Showing papers by "Nicholas A. Peppas published in 1996"
TL;DR: This review addresses several issues which clarify the central goals of bioadhesive drug delivery research and presents an overview of several proposed mechanisms of adhesion.
516 citations
TL;DR: The movement of the penetrant and polymer fronts and the drug dissolution in highly loaded swellable matrix tablets showed that the difference between the diffusion and erosion fronts is decisive for the release kinetics, leading to a new finding that the distance between diffusion and eroded fronts is the most important parameter for drug release.
244 citations
TL;DR: In this article, changes occurring in the degree of crystallinity and lamellar thickness distribution of polyvinyl alcohol (PVA) samples during dissolution in water were investigated, and a dissolution mechanism involving unfolding of the polymer chains of the crystal was proposed.
Abstract: Changes occurring in the degree of crystallinity and lamellar thickness distribution of poly(vinyl alcohol) (PVA) samples during dissolution in water were investigated. PVA samples of three different molecular weights were crystallized by annealing at 90, 110, and 120°C. The initial degrees of crystallinity measured by differential scanning calorimetry (DSC) and by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) varied from 43 to 60% and the average lamellar thicknesses measured by DSC ranged from 50 to 400 A. PVA dissolution was followed at 25, 35, and 45°C from 30 s up to 195 min. Lamellar thicknesses were determined as a function of dissolution time using DSC. There was an initial drastic decrease in the degree of crystallinity, which leveled off to a fairly constant value before reaching zero by the time the polymer dissolved completely. Increase in molecular weight led to lesser number of crystals, but with larger average lamellar thickness, which were more stable in the presence of water. Increase in crystallization temperature or decrease in dissolution temperature led to larger average lamellar thickness. Based on these findings, a dissolution mechanism involving unfolding of the polymer chains of the crystal was proposed.
230 citations
TL;DR: The hydrogels synthesized in this study were capable of pulsatile streptokinase release, with at least one order of magnitude difference in release rates between the swollen and collapsed hydrogel states, but the much smaller heparin molecule diffused equally rapidly in the collapsed and swollen polymer states.
189 citations
TL;DR: Swelling under oscillatory pH conditions revealed the dynamic sensitivity of P(MAA-g-EG) membranes as well as the diffusional mechanisms causing network expansion and collapse, and permeability was responsive to changing pH conditions, and separation of solutes was achieved.
184 citations
TL;DR: In this article, a polyethylene oxide (PEO) hydrogel was formed by crosslinking of aqueous PEO solutions of M n = 35 000, 900 000 and 5 000 000 in concentrations of 5-50% using γ-irradiation with 3-10 Mrad.
145 citations
TL;DR: In this article, the influence of possible solute binding on the transport process through polymeric networks of poly(vinyl alcohol) and poly(acrylic acid) at pH 3 or 6 was investigated.
Abstract: Solute transport through interpenetrating polymeric networks of poly(vinyl alcohol) and poly(acrylic acid) at pH 3 or 6 was studied in order to investigate the influence of possible solute binding on the transport process through the networks. Diffusion of theophylline, vitamin B12, and myoglobin was analyzed, and diffusion and partition coefficients were determined. Analysis using the free volume-based theory of Peppas and Reinhart indicated that solute binding occurred only in those hydrogels that were in the ionized state. ATR-FTIR spectroscopic studies were used to determine the level of binding in the case of myoglobin in contact with these IPN hydrogels.
141 citations
01 Jan 1996
TL;DR: This chapter explains various classes of materials used in medicine as they are applied to the selection of biomaterials and provides a table that compares some of the biomolecule immobilization techniques—physical and electrostatic adsorption, cross linking, entrapment, and covalent binding.
Abstract: Publisher Summary There is a diverse range of materials and methods available for the immobilization of biomolecules and cells on or within biomaterial supports. This chapter explains various classes of materials used in medicine. Metallic implant materials have a significant economic and clinical impact on the biomaterials field. Apart from orthopedics, there are other markets for metallic implants and devices including (1) oral and maxillofacial surgery, for example, dental implants, craniofacial plates, and screws and (2) cardiovascular surgery, for example, the parts of artificial hearts, pacemakers, balloon catheters, valve replacements, and aneurysm clips. The chapter also introduces the concepts of polymer characterization and property testing as they are applied to the selection of biomaterials. It provides a table that compares some of the biomolecule immobilization techniques—physical and electrostatic adsorption, cross linking, entrapment, and covalent binding.
125 citations
TL;DR: In this paper, the authors define the polymer structure and elucidate the swelling behavior of ionizable hydrophilic polymers (hydrogels) in water and buffered media, and demonstrate the significance of the swelling medium pH on the hydrated state of the polymers relative to crosslinking or copolymerization composition.
Abstract: SYNOPSIS The purpose of this investigation was to define the polymer structure and elucidate the swelling behavior of ionizable hydrophilic polymers (hydrogels) in water and buffered media. Poly(acry1ic acid) (PAA) and poly(acry1ic acid-co-2-hydroxyethyl methacrylate) [P(AA-coHEMA)] hydrogels were synthesized with varying degrees of hydrophilicity and crosslinking and were designed as potential bioadhesive controlled-release dosage forms. The thermal initiation procedure employed during polymerization was optimized to eliminate unreacted residuals. Equilibrium and dynamic swelling studies were undertaken to determine the polymer mesh size and molecular weight between crosslinks of the hydrogels in the ionized and nonionized states. The PAA hydrogel mesh sizes ranged from 100 to 400 8, over pH values of 3-7, whereas the P(AA-co-HEMA) hydrogel mesh sizes were between 13 and 140 A. These results demonstrated the significance of the swelling medium pH on the hydrated state of the polymers relative to crosslinking or copolymerization composition. 0 1996 John Wiley & Sons, Inc.
95 citations
TL;DR: In this article, the anomalous transport behavior of free radical polymerized polymers was analyzed and the swelling front velocity was determined, and the effect on the transport mechanism of polymer structural characteristics, such as the molecular weight between crosslinks and the concentration of ionizable pendent groups, was studied.
92 citations
TL;DR: In this paper, the authors used scaling law expressions for the disentanglement rate of polystyrene dissolution in methyl ethyl ketone and derived the mass balance at the Rubbery-solvent interface.
Abstract: Polymer dissolution was described by chain reptation incorporated into penetrant transport. The penetrant concentration field was divided into three regimes which delineate three different transport processes. Solvent penetration through the polymer was modeled to occur as a consequence of a diffusional flux and an osmotic pressure contribution. Species momentum balances were written that coupled the polymer viscoelastic behavior with the transport mechanism. Transport in the second penetrant concentration regime was modeled to occur in a diffusion boundary layer adjacent to the rubbery-solvent interface, where a Smoluchowski type diffusion equation was obtained. The disentanglement rate of the polymer is given by the ratio between the radius of gyration of the polymer and the reptation time. This rate was used to write the mass balance at the rubbery-solvent interface. Scaling law expressions for the disentanglement rate were derived. The model equations were numerically solved, and the effect of the polymer molecular weight and the diffusion boundary layer thickness on the dissolution mechanism was investigated for polystyrene dissolution in methyl ethyl ketone. The results showed that upon increasing the polymer molecular weight, the dissolution became disentanglement-controlled. Decrease in the diffusion boundary layer thickness led to a shift in the dissolution mechanism from disentanglement control to diffusion control.
TL;DR: In this article, the authors showed that PEG copolymers exhibit pH-sensitive, reversible complexation and showed that network collapse (complexation) occurred more rapidly than network expansion (decomplexation).
TL;DR: In this paper, the dissolution mechanism of rubbery polymers was analyzed by dividing the penetrant concentration field into three regimes that delineate three distinctly different transport processes: Fickian, reptation and diffusion.
Abstract: The dissolution mechanism of rubbery polymers was analyzed by dividing the penetrant concentration field into three regimes that delineate three distinctly different transport processes. The solvent penetration into the rubbery polymer was assumed to be Fickian. The mode of mobility of the polymer chains was shown to undergo a change at a critical penetrant concentration expressed as a change in the diffusion coefficient of the polymer. It was assumed that beyond the critical penetrant concentration, reptation was the dominant mode of diffusion. Molecular arguments were invoked to derive expressions for the radius of gyration, the plateau modulus, and the reptation time, thus leading to an expression for the reptation diffusivity. The disentanglement rate was defined as the ratio between the radius of gyration of the polymer and the reptation time. Transport in the second penetrant concentration regime was modeled to occur in a diffusion boundary layer adjacent to the polymer-solvent interface, where a Smoluchowski type diffusion equation was obtained. The model equations were numerically solved using a fully implicit finite difference technique. The results of the simulation were analyzed to ascertain the effect of the polymer molecular weight and its diffusivity on the dissolution process. The results show that the dissolution can be either disentanglement or diffusion controlled depending on the polymer molecular weight and the thickness of the diffusion boundary layer. © 1996 John Wiley & Sons, Inc.
TL;DR: Results indicate that although double bond conversion is low, conversion of monomer units is significantly higher, and that the shrinkage for methacrylates was less than that for acryLates.
TL;DR: Ultrapure poly(vinyl alcohol) (PVA) hydrogels prepared by exposing an aqueous solution of 15 or 20 wt% PVA to repeated cycles of freezing for 6 or 12 h at -20 degrees C and thawing for 2 hours at 25 degrees C exhibited the largest work of adhesion.
Abstract: Ultrapure poly(vinyl alcohol) (PVA) hydrogels were prepared by exposing an aqueous solution of 15 or 20 wt% PVA to repeated cycles of freezing for 6 or 12 h at -20°C and thawing for 2 hours at 25°C. The adhesive characteristics of the PVA gels in contact with a reconstituted mucus surface were quantified using a tensile technique. As the number of freezing/thawing cycles increased, the work of fracture (adhesion) decreased due to the increase in the PVA degree of crystallinity. Crystallinity was determined using differential scanning calorimetry. PVA gels prepared from the 20 wt% solution and exposed to two cycles of freezing/ thawing exhibited the largest work of adhesion. Drug delivery studies were conducted with ketanserin, a wound healing enhancer. Release studies were conducted using PVA samples prepared from a 20-wt% solution that were exposed to two or three freezing cycles for 12 h followed by thawing for 2 h. Results from the release of the drug from the PVA sample exposed to two cycles showed th...
31 Oct 1996
TL;DR: The authors present an algorithm for controlling blood glucose in the Type I diabetic patient using model predictive control (MPG) of a closed-loop insulin infusion pump, designed from a detailed 19th order model of the human glucose-insulin system.
Abstract: The authors present an algorithm for controlling blood glucose in the Type I diabetic patient using model predictive control (MPG) of a closed-loop insulin infusion pump The controller is designed from a detailed 19th order model of the human glucose-insulin system Input constraints, based on insulin pump and physiological requirements, are enforced The controller is challenged with a hyperglycemic diabetic patient (setpoint tracking), and a controlled diabetic ingesting a meal (unmeasured disturbance rejection) To improve both robustness and performance, a new controller using MPC with state estimation is synthesized Compared to the non-state estimating controller, the new controller results in a 40% improvement in overshoot, to a maximum hypoglycemic deviation of 79 mg/dl, and a 23% decrease in settling time These results demonstrate the potential use for this algorithm in a closed-loop insulin infusion pump
TL;DR: In this article, the feasibility of preparation of novel controlled release systems for the delivery of fragrances was investigated, and conditions of favorable release were established by estimating the fragrance partition coefficient.
TL;DR: In this paper, the kinetics of acrylic acid (AA) solution polymerization was investigated by polymerizing 30 wt % aqueous AA solutions at pH values ranging from 2.2 to 9.9.
Abstract: The kinetics of acrylic acid (AA) solution polymerization was investigated by polymerizing 30 wt % aqueous AA solutions at pH values ranging from 2.2 to 9.9. The polymerization rate was determined ...
TL;DR: In this article, the swelling ratio dependence on temperature was found to be significantly more prominent for block terpolymers than for the corresponding random ter polymers, even at concentrations as low as 10 mol%.
Abstract: Hydrogels prepared by block terpolymerization of N-isopropylacrylamide (NIPAAm), acrylic acid (AA) and 2-hydroxyethyl methacrylate (HEMA) exhibit significant temperature sensitivity due to the block structure of the NIPAAm moiety, even at concentrations as low as 10 mol%. pH-Sensitivity was also observed due to the ionizable AA component. The swelling ratio dependence on temperature is significantly more prominent for block terpolymers than for the corresponding random terpolymers.
TL;DR: In this article, the role of diffusion in gel/gel adhesion was examined by near-field FTIR microscopy, and compositional maps were obtained with improved spatial resolution and enhanced signal to noise ratio.
Abstract: The role of diffusion in gel/gel adhesion was examined by near-field FTIR microscopy. Using a near-field FTIR microscopy technique, compositional maps were obtained with improved spatial resolution and enhanced signal to noise ratio. With this technique, the resolution was enhanced by about a factor of 5. Polymer chain diffusion across a gel/gel interface was a substantial mechanism of adhesion. Diffusion of poly(ethylene glycol) (PEG) free chains across poly(acrylic acid) (PAA) gels was investigated. The diffusivity of PEG was on the order of 10-8 to 10-9 cm2/s for these swollen polymer gels. PEG diffusivity in PAA gels scaled to M-0.41. This was similar to values reported for PEG diffusion in aqueous solution.
TL;DR: The validity of the Lustig et al. model for penetrant transport in glassy polymers was investigated by comparing experimental results of dodecane transport in crosslinked polystyrene samples with the model.
TL;DR: These gels show great promise for a number of biomedical applications where fast biomaterial response is necessary and under changing pH conditions, network syneresis occurred more rapidly than network expansion (decomplexation) because of the rates of diffusion of specific ions causing the responses.
Abstract: Grafted poly(methacrylic acid-g-ethylene glycol) (P(MAA-g-EG)) copolymers were synthesized and their pH sensitivity investigated as a function of copolymer composition and PEG graft molecular weight. Interpolymer complexation occurred by hydrogen bonding between carboxylic groups on poly(methacrylic acid) (PMAA) and ether groups on poly(ethylene glycol) (PEG). This complexation was sensitive to the surrounding environment as complexes formed at pH levels low enough to insure substantial protonation of PMAA acid groups. At high pH, the acid groups became neutralized and did not form complexes. P(MAA-g-EG) membranes showed pH-sensitivity due to complex formation and dissociation. Uncomplexed equilibrium swelling ratios were much higher than those of the complexed states and varied according to copolymer composition and PEG graft length. Mesh sizes in the two states were determined. Swelling under oscillatory pH conditions and constant ionic strength revealed the dynamic sensitivity of P(MAA-g-EG) membranes. Under changing pH conditions, network syneresis (complexation) occurred more rapidly than network expansion (decomplexation) because of the rates of diffusion of specific ions causing the responses. No distinct water fronts were observed. Instead, water transport was continuous through the gel. These gels show great promise for a number of biomedical applications where fast biomaterial response is necessary.
TL;DR: In this article, the authors examined the swelling behavior of polyacrylates using equilibrium and dynamic swelling studies, and determined the molecular weight between crosslinks using the Flory-Rehner theory.
Abstract: Polyacrylates were prepared by solution polymerization of partially neutralized acrylic acid at 37°C. The swelling behavior of the polyacrylates was examined using equilibrium and dynamic swelling studies. Equilibrium swelling studies in deionized water were used to determine the molecular weight between crosslinks using the Flory-Rehner theory. The amount of crosslinking agent incorporated into the network was a function of the nominal crosslinking ratio. Dynamic swelling studies in saline solutions were used to investigate the initial swelling rate for the polyacrylates. Swelling studies of the polyacrylates in saline solutions under load were used to elucidate the degree of swelling under load, the compliance, and sample elasticity.
TL;DR: In this article, the swelling behavior of crosslinked hydrophilic polymers under an applied load was investigated as a function of time and absorbed weight, and the swelling capacity and creep compliance of the polyacrylates under load was found to be determined by their degree of crosslinking, which allowed to measure the relative viscous or elastic contributions of the polymer to the creep behavior.
Journal Article•
TL;DR: In this paper, a new analysis is presented of the relations between the multicomponent diffusion coefficients and the classical Kedem-Katchalsky coefficients which describe solute transport in membranes.
Abstract: A new analysis is presented of the relations between the multicomponent diffusion coefficients and the classical Kedem-Katchalsky coefficients which describe solute transport in membranes. This analysis is applied to binary and ternary systems and shows the importance of system nonideality in the calculation of solute diffusion coefficients. It is shown that the solute permeability coefficients can be calculated from independent knowledge of the nonideal thermodynamic activity coefficients and the multicomponent diffusion coefficients of the system.
01 Jan 1996
TL;DR: In this article, Nisopropyl acrylamide-containing random and block copolymers and terpolymers are presented for release of fibrinolytic enzymes and antithrombotic agents.
Abstract: Recent advances on the use of N-isopropyl acrylamide-containing random and block copolymers and terpolymers are presented. Such systems are shown to be dependent on temperature and pH (if acrylic acid is an added comonomer). Their temperature-dependence is significantly increased in the presence of block domains prepared by co- or terpolymerization. They are suited for release of fibrinolytic enzymes and antithrombotic agents. Ultrapure polyvinyl alcohol) gels are also studied for release of ketansarin and related wound healing enhancers.