Cellulose acetate phthalate
Encyclopedia
Cellulose acetate phthalate (CAP), also known as cellacefate and cellulosi acetas phthalas, is a commonly used polymer
phthalate in the formulation of pharmaceuticals, such as the enteric coating
of tablet
s or capsules and for controlled release
formulations. It is a cellulose
polymer where about half of the hydroxyl
s are esterified with acetyl
s, a quarter are esterified with one or two carboxyls of a phthalic acid
, and the remainder are unchanged. Its CAS number is [9004-38-0]. It is a hygroscopic white to off-white free-flowing powder, granules, or flakes. It is tasteless and odorless, though may have a weak odor of acetic acid
. Its main use in pharmaceutics is with enteric formulations
. It can be used together with other coating agents, e.g. ethyl cellulose
. Cellulose acetate phthalate is commonly plasticized
with diethyl phthalate
, a hydrophobic compound, or triethyl citrate
, a hydrophilic compound; other compatible plasticizers are various phthalates, triacetin
, dibutyl tartrate, glycerol
, propylene glycol
, tripropionin, triacetin citrate, acetylated monoglycerides, etc.
According to a 1944 study by Hodge, there was no histological change on rats fed CAP for a year.
in the presence of an organic solvent and a basic catalyst. The organic solvents widely used as reaction media for the phthaloylation of cellulose acetate are acetic acid
, acetone
, or pyridine
. The basic catalysts employed are anhydrous sodium acetate when using acetic acid, amines when using acetone, and the organic solvent itself when using pyridine as reaction medium.
Malm et al., records the preparation of phthalic acid derivatives of ethyl-cellulose and cellulose acetate without the use of pyridine by substituting sodium acetate as catalyst and acetic acid as a reaction solvent. Phthalyl content of the derivatives produced by this method is inversely dependent on the reaction temperature, although the rate of phthalyl introduction is faster at high temperatures. Phthalyl content also depends on proportions of acetic acid, as a reaction solvent
due to its solubility dependent on the pH of the aqueous media. Enteric coatings based on CAP are resistant to acidic gastric fluids, but easily soluble in mildly basic medium of the intestine. The pH sensitive solubility of CAP is mainly determined (as other properties of this mixed ester) by the degree of substitution (DS), namely the average number of substituent groups bound to an anhydroglucose unit (AGU), as well as by the molar ratio (acetyl and phthaloyl groups). These two structural characteristics of the polymer are dependent on the method employed for its synthesis.
Recently, its potential to inhibit infections by human immunodeficiency virus type 1 (HIV-1) and several herpes viruses in vitro
have been investigated.
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
phthalate in the formulation of pharmaceuticals, such as the enteric coating
Enteric coating
An enteric coating is a barrier applied to oral medication that controls the location in the digestive system, where it is absorbed. Enteric refers to the small intestine, therefore enteric coatings prevent release of medication before it reaches the small intestine.Most enteric coatings work by...
of tablet
Tablet
A tablet is a pharmaceutical dosage form. It comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose...
s or capsules and for controlled release
Controlled release
Controlled release is a term referring to the presentation or delivery of compounds in response to stimuli or time. This can be for purposes in several areas including agriculture, cosmetics and personal care, pharmaceuticals and food science. Most commonly it refers to time dependent release in...
formulations. It is a cellulose
Cellulose
Cellulose is an organic compound with the formula , a polysaccharide consisting of a linear chain of several hundred to over ten thousand β linked D-glucose units....
polymer where about half of the hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
s are esterified with acetyl
Acetyl
In organic chemistry, acetyl is a functional group, the acyl with chemical formula COCH3. It is sometimes represented by the symbol Ac . The acetyl group contains a methyl group single-bonded to a carbonyl...
s, a quarter are esterified with one or two carboxyls of a phthalic acid
Phthalic acid
Phthalic acid is an aromatic dicarboxylic acid, with formula C6H42. It is an isomer of isophthalic acid and terephthalic acid. Although phthalic acid is of modest commercial importance, the closely related derivative phthalic anhydride is a commodity chemical produced on a large...
, and the remainder are unchanged. Its CAS number is [9004-38-0]. It is a hygroscopic white to off-white free-flowing powder, granules, or flakes. It is tasteless and odorless, though may have a weak odor of acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
. Its main use in pharmaceutics is with enteric formulations
Enteric coating
An enteric coating is a barrier applied to oral medication that controls the location in the digestive system, where it is absorbed. Enteric refers to the small intestine, therefore enteric coatings prevent release of medication before it reaches the small intestine.Most enteric coatings work by...
. It can be used together with other coating agents, e.g. ethyl cellulose
Ethyl cellulose
Ethyl cellulose is a derivative of cellulose in which some of the hydroxyl groups on the repeating glucose units are converted into ethyl ether groups. The number of ethyl groups can vary depending on the manufacture....
. Cellulose acetate phthalate is commonly plasticized
Plasticizer
Plasticizers or dispersants are additives that increase the plasticity or fluidity of the material to which they are added; these include plastics, cement, concrete, wallboard, and clay. Although the same compounds are often used for both plastics and concretes the desired effects and results are...
with diethyl phthalate
Diethyl phthalate
Diethyl phthalate is a phthalate ester, namely the diethyl ester of phthalic acid. It is a clear substance that is liquid at room temperature and which does not occur in nature. It has a faint, disagreeable odor and can be transferred from the plastics that contain it...
, a hydrophobic compound, or triethyl citrate
Triethyl citrate
Triethyl citrate is an ester of citric acid. It is a colorless, odorless liquid used as a food additive to stabilize foams, especially as whipping aid for egg white. It is also used in pharmaceutical coatings and plastics....
, a hydrophilic compound; other compatible plasticizers are various phthalates, triacetin
Triacetin
The triglyceride 1,2,3-triacetoxypropane is more generally known as triacetin and glycerin triacetate. It is the triester of glycerol and acetic acid....
, dibutyl tartrate, glycerol
Glycerol
Glycerol is a simple polyol compound. It is a colorless, odorless, viscous liquid that is widely used in pharmaceutical formulations. Glycerol has three hydroxyl groups that are responsible for its solubility in water and its hygroscopic nature. The glycerol backbone is central to all lipids...
, propylene glycol
Propylene glycol
Propylene glycol, also called 1,2-propanediol or propane-1,2-diol, is an organic compound with formula C3H8O2 or HO-CH2-CHOH-CH3...
, tripropionin, triacetin citrate, acetylated monoglycerides, etc.
According to a 1944 study by Hodge, there was no histological change on rats fed CAP for a year.
Synthesis
The most common way to prepare cellulose acetate phthalate consists of the reaction of a partially substituted cellulose acetate (CA) with phthalic anhydridePhthalic anhydride
Phthalic anhydride is the organic compound with the formula C6H42O. It is the anhydride of phthalic acid. This colourless solid is an important industrial chemical, especially for the large-scale production of plasticizers for plastics. In 2002, approximately 4.6 billion kilograms were...
in the presence of an organic solvent and a basic catalyst. The organic solvents widely used as reaction media for the phthaloylation of cellulose acetate are acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
, acetone
Acetone
Acetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
, or pyridine
Pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...
. The basic catalysts employed are anhydrous sodium acetate when using acetic acid, amines when using acetone, and the organic solvent itself when using pyridine as reaction medium.
Malm et al., records the preparation of phthalic acid derivatives of ethyl-cellulose and cellulose acetate without the use of pyridine by substituting sodium acetate as catalyst and acetic acid as a reaction solvent. Phthalyl content of the derivatives produced by this method is inversely dependent on the reaction temperature, although the rate of phthalyl introduction is faster at high temperatures. Phthalyl content also depends on proportions of acetic acid, as a reaction solvent
Applications
CAP has been used for several decades as a pharmaceutical excipientExcipient
An excipient is generally a pharmacologically inactive substance used as a carrier for the active ingredients of a medication. In many cases, an "active" substance may not be easily administered and absorbed by the human body; in such cases the substance in question may be dissolved into or...
due to its solubility dependent on the pH of the aqueous media. Enteric coatings based on CAP are resistant to acidic gastric fluids, but easily soluble in mildly basic medium of the intestine. The pH sensitive solubility of CAP is mainly determined (as other properties of this mixed ester) by the degree of substitution (DS), namely the average number of substituent groups bound to an anhydroglucose unit (AGU), as well as by the molar ratio (acetyl and phthaloyl groups). These two structural characteristics of the polymer are dependent on the method employed for its synthesis.
Recently, its potential to inhibit infections by human immunodeficiency virus type 1 (HIV-1) and several herpes viruses in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
have been investigated.