Sodium croscarmellose

Last updated September 05, 2019

Sodium croscarmellose is an internally cross-linked sodium carboxymethylcellulose for use as a superdisintegrant in pharmaceutical formulations.^[1]

An excipient is a substance formulated alongside the active ingredient of a medication, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts, or to confer a therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or enhancing solubility. Excipients can also be useful in the manufacturing process, to aid in the handling of the active substance concerns such as by facilitating powder flowability or non-stick properties, in addition to aiding in vitro stability such as prevention of denaturation or aggregation over the expected shelf life. The selection of appropriate excipients also depends upon the route of administration and the dosage form, as well as the active ingredient and other factors. A comprehensive classification system based on structure-property-application relationships has been proposed for excipients used in parenteral medications.

E468 is the E number of crosslinked sodium carboxymethyl cellulose, used in food as an emulsifier.

E numbers are codes for substances that are permitted to be used as food additives for use within the European Union (EU) and European Free Trade Association (EFTA). Commonly found on food labels, their safety assessment and approval are the responsibility of the European Food Safety Authority (EFSA).

Background

The cross-linking reduces water solubility while still allowing the material to swell (like a sponge) and absorb many times its weight in water. As a result, it provides superior drug dissolution and disintegration characteristics, thus improving formulas′ subsequent bioavailability by bringing the active ingredients into better contact with bodily fluids.

Solubility is the property of a solid, liquid or gaseous chemical substance called solute to dissolve in a solid, liquid or gaseous solvent. The solubility of a substance fundamentally depends on the physical and chemical properties of the solute and solvent as well as on temperature, pressure and presence of other chemicals of the solution. The extent of the solubility of a substance in a specific solvent is measured as the saturation concentration, where adding more solute does not increase the concentration of the solution and begins to precipitate the excess amount of solute.

Sponges, the members of the phylum Porifera, are a basal Metazoa (animal) clade as a sister of the Diploblasts. They are multicellular organisms that have bodies full of pores and channels allowing water to circulate through them, consisting of jelly-like mesohyl sandwiched between two thin layers of cells. The branch of zoology that studies sponges is known as spongiology.

In pharmacology, bioavailability is a subcategory of absorption and is the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes, its bioavailability generally decreases or may vary from patient to patient. Bioavailability is one of the essential tools in pharmacokinetics, as bioavailability must be considered when calculating dosages for non-intravenous routes of administration.

Sodium croscarmellose also resolves formulators′ concerns over long-term functional stability, reduced effectiveness at high tablet hardness levels, and similar problems associated with other products developed to enhance drug dissolution. It is a very commonly used^[2] pharmaceutical additive approved by the U.S. Food and Drug Administration. Its purpose in most tablets – including dietary supplements – is to assist the tablet in disintegrating in the gastrointestinal tract promptly. If a tablet disintegrating agent is not included, the tablet could disintegrate too slowly, in the wrong part of the intestine or not at all, thereby reducing the efficacy and bioavailability of the active ingredients.

Croscarmellose is made by first soaking crude cellulose in sodium hydroxide, and then reacting the cellulose with sodium monochloroacetate to form sodium carboxymethylcellulose. Excess sodium monochloroacetate slowly hydrolyzes to glycolic acid and the glycolic acid catalyzes the cross-linkage to form sodium croscarmellose.^[1] Chemically, it is the sodium salt of a cross-linked, partly O-(carboxymethylated) cellulose.

Cellulose is an organic compound with the formula (C^₆H^₁₀O^₅)^_n, a polysaccharide consisting of a linear chain of several hundred to many thousands of β(1→4) linked D-glucose units. Cellulose is an important structural component of the primary cell wall of green plants, many forms of algae and the oomycetes. Some species of bacteria secrete it to form biofilms. Cellulose is the most abundant organic polymer on Earth. The cellulose content of cotton fiber is 90%, that of wood is 40–50%, and that of dried hemp is approximately 57%.

Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations Na⁺
and hydroxide anions OH⁻
.

Glycolic acid (hydroacetic acid or hydroxyacetic acid); chemical formula C₂H₄O₃ (also written as HOCH₂CO₂H), is the smallest α-hydroxy acid (AHA). This colorless, odorless, and hygroscopic crystalline solid is highly soluble in water. It is used in various skin-care products. Glycolic acid is found in some sugar-crops.

Sodium croscarmellose was first used as a stabilizer in horse supplements.^{[ citation needed ]}

Stabilizer (chemistry) chemical that is used to prevent degradation

In industrial chemistry, a stabilizer is a chemical that is used to prevent degradation. Heat and light stabilizers are added to plastics and elastomers because they ensure safe processing and protect products against aging and weathering. The trend is towards fluid systems, pellets, and increased use of masterbatches. There are monofunctional, bifunctional, and polyfunctional stabilizers. In economic terms the most important product groups on the market for stabilizers are compounds based on calcium, lead, and tin stabilizers as well as liquid and light stabilizers. Cadmium-based stabilizers largely vanished in the last years due to health and environmental concerns.

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Tablet (pharmacy) solid form for doses of drugs or medication to be taken orally

A tablet is a pharmaceutical oral dosage form (OSD). Tablets may be defined as the solid unit dosage form of medicament or medicaments with suitable excipients and prepared either by molding or by compression. It comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose. The excipients can include diluents, binders or granulating agents, glidants and lubricants to ensure efficient tabletting; disintegrants to promote tablet break-up in the digestive tract; sweeteners or flavours to enhance taste; and pigments to make the tablets visually attractive or aid in visual identification of an unknown tablet. A polymer coating is often applied to make the tablet smoother and easier to swallow, to control the release rate of the active ingredient, to make it more resistant to the environment, or to enhance the tablet's appearance.

Sodium cyclamate is an artificial sweetener. It is 30–50 times sweeter than sucrose, making it the least potent of the commercially used artificial sweeteners. It is often used with other artificial sweeteners, especially saccharin; the mixture of 10 parts cyclamate to 1 part saccharin is common and masks the off-tastes of both sweeteners. It is less expensive than most sweeteners, including sucralose, and is stable under heating. Safety concerns have led to cyclamates being banned in the United States and other countries, though the European Union recognizes them as safe.

Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars. It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities. Chondroitin sulfate is an important structural component of cartilage and provides much of its resistance to compression. Along with glucosamine, chondroitin sulfate has become a widely used dietary supplement for treatment of osteoarthritis.

Alendronic acid, sold under the brand name Fosamax among others, is a bisphosphonate medication used to treat osteoporosis and Paget's disease of bone. It is taken by mouth. Use is often recommended together with vitamin D, calcium supplementation, and lifestyle changes.

Bioequivalence is a term in pharmacokinetics used to assess the expected in vivo biological equivalence of two proprietary preparations of a drug. If two products are said to be bioequivalent it means that they would be expected to be, for all intents and purposes, the same.

Carboxymethyl cellulose (CMC) or cellulose gum is a cellulose derivative with carboxymethyl groups (-CH₂-COOH) bound to some of the hydroxyl groups of the glucopyranose monomers that make up the cellulose backbone. It is often used as its sodium salt, sodium carboxymethyl cellulose. It used to be marketed under the name Tylose, a registered trademark of SE Tylose.

Sodium bisulfate, also known as sodium hydrogen sulfate, is the sodium salt of the bisulfate anion, with the molecular formula NaHSO₄. Sodium bisulfate is an acid salt formed by partial neutralization of sulfuric acid by an equivalent of sodium base, typically either in the form of sodium hydroxide (lye) or sodium chloride (table salt). It is a dry granular product that can be safely shipped and stored. The anhydrous form is hygroscopic. Solutions of sodium bisulfate are acidic, with a 1M solution having a pH of around 1.

An enteric coating is a polymer barrier applied on oral medication that prevents its dissolution or disintegration in the gastric environment. This helps by either protecting drugs from the acidity of the stomach, the stomach from the detrimental effects of the drug, or to release the drug after the stomach. Some drugs are unstable at the pH of gastric acid, and need to be protected from degradation. Enteric coating is also an effective method to obtain drug targeting. Other drugs such as some anthelmintics may need to reach a high concentration in a specific part of the intestine. Enteric coating may also be used during studies as a research tool to determine drug absorption. Enteric coated medications pertain to the "delayed action" dosage form category. From a pharmacological point of view the term "enteric coating" is not entirely correct, as gastric resistance can be also obtained by adding enteric polymeric systems to the matrix of the dosage form. Tablets, mini-tablets, pellets and granules are the most common enteric-coated dosage forms.

Magnesium stearate is the chemical compound with the formula Mg(C^₁₈H^₃₅O^₂)^₂. It is a soap, consisting of salt containing two equivalents of stearate (the anion of stearic acid) and one magnesium cation (Mg²⁺). Magnesium stearate is a white, water-insoluble powder. Its applications exploit its softness, insolubility in many solvents, and low toxicity. It is used as a release agent and as a component or lubricant in the production of pharmaceuticals and cosmetics.

Methyl cellulose is a chemical compound derived from cellulose. It is sold under a variety of trade names and is used as a thickener and emulsifier in various food and cosmetic products, and also as a bulk-forming laxative. Like cellulose, it is not digestible, not toxic, and not an allergen.

α-Hydroxy acids, or alpha hydroxy acids (AHAs), are a class of chemical compounds that consist of a carboxylic acid substituted with a hydroxyl group on the adjacent carbon. They may be naturally occurring or synthetic. AHAs are well known for their use in the cosmetics industry. They are often found in products that aid in the reduction of wrinkles, that soften strong, defining lines, and that improve the overall look and feel of the skin. They are also used as chemical peels. AHAs have effective results through continuous treatment in the cosmeceutical industry.

Sodium ascorbate is one of a number of mineral salts of ascorbic acid (vitamin C). The molecular formula of this chemical compound is C₆H₇NaO₆. As the sodium salt of ascorbic acid, it is known as a mineral ascorbate. It has not been demonstrated to be more bioavailable than any other form of vitamin C supplement.

An orally disintegrating tablet or orally dissolving tablet (ODT) is a drug dosage form available for a limited range of over-the-counter (OTC) and prescription medications. ODTs differ from traditional tablets in that they are designed to be dissolved on the tongue rather than swallowed whole. The ODT serves as an alternative dosage form for patients who experience dysphagia or for where compliance is a known issue and therefore an easier dosage form to take ensures that medication is taken. Common among all age groups, dysphagia is observed in about 35% of the general population, as well as up to 60% of the elderly institutionalized population and 18-22% of all patients in long-term care facilities ODTs also have a faster onset of effects than tablets or capsules, and have the convenience of a tablet that can be taken without water. During the last decade, ODTs have become available in a variety of therapeutic markets, both OTC and by prescription.

Pharmaceutical formulation, in pharmaceutics, is the process in which different chemical substances, including the active drug, are combined to produce a final medicinal product. The word formulation is often used in a way that includes dosage form.

Modified-release dosage is a mechanism that delivers a drug with a delay after its administration or for a prolonged period of time or to a specific target in the body.

Thin-film drug delivery uses a dissolving film or oral drug strip to administer drugs via absorption in the mouth and/or via the small intestines (enterically). A film is prepared using hydrophilic polymers that rapidly dissolves on the tongue or buccal cavity, delivering the drug to the systemic circulation via dissolution when contact with liquid is made.

Delafloxacin is a fluoroquinolone antibiotic used to treat acute bacterial skin and skin structure infections.

Perampanel is an antiepileptic drug developed by Eisai Co. that is used in addition to other drugs to treat partial seizures and generalized tonic-clonic seizures for people older than 12 years. It was first approved in 2012 and as of 2016 its optimal role in the treatment of epilepsy relative to other drugs was not clear. It was the first antiepileptic drug in the class of selective non-competitive antagonist of AMPA receptors.

References

1 2 Swarbrick, James; James C. Boylan (1990). Encyclopedia of pharmaceutical technology. pp. 2623–2624. ISBN 978-0-8247-2824-3.
↑ "Inactive Ingredients in FDA Approved Drugs". Accessdata.fda.gov. Retrieved 2013-04-27.

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[Sworbrick-1] 1 2 Swarbrick, James; James C. Boylan (1990). Encyclopedia of pharmaceutical technology. pp. 2623–2624. ISBN 978-0-8247-2824-3.

[2] "Inactive Ingredients in FDA Approved Drugs". Accessdata.fda.gov. Retrieved 2013-04-27.