Pharmaceutical compounding is only as effective and safe as each one of its ingredients. In this guide, we explore the top active pharmaceutical ingredients (APIs) in terms of what they are, what indications they are approved for, what safety information is crucial to know, and where each API is headed in terms of future use. Our goal is to help you understand the most important information behind each API, and what value add you can pass along to your patients.
The bulk APIs that Pharmaceutica North America offers are raw materials proven to be effective, stable, and safe for compounding use. Bulk APIs are used to create personalized medications necessary for patients who are unable to take manufactured drugs. The bulk APIs offered in this guide include both FDA-approved medications as well as natural ingredients shown to be effective against various conditions.
Acetaminophen (also known as paracetamol) is a p-aminophenol derivative with analgesic, antipyretic, and mild anti-inflammatory effects. Although its mechanism of action is not fully understood, it is believed that the drug’s effects are primarily the result of its inhibition of the cyclooxygenase (COX) enzymes in the central nervous system. By blocking the peroxidase function of these enzymes, acetaminophen prevents the synthesis of prostaglandins that mediate pain, fever, and possibly inflammation. Acetaminophen is believed to be slightly selective for COX-2, but it also acts on COX-1 and possibly COX-3 in neural tissues. The analgesic effects of acetaminophen may also result from its inhibition of the nitric oxide pathway or its activation of descending serotonergic pathways.
Alba-derm is a unique oil-in-water cream base made from a homogenous mixture of white petrolatum, mineral oil, chlorocresol, cetomacrogol 1000, cetostearyl alcohol, and water. The cream is both paraben-free and stable over pHs ranging from 2 to 12, making it a superior choice for use in topical pharmaceutical medications. Alba-Derm can be used to deliver salts and lipophilic and hydrophilic drugs transdermally. The emollient is also suitable for use as a cosmetic moisturizer or ointment, perhaps for delivering topical herbal supplements and other natural remedies for rashes, dry skin, and insect bites.
Amantadine hydrochloride is a synthetic tricyclic amine with antiviral properties, developed to treat Influenza A. The drug also has antidyskinetic properties, making it suitable for treating motor control symptoms, such as tremors, stiffness, and shaking in patients with Parkinson’s Disease.
Amitriptyline hydrochloride is a dibenzocycloheptadiene derivative, classified as a tertiary amine tricyclic antidepressant that is used to restore balance to chemicals in the brain. Tricyclic antidepressants are approved to treat depression and anxiety disorders and have also been shown to be effective in reducing neuropathic pain, partially in patients suffering from fibromyalgia.
Amlodipine is a slow-channel dihydropyridine calcium agonist. The drug works by blocking the influx of calcium across cell membranes, primarily into vascular smooth muscle and cardiac muscle. The contractile processes of vascular smooth muscle and cardiac muscle are dependent the transports of calcium ions into these cells. By widening blood vessels, the drug lowers blood pressure, increases blood flow to the heart, and relieves pain due to angina. Amlodipine is used to treat hypertension, chronic stable angina, and vasospastic angina.
Baclofen is a central nervous system depressant that is commonly used as a skeletal muscle relaxant and antispasmodic. The drug works by inactivating reflexes at the spinal level, thereby blocking the release of excitatory neurotransmitters. Baclofen, chemically described as 4-amino-3-(-4-chlorophenyl)-butanoic acid, is FDA-approved to treat reversible spasticity in patients with spinal cord disease or multiple sclerosis(MS), and may also relieve muscle pain and stiffness.
Camphor is a terpenoid originally found in the wood and bark of the evergreen Cinnamomum Camphora. The drug is now available as a pure and stable synthetic formulation. As camphor is lipophilic, it is quickly absorbed and transported across mucous membranes with a substantial volume of distribution.
Citalopram hydrobromide is an antidepressant that belongs to a class of drugs known as selective serotonin reuptake inhibitors (SSRIs). The drug is highly against serotonin reuptake but has minimal effects on the reuptake of norepinephrine and dopamine. Although the exact mechanisms of action of SSRIs is not well understood, this class of drugs is thought to work by inhibiting the reabsorption of serotonin into the presynaptic cell. This increases the amount of serotonin left in the synaptic cleft that is then available to bind to postsynaptic receptors. Citalopram is intended to be used as treatment for depression but off-label has been used to treat other mental conditions, as well as menopausal hot flashes.
Clonidine hydrochloride is a centrally-acting alpha-agonist hypotensive agent. The drug is FDA-approved to treat hypotension in adults and works by changing certain nerve impulses to relax blood vessels.
Codeine, also known as 3-methylmorphine, is a phenanthrene derivative with analgesic, narcotic, and antitussive properties that works as an opioid receptor agonist. It selectively activates the mu opioid receptor in the central nervous system, which leads to the inhibition of nerve signals that transmit pain. Codeine can be converted to morphine, another opioid agonist, by the cytochrome P450 enzyme CYP2D6 in the liver, which increases its analgesic effects because morphine binds to the mu opioid receptor with greater affinity than codeine. Codeine also works as an anti-diarrheal by acting on opioid receptors in the smooth muscles of the intestines to prevent peristaltic contractions. The antitussive effects of codeine are mediated by its ability to suppress the cough reflex by decreasing activity in the medullary cough center.
Cyclobenzaprine hydrochloride is a tricyclic amine that is FDA-approved as a muscle relaxant to treat skeletal muscle spasms and the pain associated with acute musculoskeletal conditions.
Dexamethasone Sodium Phosphate (DSP) is a corticosteroid similar to a natural hormone produced in the adrenal gland.
Diclofenac Sodium is a nonsteroidal anti-inflammatory drug (NSAID) that is derived from benzene-acetic acid and is used to reduce inflammation and as an analgesic. Diclofenac sodium works by blocking the effect of cyclooxygenase (COX) enzymes.
Diphenhydramine is a first generation antihistamine commonly used for allergy relief. It belongs to the ethanolamine class of antihistamines, and it works as an inverse agonist on the histamine-1 (H1) receptor. By competitively inhibiting the H1 receptor, diphenhydramine reduces the effects of endogenous histamine on bronchial, capillary, and gastrointestinal smooth muscles.The drug also blocks intracellular sodium channels, producing local anesthetic effects. In addition, it has anticholinergic effects that result from the drug’s ability to act as a competitive antagonist on muscarinic acetylcholine receptors in the brain.
Doxepin is a dibenzoxazepine-derivative tricyclic antidepressant (TCA). Based on the location of the alkyl amine substituent on its central tricyclic ring, doxepin is classified as a tertiary amine TCA and believed to be more potent than secondary amine TCAs. The drug’s antidepressant effects are mediated by its ability to block serotonin and norepinephrine reuptake in presynaptic terminals. Doxepin also works as a sedative by blocking the histamine H(1) and H(2) receptors. It exerts anticholinergic effects by blocking muscarinic receptors and hypotensive effects by blocking alpha-1 adrenergic receptors. In oral form, doxepin is used to treat depression, anxiety, and insomnia. In topical form, doxepin works as an antipruritic by blocking the H(1) and H(2) histamine receptors, so it can relieve itching caused by several different skin conditions.
Escitalopram is an antidepressant that belongs to the class of drugs known as serotonin-reuptake inhibitors (SSRIs). It is the S-stereoisomer of another common antidepressant, citalopram, which is a bicyclic phthalane derivative. Like citalopram and other SSRIs, escitalopram works by blocking the reuptake of the neurotransmitter serotonin into the presynaptic neuron. However, compared to all other SSRIs, escitalopram is the most selective for the serotonin transporter protein rather than the norepinephrine transporter protein, so the drug has fewer side effects. Also, escitalopram has a low affinity allosteric binding site on the serotonin transporter, which stabilizes the binding to its main high-affinity site, thereby increasing the duration of its effectiveness. Escitalopram is used to treat depression and anxiety disorders.
Fluconazole belongs to a class of antifungals called triazoles, and can be administered orally or intravenously to treat “yeast” infections of the vagina as well as other fungal infections of the blood, mouth, throat, abdomen, lungs, esophagus, and other organs.
Flurbiprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is a phenylalkanoic acid derivative. Although the exact mechanism of action is not well understood, the drug is thought to work by blocking the effect of cyclooxygenase-2 (COX) enzymes.
Fluticasone Propionate is a manufactured corticosteroid that acts as a glucocorticoid to help regulate the body’s immune system. The drug selectively binds to the glucocorticoid receptor and shows both anti-inflammatory and vasoconstrictive properties. Although the exact mechanism of action of the drug is not fully known, fluticasone propionate inhibits the effects of various cells involved in the immune system, such as mast cells, eosinophils, neutrophils, macrophages, and lymphocytes. The drug also manages a variety of immune response mediators, such as histamine and cytokines response.
Gabapentin is a manufactured structural analog of the neurotransmitter gamma aminobutyric acid (GABA), and has anticonvulsant (anti-seizure) and analgesic properties. Although the mechanism of action is not known for this drug, gabapentin is known to interact with the cortical neurons of calcium channels, thereby increasing the synaptic concentration of GABA and enhancing GABA response elsewhere. Gabapentin is widely used to treat pain, especially neuropathic pain and in the treatment of epilepsy.
Glucosamine is an amino sugar typically classified as a dietary supplement that, while not approved by the FDA for medical use, is often used for treating osteoarthritis. The compound can be produced synthetically or derived from shellfish and certain vegetables, and is needed by the body to manufacture glycoproteins, glycolipids, and glycosaminoglycans. These compounds, in turn, make up many structures in the body, such tendons, ligaments and cartilage, synovial fluid, mucous membranes, various structures found in the eye, blood vessels, and heart valves. The compounds are also a major component of joint cartilage; thus glucosamine may help treat arthritis by helping to rebuild cartilage.
Indomethacin is an non-steroidal anti-inflammatory drug (NSAID) that has anti-inflammatory, analgesic, and antipyretic activity. It belongs to the acetic acid class of NSAIDs and works by inhibiting the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. These enzymes are required for the synthesis of prostaglandins, which are hormone-like molecules that regulate the body’s inflammatory response to injury. The anti-inflammatory and analgesic properties of indomethacin also derive from its ability to uncouple oxidative phosphorylation in mitochondria and inhibit the motility of polymorphonuclear leukocytes. Indomethacin is primarily used to treat moderate to severe pain and inflammation.
Itraconazole belongs to a class of antifungals called triazoles and can be administered orally or intravenously to treat a broad spectrum of fungal infections, particularly those for which Fluconazole or other antifungals are ineffective. Itraconazole works by inhibiting the synthesis of ergosterol (a key component of fungal cell membranes) via the cytochrome P450. As the drug essentially works by slowing the growth of the fungus causing the infection, itraconazole may be effective in preventing fungal infections in immunocompromised patients. Itraconazole has a broad spectrum of activity, making it the drug of choice in treating resistant fungi.
Ketoconazole belongs to a class of antifungals called triazoles and can be administered orally or through topical preparations. The drug essentially works by inhibiting the synthesis of ergosterol (a key component of fungal cell membranes) via the cytochrome P450. The drug has a broad spectrum of activity and is well-tolerated, but also inhibits testosterone production. This side effect has been exploited in terms of using the drug as an anti-androgen therapy to treat prostate cancer2 and Cushing’s disease, but is mainly used as an antifungal therapy.
Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) that has anti-inflammatory, antipyretic and analgesic properties. The drug works by inhibiting cyclooxygenase-1 and -2 (COX-1 and COX-2) enzymes reversibly. COX enzymes are associated with the production of prostaglandins at the injury site, which cause both pain and inflammation. Blocking COX enzymes decreases prostaglandin production, thereby lowering pain and inflammation. Ketoprofen is used to treat mild to moderate pain of many different causes.
Lamotrigine is a synthetic phenyltriazine that works as an anticonvulsant and a mood stabilizer. Though not fully understood, its effects are believed to be mediated through multiple mechanisms. The drug inhibits voltage-gated sodium ion channels by selectively binding to the inactive form, which prevents the release of glutamate, an excitatory neurotransmitter. Lamotrigine also increases the activity of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter that has relaxant and depressive effects because it blocks nerve transmission in the brain. In addition, lamotrigine may block calcium ion channels, which contributes to its antiepileptic effects. It may also prevent serotonin reuptake, increasing its efficacy as an antidepressant.
Levocetirizine dihydrochloride is a histamine H1-receptor antagonist derived from the second generation antihistamine cetirizine. The drug is an inverse agonist, which in turn prevents the release of other allergy chemicals that contribute to the histamine response—the drug does not actually cause mast cells to release histamine. Levocetirizine does not enter the brain or spinal cord in significant amounts, and therefore does not usually cause drowsiness in patients.
Lidocaine hydrochloride is an amide anesthetic that can be delivered topically, via injection, or by inhalation. The drug works by blocking sodium channels across the membranes of post-synaptic neurons, thereby stopping or mediating neuronal impulses and effecting local anesthetic action. This anesthetic property makes lidocaine hydrochloride a preferred drug to treat topical bites, burns, and rashes, and as a local surgical anesthetic when delivered intravenously. Lidocaine hydrochloride’s ability to block sodium channels can also affect the action potential of cardiac cells, making the drug suitable to treat ventricular tachycardia.
Loperamide hydrochloride is an opiate receptor agonist that decreases the motility of the circular and longitudinal smooth muscles of the intestinal wall. The drug prolongs the transit time of intestinal contents, decreasing loss of water and electrolytes and increasing the viscosity and bulk density of fecal contents. Loperamide hydrochloride also decreases movements of bulk in the colon and suppresses reflexes in the stomach and colon. The drug is used to manage both acute and chronic diarrhea stemming from inflammatory bowel disease, gastroenteritis, or other causes.
Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) that has anti-inflammatory, analgesic, and fever-reducing properties. The drug is a derivative of oxicam and thus falls into the enolic acid group of NSAIDs. Meloxicam works by blocking the effect of cyclooxygenase (COX) enzymes. COX enzymes are associated with the production of prostaglandins at the injury site, which cause both pain and inflammation. Blocking COX enzymes decreases prostaglandin production, thereby lowering pain and inflammation. The drug typically blocks COX-2 enzymes but blocks COX-1 enzymes at high dosages. Meloxicam is used to treat both osteoarthritis and rheumatoid arthritis as well as juvenile arthritis in patients over two years of age.
Montelukast sodium is a selective leukotriene receptor antagonist that inhibits the cysteinyl leukotriene CysLT1 receptor. The cysteinyl leukotrienes (LTC4, LTD4, LTE4) are released from different cells, such as mast cells and eosinophils, and bind CysLT receptors, in general. The CysLT1 receptor is found in airway smooth muscle cells and airway macrophages and on other pro-inflammatory cells, and are associated with asthma and allergic rhinitis. By inhibiting CysLT1, montelukast sodium reduces bronchoconstriction and thus causes less inflammation. The drug is used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies.
Mupirocin is a topical antibiotic that was originally isolated from Pseudomonas fluorescens. The drug is bacteriostatic at low concentrations and bactericidal at high concentrations, and is most effective against Gram-positive bacteria. Mupirocin works unlike other antibiotics in that it binds selectively to bacterial isoleucyl-tRNA synthetase, thereby stopping the incorporation of isoleucine into bacterial proteins and blocking further synthesis of those proteins. Mupirocin’s unique mechanism of action means that the drug may be effective against organisms that are resistant to other antibiotics. The drug is used to treat infections caused by Gram-positive bacteria, such as those seen in furuncle, impetigo, and eczema, and is also used to combat methicillin-resistant Staphylococcus aureus (MRSA) and other resistant bacteria.
Nabumetone is a naphthyl alkanone nonsteroidal anti-inflammatory drug (NSAID) that works by blocking the effect of cyclooxygenase (COX) enzymes, but preferentially blocking COX-2 enzymes. COX enzymes are associated with the production of prostaglandins at the injury site, which cause both pain and inflammation. Blocking COX enzymes decreases prostaglandin production, thereby lowering pain and inflammation. This drug belongs to a new class of NSAIDs that are absorbed well in the gastrointestinal tract and therefore have a better chance of not irritating gastrointestinal mucosa. Nabumetone is used to treat reduce pain, swelling, and joint stiffness from chronic conditions such as arthritis.
Nifedipine is a calcium channel blocker that works by relaxing the muscles of the heart and blood vessels. The drug is derived from dihydropyridine and decreases the contractile activity of smooth muscles in the arteries, inhibiting the influx of calcium ions through calcium channels. This causes dilation of both the coronary and systemic arteries, increasing oxygen delivery to myocardial tissue, and decreasing systemic blood pressure. Nifedipine is primarily used to treat hypertension and chronic stable angina.
Orphenadrine Citrate is an anticholinergic drug that also has antihistamine properties. As an anticholinergic, the drug binds to and inhibits both muscarinic acetylcholine receptors as well as N-methyl-D-aspartate (NMDA) receptors in the central nervous system, which are ion channel proteins in the nerve cells that are responsible for synaptic plasticity and memory function. Although the exact mechanism of action is unclear, orphenadrine citrate is thought to interfere with the transmission of nerve impulses from the spinal cord to the muscles, thereby relaxing the muscles. The drug is effective for treating spasms and tremors due to Parkinson’s Disease. The drug also acts as an antagonist against histamine H1 receptors, and can be used to treat allergies.
Pentoxifylline is a methylated xanthine derivative, and, as such, is a competitive nonselective phosphodiesterase inhibitor with significant vasodilatation properties. Although the exact mechanism of action for this drug is not well understood, pentoxifylline belongs to a group of drugs that enhance oxygenation of and blood flow in peripheral tissues. The drug relaxes certain smooth muscles, such as those in peripheral blood vessels, resulting in vasodilatation. Pentoxifylline also improves the flexibility of red blood cells and promotes platelet deaggregation, thereby decreasing blood viscosity. The drug is used to treat vascular disorders and other conditions associated with reduced blood flow.
Phenytoin Sodium is an anticonvulsant that is thought to act by preferentially binding to the inactive form of sodium channels. This, in turn, causes a time-dependent, voltage-dependent and use-dependent block of the channel, particularly against repetitive firing of action potentials, thereby inhibiting both seizure spread and propagation. Phenytoin sodium in known to have class IB antiarrhythmic properties due to its effect on sodium channels in both cardiac myocyte and Purkinje fiber cell membranes. Phenytoin Sodium also has muscle relaxation properties, potentially due to a reduction in the sensitivity of muscle spindles stretching, again due to limited to ion channel transport.
Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) that has anti-inflammatory, analgesic, and fever-reducing properties. The drug is a derivative of oxicam and thus falls into the enolic acid group of NSAIDs. Piroxicam works by blocking the effect of cyclooxygenase (COX) enzymes. COX enzymes are associated with the production of prostaglandins at the injury site, which cause both pain and inflammation. Blocking COX enzymes decreases prostaglandin production, thereby lowering pain and inflammation. The drug has both analgesic and antipyretic properties. Piroxicam is used to treat both osteoarthritis and rheumatoid arthritis and may have activity against dysmenorrhea, headaches, muscle pain, gout, and ankylosing spondylitis.
Prednisone is a synthetic glucocorticoid hormone. Glucocorticoids are produced by the adrenal gland and belong to the corticosteroid class of hormones. Glucocorticoids work by binding to glucocorticoid receptor proteins, which are expressed on the surface of almost every cell in the body. The activation of glucocorticoid receptors has immunosuppressive and anti-inflammatory effects, so the drug can be used to treat a wide range of conditions. However, administering synthetic hormones causes the adrenal glands to stop producing glucocorticoids naturally, so administration of prednisone, especially for periods longer than seven days, must be carefully monitored.
Prilocaine hydrochloride is an amino amide anesthetic similar to, and often combined with, Lidocaine. The drug stabilizes the neuronal membrane by preferentially binding to sodium channels, thereby preventing sodium from entering the cell. Without the influx of sodium ions. the initiation and conduction of signals is blocked. Prilocaine hydrochloride can be given by injection for use as a local anesthetic in dentistry, either through infiltration techniques (that is, delivered directly into the area of terminal nerve endings) or by nerve block. Prilocaine hydrochloride can also be applied topically as a local anesthetic to deaden nerve endings in the skin, possible in preparation for surgery or other procedures in the area.
Stera Base is an oil-in-water base that is both paraben-free and stable over a large pH range. The product can be used to carry lipophilic and hydrophilic drugs, such as hormones and analgesics. The base can also be used as a moisturizing cream, perhaps with added supplements. The non-greasy emollient is typically irritant-free and is easy to wash away.
Sumatriptan is a selective serotonin 5-hydroxytryptamine 1 (5-HT1) receptor agonist that works against receptors in intracranial blood vessels and the sensory nerves of the trigeminal system. Although the exact mechanism of action is not understood, broadly the drug works through rapid constriction of blood vessels in the brain during a headache event. The drug is also thought to act on trigeminal sensory nerve terminals within the cranial blood vessel, inhibiting the release of sensory neuropeptides that signal pain.
Tetracaine is an ester-type local anesthetic that stabilizes the neuronal membrane by preferentially binding to sodium channels, thereby preventing sodium from entering the cell. Without the influx of sodium ions, the initiation and conduction of signals are blocked. It is important to note that ester-type local anesthetics, in general, metabolize into Para-aminobenzoic acid (PABA), which antagonize the effects of sulfonamides. Tetracaine is fast-acting and has a long duration, and can be used as a spinal anesthetic or nerve block delivered via injection, or as a topical solution for short ophthalmic procedures.
Tizanidine hydrochloride is short-acting muscle relaxant that essentially works by blocking nerve impulses to the brain and relaxing muscle tone. Although the exact mechanism of action for the drug is not entirely known, tizanidine hydrochloride is a centrally acting α2-adrenergic agonist that primarily affects spinal polysynaptic reflexes. The drug increases pre-synaptic inhibition of motor neurons by impairing the release of amino acids that help motor neurons and the central nervous system communicate, and by inhibiting certain pathways in the spinal cord. Tizanidine hydrochloride is primarily used to manage and treat skeletal muscle spasms due to multiple sclerosis or spinal cord injury.
Tramadol hydrochloride is a centrally acting opioid analgesic used to treat moderate to severe pain. Although the mechanism of action is not well understood, two distinct and possible synergistic actions are thought to be responsible for the drug’s analgesic properties. The drug acts as an opioid agonist with selectivity for the μ-receptor, thus acting against nociception, and as an inhibitor against the reuptake of norepinephrine, which stimulates intrasynaptic serotonin release.1 Tramadol hydrochloride is well-tolerated and is therefore used to manage both acute pain, such as postoperative pain, and chronic pain, such as back pain.
Verapamil hydrochloride is an L-type calcium channel blocker that works by selectively inhibiting the influx of calcium ions to conductile and contractile myocardial cells and vascular smooth muscle cells. The drug has antiarrhythmic properties due to its effect in slowing atrioventricular conduction, thereby reducing the ventricular rate and quickening the ventricular response. Verapamil hydrochloride also has a vasodilation response, which increases blood flow and oxygen supply to the heart. This drug can be used to treat angina and arrhythmia, hypertension, and certain types of headaches.