Cellulose acetate phthalate (CAP), also known as cellacefate (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

) and cellulosi acetas phthalas, is a commonly used

polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...

phthalate Phthalates (, ), or phthalate esters, are esters of phthalic acid. They are mainly used as plasticizers, i.e., substances added to plastics to increase their flexibility, transparency, durability, and longevity. They are used primarily to soften ...

in the formulation of

pharmaceuticals A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...

, such as the

enteric coating An enteric coating is a polymer barrier applied to 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 ef ...

of tablets or capsules and for

controlled release Modified-release dosage is a mechanism that (in contrast to immediate-release dosage) delivers a drug with a delay after its administration (delayed-release dosage) or for a prolonged period of time (extended-release R, XR, XLdosage) or to a spe ...

formulations. It is a

cellulose Cellulose is an organic compound with the formula , 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 ...

polymer where about half of the

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

s are esterified with

acetyl In organic chemistry, acetyl is a functional group with the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, acetyl is called ethanoyl, ...

s, a quarter are esterified with one or two carboxyls of a

phthalic acid Phthalic acid is an aromatic dicarboxylic acid, with formula C6H4(CO2H)2. Although phthalic acid is of modest commercial importance, the closely related derivative phthalic anhydride is a commodity chemical produced on a large scale. Phthalic aci ...

, and the remainder are unchanged. 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 , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main component ...

. Its main use in pharmaceutics is with enteric formulations. It can be used together with other coating agents, e.g.

ethyl cellulose Ethyl cellulose (or ethylcellulose) 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 manufacturer. It i ...

. Cellulose acetate phthalate is commonly plasticized with

diethyl phthalate Diethyl phthalate (DEP) is a phthalate ester. It occurs as a colourless liquid without significant odour but has a bitter, disagreeable taste. It is more dense than water and insoluble in water; hence, it sinks in water. Synthesis and application ...

, a

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, th ...

compound, or

triethyl citrate Triethyl citrate is an ester of citric acid. It is a colorless, odorless liquid used as a food additive (E number E1505) to stabilize foams, especially as whipping aid for egg white. It is also used in pharmaceutical coatings and plastics. Trie ...

, a

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are no ...

compound; other compatible plasticizers are various phthalates,

triacetin Triacetin, is the organic compound with the formula . It is classified as a triglyceride, i.e., the triester of glycerol. It is a colorless, viscous, and odorless liquid with a high boiling point and a low melting point. It has a mild, sweet tast ...

, dibutyl tartrate,

glycerol Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...

propylene glycol Propylene glycol (IUPAC nomenclature, IUPAC name: propane-1,2-diol) is a viscous, colorless liquid, which is nearly odorless but possesses a faintly sweet taste. Its chemical formula is CH3CH(OH)CH2OH. Containing two Alcohol (chemistry), alcoho ...

, tripropionin, triacetin citrate, acetylated monoglycerides, etc.

Synthesis

The most common way to prepare cellulose acetate phthalate consists of the reaction of a partially substituted cellulose acetate (CA) with

phthalic anhydride Phthalic anhydride is the organic compound with the formula C6H4(CO)2O. It is the anhydride of phthalic acid. Phthalic anhydride is a principal commercial form of phthalic acid. It was the first anhydride of a dicarboxylic acid to be used commerc ...

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

acetone Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour. Acetone is miscib ...

, or

pyridine Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a d ...

. 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.C.J. Malm, J.W. Mench, Brazelton Fulkerso, and G.D. Hiatt, Preparation of Phthalic Acid Esters of Cellulose, Journal of Industrial and Engineering Chemistry 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

excipient 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 (thus often referred ...

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 The anhydroglucose unit (AGU) refers to a single sugar molecule in a polymer. Each AGU is reduced to its functional groups, 3 hydroxyl groups per AGU. Carbohydrate AGU: Cellulose AGU: {, class="wikitable" !Polymer !AGU{{Cite book, title=Cellulo ...

(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.

Stability

The extinction coefficient of CAP changes during its forced degradation by heat, a fact that will have to be accounted for in pharmaceutical stability studies should it be manufactured as a

microbicide An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ar ...

active pharmaceutical ingredient An active ingredient is any ingredient that provides biological activity, biologically active or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the body of h ...

Research

The potential of CAP to inhibit infections by

human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the ...

type 1 (HIV-1) and several herpes viruses ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

'' have been investigated. According to a 1944 study by Hodge, there was no

histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...

change in rats fed CAP for a year.

References

{{more footnotes needed, date=January 2019 * Pharmaceutical Development and Technology, 6(4), 607-6149 (2001) * Iranian Polymer Journal 14(12), 2005, 1058-1065 Cellulose Phthalate esters Acetate esters Excipients