Dissolution Rate Of Polymer Research Articles

Modeling the Solvolysis of Composite Materials of Wind Turbine Blades

A computational model of the depolymerization of composites during solvolysis of wind turbine blades is developed. The model is based on a phenomenological approach, describing the dissolution of an epoxy matrix as a local phase transition influenced by temperature, solvent diffusion, and local microstructures. The model is implemented in the finite element code Abaqus, using the user‐defined field and heat flux subroutines. Parametric studies are carried out to study the influence of defects and heterogeneities on the depolymerization of composite materials. The results show that variations of the solvent diffusivity in the vicinity of fiber/matrix lead to nonhomogeneity of depolymerization, and smaller diffusivity may explain matrix residues remaining on the fibers. Fiber volume density and distribution influence the polymer dissolution rate because the resistance to solvent diffusion arises between fibers. Further, voids in the polymer may lead to a local acceleration of the polymer dissolution. This work also looks into the contributions of diffusion and reaction to depolymerization, and the former dominates. The rate and homogeneity of depolymerization, therefore, depend significantly on the manufacturing quality of composites.

NMR spectroscopy study of the structure of hypromellose phthalate, a component of enteric coatings of medicinal products

Scientific relevance. Hypromellose phthalate is a component of enteric coatings used to modify active substance release from oral medicinal products in the small intestine. The release rate directly depends on the non-stoichiometric composition of the polymer, first of all, on the proportion of phthalate groups in the macromolecule. It is therefore necessary to develop reliable analytical procedures for determining the structure of hypromellose phthalate to evaluate the dissolution rate of medicinal products containing the polymer.Aim. The study aimed to develop an analytical procedure for quantifying the proportion of phthalate groups in hypromellose phthalate samples using NMR spectroscopy and to determine the relationship between the polymer dissolution rate in aqueous buffer solutions and its structural features (degree of molar substitution and molecular mass).Materials and methods. The study examined hypromellose phthalate samples isolated from enteric coatings of proton-pump inhibitors and used the reference standard for hypromellose phthalate. The non-stoichiometric composition of the polymer was determined by 13C NMR spectroscopy.Results. The authors established the conditions required to separate hypromellose phthalate from the other coating components and identified the characteristic 13C NMR signals that may be used to differentiate between the structural fragments of hypromellose phthalate. The study demonstrated the relationship between the dissolution rate and the structure of the polymer. Commercial grades of hypromellose phthalate were shown to differ in composition and, as a result, in their dissolution kinetics (in particular, the threshold pH for the onset of dissolution (5.0–5.5), as well as the dissolution rates at the same pH).Conclusions. The authors developed NMR-based procedures to determine the proportion of phthalate groups on the basis of their mass fraction in a weighted hypromellose phthalate sample and the degree of molar substitution of the polymer. The results support the applicability of these analytical procedures to the characterisation of sample composition in polymer dissolution rate studies. In principle, it is possible to derive a multiple linear regression equation that describes the dissolution rate of hypromellose phthalate as a function of the molecular mass and the molar substitution with phthalate groups. Further investigation of a larger number of polymer samples with different compositions is needed to improve the regression model and demonstrate its statistical significance. In addition to the proportion of phthalate groups, the pharmacopoeial analysis of hypromellose phthalate should also control the molecular mass of the polymer.

Drug Release from Surfactant-Containing Amorphous Solid Dispersions: Mechanism and Role of Surfactant in Release Enhancement.

To understand how surfactants affect drug release from ternary amorphous solid dispersions (ASDs), and to investigate different mechanisms of release enhancement. Ternary ASDs containing ritonavir (RTV), polyvinylpyrrolidone/vinyl acetate (PVPVA) and a surfactant (sodium dodecyl sulfate (SDS), Tween 80, Span 20 or Span 85) were prepared with rotary evaporation. Release profiles of ternary ASDs were measured with surface normalized dissolution. Phase separation morphologies of ASD compacts during hydration/dissolution were examined in real-time with a newly developed confocal fluorescence microscopy method. The water ingress rate of different formulations was measured with dynamic vapor sorption. Microscopy was employed to check for matrix crystallization during release studies. All surfactants improved drug release at 30% DL, while only SDS and Tween 80 improved drug release at higher DLs, although SDS promoted matrix crystallization. The dissolution rate of neat polymer increased when SDS and Tween 80 were present. The water ingress rate also increased in the presence of all surfactants. Surfactant-incorporation affected both the kinetic and thermodynamics factors governing phase separation of RTV-PVPVA-water system, modifying the phase morphology during ASD dissolution. Importantly, SDS increased the miscibility of RTV-PVPVA-water system, whereas other surfactants mainly affected the phase separation kinetics/drug-rich barrier persistence. Incorporation of surfactants enhanced drug release from RTV-PVPVA ASDs compared to the binary system. Increased drug-polymer-water miscibility and disruption of the drug-rich barrier at the gel-solvent interface via plasticization are highlighted as two key mechanisms underlying surfactant impacts based on direct visualization of the phase separation process upon hydration and release.

Stability and intrinsic dissolution of vacuum compression molded amorphous solid dispersions of efavirenz

In this study, the stability and intrinsic dissolution of vacuum compression molded (VCM) amorphous solid dispersions (ASDs) of efavirenz (EFV) were investigated in relation to its solubility limits in seven polymers determined by the melting point depression (MPD) method. The extrapolated solubility limits of EFV at 22 °C ranged from 3 to 68% (w/w) with PVOH being the only polymer suggesting immiscibility with EFV according to both MPD and Hansen solubility parameters (HSPs). All ASDs with EFV loadings below or close to their calculated solubility limit did not show any signs of crystallization upon conditioning for 7 months at either 22 or 37 °C and 23 or 75% relative humidity. However, all ASDs with EFV loading above the solubility limit crystallized at high humidity, while the ASDs with cellulose derived carrier polymers proved kinetically stable at low humidity over 7 months. While the EFV intrinsic dissolution rates from the VCM ASDs were partly depending on the polymer dissolution rate, no correlation was observed between EFV matrix crystallization and its miscibility in the polymer. Altogether, the observations of the study underline the importance of combining preformulation miscibility determination and dissolution studies to rationally decide on both stability and viability of ASD formulations.

High Molecular Weight AB-Polybenzimidazole and Its Solutions in a Complex Organic Solvent: Dissolution Kinetics and Rheology.

AB-polybenzimidazole (ABPBI) dissolution kinetics in an eco-friendly complex acid-free solvent based on dimethyl sulfoxide (DMSO), methanol and KOH, and the rheological behavior of their solutions are investigated. The optimal component ratio of solvent providing the complete ABPBI dissolution is determined. Methanol containing dissolved KOH contributes to the creation of a single-phase superbasic medium, which accelerates and improves the polymer solubility in a mixture with DMSO, significantly reducing the viscoelasticity of the resulting solution. The optimum methanol content is up to 60 wt.% related to DMSO. The polymer dissolution rate increases by 5 times in this composition. It found the polymer concentration of 9% is close to the dissolution limit due to the strong solution structuring, which is probably associated with an increase in the amount of water released during the KOH-methanol-DMSO interactions. As a result, the conditions for obtaining high concentrated solutions in a complex, mainly organic solvent for fiber spinning are developed. The viscoelastic properties of solutions are measured in the concentration range of 1-9% at temperatures of 20-50 °C. The flow activation energy for 7 and 9% solutions decreases by 1.5 and 2.3 times, respectively, as the content of methanol in the complex solvent increases from 10 to 60%.

Comparison of Microemulsion and Solvent Evaporation Technique for Solubility Enhancement of Amlodipine Besylate

Introduction: Amlodipine besylate is a calcium channel blocker indicated for hypertension and angina. It is described as slightly soluble in water and due to its limited solubility, it may result in poor bioavailability. The aim of this study is to enhance the solubility of amlodipine besylate using solvent evaporation method and microemulsion technique and to compare the two methods. Method: Solid dispersions (SD) of amlodipine besylate were developed by employing solvent evaporation method. PEG6000 was the polymer of choice and different drug:polymer ratios were used. Evaluation of the prepared SDs include solubility studies, dissolution studies and scanning electron microscopy (SEM). As for the microemulsion technique, microemulsions were prepared by phase titration method and the optimized microemulsion formulation was then characterized for solubility studies and dissolution studies. Results: SD3 with drug:polymer ratio of 1:4 achieved the highest solubility which was 96.97 mg/ml ± 0.92 whereas the solubility of the optimized microemulsion was found to be 112.54 mg/ml ± 0.92. In solvent evaporation method, as the drug:polymer ratio increases, the solubility and dissolution rate of SDs increases. Conclusion: The two methods had significantly enhance the solubility of amlodipine besylate however the microemulsion technique showed better solubility profile.

Patterns of drug release as a function of drug loading from amorphous solid dispersions: A comparison of five different polymers.

To reduce the pill burden associated with amorphous solid dispersions (ASDs), which arises from the large quantity of polymer used in the formulation, it is of interest to understand the relationship between drug loading and release properties. The aim of this study was to comprehensively evaluate drug release mechanisms from ASDs with polymers of varying hydrophobicity as a function of drug loading. Surface normalized dissolution rates of drug and polymer were studied for felodipine ASDs with polyvinylpyrrolidone (PVP), polyvinylpyrrolidone/vinyl acetate (PVPVA), EudragitⓇ S 100 (EUDS), hydroxypropylmethylcellulose (HPMC), and hydroxypropylmethylcellulose acetate succinate (HPMCAS), as a function of drug loading. The water sorption profiles and water contact angle measurements suggested the following rank order for hydrophobicity of the different polymers: HPMCAS ≃ EUDS > HPMC > PVPVA > PVP. For ASDs with relatively hydrophilic polymers (PVP, PVPVA and HPMC), drug release rates were polymer-controlled at low drug loadings (≤15%), whereas at higher drug loadings, release rates were more similar to that of the amorphous drug. The sudden decline in the release performance of ASDs with hydrophilic polymers when a certain drug loading was reached, was attributed to water-induced phase separation. For ASDs with more hydrophobic polymers (HPMCAS and EUDS), the dissolution rate of both drug and polymer was polymer-controlled for drug loadings as high as 50%, with a more gradual decline in drug release rate at higher drug loadings. Notably, at low drug loadings and across the different polymers, when the polymer dictated the drug release rate, ASDs prepared with the most hydrophilic polymers showed the fastest drug release. This suggested a ‘trade-off’ in choosing between higher release rates with more hydrophilic polymers at low drug loadings and higher drug loadings achievable with more hydrophobic polymers at the expense of lowered release rates. The findings described herein have significant implications for rational selection of polymers for formulation of ASDs with high drug loading and enhanced dissolution performance.

Rapid and continuous polymer dissolution by rotating packed bed for enhanced oil recovery

Polymer flooding has been widely used for enhancing the on-shore oil recovery. However, this method is greatly restricted for offshore application because of the large space occupation and low polymer dissolution rate in traditional batch stirred tank reactor (STR). A rapid and continuous polymer dissolution approach via Higee intensification is firstly proposed. Study of this approach is investigated by partially hydrolyzed polyacrylamide (HPAM) dissolution testing in rotating packed bed (RPB). The effects of different operation parameters, including rotational speed, packing thickness, liquid flow rate and temperature of the dissolution performance are experimentally studied. The basic physical property, rheological property and stability testing results show that the quality of the as-obtained polymer solution is basically equivalent or slightly superior to that obtained by traditional STR method. The core flooding test of the polymer solution obtained by Higee technique exhibits nearly one percent higher improved oil recovery than that of the STR approach. Moreover, a 3-month pilot test (30 m3/h scale) of this Higee rapid polymer dissolution approach achieved 83.93 % space occupation reduction and 32.84 % power consumpation saving compared with the existing STR process. This method exhibits well prospect in polymer flooding for EOR, especially for offshore applications.

Co-printing of vertical axis aligned micron-scaled filaments via simultaneous dual needle electrohydrodynamic printing

In this study dual-needle electrohydrodynamic co-printing (DN-EHDCP) was developed to fabricate unique micron-scaled architectures based on multi-material fibrous (filamentous) morphologies. Two stainless steel needles (contributing towards dual needle design) were used to simultaneously co-print poly(ɛ-caprolactone) (PCL) and polyvinylpyrrolidone (PVP) polymers (using solvent based formulations including Fe3O4 nanoparticles and active pharmaceutical ingredient (API). Differences in polymer hydrophobicity and dissolution rate were used to modulate drug release (tetracycline hydrochloride, TE-HCL) from various co-printed configurations. Optical, scanning electron and fluorescent microscopy confirmed precision alignment and vertical stacking of both PVP and PCL printed filaments. Process parameters were found to strongly influence co-print construct diameter. Fourier Transform Infrared (FTIR) spectroscopy confirmed spatial locations of both PVP and PCL filaments. TE-HCL release from co-printed formulations exhibited two phases; rapid and sustained. In vitro biological assay (using L929 cell lines) demonstrated construct biocompatibility. However, selective integration (spatial and quantity) of sacrificial PVP fibers (after rapid dissolution) provided a method of in situ void engineering for enhanced interfacial interaction for remaining PCL structures. The present study shows the development and use of simultaneously co-printed filaments in the vertical axis with potential to control drug release through alignment of individual filaments and material type. Furthermore, the use of composite matrix under an external stimulus is also demonstrated indicating multiple approaches to modulate API release.

Development of random and ordered composite fiber hybrid technologies for controlled release functions

Fibrous technologies (such as membranes, films, patches and filters) and their enabling engineering platforms have gained considerable interest over the last decade. In this study, novel fibrous constructs from a unique engineering platform were developed based on hybrid electrohydrodynamic (EHD) technology; incorporating functional and bioactive materials within random and aligned fibrous formulation geometries. Complex constructs were engineered using 3D printing (polycaprolactone, PCL, for sustained delivery) and electrospinning (polyvinylpyrrolidone, PVP, for rapid release) in an intercalating material layer-by-layer format using a side-by-side technological approach. Here, structure generation proceeded with deposition of ordered PCL fibers enabling well-defined void size and overall dimension, after which randomly spun PVP fibers formed a construct overcoat (as a membrane). Differences between polymer dissolution rate, hydrophilicity, mechanical properties and functional material hosting (and linked external auxiliary magnetic field trigger) provided opportunities to modulate antibiotic drug (tetracycline hydrochloride, TE-HCl) release. In vitro cell studies using human umbilical vein blood vessel cell line demonstrated device biocompatibility and Escherichia Coli (E. coli) was selected to demonstrate anti-bacterial function. Overall, a new hybrid engineering platform to prepare customizable and exciting multi-faceted drug release constructs is elucidated.

Initial Drug Dissolution from Amorphous Solid Dispersions Controlled by Polymer Dissolution and Drug-Polymer Interaction.

To identify the key formulation factors controlling the initial drug and polymer dissolution rates from an amorphous solid dispersion (ASD). Ketoconazole (KTZ) ASDs using PVP, PVP-VA, HMPC, or HPMC-AS as polymeric matrix were prepared. For each drug-polymer system, two types of formulations with the same composition were prepared: 1. Spray dried dispersion (SDD) that is homogenous at molecular level, 2. Physical blend of SDD (80% drug loading) and pure polymer (SDD-PB) that is homogenous only at powder level. Flory-Huggins interaction parameters (χ) between KTZ and the four polymers were obtained by Flory-Huggins model fitting. Solution (13)C NMR and FT-IR were conducted to investigate the specific drug-polymer interaction in the solution and solid state, respectively. Intrinsic dissolution of both the drug and the polymer from ASDs were studied using a Higuchi style intrinsic dissolution apparatus. PXRD and confocal Raman microscopy were used to confirm the absence of drug crystallinity on the tablet surface before and after dissolution study. In solid state, KTZ is completely miscible with PVP, PVP-VA, or HPMC-AS, demonstrated by the negative χ values of -0.36, -0.46, -1.68, respectively; while is poorly miscible with HPMC shown by a positive χ value of 0.23. According to solution (13)C NMR and FT-IR studies, KTZ interacts with HPMC-AS strongly through H-bonding and dipole induced interaction; with PVPs and PVP-VA moderately through dipole-induced interactions; and with HPMC weakly without detectable attractive interaction. Furthermore, the "apparent" strength of drug-polymer interaction, measured by the extent of peak shift on NMR or FT-IR spectra, increases with the increasing number of interacting drug-polymer pairs. For ASDs with the presence of considerable drug-polymer interactions, such as KTZ/PVPs, KTZ/PVP-VA, or KTZ /HPMC-AS systems, drug released at the same rate as the polymer when intimate drug-polymer mixing was ensured (i.e., the SDD systems); while drug released much slower than the polymer when molecular level mixing or drug-polymer interaction was absent (SDD-PB systems). For ASDs without drug-polymer interaction (i.e., KTZ/HPMC systems), the mixing homogeneity had little impact on the release rate of either the drug or the polymer thus SDD and SDD-PB demonstrated the same drug or polymer release rate, while the drug released slowly and independently of polymer release. The initial drug release from an ASD was controlled by 1) the polymer release rate; 2) the strength of drug-polymer interaction, including the intrinsic interaction caused by the chemistry of the drug and the polymer (measured by the χ value), as well as that the apparent interaction caused by the drug-polymer ratio (measure by the extent of peak shift on spectroscopic analysis); and 3) the level of mixing homogeneity between the drug and polymer. In summary, the selection of polymer, drug-polymer ratio, and ASD processing conditions have profound impacts on the dissolution behavior of ASDs. Graphical Abstract Relationship between initial drug and polymer dissolution rates from amorphous solid dispersions with different mixing uniformity and drug-polymer interactions.

The effect of drug and EUDRAGIT® S 100 miscibility in solid dispersions on the drug and polymer dissolution rate

Amorphous solid dispersions of phenytoin (diphenylhydantoin: DPH) and glibenclamide (GBM) with Eudragit® S 100 (S100) were prepared by a spray-drying. At low drug loading ratios, DPH dissolved simultaneously with S100. However, at high drug loading ratios the DPH dissolution rates were significantly reduced in comparison with those of S100 because of the rapid crystallization of DPH during the dissolution test. All of the DPH molecules in the low drug loading spray-dried sample (SPD) intimately interacted with the S100 matrix. In the SPDs with high drug loadings, only some of the DPH molecules interacted with the S100 matrix, while the excess DPH formed DPH-rich domains. When these domains contacted the water during the dissolution test, the amorphous DPH were more easily transformed into a crystalline form. In contrast to the solid dispersion of DPH/S100, that of GBM/S100 showed the simultaneous dissolution independent of the drug loading ratio. GBM was retained in an amorphous state during the dissolution test even at high drug loadings, although GBM-rich domains were formed. The miscibility at the molecular level as well as the stability of the amorphous state of drug are crucial factors to enhance the drug dissolution rate by the simultaneous dissolution with the polymer.

Monitoring the Dissolution Mechanisms of Amorphous Bicalutamide Solid Dispersions via Real-Time Raman Mapping.

Real-time in situ Raman mapping has been employed to monitor, during dissolution, the crystallization transitions of amorphous bicalutamide formulated as a molecular dispersion in a copovidone VA64 matrix. The dissolution performance was also investigated using the rotating disc dissolution rate methodology, which allows simultaneous determination of the dissolution rate of both active ingredient and polymer. The dissolution behavior of two bicalutamide:copovidone VA64 dispersion formulations, containing 5% (w/w) and 50% (w/w) bicalutamide, respectively, was investigated, with the aim of exploring the effect of increasing the bicalutamide loading on the dissolution performance. Spatially time-resolved Raman maps generated using multivariate curve resolution indicated the simultaneous transformation of amorphous bicalutamide present in the 50% drug-loaded extrudate into metastable polymorphic form II and low-energy polymorphic form I. Fitting a kinetic model and spatially correlating the data extracted from the Raman maps also allowed us to understand the re-crystallization mechanisms by which the low-energy form I appears. Form I was shown to crystallize mainly directly from the amorphous solid dispersion, with crystallization from the metastable form II being a minor contribution.

Pyrolysis–gas chromatography–mass spectrometry for studying N-vinyl-2-pyrrolidone- co-vinyl acetate copolymers and their dissolution behaviour

Knowledge on the solubility behaviour and dissolution rate of speciality and commodity polymers is very important for the use of such materials in high-tech applications. We have developed methods for the quantification and characterization of dissolved copolymers of N-vinyl-2-pyrrolidone (VP) and vinyl acetate (VA) during dissolution in water. The methods are based on pyrolysis (Py) performed in a programmed-temperature vaporization injector with subsequent identification and quantification of the components in the pyrolysate using capillary gas chromatography–mass spectrometry (GC–MS). By injecting large volumes and applying cryo-focussing at the top of the column, low detection limits could be achieved. The monomer ratio was found to have the greatest effect on the dissolution rate of the PVP- co-VA copolymers. The material with the highest amount of VA (50%) dissolves significantly slower than the other grades. Size-exclusion chromatography (SEC) and Py–GC–MS were used to measure molecular weights and average chemical compositions, respectively. Combined off-line SEC//Py–GC–MS was used to determine the copolymer composition (VP/VA ratio), as a function of the molecular weight for the pure polymers. In the dissolution experiments, a constant VP/VA ratio across the dissolution curve was observed for all copolymers analysed. This suggests a random distribution of the two monomers over the molecules.

A novel concept in enteric coating: A double-coating system providing rapid drug release in the proximal small intestine

A novel double-coating enteric system was developed to accelerate drug release in conditions resembling the upper small intestine. The system comprises an inner coat (partially neutralised EUDRAGIT® L 30 D-55 and organic acid) and an outer coat (standard EUDRAGIT® L 30 D-55). Prednisolone tablets were coated with double layer formulations with inner coats neutralised to pH 5.6 in the presence of 10% citric acid or adipic acid. A conventional single coating was also applied for comparison purposes. There was no drug release from the single coated or double-coated tablets in 0.1M HCl for 2 h using USP II apparatus. The lag times of drug release in subsequent pH 5.6 phosphate buffer (to resemble the pH condition of the proximal small intestine) were 102, 42 and 28 min for the single coated, adipic acid and citric acid double-coated tablets respectively. The lag time for release from the double-coated tablets was further reduced to 5 min when the inner coat was neutralised to pH 6.0 in the presence of 10% citric acid. The rapid drug release from the double-coating system was associated with faster polymer dissolution rates compared to the single coating. The novel double-coated system has the potential to provide rapid drug release in the proximal small intestine, overcoming the limitations of conventional enteric coatings.

Formation of poly(vinylidene fluoride) crystalline phases from tetrahydrofuran/N, N-dimethylformamide mixed solvent

Poly(vinylidene fluoride) (PVDF) is one of the semicrystalline polymers with at least four crystalline forms referred to as a, b, c, and d phase, among which the b phase has gained substantial importance due to its advantageous pyroand piezo-electric properties [1, 2]. It requires a better method to induce the formation of b phase crystal in order to improve the electrical properties of PVDF. b phase is not usually obtained by crystallization from the melt, but it is normally obtained by various methods including tensile deformation and uniaxial compressional deformation of a phase [3, 4], blending with small contents of poly(methyl methacrylate) (PMMA) [5, 6] or poly(o-methoxyaniline) (POMA) [7], quenching and then annealing process [8], applying a strong electric field [9] and crystallizing from solution at appropriate conditions [10–12]. In all these methods which used to prepare b phase of PVDF, the one grown from a single solvent is widely used because of its facility and controllability. However, few literatures are concentrated on the solvent-induced b phase formation in the mixed solvent. In this letter a novel method to achieve the b phase of PVDF is carried out by crystallizing from swelling agent/solvent mixture. Dissolution of a semicrystalline polymer, such as PVDF, requires disruption of strong interchain forces in order regions. So the rate of polymer dissolution is dependent on the type of liquid [13]. It has been reported that tetrahydrofuran (THF) is a good swelling agent at 60 C for PVDF; N, N-dimethylformamide (DMF) is a solvent for it at 20 C [13]. The aim of this study is to include the effects of the THF/ DMF mixture with various mass ratios of each component on the crystalline phase formation and crystallization behavior in the PVDF film by solution casting. It was characterized by Fourier transform infrared (FTIR), wide angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), and scanning electron microscope (SEM) techniques. The PVDF (Kynar K-761, Mw = 441000) utilized in this work was supplied by Elf Atochem of North America Inc. (USA). PVDF resin was dissolved in the THF/ DMF mixture with different mass ratio (m/m composition of THF/DMF = 9:1, 8:2, and 5:5) at 50 C. The solubility of the PVDF was improved by an increase of DMF content in the mixture of solvents because of the reinforced disruption of the intermolecular polymer bonds (via interaction of the C = O dipole with the CH2CF2 dipole or by limited hydrogen bonding) [14, 15]. Films (thickness: *50 lm) of PVDF were quiescently cast from each solution with 10 wt% PVDF (initial polymer concentration) at 50 C, and the glass substrate was used for solution casting. After the solvents evaporated the films were peeled off from the glass substrate at room temperature. The residue of DMF and THF was allowed to evaporate in an air oven for about 1 week at room temperature. FTIR spectra of films were obtained on a FTIR spectrometer (Bruker Vector-22). WAXD was done in a Shimadzu XRD-6000 diffractometer (Cu Ka radiation, 40 kV and 30 mA) at a scanning velocity of 4 /min. The melting behavior of the films was measured with a Perkin– Elmer DSC-7C differential scanning calorimeter using a heating rate of 10 C/min. SEM micrographs were taken on a Jeol JSM-5900 microscope. W. Ma J. Zhang (&) College of Materials Science and Engineering, Nanjing University of Technology, No.5, Xin Mo Fan Road, Nanjing 210009, P.R. China e-mail: zhangjun@njut.edu.cn

Dissolution of polymer films in supercritical carbon dioxide using a quartz crystal microbalance

The dissolution kinetics of polymeric materials in CO 2 is crucial to the understanding, design and control of CO 2-based environmentally benign lithography processes. This study utilizes the quartz crystal microbalance (QCM) to monitor and evaluate the dissolution of poly(1,1-dihydroperfluorooctyl methacrylate- r-2-tetrahydropyranyl methacrylate), poly(FOMA- r-THPMA), polymer films in supercritical CO 2 over a range of temperatures and pressures. Polymer dissolution rates at the range of pressures studied were evaluated to quantify the dissolution kinetics for the polymer. The experiments revealed that the polymer dissolution in supercritical CO 2 undergoes two apparent processes: a rapid absorption of CO 2 into the polymer film followed by a gradual dissolution of polymer film into the CO 2 at the polymer–CO 2 interface. The nature of these interfacial phenomena and their associated effect on the rate are discussed.

Sustained-release from Layered Matrix System Comprising Chitosan and Xanthan Gum

ABSTRACTSustained-release tablets of propranolol HCl were prepared by direct compression using chitosan and xanthan gum as matrix materials. The effective prolongation of drug release in acidic environment was achieved for matrix containing chitosan together with xanthan gum which prolonged the drug release more extensive than that containing single polymer. Increasing lactose into matrix could adjust the drug release characteristic by enhancing the drug released. Component containing chitosan and xanthan gum at ratio 1:1 and lactose 75% w/w was selected for preparing the layered matrix by tabletting. Increasing the amount of matrix in barrier or in middle layer resulted in prolongation of drug release. From the investigation of drug release from one planar surface, the lag time for drug release through barrier layer was apparently longer as the amount of barrier was enhanced. Least square fitting the experimental dissolution data to the mathematical expressions (power law, first order, Higuchi's and zero order) was performed to study the drug release mechanism. Layering with polymeric matrix could prolong the drug release and could shift the release pattern approach to zero order. The drug release from chitosan-xanthan gum three-layer tablet was pH dependent due to the difference in charge density in different environmental pH. FT-IR and DSC studies exhibited the charge interaction between of NH3+ of chitosan molecule and COO− of acetate or pyruvate groups of xanthan gum molecule. The SEM images revealed the formation of the loose membranous but porous film that was due to the gel layer formed by the polymer relaxation upon absorption of dissolution medium. The decreased rate of polymer dissolution resulting from the decreased rate of solvent penetration was accompanied by a decrease in drug diffusion due to ionic interaction between chitosan and xanthan gum. This was suggested that the utilization of chitosan and xanthan gum could give rise to layered matrix tablet exhibiting sustained drug release.

Evaluation of the USP dissolution test method A for enteric-coated articles by planar laser-induced fluorescence

The USP drug release standard for delayed-release articles method A was evaluated using planar laser-induced fluorescence (PLIF). Prior authors have suggested that high pH “hot spots” could develop during the buffer medium addition of the method A enteric test. Additionally, previous studies have shown heterogeneous flow patterns and low-shear regions in the USP Apparatus II dissolution vessel, which may result in poor mixing of the buffer and acid media during the pH neutralization step of the method A enteric test. In this study, PLIF was used to evaluate the mixing patterns and evolution of pH neutralization during the buffer medium addition with rhodamine-B dye and the pH-sensitive dye fluorescein, respectively. Additionally, a comparison of the methods A and B enteric tests was performed with enteric-coated tablets containing rhodamine-B in the film so as to image the dissolution rate of the coating polymer with PLIF in order to determine if rapid buffer addition for the method A procedure accelerates the rate of film coat dissolution. Rapid addition of the 250 mL of buffer medium over 5 s to the 750 mL of acidic medium shows efficient mixing and pH neutralization due to the generation of large-scale stirring and enhanced turbulence resulting from the descending buffer medium. Slow addition near the paddle shaft over 5 min showed segregation in the recirculating region around the paddle shaft. In contrast, slow addition near the vessel wall introduces the medium into fluid outside of the recirculation region and enables transport over the entire vessel. Enteric-coated tablets tested according to method A with rapid medium addition and method B enteric tests performed identically, indicating no difference in polymer dissolution rate between the two tests. From the results of the PLIF imaging studies with rhodamine-B, fluorescein, and enteric-coated tablets, it was seen that “hot spots” affecting the dissolution performance of enteric dosage forms are not generated during the neutralization step of the method A enteric test namely when the media is added rapidly or outside of the recirculating region that surrounds the paddle shaft.

A model for the drug release from a polymer matrix tablet—effects of swelling and dissolution

A model for simulating the drug release from a swelling and dissolving polymer tablet is presented and verified to data. The model is based on a mechanistic approach, and it can therefore be employed to study the sensitivity of true physical constants, for instance the drug diffusion coefficient or the drug solubility. The model generates the drug and polymer release profiles and the front positions of the total tablet, the solid core, and of the solid–drug–solubilized-drug interface. The convective contribution to mass transfer is shown to be of great importance. This is most markedly noticed for slowly diffusing drugs. In a simulation with a low value of the drug diffusion coefficient, it is shown that the initial drug release rate is faster than the polymer dissolution rate, followed by a second stage with a slower drug release rate. Furthermore, it is shown that polymer dissolution influences the drug release profile significantly, but not the front position of saturated drug in the gel layer. The model is verified against drug release and polymer dissolution data for the slightly soluble drug Methyl paraben and the soluble drug Saligenin in a poly (ethylene oxide) tablet, resulting in good agreement between model and experiments.