Nikolaos A. Peppas

Mechanisms of solute release from porous hydrophilic polymers

Abstract Porous hydrophilic discs were prepared from two grades of poly(vinyl alcohol) of varying degree of hydrolysis. The influence of the molecular size of the tracer used (potassium chloride, phenylpropanolamine hydrochloride and bovine serum albumin), that of the addition of a second water-soluble polymer poly(N-vinyl-2-pyrrolidone) and poly(ethylene glycol)) and the effect of the tracer/excipient ratio on the release profile were examined. Finally the role of the dynamic swelling and the dissolution of the polymer matrix on the release mechanism are discussed.

A simple equation for description of solute release II. Fickian and anomalous release from swellable devices

Abstract The previously (Ritger and Peppas, 1987) introduced exponential relation M t /M ∞ = kt n may be used to describe the Fickian and non-Fickian release behavior of swelling-controlled release systems which swell to a moderate equilibrium degree of swelling and are prepared by incorporation of a drug in a hydrophilic, initially glassy polymer. Again the diffusional exponent, n , is an important indicator of the mechanism of transport of a drug through the polymer. Analysis is presented for solute release from sheets, cylinders, spheres and polydisperse samples.

A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs

The simple exponential relation Mt/M∞ = ktn is introduced to describe the general solute release behavior of controlled release polymeric devices, where Mt/M∞ is the fractional solute release, t is the release time, k is a constant, and n is the diffusional exponent characteristic of the release mechanism. It is shown that this equation can adequately describe the release of drugs or other solutes from slabs, spheres, cylinders and discs (tablets), regardless of the release mechanism. It is shown that in cases of pure Fickian release the exponent n has the limiting values of 0.50, 0.45 and 0.43 for release from slabs, cylinders and spheres, respectively. For tablets, and depending on the aspect ratio, i.e., the ratio of diameter to thickness, the Fickian diffusion mechanism is described by 0.43<n< 0.50. For drug release from spherical polymer particles of a wide distribution, the value of the exponent n for Fickian diffusion depends on the width of the distribution.

Structure and Applications of Poly(vinyl alcohol) Hydrogels Produced by Conventional Crosslinking or by Freezing/Thawing Methods

Poly(vinyl alcohol) (PVA) is a polymer of great interest because of its many desirable characteristics specifically for various pharmaceutical and biomedical applications. The crystalline nature of PVA has been of specific interest particularly for physically cross-linked hydrogels prepared by repeated cycles of freezing and thawing. This review includes details on the structure and properties of PVA, the synthesis of its hydrogels, the crystallization of PVA, as well as its applications. An analysis of previous work in the development of freezing and thawing processes is presented focusing on the implications of such materials for a variety of applications. PVA blends that have been developed with enhanced properties for specific applications will also be discussed briefly. Finally, the future directions involving the further development of freeze/thawed PVA hydrogels are addressed.

A simple equation for the description of solute release. III. Coupling of diffusion and relaxation

Abstract The exponential expression of solute release from polymeric devices can be written in terms of the release mechanisms diffusional and relaxational contributions. The general form of this equations exponent is related to the geometric shape of the releasing device through its aspect ratio. A methodology is presented for general analysis of the release behavior of controlled release systems using a coupled diffusion/relaxation model.

Surface, interfacial and molecular aspects of polymer bioadhesion on soft tissues

Abstract Interfacial phenomena related to the adhesive properties of synthetic polymers, hydrocolloids and related systems in contact with soft, natural tissues are discussed. The nature of the adhesive interface, the surface roughness, the chemical structure of the bioadhesive-candidate material, the swelling (hydration) at the adhesive interface, and the dynamic development of the bioadhesive bond strength are analyzed in terms of molecular and surface theories. Available in vitro testing techniques for bioadhesion provide an indication of the efficiency of proposed polymers as bioadhesives. These theoretical analyses and experimental results are used to establish general guidelines for the development of bioadhesive controlled release systems of bioactive agents for buccal, nasal, gastric, intestinal, urinary and rectal uses.

Present and future applications of biomaterials in controlled drug delivery systems

Abstract In this paper we review controlled drug release polymeric systems with emphasis on the polymer carriers as biomaterials. Polymer structure affects the diffusion mechanism and release behaviour of various drugs. Zero-order release can be achieved under certain conditions of polymer preparation and for specific geometric shapes. Physical, physicochemical, diffusive and toxicological tests for biomaterials used in controlled release applications are also discussed.

Poly(ethylene glycol)-containing hydrogels in drug delivery

The use of hydrogels as carriers for protein delivery has been a subject of significant recent research. In our recent work, we have shown that diffusion controlled delivery of proteins from hydrogels containing poly(ethylene glycol) (PEG) can be possible and controlled by the three-dimensional structure. In addition, a number of these hydrogel carriers are mucoadhesive and can be used for protein delivery. PEG star polymer gels have also been prepared by gamma-irradiation and have been used for protein delivery with and without molecular imprinting. The presence of a large number of functional groups in a small volume makes these polymers important for use in biological and pharmaceutical applications. PEG star polymer hydrogels were synthesized using gamma-irradiation and were characterized using swelling techniques. Equilibrium swelling studies were conducted to investigate the effects of molecular weight, number of star arms, concentration, and radiation dose.

Preparation, structure and diffusional behavior of hydrogels in controlled release

Abstract The release of drugs, peptides and proteins from hydrogels is controlled by the macromolecular structure of the carrier as defined by the degree of crosslinking, the degree of swelling and related parameters. Ionic interactions play an important role in drug transport. For swelling-controlled systems, the coupling of diffusion and macromolecular relaxation control the mechanism of drug release, providing conditions of zero-order release. Application of such systems in various delivery situations is discussed with emphasis on the delivery rate and the stability of the releasing bioactive agents.

Hydrogels as mucoadhesive and bioadhesive materials: a review.

The primary goal of bioadhesive controlled drug delivery is to localize a delivery device within the body to enhance the drug absorption process in a site-specific manner. Bioadhesion is affected by the synergistic action of the biological environment, the properties of the polymeric controlled release device, and the presence of the drug itself. The delivery site and the device design are dictated by the drugs molecular structure and its pharmacological behaviour. This review addresses several issues which clarify the central goals of bioadhesive drug delivery research. Subsequently, a brief review of a wide variety of techniques which have been used to characterize bioadhesives is presented. This is followed by an overview of several proposed mechanisms of adhesion. The primary mechanisms for polymer systems, adsorption and diffusion, are examined in more detail.