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Biomedical subjects

N A Peppas

Publications and source records attributed to N A Peppas.

At least 19 recordsLinked to original sources
PubMed2004

Devices based on intelligent biopolymers for oral protein delivery.

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. An important contributor to good adhesion is the presence of molecular adhesion promoters such as polymer-tethered structure (e.g., poly(ethylene glycol) chains grafted to crosslinked networks) or even linear chains which are free to diffuse across the gel/gel interface. Recently, we have developed a very promising class of carriers for drug and especially protein delivery. Copolymer networks of poly(methacrylic acid) grafted with poly(ethylene glycol) exhibit reversible, pH-dependent swelling behavior due to the formation of interpolymer complexes between protonated pendant acid groups and the etheric groups on the graft chains. Gels containing equimolar amounts of MAA/EG exhibited the lowest degree of swelling at low pH increased complexation. The average network mesh size or correlation length was dramatically affected by the pH of the swelling solution. The in vitro release of insulin from P(MAA-g-EG) gels containing PEG grafts of molecular weight 1000 indicates a significant release of insulin as the gel decomplexes and insulin is freed through the structure. The results of additional in vitro studies have shown that insulin release rates can be controlled by appropriate adjustment of the structure of the gels.

Administration, Oral↗
PubMed2004

Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications.

This review presents a critical analysis of covalently and ionically crosslinked chitosan hydrogels and related networks for medical or pharmaceutical applications. The structural basis of these hydrogels is discussed with reference to the specific chemical interactions, which dictate gel formation. The synthesis and chemistry of these hydrogels is discussed using specific pharmaceutical examples. Covalent crosslinking leads to formation of hydrogels with a permanent network structure, since irreversible chemical links are formed. This type of linkage allows absorption of water and/or bioactive compounds without dissolution and permits drug release by diffusion. pH-controlled drug delivery is made possible by the addition of another polymer. Ionically crosslinked hydrogels are generally considered as biocompatible and well-tolerated. Their non-permanent network is formed by reversible links. Ionically crosslinked chitosan hydrogels exhibit a higher swelling sensitivity to pH changes compared to covalently crosslinked chitosan hydrogels. This extends their potential application, since dissolution can occur in extreme acidic or basic pH conditions.

Biomedical Technology↗
PubMed2003

Evaluation of the swelling, hydration and rupturing properties of the swelling layer of a rupturable pulsatile drug delivery system.

The objective of this study was to investigate the swelling characteristics of various swellable polymers in swelling layers that induce the rupturing of an outer polymer coating in pulsatile drug delivery systems (DDS). An apparatus was designed to measure simultaneously the swelling energy/force and water uptake of discs, made of polymers. The swelling energy of several excipients decreased in the following order: croscarmellose sodium (Ac-Di-Sol) > low-substituted hydroxypropyl cellulose (L-HPC) > sodium starch glycolate (Explotab) > crospovidone (Kollidon CL) > hydroxypropyl methylcellulose (Methocel K100M). A linear correlation existed between the swelling energy and the water uptake. The swelling behavior of Ac-Di-Sol depended on the ionic strength and the pH of the medium due to a competition for free water and the acidic nature of this polymer. Analysis of the time-dependent swelling force data with a previously developed exponential equation confirmed a diffusion-controlled swelling force development, predominantly controlled by the penetration rate of the medium. The swelling behavior and the rupture of the outer polymeric coating of a pulsatile DDS were demonstrated in simulation tests.

Capsules↗
PubMed2003

Time-dependent mechanical properties of polymeric coatings used in rupturable pulsatile release dosage forms.

The mechanical properties of polymer films used in pharmaceutical coatings of pulsatile drug delivery systems were evaluated in the dry and the wet state by a newly developed puncture test, which allowed the time-dependent measurement of the mechanical properties on the same film specimen. Force, puncture strength, energy at break, modulus, and strain were investigated as a function of water exposure time with respect to the type of polymer and the type and concentration of plasticizer and pore former (hydroxypropyl methylcellulose, HPMC). Eudragit RS films were very flexible, had a high strain, and broke upon puncture with only small cracks. In contrast, ethylcellulose films were more brittle with a lower strain and showed complete film rupture. Increased amounts of the hydrophilic pore former, HPMC, resulted in a reduced puncture strength and in an increase in water uptake and weight loss of the films. The puncture strength decreased with increasing plasticizer concentration and was lower with the lipophilic dibutyl sebacate than with the hydrophilic triethyl citrate.

Acrylic Resins↗
PubMed2002

Preparation of poly(methacrylic acid-g-poly(ethylene glycol)) nanospheres from methacrylic monomers for pharmaceutical applications.

Nanospheres of poly(methacrylic acid-grafted-poly(ethylene glycol)) were prepared by solution/precipitation polymerization. As colloidal drug delivery carriers, they present unique properties that render them promising candidates for oral protein delivery. The polymerization was carried out in water and the resulting suspension was freeze-dried. As with many colloidal systems, the freeze-dried suspension showed strong agglomeration after drying. The effects of preparation conditions on the particle size and redispersion were investigated using photon correlation spectroscopy. Furthermore, the ability of different types and concentrations of stabilizers (cryoprotectants and steric stabilizers) in preventing this phenomenon was addressed. Pluronics, block copolymers widely used as nonionic surfactants, were the most effective in stabilizing the particles during the freeze-drying process. Pluronic P123, however, increased significantly the particle size of the nanospheres. On the other hand, lyophilizates obtained in the presence of Pluronic F68 had good redispersion properties and no change in particle size was observed.

Drug Compounding↗
PubMed2002

Understanding and predicting drug delivery from hydrophilic matrix tablets using the "sequential layer" model.

PURPOSE: The objectives of this work were (i) to study and understand the physicochemical phenomena which are involved in the swelling and drug release from hydrophilic matrix tablets using the "sequential layer" model, and (ii) to predict the effect of the initial radius height and size of the tablets on the resulting drug release profiles. METHODS: Tablets were prepared by direct compression, using hydroxypropyl methylcellulose (HPMC) grades with different average molecular weights as matrix-forming polymers. The in vitro release of chlorpheniramine maleate, propranolol HCl, acetaminophen, theophylline and diclofenac sodium was studied in phosphate buffer (pH 7.4) and 0.1 M HCl, respectively. The initial drug loading varied from 1 to 70%, while the radius and height of the tablets varied from 1 to 8 mm. RESULTS: The "sequential layer" model considers water and drug diffusion with non-constant diffusivities and moving boundary conditions, non-homogeneous polymer swelling, drug dissolution, and polymer dissolution. We showed that this model was able to predict the resulting drug release kinetics accurately in all cases. CONCLUSIONS: The "sequential layer" model can be used to elucidate the swelling and drug release behavior from hydrophilic matrix tablets and to simulate the effect of the device geometry on the drug release patterns. Hence, it can facilitate the development of new pharmaceutical products.

Drug Delivery Systems↗
PubMed2002

Morphology of poly(methacrylic acid)/poly(N-isopropyl acrylamide) interpenetrating polymeric networks.

The morphology of interpenetrating polymeric networks (IPNs) composed of the temperature-sensitive poly(N-isopropyl acrylamide) (PNIPAAm) and the pH-sensitive poly(methacrylic acid) (PMAA) were investigated by scanning electron microscopy (SEM). The IPN hydrogels were prepared by a sequential UV polymerization method. SEM studies were conducted on IPN hydrogel samples dried by different methods, and the influence on the IPN structure was discussed. The environmental conditions induced morphological changes for these dual sensitive IPN hydrogels which were studied by cryogenic SEM, when the gels were analyzed in their wet state. The results showed that the porous size in the IPN was strongly influenced by the environmental pH and temperature. Decrease in pH and increase in temperature resulted in significant pore size decrease for the swollen IPNs hydrogels.

Acrylic Resins↗
PubMed2001

Micropatterning of biomedical polymer surfaces by novel UV polymerization techniques.

The "living" radical polymerization with an iniferter was used to create micropatterned biomedical surfaces. Novel, photosensitive biomedical polymers were created by the incorporation of dithiocarbamate groups from iniferters. A second monomer layer was then irradiated onto the photosensitive polymer substrate created with the iniferter to form a copolymer. Patterns were created on the films by application of modified microfabrication-based photolithographic techniques. The technique was used to create patterns with depths from 5 to 80 microm. In addition, various polymers were incorporated, including polyethylene glycol methacrylates, styrene, and methacrylic acid, to synthesize regions with different physico-chemical properties. Applications include novel surfaces for biosensors and biomaterials for the selective adhesion of cells and proteins.

Biocompatible Materials↗
PubMed2001

Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC).

The objective of this article is to review the spectrum of mathematical models that have been developed to describe drug release from hydroxypropyl methylcellulose (HPMC)-based pharmaceutical devices. The major advantages of these models are: (i) the elucidation of the underlying mass transport mechanisms; and (ii) the possibility to predict the effect of the device design parameters (e.g., shape, size and composition of HPMC-based matrix tablets) on the resulting drug release rate, thus facilitating the development of new pharmaceutical products. Simple empirical or semi-empirical models such as the classical Higuchi equation and the so-called power law, as well as more complex mechanistic theories that consider diffusion, swelling and dissolution processes simultaneously are presented, and their advantages and limitations are discussed. Various examples of practical applications to experimental drug release data are given. The choice of the appropriate mathematical model when developing new pharmaceutical products or elucidating drug release mechanisms strongly depends on the desired or required predictive ability and accuracy of the model. In many cases, the use of a simple empirical or semi-empirical model is fully sufficient. However, when reliable, detailed information are required, more complex, mechanistic theories must be applied. The present article is a comprehensive review of the current state of the art of mathematical modeling drug release from HPMC-based delivery systems and discusses the crucial points of the most important theories.

Delayed-Action Preparations↗
PubMed2001

Surface modifications and molecular imprinting of polymers in medical and pharmaceutical applications.

Recent developments in the field of biomaterials are based on molecular design of polymers with improved surface and bulk properties. Novel techniques of surface modification by addition of tethered chains can lead to materials with the ability to recognize biological and pharmaceutical compounds. Methods based on molecular imprinting can increase the recognition capabilities of such systems. Chain tethering can also can improve the mucoadhesive behavior of a delivery device and the effectiveness of a drug by allowing targeting and localization of a drug at a specific site. Acrylic-based hydrogels are well-suited for mucoadhesion due to their flexibility and nonabrasive characteristics which reduce damage-causing attrition to the tissues in contact. However, the adhesive and drug delivery capabilities of these devices can continue to be improved as presently known bioadhesive materials are modified and more bioadhesive materials are discovered. Tethering of long PEG chains on PAA hydrogels and their copolymers can be achieved by grafting reactions involving thionyl chloride, followed by PEG grafting. The ensuing materials exhibit mucoadhesive properties due to enhanced anchoring of the chains with the mucosa. Theoretical calculations can lead to optimization of the tethered structure.

Biocompatible Materials↗
PubMed2001

Preparation of controlled release systems by free-radical UV polymerizations in the presence of a drug.

UV free-radical polymerization techniques are often used to synthesize hydrogels for controlled release applications. Numerous techniques exist for immobilizing drugs or solutes in the gel. This work focuses on the entrapment of solute in a hydrogel by conducting a photopolymerization in the presence of the monomer and the solute. A kinetic gelation model has been developed to examine the effect of the solute material on the polymerization process and the ensuing network structure. Kinetic experiments have also been conducted of the polymerization of poly(ethylene glycol) methacrylate in the presence of theophylline. It was found that the presence of the solute led to a more heterogeneous network with numerous microgel regions present. The effect of the size of the solute on the polymerization was also investigated.

Delayed-Action Preparations↗
PubMed2001

Translocation of drug particles in HPMC matrix gel layer: effect of drug solubility and influence on release rate.

The aim of this work was to study the release mechanisms of drugs having different solubility (buflomedil pyridoxalphosphate 65%, sodium diclofenac 3.1%, nitrofutantoin 0.02% w/v,) from hydroxypropyl methylcellulose (HPMC) matrices by concomitantly studying swelling, diffusion and erosion fronts movement and drug delivery. The main goal was to clarify the role played by polymer swelling in drug transport. The results showed that the rate and amount of drug released from swellable matrices was dependent not only from drug dissolution and diffusion but also from solid drug translocation in the gel due to polymer swelling. In fact, as drug solubility decreased, the slower drug dissolution rate in the gel layer allowed drug particles to be transported close to the matrix erosion front. The presence of solid particles in the gel reduced the swelling and the entanglement of polymer chains and affected the resistance of gel towards erosion. As a consequence, the matrix became more erodible. The erosive delivery accelerated after the matrix had been completely transformed into the rubbery state, particularly when a considerable amount of solid drug particles remained in the gel phase.

Diclofenac↗
PubMed2000

Bimodal drug release achieved with multi-layer matrix tablets: transport mechanisms and device design.

The aim of this study was to develop new multi-layer matrix tablets to achieve bimodal drug release profiles (fast release/slow release/fast release). Hydroxypropyl methylcellulose acetate succinate (HPMCAS, type MF) was chosen as a matrix former, because it is water-insoluble at low, and water-soluble at high pH values. Studies focused on the elucidation of the drug release mechanisms from HPMCAS-MF:drug tablets. In 0.1 N HCl the resulting release kinetics can be described using Fick's second law of diffusion, taking into account axial and radial mass transfer in cylindrical geometry. As the diffusion coefficients are found to be constant and the boundary conditions to be stationary, these systems are purely drug diffusion-controlled. In contrast, the dominating mass transport phenomena in phosphate buffer pH 7.4 are more complex. Due to polymer dissolution the resulting matrix structure is time-variant, leading to increasing drug diffusion coefficients and decreasing tablet dimensions, and thus moving boundary conditions. Drug release is affected by water imbibition, drug diffusion and polymer dissolution and is faster compared to 0.1 N HCl. With knowledge of these underlying release mechanisms, multi-layer matrix tablets were developed to achieve bimodal drug release. HPMCAS-MF:drug mixtures were used as tablet cores. As expected, changing the release medium from 0.1 N HCl to phosphate buffer pH 7. 4 after 2 h, lead to a significant increase in drug release. The abruptness of this rate change could be enhanced by adding two drug-free HPMCAS-MF barrier layers (one on each side) to the system. The addition of a fourth, drug-containing and fast disintegrating initial dose layer yielded the desired bimodal drug release patterns. The process and formulation parameters affecting the resulting release rates were investigated using theophylline and acetaminophen as model drugs.

Acetaminophen↗
PubMed2000

Glucose-sensitivity of glucose oxidase-containing cationic copolymer hydrogels having poly(ethylene glycol) grafts.

Glucose oxidase and catalase were immobilized on poly(diethylaminoethyl methacrylate-g-ethylene glycol) gels by copolymerization of the constituent monomers and the functionalized enzyme solutions. The hydrogels were prepared in the form of discs and microparticles. The amount and the activity of enzymes immobilized in the matrix were determined. The hydrogels were tested for their response to glucose by exposing microparticles to varying concentrations of glucose. The generation of gluconic acid as a result of the reaction of glucose with oxygen was investigated as a function of polymer parameters, such as crosslinking ratio and enzyme loading. Pulsatile variation of the glucose concentration was used to confirm the glucose-dependent swelling properties of these hydrogels.

Enzymes, Immobilized↗
PubMed2000

Calculation of the required size and shape of hydroxypropyl methylcellulose matrices to achieve desired drug release profiles.

The aim of this study was to develop methods for the design of hydroxypropyl methylcellulose (HPMC) tablets with specified drug profiles. This was achieved by the use of a mathematical model developed to predict the release kinetics of water-soluble drugs from HPMC matrices. The required model parameters were determined experimentally for propranolol HCl and chlorpheniramine maleate in 0. 1 N HCl and phosphate buffer pH 7.4, respectively. Then, the effects of the dimensions and aspect ratio (radius/height) of the tablets on the drug release rate were evaluated. Independent experiments were conducted to verify the theoretical predictions. Acceptable agreement between theory and experiment was found, irrespective of the type of release medium and drug. However, statistical analysis revealed a structure in the resulting residuals. Drug release rates are overestimated at the beginning and underestimated at the end of the process. Possible explanations and modifications of the model are thoroughly discussed. Both, theoretical and experimental data showed that a broad spectrum of drug release patterns can be achieved by varying the size and shape of the tablet. The effect of the initial matrix radius on release was found to be more pronounced than the effect of the initial thickness. The practical benefit of the proposed method is to predict the required size and shape of new controlled drug delivery systems to achieve desired release profiles, thus significantly facilitating the development of new pharmaceutical products.

Algorithms↗
PubMed2000

Molecular aspects of muco- and bioadhesion: tethered structures and site-specific surfaces.

Mucoadhesive controlled-release devices can improve the effectiveness of a drug by maintaining the drug concentration between the effective and toxic levels, inhibiting the dilution of the drug in the body fluids, and allowing targeting and localization of a drug at a specific site. Acrylic-based hydrogels have been used extensively as mucoadhesive systems. They are well suited for bioadhesion due to their flexibility and nonabrasive characteristics in the partially swollen state, which reduce damage-causing attrition to the tissues in contact. Crosslinked polymeric devices may be rendered adhesive to the mucosa. For example, adhesive capabilities of these hydrogels can be improved by tethering of long flexible chains to their surfaces. Tethering of long poly(ethylene glycol) (PEG) chains on poly(acrylic acid) hydrogels and their copolymers can be achieved by grafting reactions, or by copolymerization in the presence of several PEG-containing acrylates. The ensuing hydrogels exhibit mucoadhesive properties due to enhanced anchoring of the chains with the mucosa. Theoretical calculations can lead to optimization of the tethered structure. Experimental results indicate that the chain interpenetration is a strong function of the PEG molecular weight, the polymer swelling ratio and the mucosa composition.

Adhesiveness↗
PubMed2000

Transmucosal delivery systems for calcitonin: a review.

The commercial availability of peptides and proteins and their advantages as therapeutic agents have been the basis for tremendous efforts in designing delivery systems for such agents. The protection of these agents from biological fluids and physiological interactions is crucial for the treatment efficacy. One such agent is salmon calcitonin, a 32 amino-acid polypeptide hormone used in the treatment of bone diseases such as Paget's disease, hypercalcemia and osteoporosis. Researchers have studied different routes to deliver salmon calcitonin more effectively, including nasal, oral, vaginal and rectal delivery. These systems are designed to protect the polypeptide from the biological barriers that each delivery route imposes. Oil-based and polymer-based delivery systems are discussed.

Acrylic Resins↗