Plasticizing effect of ibuprofen induced an alteration of drug released from Kollidon SR matrices produced by direct compression

The objectives of this study were to investigate the effect of storage temperature on drug release from matrices containing 10, 40 and 70% w/w ibuprofen in Kollidon® SR (KSR). The matrix tablets were produced by direct compression and then kept at 30 and 45?°C for 3 months. Drug release from the matrix tablets was examined after storage for 0, 1, 4 and 12 weeks. Scanning electron microscope was used to reveal physical appearance of the tablet surface at the respective time intervals. In addition, differential scanning calorimeter was used to investigate glass transition temperature (T_g) of ibuprofen in KSR at 0–100% w/w based on the principle of Gordon–Taylor equation. At 45?°C, the dissolution of ibuprofen in KSR as well as the coalescence of polymer particles were observed to be higher than those of storage at 30?°C. The physical state of ibuprofen dispersed in the polymeric matrix and degree of polymer coalescence led to the variation of drug release. The coalescence of polymer particles was a result of the polymer transition from glassy to rubbery state according to water absorption of KSR and plasticizing effect of ibuprofen. The reduction of the T_g of ibuprofen blended with KSR could be better described by the Kwei equation, a modified version of Gordon–Taylor equation.     

Design of antihistaminic transdermal films based on alginate–chitosan polyelectrolyte complexes: characterization and permeation studies

The purpose of this study was to develop suitable matrix-type transdermal drug delivery systems of Ketotifen fumarate (KF) as antiasthmatic drugs. Chitosan–alginate polyelectrolyte complex (PEC) films were used as drug release regulators for KF. Antihistaminic films with variable PEC compositions were prepared using different ratios of chitosan (CTS) to sodium alginate (ALG). Propylene glycol (PG) was used as plasticizer; Tween 80 (T₈₀) and Span 20 (S₂₀) were used as permeability enhancers. Nine formulations were obtained by film casting method and characterized in terms of weight uniformity, thickness, folding endurance, moisture lost, and moisture absorption. In addition, drug release and permeation through rat abdominal skin mounted in Franz cell were investigated. All formulations were found to be suitable in terms of physicochemical characteristics, and there was no significant interaction between the used drug and polymers. It was noticed that when T₂₀ is used as permeation enhancer, a satisfactory drug release pattern was found where 99.88% of drug was released and an amount of 2.121?mg/cm² of KF was permeated after 24?h. For the optimal formulation, a permeability coefficient of 14.00?±?0.001?cm h^?1 and a latency time of 0.35?±?0.02?h were found. The in-vitro analysis showed controlled release profile which was fitted by Korsmeyer–Peppas model (R²?=?0.998). The obtained results suggested that new controlled release transdermal formulations of asthmatic drugs could be suitably designed as an alternative to the common forms.     

Damar Batu as a novel matrix former for the transdermal drug delivery: in vitro evaluation

Purpose: Damar Batu (DB) is a novel film-forming biomaterial obtained from Shorea species, evaluated in this study for its potential application in transdermal drug delivery system. Methods: DB was characterized initially in terms of acid value, softening point, molecular weight (M_w), polydispersity index (M_w/M_n), and glass transition temperature (T_g). Neat, plasticized films of DB were investigated for mechanical properties. The biomaterial was further investigated as a matrix-forming agent for transdermal drug delivery system. Developed matrix-type transdermal patches were evaluated for thickness and weight uniformity, folding endurance, drug content, in vitro drug release study, and skin permeation study. Results: On the basis of in vitro drug release and in vitro skin permeation performance, formulation containing DB/Eudragit RL100 (60 : 40) was found to be better than other formulations and was selected as the optimized formulation. IR analysis of physical mixture of drug and polymer and thin layer chromatography study exhibited compatibility between drug and polymer. Conclusion: From the outcome of this study, it can be concluded that applying suitable adhesive layer and backing membrane-developed DB/ERL100, transdermal patches can be of potential therapeutic use.     

Mucoadhesive plasticized system of branched poly(lactic-co-glycolic acid) with aciclovir

Commercially available antibacterial semisolid preparations intended for topical application provide only short-term drug release. A sustained kinetics is possible by exploitation of a biodegradable polymer carrier. The purpose of this work is to formulate a mucoadhesive system with aciclovir (ACV) based on a solid molecular dispersion of this drug in poly(lactic-co-glycolic acid) branched on tripenterythritol (PLGA/T). The ACV incorporation into PLGA/T was carried out either by solvent method, or melting method, or plasticization method using various plasticizers. The drug–polymer miscibility, plasticizer efficiency and content of residual solvent were found out employing DSC. Viscosity was measured at the shear rate range from 0.10 to 10.00?s^?1 at three temperatures and data were analyzed by Newtonian model. The mucoadhesive properties were ascertained in the tensile test on a mucin substrate. The amount of ACV released was carried out in a wash-off dissolution test. The DSC results indicate a transformation of crystalline form of ACV into an amorphous dissolved in branched polyester carrier, and absence of methyl formate residuals in formulation. All the tested plasticizers are efficient at T_g depression and viscosity decrease. The non-conventional ethyl pyruvate possessing supportive anti-inflammatory activity was evaluated as the most suitable plasticizer. The ACV release was strongly dependent on the ethyl pyruvate concentration and lasted from 1 to 10 days. The formulated PLGA/T system with ACV exhibits increased adhesion to mucosal hydrophilic surfaces and prolonged ACV release controllable by degradation process and viscosity parameters.     

Stabilization of fenofibrate in low molecular weight hydroxypropylcellulose matrices produced by hot-melt extrusion

Abstract

The objective of this study was to improve the dissolution rate and to enhance the stability of a poorly water-soluble and low glass-trasition temperature (T_g) model drug, fenofibrate, in low molecular weight grades of hydroxypropylcellulose matrices produced by hot-melt extrusion (HME). Percent drug loading had a significant effect on the extrudability of the formulations. Dissolution rate of fenofibrate from melt extruded pellets was faster than that of the pure drug (p < 0.05). Incorporation of sugars within the formulation further increased the fenofibrate release rates. Differential scanning calorimetry results revealed that the crystalline drug was converted into an amorphous form during the HME process. Fenofibrate is prone to recrystallization due to its low T_g. Various polymers were evaluated as stabilizing agents among which polyvinylpyrrolidone 17PF and amino methacrylate copolymer exhibited a significant inhibitory effect on fenofibrate recrystallization in the hot-melt extrudates. Subsequently immediate-release fenofibrate tablets were successfully developed and complete drug release was achieved within 5 min. The dissolution profile was comparable to that of a currently marketed formulation. The hot-melt extruded fenofibrate tablets were stable, and exhibited an unchanged drug release profile after 3-month storage at 40°C/75% RH.     

Application of Differential Scanning Calorimetry to Evaluate Thermal Properties and Study of Microstructure of Biodegradable Films

The glass transition temperature (T _g) and melting temperature (T _m) of gelatin–starch films were determined using differential scanning calorimetry. Also, the microstructure was observed using scanning electron microscopy (SEM) and the crystalline structure by means of X-ray diffraction (XRD). The effect of starch and glycerol concentrations in films on the thermal properties was evaluated through response surface methodology (RSM). The highest values of T _m were obtained at starch concentration intervals of (0.26 to 0.54) %w/w and glycerol concentrations lower than 0.5 (%w/w). On the other hand, the T _g values diminished as the glycerol concentration increased. Mathematical models for both transitions were fitted to the experimental data. The micrographs obtained by SEM show the influence of glycerol in the microstructure of the films, being more “gummy” as the content of the plasticizer increased. The XRD patterns of the films demonstrate the existence of some pseudo-crystalline regions in the biodegradable materials.     

Controlled release of drugs from cellulose acetate matrices produced from sugarcane bagasse: monitoring by square-wave voltammetry

In this paper, cellulose triacetate (CTA) was produced from sugarcane bagasse and used as matrices for controlled release of paracetamol. Symmetric and asymmetric membranes were obtained by formulations of CTA/dichloromethane/drug and CTA/dichloromethane/water/drug, respectively, and they were characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). Different morphologies of membranes were observed by SEM, and the incorporation of paracetamol was confirmed by lowering of the glass transition temperature (T_g) in the DSC curves. This indicates the existence of interactions between the matrix and the drug. The evaluation of drug release was based on the electrochemical monitoring of paracetamol through its oxidation at a glassy carbon electrode surface using square-wave voltammetry (SWV), which provides fast, precise and accurate in situ measurements. The studies showed a content release of 27% and 45% by the symmetric and asymmetric membranes, respectively, during 8?h.     

Design and evaluation of matrix diffusion controlled transdermal patches of verapamil hydrochloride

Transdermal patches of verapamil hydrochloride were prepared using four different polymers (individual and combination): Eudragit RL100 (ERL100), Eudragit RS100 (ERS100), hydroxypropyl methylcellulose 15 cps (HPMC), and ethyl cellulose (EC), of varying degrees of hydrophilicity and hydrophobicity. The effect of the polymers on the technological properties, i.e., drug release, water vapor transmission rate (WVTR), and percentage moisture loss (ML), percentage moisture absorption (MA), folding endurance, and thickness, was investigated. Different formulations were prepared in accordance with the 2³ factorial design, with ERL100 being the parent polymer. The patch containing ERL100 alone showed maximum WVTR, % MA, and % ML, which could be attributed to its hydrophilic nature. As expected, substitution with ERS100, HPMC, and EC decreased all the above values in accordance with their decreasing degree of hydrophilicity. In vitro release studies showed zero-order release of the drug from all the patches, and the mechanism of release was diffusion mediated. Moreover, the release of the drug was sustained and it extended over a period of 24 hr in all formulations. A12 emerged as the most satisfactory formulation insofar as its technological properties were concerned. Further, release and permeation of the drug from the most satisfactory formulation (A12) was evaluated through different biological barriers (shed snake skin, rabbit skin, and rat skin) to get an idea of the drug permeation through human skin. Shed snake's skin was found to be most permeable (82.56% drug release at 24 hr) and rat skin was least permeable (52.38%). Percutaneous absorption studies were carried out in rabbits. The pharmacokinetic parameters calculated from blood levels of the drug revealed a profile typical of a sustained release formulation, with the ability to maintain adequate plasma levels for 24 hr. [AUC: 3.09 mg/mL hr, C_max: 203.95 µg/mL, T_max: 8 hr]. It can therefore be concluded that the patch containing ERL100 and HPMC in the ratio 8:2 has achieved the objectives of transdermal drug delivery system, such as avoidance of first pass effect, extended release, and reduced frequency of administration.     

Influence of Plasticizers and Drugs on the Physical-Mechanical Properties of Hydroxypropylcellulose Films Prepared by Hot Melt Extrusion

Hydroxypropylcellulose (HPC) films containing drugs or hydrophilic or hydrophobic plasticizers were prepared by a hot melt extrusion process. Polyethylene glycol 8000 (PEG 8000) 2%, triethyl citrate (TEC) 2%, acetyltributyl citrate (ATBC) 2%, and polyethylene glycol 400 (PEG 400) 1% were the plasticizing agents studied. In addition, either hydrocortisone (HC) 1% or chlorpheniramine maleate (CPM) 1% was incorporated into the films as a model drug. The physical-mechanical properties of the films that were investigated included tensile strength (TS), percentage elongation (%E), and Young's modulus (YM). Differential scanning calorimetry (DSC) was utilized to determine glass transition temperatures (T_g' s). These parameters were studied as a function of time and temperature. The glass transition temperatures initially decreased with the inclusion of the drugs and plasticizers. However, after 6 months aging, films containing PEG 400 and HC showed a marked increase in T_g. The films containing PEG 400 showed physical-mechanical instability in all parameters studied. All extruded films exhibited a marked decrease in TS in contrast to a large increase in %E when testing was performed perpendicular to flow versus in the direction of flow. In addition, a consistent film of HPC in the absence of drugs or plasticizers could not be extruded due to the excessive stress on the equipment. Although the theoretical percentage of CPM on aging remained fairly constant over the processing temperature ranges in this study, the HC levels remaining in the extruded films during storage were a function of time and temperature.     

Mechanical properties and drug release of venlafaxine HCl solid mini matrices prepared by hot-melt extrusion and hot or ambient compression

Objective/significance: To elucidate the role of plasticizers in different mini matrices and correlate mechanical properties with drug release.

Methods: Cylindrical pellets were prepared by hot-melt extrusion (HME) and mini tablets by hot (HC) and ambient compression (AC). Venlafaxine HCl was the model drug, Eudragit^® RSPO the matrix former and citric acid or Lutrol^® F127 the plasticizers. The matrices were characterized for morphology, crystallinity, and mechanical properties. The influence of plasticizer’s type and content on the extrusion pressure (P_e) during HME and ejection during tableting was examined and the mechanical properties were correlated with drug release parameters.

Results: Resistance to extrusion and tablet ejection force were reduced by Lutrol^® F127 which also produced softer and weaker pellets with faster release, but harder and stronger HC tablets with slower release. HME pellets showed greater tensile strength (T) and 100 times slower release than tablets. P_e correlated with T and resistance to deformation of the corresponding pellets (r²?=?0.963 and 0.945). For both HME and HC matrices the decrease of drug release with T followed a single straight line (r²?=?0.990) and for HME the diffusion coefficient (D_e) and retreat rate constant (k_b) decreased linearly with T (r²?=?0.934 and 0.972).

Conclusions: Lutrol^® F127 and citric acid are efficient plasticizers and Lutrol^® F127 is a thermal binder/lubricant in HC compression. The different bonding mechanisms of the matrices were reflected in the mechanical strength and drug release. Relationships established between T and drug release parameters for HME and HC matrices may be useful during formulation work.     

The Potential of Small-Scale Fusion Experiments and the Gordon-Taylor Equation to Predict the Suitability of Drug/Polymer Blends for Melt Extrusion

The aim of this study was to investigate the use of small-scale fusion experiments and the Gordon-Taylor (GT) equation to predict whether melt extrusion of a drug with an amorphous polymer produces a stable amorphous dispersion with increased drug dissolution. Indomethacin, lacidipine, nifedipine, piroxicam, and tolbutamide were used as poorly soluble drugs. Drug/polyvinylpyrrolidone (PVP) blends were prepared at a 1:1 mass ratio. Small-scale fusion experiments were performed in a differential scanning calorimeter (DSC) and in stainless steel beakers. Extrusion was performed in a Brabender Plasti-corder. The glass transition temperatures T_g were determined by DSC. Taking an average T_g from the DSC melt, beaker melt, and GT equation accurately predicted the extrudate T_g. Physical stability of beaker melt and extrudate samples was tested by X-ray powder diffraction (XRPD) and DSC after storage at 30°C (beaker melt) or 25°C (extrudate) and less than 10%, 60%, and 75% relative humidity (RH). Beaker melts were amorphous, apart from some residual crystallinity. Extrudates were amorphous after preparation. Except for indomethacin/PVP, which remained amorphous, the crystallinity of beaker melts and extrudates increased only at 75% RH. Recrystallization occurred even when the T_g of the sample was well above the storage temperature. Chemical stability of the beaker melts and extrudates was tested by capillary electrophoresis and high-performance liquid chromatography (HPLC). Stability was slightly improved in the extrudate compared to the beaker melt. In general, the order for rate of dissolution was crystalline drug was less than the physical mixture, which was less than the drug/PVP beaker melt, which was approximately equal to the extrudate. The use of beaker melts allows a conservative estimate of the potential to melt extrude a drug. To predict physical stability, analysis of the T_g must be combined with physical stability experiments.     

Development of a HPMC-based controlled release formulation with hot melt extrusion (HME)

The objective of this study was to develop hydroxypropyl methylcellulose (HPMC) based controlled release (CR) formulations via hot melt extrusion (HME) with a highly soluble crystalline active pharmaceutical ingredient (API) embedded In the polymer phase. HPMC is considered a challenging CR polymer for extrusion due to its high glass transition temperature (T_g), low degradation temperature, and high viscosity. These problems were partially overcome by plasticizing the HPMC with up to 40% propylene glycol (PG). Theophylline was selected as the model API. By using differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), dynamic mechanical analysis (DMA), and X-ray powder diffraction (XRPD), the physical properties of the formulations were systematically characterized. Five grades of HPMC (Methocel^®) – E6, K100LV, K4M, K15M, and K100M – were tested. The extrusion trials were conducted on a 16?mm twIn screw extruder with HPMC/PG placebo and formulations containing theophylline/HPMC/PG (30:42:28, w/w/w). The dissolution results showed sustained release profiles without burst release for the HPMC K4M, K15M, and K100M formulations. The extrudates have good dissolution stability after being stressed for 2 weeks under 40°C/75% RH open dish conditions and the crystalline API form did not change upon storage. Overall, the processing windows were established for the HPMC based HME-CR formulations.     

The Influence of Different Plasticizers and Polymers on the Mechanical and Thermal Properties,Porosity and Drug Permeability of Free Shellac Films

ABSTRACT

The effect of triethyl citrate (TEC) and different molecular weights and concentrations of polyethylene glycol (PEG), in addition to the effect of different water-soluble polymers and dispersions at different levels, hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), carbomer 940, polyvinyl alcohol (PVA), ethyl cellulose (EC), on the mechanical and thermal properties, drug permeability, and porosity of free shellac films were investigated. Shellac films were cast from aqueous solutions, and their mechanical properties were studied by tensile test. Thermal analyses were performed using differential scanning calorimetry (DSC).

The results showed that the addition of plasticizer caused a decrease in both elastic modulus and glass transition temperature (T_g) and an increase in elongation at break of free shellac films. This effect was related to the concentrations of plasticizers. Different molecular weights of PEGs have different plasticization mechanisms.

Moreover, the incorporation of different amounts of HPMC, MC, or carbomer in free shellac films caused an increase in the flexibility, decrease in T_g, and a marked increase in drug permeability of free shellac films, whereas the addition of PVA caused a decrease in flexibility and drug permeability and an increase in T_g. Addition of EC resulted in a slight decrease of the elasticity and a small decrease in drug permeability. However it does not show a considerable effect on the T_g. In addition, it was found that the drug permeability is directly related to the mechanical properties and T_g of shellac films.     

Prediction of in vivo plasma concentration–time profile from in vitro release data of designed formulations of milnacipran using numerical convolution method

The aim of this study was to predict the in vivo plasma drug level of milnacipran (MIL) from in vitro dissolution data of immediate release (IR 50?mg and IR 100?mg) and matrix based controlled release (CR 100?mg) formulations. Plasma drug concentrations of these formulations were predicted by numerical convolution method. The convolution method uses in vitro dissolution data to derive plasma drug levels using reported pharmacokinetic (PK) parameters of a test product. The bioavailability parameters (C_max and AUC) predicted from convolution method were found to be 106.90?ng/mL, 1138.96?ng/mL?h for IR 50?mg and 209.80?ng/mL, 2280.61?ng/mL?h for IR 100?mg which are similar to those reported in the literature. The calculated PK parameters were validated with percentage predication error (% PE). The % PE values for C_max and AUC were found to be 7.04 and ?7.35 for IR 50?mg and 11.10 and ?8.21 for IR 100?mg formulations. The C_max, T_max, and AUC for CR 100?mg were found to be 120?ng/mL, 10?h and 2112.60?ng/mL?h, respectively. Predicted plasma profile of designed CR formulation compared with IR formulations which indicated that CR formulation can prolong the plasma concentration of MIL for 24?h. Thus, this convolution method is very useful for designing and selection of formulation before animal and human studies.     

Mechanical and thermal properties of poly(butylene terephthalate)/poly(ethylene naphthalate), and Nylon66/poly(ethylene naphthalate) blends

The tensile modulus, tensile strength and impact strength of melt blends of (a) poly(ethylene naphthalate) (PEN) and poly(butylene terephalate) (PBT) with 30, 40, 50, 60 and 70 wt% PEN, (b) Nylon66 and PEN with 30, 50 and 70 wt% Nylon66 were measured, and thermal/thermomechanical properties were analysed by differential scanning calorimetry and dynamic mechanical thermal analysis. Scanning electron microscopy was used for examination of the fracture surfaces of the blends.All PBT/PEN blends show two glass transitions corresponding to the presence of two phases: the glass transition temperature, T _g, of the phase with the lower T _g increases with increasing PEN content, and T _g for the phase with higher T _g decreases with increasing PBT content. The implication is that the two polymers are partially miscible, and scanning electron microscopy of fracture surfaces reveals a very small (sub-micron) domain size. Nylon66/PEN blends also show two phases, but the domain size is of the order of m and there is no evidence of partial miscibility.Up to 50 weight proportions PBT does not lower the tensile strength of PBT/PEN blends, and the tensile strength lies between values predicted by the rule of mixtures and a modified rule of mixtures. Incorporation of at least 40% PEN in PBT increases impact strength, but blending with smaller proportions of PEN decreases impact strength. By contrast, blending of Ny66 and PEN results in reduction of tensile strength for all blend compositions.     

Mechanical properties of thermosets

The tensile properties of a DGEBA (diglycidylether of bisphenol A)-norbornene anhydride network (T _g130±5 °C), were studied in the range (220 K-T _g); 4×10^–4 to 14×10^–3S^–1. The viscoelastic spectrum (1 Hz) reveals a low transition at 220 K. The bulk modulus is practically constant between 200 K andT _g — 20 K. The Poisson's ratio increases very slowly untilT _g — 30 K. Then it increases rapidly to reach its asymptotic value (0.5) near toT _g. The tensile (E) and shear (G) moduli display the classical behaviour linked to viscoelasticity. Plastic yielding occurs atT 80 °C, the elongation at yield is almost temperature and strain rate independent (G3_y = 0.035), whereas the yield stress obeys Kambour's relationship: _y = 1.1 (T _g —T) and Eyring's law (activation volume = 914cm³mol^–1). Physical ageing at 120 °C strongly affects the yield stress and the ductility. The maximum draw ratio, obtained atT T _g, is _RC = 1.35, which seems to be consistent with the network's crosslink density.     

Preparation of Codeine-Resinate and Chlorpheniramine-Resinate Sustained-Release Suspension and its Pharmacokinetic Evaluation in Beagle Dogs

ABSTRACT

Using ion exchange resins (IERs) as carriers, a dual-drug sustained release suspension containing codeine, and chlorpheniramine had been prepared to elevate drug safety, effectiveness and conformance. The codeine resinate and chlorpheniramine resinate beads were prepared by a batch process and then impregnated with Polyethylene glycol 4000 (PEG 4000), respectively. The PEG impregnated drug resinate beads were coated with ethylcellulose as the coating polymer and di-n-butyl-phthalate as plasticizer in ethanol and methylene chloride mixture by the Wurster process. The coated PEG impregnated drug resinate beads were dispersed in an aqueous suspending vehicle containing 0.5% w/w xanthan gum and 0.5% w/w of hydroxypropylmethylcellulose of nominal viscosity of 4000 cps, obtaining codeine resinate and chlorpheniramine resinate sustained-release suspension (CCSS).

Codeine phosphate and chlorpheniramine maleate were respectively loaded onto AMBERLITE® IRP 69, and PEG 4000 was used to impregnate drug resinate beads to maintain their geometry. Ethylcellulose with di-n-butyl-phthalate in ethanol and methylene chloride mixture for the coating of drug resinate beads was performed in Glatt fluidized bed coater, where the coating solution flow rate was 8–12 g/min, the inlet air temperature was 50–60°C, the outlet air temperature was 32–38°C, the atomizing air pressure was 2.0 bar and the fluidized air pressure was adjusted as required. Few significant agglomeratation of circulating drug resinate beads was observed during the operation. The film weight gained 20% w/w and 15% w/w were suitable for the PEG impregnated codeine resinate and chlorpheniramine resinate beads, respectively. Residual solvent content increased with coating level, but inprocess drying could reduce residual solvent content.

In the present study, the rates of drug release from both drug resinate beads were measured in 0.05M and 0.5M KCl solutions. The increased ionic strength generally accelerated the release rate of both drugs. But the release of codeine from its resinate beads was much more rapid than chloropheneramine released from its resinate beads in the same ionic strength release medium. The drug release specification of the CCSS, where release mediums were 0.05M KCl solution for codeine and 0.5M KCl solution for chlorpheniramine, was established to be in conformance with in vivo performance.

Relative bioavailability and pharmacokinetics evaluation of the CCSS, using commercial immediate-release tablets as the reference preparation, were performed following a randomized two-way crossover design in beagle dogs. The drug concentrations in plasma were measured by a validated LC-MS/MS method to determine the pharmacokinetic parameters of CCSS. This LC-MS/MS method demonstrated high accuracy and precision for bioanalysis, and was proved quick and reliable for the pharmacokinetic studies. The results showed that the CCSS had the longer value of T_max and the lower value of C_max, which meant an obviously sustained release effect, and its relative bioavailability of codeine and chlorpheniramine were (103.6 ± 14.6)% and (98.1 ± 10.3)%, respectively, compared with the reference preparation. These findings indicated that a novel liquid sustained release suspension made by using IERs as carriers and subsequent fluidized bed coating might provide a constant plasma level of the active pharmaceutical ingredient being highly beneficial for various therapeutic reasons.     

Devitrification and vitrification of tellurite glasses

The crystallization of pure tellurite glass during various heating rates was studied. The activation energy for crystallization was 115 × 10²² eV mol^–1. The glass transformation, T _g, starting crystallization, T _x, crystallization, T _c and melting temperatures, T _m, have been reported for binary tellurite glasses of the form (1 – x) TeO₂–xA_nO_m [A_nO_m = MnO₂, Co₃O₄ and MoO₃]. Among many different parameters of the glass forming potential the two-thirds rule, T _g/T _m, the glass stabilization range, T= T _x – T _g, and the glass forming tendency, K _g= (T _c– T _g)/(T _m – T _c), are reported for the first time for tellurite glasses.     

Transport Properties of a Tl-2201 Film Close to the Critical Temperature: The Vortex Glass Transition

We have studied the I-V characteristics of a Tl-2201 film at zero field. In the regime in which flux creep is the dominant dissipation mechanism, the J _c -T curve is divided into two parts at a temperature T _g (about 82 K), close to the critical temperature (84 K). The I-V characteristics around T _g are well described using a flux creep model. For T>T _g , J _c /J _c (0) =0.445x(l-0.525t-0.5t ² ); for T _g , J _c /J _c (0) = 0.9x(1-0.595t-0.44t ² ). Differential resistance (dV/dI) as a function of the measuring current shows a change in curvature close to T _g . The I-V curves collapsed nicely into two branches by plotting (V/I)/|T–T _g | ^v(z-1) vs. (I/T)/|T _g –T| ^2v , indicating a current–reduced vortex glass transition.     

Drug release from heat-treated polyvinyl alcohol films

Abstract

Polyvinyl alcohol (PVA) films containing 10% w/w of a model drug, sulphathiazole, were cast from aqueous solutions and subjected to heat treatment at specific temperatures for known periods of time. Heat treatment at temperatures above the T_g of the PVA films slowed down the rate of drug release from the films. Increasing the temperature of heat treatment from 120°C to 160°C further decreased the rate of drug release. On the other hand, if the heat treatment were conducted at a temperature below the T_g e.g. at 80°C, there were insignificant differences between the release profile of sulphathiazole from heat-treated films and that from untreated films. The duration of heat treatment affected the rate of drug release to a smaller extent compared to the temperature of heat treatment. These results correlated with the heat induced changes in the morphology of, and in the extent of water uptake by the PVA films.