Cellulose acetate phthalate, dissolution

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). 

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. 

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. 

Cellulose acetate phthalate (CAP) Above pH 6 High pH required for dissolution a disadvantage forms brittle films, so must be combined with other polymers... 

Until recently, hot-melt extrusion had not received much attention in the pharmaceutical literature. Pellets comprising cellulose acetate phthalate were prepared using a rudimentary ram extruder in 1969 and studied for dissolution rates in relation to pellet geometry. More recently, production of matrices based on polyethylene and polycaprolactone were investigated using extruders of laboratory scale. Mank et al. reported in 1989 and 1990 on the extrusion of a number of thermoplastic polymers to produce sustained release pellets.A melt-extrusion process for manufacturing matrix drug delivery systems was reported by Sprockel and coworkers.As one can see, a review of the pharmaceutical scientific literature does not elucidate many applications for hot-melt extrusion in this field. 

Spitael J, Kinget R, Naessens K. Dissolution rate of cellulose acetate phthalate and Bronsted catalysis law. Pharm Ind 1980 42 846-849. 

Physicochemical studies of other aliphatic, carboxylic esters of polysaccharides include (a) assessment of the gel-permeation properties of the series cellulose propionate-cellulose heptanoate, (b) dissolution of cellulose acetate phthalate, (c) monolayer properties of amylose acetate, and (d) melting and transition temperatures of the series amylose acetate-amylose hexanoate. Amylose acetate assumes a helical conformation at air-water interfaces and in oriented films, and the X-ray-analysis data for mannan acetate imply a threefold screw-axis... 

Physicochemical studies of the solution properties of amylose benzoate by light-scattering, osmometric, and viscosimetric techniques showed that the molecules behave as coils. Factors affecting the rate of dissolution of cellulose acetate phthalate in aqueous solution are important from the point of view of use as an enteric-coating material. The removal of the benzoyl group during methanolysis is slow and concurrent with the methanolysis, " whereas deacetylation precedes methanolysis. 

The rate constants for the dissolution of cellulose acetate phthalate in solutions of different basic salts were determined using an automatic pH-stat method. A linear relationship between the logarithm of the rate constants and the pRg of the basic salts was observed. Evidence was given that the rate of proton transfer, which leads to the dissociation and, consequently, to the dissolution of the polymer, is the rate determining step and is governed by the Bronsted catalysis law."... 

Drug release rate from cellulose esters microspheres is dependent on the porosity of the matrix, and on the solubility of the drug in the matrix material or in the dissolution medium. Hydrophobic drugs exhibit prolonged release rates that can be modified using hydrophilic polymers such as PEG4000 and HPC. Cellulose acetate phthalate (CAPh) is a pH dependent cellulose ester, frequently employed alone, or in combination with other polymers to obtain microspheres with enteric properties. ... 

Finally, the cellulose derivatives are mosdy used as matrix formers for sustained release pellets due to their hydration and gel formation ability, with formation of a diffusion layer around the drug particles and delays its release into the dissolution medium. Certain cellulose esters, such as hydroxypropyl methylcellulose acetate succinate (Aqoat-AS ) or cellulose acetate phthalate, are used for the production of enteric release pellets, because they are soluble in the mildly basic intestinal fluid. 

Vervaet et al. investigated another example of a core-sheU microcapsule system via HME technology in 2005. 2 These researchers used HME as an alternative technique for enteric delivery. Polyvinyl acetate phthalate and hydroxypropyl methyl cellulose acetate succinate (HPMC AS) enteric coating polymers were premixed with plasticizers and extruded into hollow cylinders. A model drug was then filled into these hollow cylinders and both open ends were sealed. Dissolution... 

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