DESIGN AND EVALUATION OF PHARMACEUTICAL AQUEOUS COATING SYSTEMS EMPLOYING CELLULOSIC AND VINYL PHTHALATE ENTERIC POLYMERS
Abstract
Recently identified disadvantages of solvent-based film coating have led to renewed interest in totally aqueous film coating. This study was undertaken to develop aqueous-based coating systems containing the enteric polymers, cellulose acetate phthalate (CAP), polyvinyl acetate phthalate (PVAP), and hydroxypropyl methylcellulose phthalate (HPMCP), with particular interest in systems containing CAP. Initially, the ionization and dissolution properties of the polymers were examined. Apparent pKa values were obtained potentiometrically, differed by less than one pH unit, and increased as the distance between adjacent ionizable groups on the polymer decreased. Dissolution rate pH profiles of the polymers were similar in shape even though the measured dissolution rates differed from polymer to polymer at each buffer pH. Polymer pKa, and whether or not the unphthalated polymer backbone is water-soluble, appeared to influence polymer dissolution rates. Also differences in the dissolution rates of the polymers became less significant as pH increased. The first aqueous-based enteric coating system developed was a mechanically produced, colloidal dispersion, called a pseudolatex, which is a high solids content dispersion, and is intended for marketing as a ready-to-use product. Direct application of a plasticized CAP pseudolatex to tablets by air-suspension coating was shown to produce enteric coatings compendial standards. The chemical and physical stabilities of various enteric polymer pseudolatices were studied through periodic measurement of pseudolatex pH and free phthalic acid content with concurrent observation of pseudolatex appearance. The effects of storage temperature, pseudolatex pH, enteric polymer content, and enteric polymer type (i.e., CAP, PVAP, or HPMCP) were determined. As an alternative to pseudolatex enteric coating systems, extemporaneously prepared formulations were developed which contained CAP, solubilized in water as the ammonium salt. These CAP solutions were combined with the ethylcellulose dispersion, Aquacoat, and were plasticized using a single plasticizer or a 50:50 combination of two plasticizers. Effective plasticizers were first identified through a screening process involving spray coating of individual tablets by hand. Selected formulations, applied to tablets by the air-suspension technique, produced coated tablets meeting compendial standards. Other film properties, such as residual ammonium content and permeability to simulated gastric fluid, were measured.
Degree
Ph.D.
Subject Area
Pharmacology
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