can lead to severe kidney damage and even death.

Patients on warfarin may require their doses to be reduced as gemfibrozil can increase warfarin’s effects on the body leading to bleeding.

Colestipol is also known to reduce the absportion of gemfibrozil and thereby reduce its effectiveness. In this way, gemfibrozil should be given one hour before, or 4-6 hours after administering colestipol or cholestyramine.


Azithromycin API

Azithromycin is a macrolide antibiotic used in the treatment of chest, skin and ear conditions. Similar to other macrolide antibiotics, azithromycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit of the bacterial 70S ribosome. Marketed primarily under the name Zithromax, it is easily one of the world’s best selling antibiotics with sales peaking at $2 billion in 2005. Azithromycin is also marketed under the names Clamelle, Azithrocin, Zmax and Azin. The world’s largest Azithromycin supplier to the pharmaceutical industry is TAPI (Teva API).


Azithromycin is used to treat a vast variety of bacterial infections especially in those with weaker immune systems such as children. The most common conditions it is used for are strep throat, pneumonia, typhoid and sinusitis. It has also however shown significant efficacy in handling sexually transmitted infections like chlamydia and cervicitis.

Azithromycin has also shown to be useful with the treatment of malaria when used in conjunction with artesunate or quinine.

It is commonly administered as a tablet or oral suspension, with tablet dosages coming at 250mg and 500mg.

Mechanism of Action

Azithromycin works by interfering with bacterial protein synthesis, thus preventing them from growing. It binds well to the 50S subunit of the bacterial ribosome, which in turn inhibits translation of mRNA.

It also possesses a long half-life which means that once daily doses as well as shorter administration durations are necessary. For a further read about Azithromycin’s mechanism of action we recommend visiting this page.

Side Effects

Upon taking azithromycin, a minority of individuals are susceptible to nausea, diarrhea and vomiting.

Active Pharmaceutical Ingredients Explained

Active pharmaceutical ingredients or APIs can be defined as the chemicals used to manufacture pharmaceutical drugs. The active ingredient (AI) is the substance or substances that are biologically active within the drug and is the specific component responsible for the desired effect it has on the individual taking it.

Any drug or medication is composed of two components. The first is the API – which is the central ingredient. The second is known as the excipient, which is the inactive substance that serves as the vehicle for the API itself. If the drug is in a syrup form, then the excipient is the liquid that has been used to make it as such.

APIs are generally manufactured through a variety of processes that include:

  • Chemical synthesis
  • Fermentation processes
  • Recombinant DNA
  • Isolation and recovery from natural sources
  • A combination of these processes

The purpose of APIs according to the FDA is to cause ‘pharmacological activity or other direct effects in the diagnosis, cure, mitigation, treatment or prevention of disease or to affect the structure and function of the human body.

There are however certain APIs that are unknown and so require additional substances that work in conjunction with the API to produce the required effect. This is very visible in herbal medicines in which the API is frequently a combination of several mixtures and/or substances which when used together cause pharmacological activity on the body. In these situations, the API is not a single substance but the culmination of various ingredients.

By drawing these distinctions between APIs and the drugs themselves, manufacturers are able to specialize and pharmacists able to align generic equivalents with brand names. This is of vital important and underlies one of the most solid principles and regulations of modern pharmacy.

Gabapentin API

Gabapentin is a GABA analogue originally developed to treat epilepsy and epileptic seizures. A seizure is a short episode where there is an abnormal burst of electrical activity in the brain. Gabapentin works by reducing the amount of electrical activity occurring and in this way controls the seizures and their symptoms. However, how exactly it does this is not fully known.


Aside from its use in treating epilepsy, gabapentin is also currently used in the treatment of neuropathic pain and has showed positive benefits for 1/3 of fibromyalgia sufferers. Neuropathic pain can also be caused by a number of diseases including diabetes and shingles. Although gabapentin is only licensed for use in the treatment of epilepsy and neuropathic pain it can also be prescribed to prevent migraine attacks.

Dosages generally start at 300mg and can increase to anywhere up to 3600mg/day.

Mechanism of Action

Though there are some proposed mechanisms of action, there is no real consensus and much still needs to be researched about how gabapentin actually works. According to one study halting the formation of new synapses in the brain causes the resultant analgesic effect.

Side Effects

Roughly 1 in 10 people who take gabapentin will feel some side effects. These include: lethargy, blurred vision, vomiting, diarrhea, constipation and peripheral edema.

Simvastatin API

Simvastatin is a cholesterol-lowering drug belonging to the class of HMG-CoA reductase inhibitors, otherwise known as ‘statins’. Other statins include atorvastatin (Lipitor), fluvastatin (Lescol) and rosuvastatin (Crestor). Marketed under the trade name Zocor, Simvastatin is a synthetic derivative of a fermentation product of Aspergillus terreus. In 2005 Simvastatin was Merck & Co’s highest selling cholesterol drug in the world, recording sales of $4.3 billion.


Simvastatin is used in the treatment of dyslipidaemia and to prevent cardiovascular disease. It is generally only used when various other measures such as changes in diet and exercise have failed to improve cholesterol levels sufficiently.

The usual dosage of Simvastatin ranges from 5mg to 80mg and can reduce low-density lipoprotein (LDL) levels by up to 50%. At higher doses have been found to be too toxic and give only minimal benefit in lowering cholesterol levels.

Mechanism of Action

Like all statins, Simvastatin works by inhibiting 3-hydroxy-3-methylglutaryl (HMG-CoA) in the rate-limiting step of the metabolic pathway that leads to cholesterol production. In this way low-density lipoprotein (LDL) or ‘bad’ cholesterol is significantly reduced. Simvastatin also works to increase high density lipoprotein (HDL) or ‘good’ cholesterol which may slow conditions such as coronary artery disease.

There is also plenty of evidence to suggest that statins like Simvastatin reduce cardiovascular disease events and total mortality regardless of initial cholesterol level – otherwise known as pleitropic effects.


Simvastatin is contraindicated with pregnancy as it may lead to severe birth defects. It is also contraindicated with breast feeding and liver disease.

External information about Simvastatin: 

Simvastatin manufacturers:

Pravastatin API

Pravastatin is part of a class of medications known as ‘statins’ or HMG-CoA reductase inhibitors. Also known as Pravachol or Selektine, it works to decrease the level of cholesterol that may have built up on artery walls blocking blood flow to the heart, brain and other vital organs. If left untreated, over time these patches can make a blood vessel narrower, a condition called atherosclerosis or ‘hardening of the arteries’. This is known to increase the risk heart attack and stroke.


Pravastatin is primarily used in the treatment of dyslipidemia and prevention of cardiovascular disease. In this way, pravastatin is a lipid-regulating drug and is used to reduce the risk of heart and blood vessel disease in patients where changes in diet, exercise and other weight reduction techniques have not improved cholesterol levels.

The usual dosage of Pravastatin ranges from 10mg to 80mg daily.

Mechanism of Action

Pravastatin acts as a lipoprotein-lowering drug through two pathways. The first and major pathway is to inhibit HMG-CoA (hydroxymethylglutaryl-CoA reductase). Its function as a reversible competitive inhibitor means it works by sterically hindering HMG-CoA by occupying the active site of the enzyme.

This enzyme is primarily responsible for the conversion of HMG-CoA to mevalonate in the rate-limited step of the pathway for cholesterol.

Pravastatin also works as an inhibitor of very low-density lipoproteins which leads to an increase in the number of cellular LDL receptors, thus increasing LDL uptake and removing it from the bloodstream. The end result is a reduction in circulating cholesterol and LDL. Minor reductions in triglycerides and increases in high-density lipoproteins (HDL) are also common.