Influence of plasticizer type and storage conditions on properties of poly(methyl vinyl ether-co-maleic anhydride) bioadhesive films

Poly(methyl vinyl ether-co-maleic anhydride) formed films from aqueous formulations with characteristics that are ideal as a basis for producing a drug-containing bioadhesive delivery system when plasticized with a monohydroxyl functionalized plasticizer. Hence, films containing a novel plasticizer, tripropylene glycol methyl ether (TPME), maintained their adhesive strength and tensile properties when packaged in aluminized foil for extended periods of time. Films plasticized with commonly used polyhydric alcohols, such as the glycerol in this study, underwent an esterification reaction that led to polymer crosslinking, as shown in NMR studies. These revealed the presence of peaks in the ester/carbonyl region, suggesting that glyceride residue formation had been initiated. Given the polyfunctional nature of glycerol, progressive esterification would result in a polyester network and an accompanying profound alteration in the physical characteristics. Indeed, films became brittle over time with a loss of both the aqueous solubility and bioadhesion to porcine skin. In addition, a swelling index was measurable after 7 days, a property not seen with those films containing TPME. This change in bioadhesive strength and pliability was independent of the packaging conditions, rendering the films that contain glycerol as unsuitable as a basis for topical bioadhesive delivery of drug substances. Consequently, films containing TPME have potential as an alternative formulation strategy.

Ionic liquid as plasticizer for europium(III)-doped luminescent poly(methyl methacrylate) films

Flexible luminescent polymer films were obtained by doping europium(III) complexes in blends of poly(methyl methacrylate) (PMMA) and the ionic liquid 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C(6)mim][Tf2N]. Different europium(III) complexes have been incorporated in the polymer/ionic liquid matrix: [C(6)mim][Eu(nta)(4)], [C(6)mim][Eu(tta)(4)], [Eu(tta)(3)(phen)] and [choline](3)[Eu(dpa)(3)], where nta is 2-naphthoyltrifluoroacetonate, tta is 2-thenoyltrifluoroacetonate, phen is 1,10-phenanthroline, dpa is 2,6-pyridinedicarboxylate ( dipicolinate) and choline is the 2-hydroxyethyltrimethyl ammonium cation. Bright red photoluminescence was observed for all the films upon irradiation with ultraviolet radiation. The luminescent films have been investigated by high-resolution steady-state luminescence spectroscopy and by time-resolved measurements. The polymer films doped with beta-diketonate complexes are characterized by a very intense D-5(0) -> F-7(2) transition ( up to 15 times more intense than the D-5(0) -> F-7(1)) transition, whereas a marked feature of the PMMA films doped with [choline](3)[Eu(dpa)(3)] is the long lifetime of the D-5(0) excited state (1.8 ms).

Effect of plasticizer viscosity on the sensitivity of an [RU(bpy)(3)(2+)(Ph4B-)(2)]-based optical oxygen sensor

The quenching of the electronically-excited, lumophoric state of [Ru(bpy)(3)(2+)(Ph4B-)(2)] by oxygen is studied in a wide variety of neat plasticizers. The Stern-Volmer constant, K-SV, is found to be inversely dependent upon the viscosity of the quenching medium, although the natural lifetime of the electronically excited state of [RU(bPY)(3)(2+)(Ph4B-)(2)] is largely independent of medium. The least viscous of the plasticizers tested, triethyl phosphate, did not, however, produce highly sensitive optical oxygen sensors when used to plasticize [RU(bPY)(3)(2+)(Ph4B-)(2)]-containing cellulose acetate butyrate (CAB) and poly(methyl methacrylate) (PMMA) films, Instead, the compatibility of the polymer-plasticizer combination, as measured by the difference in the values of the solubility parameter of the two, appears to be a major factor in determining the overall oxygen sensitivity of the thin plastic films. For highly compatible polymer-plasticizer combinations, the plasticizer with the lowest viscosity produces films of the highest oxygen sensitivity. This situation arises because in the film the quenching process is partly diffusion-controlled and, as a result, the quenching rate constant is inversely proportional to the effective viscosity of the reaction medium.

Effect of plasticizer-polymer compatibility on the response characteristics of optical thin CO2 and O-2 sensing films

A homologous family of dialkyl phthalates has been used to investigate the effect of plasticizer/polymer compatibility on the response characteristics of transparent, plastic, thin optical gas sensing films for CO2 and oxygen. Plasticizer/polymer compatibilities were determined through the value of the difference in solubility parameter, i.e. Delta delta, for the plasticizer and polymer with a Delta delta value of zero indicating high compatibility. A strong correlation was found between plasticizer/polymer compatibility and sensitivity in phenol red/ethyl cellulose CO2-sensitive films and this relationship extended to CO2-sensitive films based on other polymers such as polystyrene and poly(methyl methacrylate). It extended also to optical O-2-sensitive films implying that the relationship is general for thin-film optical sensors. Other results from the CO2-sensitive films in different polymers indicated that the film sensitivity is largely independent of the polymer matrix regardless of its inherent gas permeability, when a sufficient quantity of compatible plasticizer is present. (C) 1998 Elsevier Science B.V.

Thin plastic film colorimetric sensors for carbon dioxide: Effect of plasticizer on response

Different plasticizers, including phosphate-, phthalate-and adipate-based types were used in the creation of a range of colorimetric plastic film sensors for CO2, The different types of plasticizer used in the formulation of a colorimetric plastic film sensor for CO2 affect the response and recovery times of the sensor differently, An effective plasticizer was taken as one that decreased the response and recovery times of the final film sensor when exposed to an alternating atmosphere of 0-5% CO2. On this basis, the most efficient plasticizers appeared to be phosphate-based, followed by phthalate- and adipate-based plasticizers, This trend appears to reflect the degree of the polymer-plasticizer compatibility. Increasing the amount of plasticizer in the film formulation decreased the response and recovery times of the sensor dramatically, The sensitivity of the film sensor towards CO2 appears to decrease with increasing plasticizer effectiveness; thus, the general order of film CO2 sensitivity with respect to plasticizer type was found to be adipate > phthalate > phosphate. In general, the response of the optical films towards CO2 was found to be temperature sensitive [typically, Delta H = -(44-55) kJ mol(-1)], The phosphate-based plasticized films appear to be less temperature sensitive than the other plasticized films, and 2-ethylhexyl diphenylphosphate appears particularly effective in this respect (Delta H = -18.5 kJ mol(-1)).

The manufacture and characterisation of hot-melt extruded enteric tablets

The aim of this highly novel study was to use hot-melt extrusion technology as an alternative process to enteric coating. In so doing, oral dosage forms displaying enteric properties may be produced in a continuous, rapid process, providing significant advantages over traditional pharmaceutical coating technology. Eudragit (R) L100-55, an enteric polymer, was pre-plasticized with triethyl citrate (TEC) and citric acid and subsequently dry-mixed with 5-aminosalicylic acid, a model active pharmaceutical ingredient (API), and an optional gelling agent (PVP (R) K30 or Carbopol (R) 971P). Powder blends were hot-melt extruded as cylinders, cut into tablets and characterised using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and dissolution testing conducted in both pH 1.2 and pH 6.8 buffers. Increasing the concentration of TEC significantly lowered the glass transition temperature (T,) of Eudragit (R) L100-55 and reduced temperatures necessary for extrusion as well as the die pressure. Moreover, citric acid (17% w/w) was shown to act as a solid-state plasticizer. HME tablets showed excellent gastro-resistance, whereas milled extrudates compressed into tablets released more than 10% w/w of the API in acidic media. Drug release from HME tablets was dependent upon the concentration of TEC, the presence of citric acid, PVP K30, and Carbopol (R) 971P in the matrix, and pH of the dissolution media. The inclusion of an optional gelling agent significantly reduced the erosion of the matrix and drug release rate at pH 6.8; however, the enteric properties of the matrix were lost due to the formation of channels within the tablet. Consequently this work is both timely and highly innovative and identifies for the first time a method of producing an enteric matrix tablet using a continuous hot-melt extrusion process.

Physicochemical Characterization of Poly(ethylene glycol) Plasticized Poly(methyl vinyl ether-co-maleic acid) Films

The influence of the poly(ethylene glycol) (PEG) plasticizer content and molecular weight on the physicochemical properties of films cast from aqueous blends of poly(methyl vinyl ether-co-maleic acid) (PMVE/MA) was investigated with tensile mechanical testing, thermal analysis, and attenuated total reflectance/Fourier transform infrared spectroscopy. Unplasticized films and those containing high copolymer contents were very difficult to handle and proved difficult to test. PEG with a molecular weight of 200 Da was the most efficient plasticizer. However, films cast from aqueous blends containing 10% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000 when the copolymer/plasticizer ratio was 4 : 3 and those cast from aqueous blends containing 15% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000 when the copolymer/plasticizer ratio was 2 : 1 possessed mechanical properties most closely mimicking those of a formulation we have used clinically in photodynamic therapy. Importantly, we found previously that films cast from aqueous blends containing 10% (w/w) PMVE/MA performed rather poorly in the clinical setting, where uptake of moisture from patients' skin led to reversion of the formulation to a thick gel. Consequently, we are now investigating films cast from aqueous blends containing 15% (w/w) PMVE/MA and either PEG 1000 or PEG 10,000, where the copolymer/plasticizer ratio is 2 : 1, as possible Food and Drug Administration approved replacements for our current formulation, which must currently be used only on a named patient basis as its plasticizer, tripropylene glycol methyl ether, is not currently available in pharmaceutical grade

Application of ionic liquids as plasticizers for poly(methyl methacrylate)

The room temperature ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate, [C(4)mim][PF6] was found to be an efficient plasticizer for poly( methyl methacrylate), prepared by in situ radical polymerization in the ionic liquid medium; the polymers have physical characteristics comparable with those containing traditional plasticizers and retain greater thermal stability.

Investigation of swelling and network parameters of poly (ethylene glycol)-crosslinked poly (methyl vinyl ether-co-maleic acid) hydrogels

he influence of poly(ethylene glycol) (PEG) plasticiser content and molecular weight on the physicochemical properties of films cast from aqueous blends of poly(methyl vinyl ether-co-maleic acid) was investigated using thermal analysis, swelling studies, scanning electron microscopy (SEM) and attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy. FTIR spectroscopy revealed a shift of the CO peak from 1708 to 1731 cm-1, indicating that an esterification reaction had occurred upon heating, thus producing crosslinked films. Higher molecular weight PEGs (10,000 and 1000 Da, respectively), having greater chain length, producing hydrogel networks with lower crosslink densities and higher average molecular weight between two consecutive crosslinks. Accordingly, such materials exhibited higher swelling rates. Hydrogels crosslinked with a low molecular weight PEG (PEG 200) showed rigid networks with high crosslink densities and, therefore, lower swelling rates. Polymer:plasticizer ratio alteration did not yield any discernable patterns, regardless of the method of analysis. The polymer–water interaction parameter (?) increased with increases in the crosslink density. SEM studies showed that porosity of the crosslinked films increased with increasing PEG MW, confirming what had been observed with swelling studies and thermal analysis, that the crosslink density must be decreased as the Mw of the crosslinker is increased. Hydrogels containing PMVE/MA/PEG 10,000 could be used for rapid delivery of drug, due to their low crosslink density. Moderately crosslinked PMVE/MA/PEG 1000 hydrogels or highly crosslinked PMVE/MA/PEG 200 systems could then be used in controlling the drug delivery rates. We are currently evaluating these systems, both alone and in combination, for use in sustained release drug delivery devices.

Novel photocatalyst-based colourimetric indicator for oxygen

The preparation and characterisation of a novel, UV-activated solvent-based, colourimetric indicator for O-2 is described, comprising a redox dye (methylene blue, MB), semiconductor photocatalyst (TiO2), and a sacrificial electron donor (SED), all dispersed/dissolved in a polymer medium (sulfonated polystyrene, SPS). Upon exposure, the indicator is readily photobleached as the MB is converted into its oxygen-sensitive, leuco form, LMB. Unlike its water-based counterpart, the recovery of the original colour is very slow (ca. 5 days cf. 6 min), probably due to the largely hydrophobic nature of the polymer encapsulation medium. The kinetics of film photobleaching appear to fit very well, in terms of: irradiance, [TiO2] and [MB], to the usual Langmuir-Hinshelwood type equation associated with a photocatalytic process. The glycerol appears not only to function as a SED, but also a plasticizer and medium for dye dissolution. The kinetics of colour recovery of the photobleached film appear directly dependent upon the ambient level of O-2 but shows a more complex dependence upon the relative humidity, RH. The photobleached film does not recover any of its colour over a 24 h period if the RH

Water-based colourimetric optical indicators for the detection of carbon dioxide

Water-based colourimetric indicator films are shown to have increased operational lifetimes under ambient conditions compared to similar solvent-based counterparts. The response and sensitivity characteristics of a water-based, carbon dioxide-responsive ink are characterised and compared and contrasted to those of a similar solvent-based indicator. The changes in the response characteristics of the ink as a function of the amount of base (sodium hydrogen carbonate) and plasticizer (glycerol) contained in the ink are reported, as are the effects of varying ambient temperature and humidity. The ink is incorporated into a felt tip pen and applied to a number of different substrates, producing a distinct, reversible colour change on all tested surfaces, when a sufficient level of carbon dioxide is present. The possible application of the indicator is discussed briefly.

Controlling the response characteristics of luminescent porphyrin plastic film sensors for oxygen

Two porphyrins, platinum(II) octaethylporphyrin (Pt-OEP) and palladium(II) octaethylporphyrin (Pd-OEP), are incorporated into a wide variety of different encapsulating matricies and tested as oxygen sensors, The excited state lifetimes of the two porphyrins are quite different, 0.091 ms for Pt-OEP and 0.99 ms for Pd-OEP, and Pt-OEP-based oxygen sensors are found to be much less sensitive than Pd-OEP-based ones to quenching by oxygen, Two major response characteristics of an oxygen sensor are (i) its sensitivity toward oxygen and (ii) its response and recovery times when exposed to an alternating atmosphere of nitrogen and air. The response characteristics of a rang of Pt-OEP, and Pd-OEP-based oxygen sensors were determined using cellulose acetate butyrate (CAB), poly(methyl methacrylate) (PMMA), and PMMA/CAB polymer blends as the encapsulating media. Pt-OEP and Pd-OEP oxygen sensors have better response characteristics (i.e., more sensitive and lower response and recovery times) when CAB is used as the encapsulating medium rather than PMMA. For both Pt-OEP- and Pd-OEP-based oxygen sensors, in either polymer, increasing the level of tributyl phosphate plasticizer improves the response characteristics of the final oxygen-sensitive film. Pt-OEP in different unplasticized PMMA/CAB blended films produced a range of oxygen sensors in which the response characteristics improved with increasing level of CAB present.

Fluorescence-based thin plastic film ion-pair sensors for oxygen

A general method of preparation of thin-film sensors for O-2, incorporating the dye ion-pair tris(4,7-diphenyl-1,10-phenanthroline) rutheninm(II) ditetraphenylborate, in a variety of different thin film polymer/plasticizer matrices is described, The sensitivity of the sensor depends upon the nature of the polymer matrix and plasticizer, A detailed study of one of these systems utilising the polymer poly(methyl methacrylate), PMMA, is reported. The sensitivity of this O-2 sensor depends markedly upon the plasticizer concentration and is largely independent of temperature (24,5-52.5 degrees C) and age (up to 30 d), When exposed to an alternating atmosphere of O-2 and N-2, a typical oxygen film sensor in PMMA exhibits a 0-90% response and recovery time of 0.4 and 4.5 s, respectively.

Preparation and Evaluation of Sustained-Release Matrix Tablets Based on Metoprolol and an Acrylic Carrier Using Injection Moulding

Sustained-release matrix tablets based on Eudragit RL and RS were manufactured by injection moulding. The influence of process temperature; matrix composition; drug load, plasticizer level; and salt form of metoprolol: tartrate (MPT), fumarate (MPF) and succinate (MPS) on ease of processing and drug release were evaluated. Formulations composed of 70/30% Eudragit RL/MPT showed the fastest drug release, substituting part of Eudragit RL by RS resulted in slower drug release, all following first-order release kinetics. Drug load only affected drug release of matrices composed of Eudragit RS: a higher MPT concentration yielded faster release rates. Adding triethyl citrate enhanced the processability, but was detrimental to long-term stability. The process temperature and plasticizer level had no effect on drug release, whereas metoprolol salt form significantly influenced release properties. The moulded tablets had a low porosity and a smooth surface morphology. A plasticizing effect of MPT, MPS and MPF on Eudragit RS and Eudragit RL was observed via DSC and DMA. Solubility parameter assessment, thermal analysis and X-ray diffraction demonstrated the formation of a solid solution immediately after production, in which H-bonds were formed between metoprolol and Eudragit as evidenced by near-infrared spectroscopy. However, high drug loadings of MPS and MPF showed a tendency to recrystallise during storage. The in vivo performance of injection-moulded tablets was strongly dependent upon drug loading. © 2012 American Association of Pharmaceutical Scientists.

Investigation of swelling and network parameters of poly(ethylene glycol)-crosslinked poly(methyl vinyl ether-co-maleic acid) hydrogels

The influence of poly(ethylene glycol) (PEG) plasticiser content and molecular weight on the physicochemical properties of films cast from aqueous blends of poly(methyl vinyl ether-co-maleic acid) was investigated using thermal analysis, swelling studies, scanning electron microscopy (SEM) and attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy. FTIR spectroscopy revealed a shift of the C{double bond, long}O peak from 1708 to 1731 cm, indicating that an esterification reaction had occurred upon heating, thus producing crosslinked films. Higher molecular weight PEGs (10,000 and 1000 Da, respectively), having greater chain length, producing hydrogel networks with lower crosslink densities and higher average molecular weight between two consecutive crosslinks. Accordingly, such materials exhibited higher swelling rates. Hydrogels crosslinked with a low molecular weight PEG (PEG 200) showed rigid networks with high crosslink densities and, therefore, lower swelling rates. Polymer:plasticizer ratio alteration did not yield any discernable patterns, regardless of the method of analysis. The polymer-water interaction parameter (?) increased with increases in the crosslink density. SEM studies showed that porosity of the crosslinked films increased with increasing PEG MW, confirming what had been observed with swelling studies and thermal analysis, that the crosslink density must be decreased as the M of the crosslinker is increased. Hydrogels containing PMVE/MA/PEG 10,000 could be used for rapid delivery of drug, due to their low crosslink density. Moderately crosslinked PMVE/MA/PEG 1000 hydrogels or highly crosslinked PMVE/MA/PEG 200 systems could then be used in controlling the drug delivery rates. We are currently evaluating these systems, both alone and in combination, for use in sustained release drug delivery devices. © 2008 Elsevier Ltd. All rights reserved.