Drug Release Mechanisms of Buccal Drug Delivery Systems

The suitability of the oral cavity for systemic absorption and the clinical outcome of such delivery depend on:

• The ability to maintain plasma concentration within the therapeutic range.

• The physicochemical properties of drug.

• Release mechanism of the delivery system.

If the active ingredient has favorable physicochemical properties the release profile must then be designed to deliver the requisite plasma concentrations.

A number of dosage form types have been used for transmucosal delivery, including chewing gums, hollow fibers, bioadhesive tablets, laminated systems, and patches [9-13]. All can provide different drug release characteristics depending on the drug, the excipients, and the manufacturing process.

Mechanism of drug release can be broadly classified as either diffusion controlled, erosion controlled, or combinations thereof (Fig. 16.2). An understanding of the release mechanism provides better understanding for designing systems for optimum effect.

Equation (16.1) can be used to describe the kinetics of drug release (or dissolution) [14]:

where

M/Mro is the fraction of drug released, "t" is the release time, "k" is a kinetic constant characteristic of the drug polymer system, "n" is a release exponent indicative of the release mechanism of the drug.

When n=0.5, drug is released via Fickian diffusion. For 0.5 < n < 1, a non-Fickian solute diffusion is observed. When n=1 case II transport (erosion) pertains, with zero order kinetics [15].

In matrix systems, drug release rate is mainly controlled by diffusion; the release exponent is 0.5 for planar surfaces. These systems require that the polymeric carrier be an insoluble but swellable, inert matrix or a polymer of high viscosity grade in which the drug is appreciably soluble or diffusible. For release rate to be diffusion controlled, the rate of dissolution of drug in the solution within the matrix should be much faster than the diffusion rate of the dissolved drug leaving the matrix. Hence, drug solubility is important. Equations for release rates from such matrices are based on Fick's Laws and have been derived by Higuchi [16], indicating that the amount of drug released is a function of the square root of time.

In general, for erosion to be the dominant release mechanism the matrix should contain a hydrophilic polymer of low viscosity grade and the incorporated drug should have low water solubility and/or low diffusivity. Drug dispersed in such a matrix is then released primarily due to erosion of the polymer. There are two

Ghost layer (or) drug depletion zone

Core

Drug in the surrounding medium

Core

Gel layer

Drug in the surrounding medium Core

Eroding matrix

Drug in the surrounding medium Core

Eroding gel layer

Drug in the surrounding medium

Core

Rate limiting polymer membrane

Fig. 16.2 Mechanisms of drug release for transmucoasl drug delivery devices. (a) Matric diffusion systems: (a-1) swellable matrix (hydrophilic polymers), (a-2) nonswellable matrix (Lipophilic matrix); (b) matrix erosion systems; (c) matrix diffusion and erosion systems; (d) reservoir systems types of release from the matrix erosion systems based on the properties of the polymer and the drug:

• If the drug is covalently linked to the polymer backbone directly or via a spacer group, then the drug is released when its bond with the backbone is cleaved by chemical hydrolysis or enzymatic cleavage.

• When the active agent (which is practically insoluble) is homogenously dispersed in an erodible polymer, drug release occurs by dissolution or erosion of the gel layer formed, or by polymer disintegration. This mechanism may exhibit zero-order release kinetics with a release exponent equal to 1.0, as described earlier.

A combination of two hydrophilic gel formers, which influence each other's swelling process, may also give a zero-order release profile. Researchers have formulated a hot-melt extruded matrix erodible film system containing low molecular weight hydroxypropyl cellulose (HPC) and a low molecular weight polyethylene oxide (PEO) incorporated with a poorly soluble drug (clotrimazole) [17].

Ghost layer (or) drug depletion zone

Core

Drug in the surrounding medium

Core

Gel layer

Fig. 16.2 Mechanisms of drug release for transmucoasl drug delivery devices. (a) Matric diffusion systems: (a-1) swellable matrix (hydrophilic polymers), (a-2) nonswellable matrix (Lipophilic matrix); (b) matrix erosion systems; (c) matrix diffusion and erosion systems; (d) reservoir systems

Zero-order release was exhibited by the matrix [17]. Such surface erodible systems, though difficult to achieve, have several advantages, including the ability to control the rate of drug delivery and the ability to deliver a variety of therapeutic agents. This may be accomplished by varying the drug loading within the matrix, thereby controlling the functioning life of the matrix, by varying its thickness and other physical attributes. Such a "platform technology" may have wide applicability.

Matrix diffusion and erosion systems are formed by polymers that do not possess highly resistant gel structures. A combination of two different low viscosity polymers having desired characteristics can be used to achieve this type of release. Release rate follows anomalous transport and does not obey Fick's laws, with the release exponent between 0.5 and 1.0 for planar surfaces. Release from such matrices is controlled both by diffusion of the drug and erosion of the gelled polymer. They may be employed to sustain release of both water soluble and insoluble drugs and can release 100% of the incorporated drug, unlike its matrix diffusion-only counterpart. Zero-order release may also be possible with such systems if care is taken in polymer selection [17].

Was this article helpful?

0 0

Post a comment