where [H ]s = hydrogen ion concentration at the solid surface C0 = intrinsic solubility Ka = acid dissociation constant

5.2.2 Dissolution of coated systems

Modification of the temporal and spatial aspects of drug release using coating involves applying a layer or layers of retardant material between the drug and the elution/dissolution medium. If the coating material is water soluble, drug release will be controlled by dissolution of the coat, which usually consists of a slowly dissolving polymeric material. Once the polymeric membrane has dissolved, the drug inside the membrane is immediately available for dissolution and absorption.7 At that stage, release will depend on the core properties (drug and excipients) such as porosity, drug solubility, and dissolution rate in the dissolution medium. Cores can be immediate release systems or controlled release matrix systems.

For hydrophilic water-soluble polymers, hydration is the first step of dissolution in aqueous solutions, followed by dissolution of the hydrated phase. The latter step involves disentanglement of polymer molecules. In general, the dissolution kinetics follow Eq. (5.2), suggesting that the solubility of polymers and the viscosity of the hydrated phase are the major variables affecting the dissolution rate. Diffusion of dissolved drug molecules through the hydrated polymer layer also may contribute to the overall release kinetics.

One of the most common designs used for delayed release is the enteric-coated drug delivery system. This is a type of activation-controlled drug delivery system that permits targeting the delivery of a drug only in a selected pH range. Polymers (often esters of phthalic acid) are used as enteric coatings, and they commonly possess carboxylic acid groups that are un-ionized in the relatively low pH of the stomach (normally about 1.5 to 4.5) but ionize and thus repel one another as the pH rises when the delivery system enters the small intestine, thus causing coating disruption. A quantitative model describing the mechanism and kinetics of drug release from enteric-coated tablets was developed by Ozturk et al.8 Polymers used for enteric coatings are weak acids containing carboxyl groups in a substantial proportion of their monomeric units. Rapid dissolution of these polymers requires pH values of dissolution media much higher than the pKa values of polymers. However, when hydrated, these polymers are slightly permeable to the confined drug even at pH values lower than the pKa values of the polymers.

A schematic of an enteric polymer (HP) dissolution and drug release (weak acid, HA) from enteric-coated tablets into a buffered medium (HB) is shown in Fig. 5.2, wherein P-, A-, and B- represent the ionized forms of the polymer, drug, and buffer, respectively. The polymer has an initial thickness of R2-R1 surrounding a drug core of radius R1, and h is the thickness of the stagnant diffusion layer adjacent to the polymer coating. The two interfaces at r = R1 and r = R correspond to the drug-polymer and polymer—stagnant diffusion layer interfaces, respectively; the latter moves with time from the initial position at R2. The position at time t is represented by R. The drug diffuses first through the polymer and then through the stagnant diffusion layer. During this transfer, the drug simultaneously reacts with the incoming buffer B to yield lonizable drug, y e.g., aspirin /

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