Cellulose acetate phthalate

This cellulose derivative is a partial acetate ester of cellulose, which has been reacted with phthalic anhydride. One carboxyl residue of the phthalic acid is esterified with cellulose acetate. The final product contains about 20% acetate groups and about 35% phthalate groups. In the acid form, it is soluble in organic solvents and insoluble in water, whereas in the salt form it is readily soluble in water. This combination of properties makes it useful in coating of tablets because it is resistant to acids of the stomach but it is readily soluble in the more alkaline environment of the intestinal tract. 

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Mixed cellulose esters containing the dicarboxylate moiety, eg, cellulose acetate phthalate, have commercially useful properties such as alkaline solubihty and excellent film-forming characteristics. These esters can be prepared by the reaction of hydrolyzed cellulose acetate with a dicarboxyhc anhydride in a pyridine or, preferably, an acetic acid solvent with sodium acetate catalyst. Cellulose acetate phthalate [9004-38-0] for pharmaceutical and photographic uses is produced commercially via the acetic acid—sodium acetate method. 

Mixed esters containing the dicarboxylate moiety, eg, cellulose acetate phthalate, are usually prepared from the partially hydroly2ed lower aUphatic acid ester of cellulose in acetic acid solvent by using the corresponding dicarboxyhc acid anhydride and a basic catalyst such as sodium acetate (41,42). Cellulose acetate succinate and cellulose acetate butyrate succinate are manufactured by similar methods as described in reference 43. 

The most commonly used polymers are cellulose acetate phthalate [9004-38-0] (CAP), poly(vinyl acetate phthalate) [34481-48-6] (PVAP), hydroxypropylmethyl-ceUulosephthalate [71138-97-1] (HPMCP), and polymethacrylates (111) (see Cellulose esters). Acrylate copolymers are also available (112). Eigure 11 shows the dissolution behavior of some commercially available enteric materials. Some manufacturers supply grades designed to dissolve at specific pH values with increments as small as 0.5 pH unit (113). 

Carboxymcthyl cellulose Cellulose acetate phthalate Cellulose Dextrin... 

In the past, the initial layers of coating (the sealing coat) were achieved by applying one or two coats of shellac. However, due to the variability between batches of this material, PVP-stabilized types of shellac or other polymeric materials, such as cellulose acetate phthalate (CAP) and poly(vinyl acetate phthalate) (PVAP), are now more popular. It should be appreciated that a fine balance must exist between minimizing the thickness of the sealing coat and providing an adequate moisture barrier. 

Benzoic acid cellulose acetate phthalate chlorpropamide ibuprofen indomethacin nicotinic acid oxyphenbutazone phosphoric acid phenylbutazone and salicylic acid. 

Some of the exchanged resins were coated with cellulose acetate butyrate or cellulose acetate phthalate. The results showed relaxation rate enhancement in 25% water suspensions containing 2% carboxymethylcellulose (CMC) as a surfactant. The relaxivities, however, were rather low. It should be noted, however, that the measurements were made at high field, 300 MHz, where the relaxivity enhancements are always smaller. 

Are coated with keratin, cellulose acetate phthalate, which do not dissolve in the stomach and only dissolve in alkaline juice of the intestine where the drug is liberated e.g. tab. erythromycin. 

Ketoprofen (SIMS), hydroxypropylmethylcellulose E5 (HPMC, t =2%, 5mPas, Dow Chemical), glyceryl monostearate (Precirol, Gattefosse), Eudragit E 30 D (Rhom Pharma), Polyethylene glycol 400 (PEG 400, Merck) and cellulose acetate phthalate (CAP, Ambrochim) were used directly without any prior purification. 

Aquatic aqueous enteric coating (cellulose acetate phthalate, distilled acetylated monoglycerides, and poloxamer 188) Film coating for tablets and capsules Repeat-dose toxicity with routine end points (90 days—diet rat), reproduction toxicity (embryo-fetal study in rat) and genotoxicity (2 in vitro and 1 in vivo studies) No adverse toxicity, reprotoxicity, or genotoxicity 31, 32... 

Cellulose acetate phthalate (CAP) dissolves at pH higher than 6 and is soluble in ketones, ethers, esters, and alcohols. Permeation of water vapor and gastric fluids is a concern but can be overcome by adding other materials such as shellac. Plasticizers that are used with CAP include diethyl phthalate, triacetin, tributyl citrate, and acetylated monoglyceride. 

Plant — Arabic gum — Tragacanth gum — Karaya gum — Ghatti gum Cellulose derivatives — Carboxymethylcellulose — Methylcellulose — Hydroxyethylcellulose — Cellulose acetate phthalate... 

Cellulose acetate phthalate Coating agent Polyethylene glycol 400, 3350 Vehicle... 

Cellulose acetate phthalate Dextrin-2-sulfate Sodium lauryl sulfate Lactobacillus crispatus Polystyrene sulfonate Polyherbal extracts Naphthalene sulfonate polymer C31G... 

Cellulose (Figure 8.19) may be extracted from wood pulp, and is usually partially hydrolysed with acid to give microcrystalline cellulose. These materials are used as tablet diluents. Semi-synthetic derivatives of cellulose, e.g. methylcellulose, hydroxymethylcellulose, and carboxymethylcellulose, are used as emulsifying and suspending agents. Cellulose acetate phthalate is cellulose with about half the hydroxyl groups acetylated, and the remainder esterified with phthalic acid. It is used as an acid-resistant enteric coating for tablets and capsules. 

R. O. Williams III and J. Liu. Influence of processing and curing conditions on beads coated with an aqueous dispersion of cellulose acetate phthalate. Eur. J. Pharm. Biopharm. 49 243-252, 2000. 

Crawford, R. R., and Esmerian, O. K. Effect of plasticizers on some physical properties of cellulose acetate phthalate films. J. Pharm. Sci. 60(2) 312—314, 1971. 

The salt form of the polymer may also play a role in determining the performance of the formulation. Kane et al. [32] found that cellulose acetate phthalate was more effective than cellulose acetate trimellitate in controlling the dissolution of sulfothiazole-sodium tablets with cellulose acetate. The enteric properties of hydroxypropylmethylcellulose phthalate (HPMCP) were found to depend on the solubility of the drug that was coated. 

As another example, small microcapsules of ibuprofen were film coated with cellulose acetate phthalate and dispersed in water before administration [54], Plasma levels were as expected and did not differ from those of a conventional enteric-coated tablet. 

As previously discussed, food effects are an important parameter for enteric-coated systems, especially for drugs, that are sensitive to food. Pancreatic enzyme-containing products fail when they come in contact too early with lipids, proteins, and carbohydrates present in food. The clinical efficacy of pancreatic enzymes formulated as enteric-coated tablets was investigated in man and dog [44], The enteric materials examined were hydroxypropyl methylcellulose phthal-ate (HPMCP), cellulose acetate phthalate (CAP), and the methacrylic acid copolymer USP/NF Type C. In vivo behavior monitored by x-ray scintigraphy showed clear differences between the three coating formulations. HPMCP-coated products adhered to the gastric mucosa, whereas CAP and methacrylate copolymer... 

Naproxen sodium tablets were used in an in vivo-in vitro evaluation with four different polymeric dispersions, cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), 50 50 CAP/CAT, and methacrylic acid copolymer [64], The study indicated that coating material that dissolves at a more acidic pH in vitro (such as CAT at pH 4.5) will also dissolve at a more acidic pH in vivo (i.e., the coating dissolves higher up in the GI tract). In addition, it was found that aging did not markedly affect dissolution characteristics of CAT or methacrylic acid copolymer-coated tablets. 

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