Mikhail M. Feldstein

Relation of glass transition temperature to the hydrogen bonding degree and energy in poly(N-vinyl pyrrolidone) blends with hydroxyl-containing plasticizers: 3. Analysis of two glass transition temperatures featured for PVP solutions in liquid poly(ethylene glycol)

Abstract The phase behaviour of poly(N-vinyl pyrrolidone)–poly(ethylene glycol) (PVP–PEG) blends has been examined in the entire composition range using Temperature Modulated Differential Scanning Calorimetry (TM-DSC) and conventional DSC techniques. Despite the unlimited solubility of PVP in oligomers of ethylene glycol, the PVP–PEG system under consideration demonstrates two distinct and mutually consistent glass transition temperatures (Tg) within a certain concentration region. The dissolution of PVP in oligomeric PEG has been shown earlier (by FTIR spectroscopy) to be due to hydrogen bonding between carbonyl groups in PVP repeat units and complementary hydroxyl end-groups of PEG chains. Forming two H-bonds through both terminal OH-groups, PEG acts as a reversible crosslinker of PVP macromolecules. To characterise the hydrogen bonded complex formation between PVP (Mw=106) and PEG (Mw=400) we employed an approach described in the first two papers of this series that is based on the modified Fox equation. We evaluated the fraction of crosslinked PVP units and PEG chains participating to the complex formation, the H-bonded network density, the equilibrium constant of complex formation, etc. Based on the established molecular details of self-organisation in PVP–PEG solutions, we propose a three-stage mechanism of PVP–PEG H-bonded complex formation/breakdown with increase of PEG content. The two observed Tgs are assigned to a coexisting PVP–PEG network (formed via multiple hydrogen bonding between a PEG and PVP) and a homogeneous PVP–PEG blend (involving a single hydrogen bond formation only). Based on the strong influence of coexisting regions on each other and the absence of signs of phase separation (evidenced by Optical Wedge Microinterferometry) we conclude that the PVP–PEG blend is fully miscible on a molecular scale.

Relation of glass transition temperature to the hydrogen-bonding degree and energy in poly(N-vinyl pyrrolidone) blends with hydroxyl-containing plasticizers. Part 1. Effects of hydroxyl group number in plasticizer molecule

Abstract The well-known Fox equation has been modified to express the glass transition temperature, Tg, as an explicit function of the number of polymer–plasticizer hydrogen bonds in miscible poly(N-vinyl pyrrolidone) (PVP) blends with ethyl alcohol, water, short-chain poly(ethylene glycol) (PEG), and glycerol. The plasticization effect has been found to be dependent on the fraction of hydroxyl groups in the blend rather than on the plasticizer weight fractions. Negative deviations of the blend Tg from the relationship predicted with the original form of the Fox equation were shown to be in direct proportion to the number of hydroxyl groups in the plasticizer molecule. The following quantities can be evaluated based on the Tg–composition profiles: binding degree, fraction of plasticizer hydroxyl groups forming hydrogen bonds to PVP repeat units, the fraction of plasticizer molecules crosslinking the polymer units by hydrogen bonding through two or more hydroxyl groups in their molecule. The dynamics of PVP–PEG hydrogen bonding over the entire compositional range has been evaluated in terms of hydrogen-bonded network density. The stoichiometric composition of the PVP–PEG hydrogen-bonded complex, determined from the Tg–composition relationship, corresponds to the data obtained with independent methods.

Coherence of thermal transitions in poly(N-vinyl pyrrolidone)-poly(ethylene glycol) compatible blends. 1. Interrelations among the temperatures of melting, maximum cold crystallization rate and glass transition

Abstract The phase behaviour of blends of high-molecular weight poly( N -vinyl pyrrolidone) (PVP) with short-chain poly(ethylene glycol) (PEG) of M w =400, prepared by drying their solutions in a common solvent (ethyl alcohol), was studied using DSC. Upon heating of cool-quenched samples a single glass transition was observed, followed by an exotherm corresponding to cold crystallization of excess PEG, a melting endotherm, and an endotherm corresponding to vaporization of absorbed water. The temperatures of glass transition ( T g ), PEG cold crystallization ( T c ), and melting ( T m ), along with the change in heat capacity (Δ C p ) between the polymers glassy and rubbery states at T g , vary with blend composition and hydration. As a result the T g / T m , T c / T m and T c / T g ratios for PVP–PEG blends are functions of composition. PVP–PEG compatibility is due to H-bonding of PEG terminal hydroxyls to the carbonyls in the PVP repeating units. Large negative deviations of T g values from the calculated weight averages, found mainly for PVP-overloaded blends, signify strong PVP–PEG interaction and free volume formation.

Modeling of percutaneous drug transport in vitro using skin-imitating Carbosil membrane.

A comparative study of the barrier function of human skin and polydimethylsiloxane-polycarbonate block copolymer Carbosil membrane was performed in vitro using 14 drugs spanning a wide range of structures and therapeutic classes. The drug permeability coefficients across the skin and the Carbosil membrane wee examined as an explicit dependence of permeant molecular weight, melting point, solubility in aqueous solution in aqueous solution and octanol-water partition coefficient. Owing to heterophase and heteropolar structure, Carbosil membranes and human skin epidermis share a common solubility-diffusion mechanism of drug transport. This synthetic membrane is shown to provide a mechanistically substantiated model for percutaneous drug absorption. Carbosil membrane can be used both foe quantitative prediction for transdermal drug delivery rate and as a skin-imitating standard membrane in the course of in vitro drug delivery kinetics evaluation.

Hydrophilic polymeric matrices for enhanced transdermal drug delivery

Abstract For many drugs with various chemical structures, delivery rates from the hydrophilic polyvinylpyrrolidone (PVP)-polyethylene oxide (PEO) based pressure sensitive adhesive (PSA) matrices of transdermal therapeutic systems (TTS) are higher compared to the hydrophobic TTS matrices. Delivery of propranolol, glyceryl trinitrate (GTN) and isosorbide dinitrate (ISDN) from the hydrophilic water soluble TTS matrix across human cadaver skin epidermis or skin-imitating polydimethylsiloxane-polycarbonate block copolymer Carbosil membrane in vitro is characterized by high rate values and zero-order drug delivery kinetics up to the point of 75–85% drug release from their initial contents in matrix. Both in vitro and in vivo drug delivery rates from the TTS hydrophilic diffusion matrix are controlled by the skin or membrane permeability and may be described by Ficks law. The contributions of various physicochemical determinants to the control of transdermal drug delivery kinetics are discussed. Pharmacokinetic and pharmacodynamic properties of hydrophilic TTS matrix with propranolol, GTN and ISDN are described.

Pressure-sensitive adhesion in the blends of poly(N-vinyl pyrrolidone) and poly(ethylene glycol) of disparate chain lengths

Adhesive behavior in blends of high molecular weight poly(N-vinyl pyrrolidone (PVP) with a short-chain, liquid poly(ethylene glycol) (PEG) has been studied using a 180° peel test as a function of PVP-PEG composition and water vapor sorption. Hydrophilic pressure-sensitive adhesives are keenly needed in various fields of contemporary industry and medicine, and the PVP-PEG blends, pressure-sensitive adhesion has been established to appear within a narrow composition range, in the vicinity of 36 wt% PEG, and it is affected by the blend hydration. Both plasticizers, PEG and water, behave as tackifiers (enhancers of adhesion) in the blends with glassy PVP. However, PEP alone is shown to account for the occurrence of adhesion, and the tackifying effect of PEG is appreciably stronger than that of sorbed water. Blend hydration enhances adhesion for the systems that exhibit an apparently adhesive type of debonding from a standard substrate (at PEG content less than 36 wt%), but the same amounts of sorbed water are also capable of depressign adhesion in the PEG-overloaded blends, where a cohesive mechanism of adhesive joint failure is typical. The PVP-PEG blend with 36% PEG couples both the adhesive and cohesive mechanisms of bond rupture (i.e., the fibrillation of adhesive polymer under debonding force and predominantly adhesive locus of failure). Blend hydration effect on adhesion has been found to be reversible. The micromechanics of adhesive joint failure for PVP-PEG hydrogels involves the fibrillation of adhesive polymer, followed by fibrils stretching and fracturing as their elongation attains 1000-1500%. Peel force to rupture the adhesive bond of PVP-PEG blends increases with increasing size of the tensile deformation zone, increasing cohesive strength of the material, and increasing tensile compliance of the material, obeying the well-known Kaelble equation, derived originally for conventional rubbery pressure-sensitive adhesives. The major deformation mode upon peeling the PVP-PEG adhesive from a standard substrate is extension, and direct correlations have been established between the composition behaviour of peel strength and that of the total work of viscoelastic strain to break the PVP-PEG films under uniaxial drawing. As a result of strong interfacial interaction with the PET backing film, the PVP-PEG adhesive has a heterogeneous two-layer structure, where different layers demonstrate dissimilar adhesive characteristics.

Modeling of the drug delivery from a hydrophilic transdermal therapeutic system across polymer membrane.

A mathematical simulation is presented which describes the in vitro drug delivery kinetics from hydrophilic adhesive water-soluble poly-N-vinylpyrrolidone (PVP)-polyethylene glycol (PEG) matrices of transdermal therapeutic systems (TTS) across skin-imitating hydrophobic Carbosil membranes. Propranolol is employed as the test drug. The contributions of the following physicochemical determinants to drug delivery rate control have been estimated: the drug diffusion coefficients both in the matrix and the membrane; the membrane-matrix drug partition coefficient: the drug concentration in the matrix and the membrane thickness. Drug transfer from the hydrophilic matrix across the membrane is shown to be controlled by the drug partitioning from the matrix into the membrane. The best correlation between simulation data and experimental results is obtained when the effect of membrane hydration is taken into consideration during in vitro drug release.

Dynamic mechanical and tensile properties of poly(N-vinyl pyrrolidone)-poly(ethylene glycol) blends

Abstract Mechanical properties of miscible blends of high molecular weight poly(N-vinyl pyrrolidone) (PVP) with a short-chain, liquid poly(ethylene glycol) (PEG) of molecular weight 400 g/mol have been examined as a function of PVP–PEG composition and degree of hydration. The small-strain behavior in the linear elastic region has been evaluated with the dynamic mechanical analysis and compared with the viscoelastic behavior of PVP–PEG blends under large strains in the course of uniaxial drawing to fracture and under cyclic extension. A strong decoupling between the small-strain and the large strain properties of the blends has been observed, indicative of a pronounced deviation from rubber elasticity in the behavior of the blends. This deviation, also seen on tensile tests under fast drawing, is attributed to the peculiar phase behavior of the blends and the molecular mechanism of PVP–PEG interaction. Nevertheless, for the PVP blend with 36% PEG, under comparatively low extension rates, the reversible contribution to the total work of deformation up to e=300% has been found to be maximum at around 70%, while the blends containing 31 and 41% PEG behave rather as an elastic–plastic solid and a viscoelastic liquid, respectively.

Peculiarities of glass transition temperature relation to the composition of poly(N-vinyl pyrrolidone) blends with short chain poly(ethylene glycol)

Abstract Analysis of compositional Tg behaviour in poly(N-vinyl pyrrolidone) (PVP)–poly(ethylene glycol) (PEG) blends, performed in the terms of the equations offered by Gordon and Taylor, Couchman and Karasz, Kovacs and Braun–Kovacs provides an insight into the PVP–PEG complexation mechanism. Blending PVP with short chain PEG has been shown to be a two-stage process. At the first stage, the enhanced PVP–PEG interaction and excess free volume formation proceeds (the stage of formation of stoichiometric PVP–PEG hydrogen bonded complex) followed by nearly ideal mixing of the formed PVP–PEG stoichiometric complex with an excess amount of liquid PEG (the stage of weak favourable interaction in which no excess volume formation occurs). The first stage may be defined as PVP plasticization, whereas the second stage consists in gradual dissolving the plasticized PVP in excess PEG. The blend containing 36% of PEG-400 may be taken as an edge between the stages. This work complements the results of Tg analysis by including into consideration the effects of polymer chains mutual orientation, free volume and interaction within the PVP–PEG blends. To accomplish this aim, the Brekner–Schneider–Cantow (BSC) approach has been employed. In the ladder-like interpolymeric complexes, formed due to the interaction of complementary groups in repeating polymer chain units, the complexation is accompanied usually by the mutual orientation of polymer backbones and the decrease of blend free volume. In contrast, in PVP–PEG systems, the location of reactive hydroxyl groups at the PEG chain ends results in the increase of free volume and in formation of a carcass-like, flexible network. These particular features of PVP–PEG interaction have been demonstrated to be embedded in a specific compositional behaviour of the blend glass transition temperature.

Coherence of thermal transitions in poly(N-vinyl pyrrolidone)–poly(ethylene glycol) compatible blends2. The temperature of maximum cold crystallization rate versus glass transition

Abstract Differential scanning calorimeteric (DSC) heating thermograms of amorphous poly( N -vinyl pyrollidone) (PVP) blends with short-chain poly(ethylene glycol) (PEG) feature exotherms of cold crystallization coupled with symmetric melting endotherms, which relate to the state of the crystalline component, PEG, while PVP–PEG hydrogen-bonded complex reveals itself as an amorphous phase. As PEG content in blends exceeds a characteristic level, PEG cold crystallization occurs upon heating of the cool-quenched samples through their glass transition temperatures ( T g ). The contributions of both thermodynamic and kinetic factors to the occurrence of non-crystallizable PEG have been analysed by considering the dependence of the PEG cold crystallization temperature, T c , on blend T g and composition along with the compositional dependence of the heat of melting of PEG. The stoichiometry of the PVP–PEG H-complex was evaluated from DSC thermograms as the amount of non-crystallizable PEG in PVP-underloaded blends.