Influence of plasticizer level on the drug release from sustained release film coated and hot-melt extruded dosage forms

In the current study, the influence of plasticizer level on drug release was investigated for solid dosage forms prepared by hot-melt extrusion and film coating. The properties of two highly water-soluble compounds, diltiazem hydrochloride (DTZ) and chlorpheniramine maleate (CPM), and a poorly water-soluble drug, indomethacin (IDM), were investigated in the melt extrudates containing either Eudragit RSPO or Eudragit RD 100 and triethyl citrate (TEC) as the plasticizer. In addition, pellets containing DTZ were film coated with Eudragit RS 30D and varying levels of TEC using a fluidized bed coating unit. Differential scanning calorimetry (DSC) demonstrated that both CPM and IDM exhibited a plasticization effect on the acrylic polymers, whereas no plasticizing effect by DTZ on Eudragit RSPO was observed. Thermogravimetric analysis (TGA) was used to investigate the thermal stability of the DTZ, Eudragit RSPO and TEC at 140 degrees C, the maximum temperature used in the hot-melt extrusion process. The chemical stability of DTZ and IDM in the extrudate following hot-melt processing was determined by high pressure liquid chromatography (HPLC). Drug release rates of both DTZ and CPM from hot-melt extrudates increased with an increase in the TEC level in the formulations, while the release rate of DTZ from the Eudragit RS 30D-coated pellets decreased with an increase in TEC in the coating dispersion. This phenomenon was due to the formation of a reservoir polymeric structure as a result of the thermal stress and shear stress involved in the hot-melt extrusion process regardless of the TEC level. In contrast, coalescence of the polymer particles in the film coating process was enhanced with higher levels of TEC, as demonstrated by scanning electron microscopy (SEM). The addition of TEC (0% to 8%) in the IDM hot-melt extrudate formulation had no influence on the drug release rate as the drug release rate was controlled by drug diffusion through the inside of the polymeric materials rather than between the polymer particles.     

Influence of Fumed Silicon Dioxide on the Stabilization of Eudragit® RS/RL 30 D Film-Coated Theophylline Pellets

The objective of this study was to investigate the influence of various grades of fumed silicon dioxide on the drug release rate and physical aging of theophylline pellets coated with Eudragit® RS 30 D and RL 30 D. Free films were assessed for both physicomechanical properties and water vapor permeability with respect to time and storage conditions. The release rate of theophylline was influenced by the physical properties of the silicon dioxide employed. As the particle size of the silica dioxide decreased, there was an increase in dispersion viscosity, as well as a decrease in the theophylline release rate from the coated pellets. Films prepared from formulas containing Aeroperl® 300 had twice the water vapor transmission rate of films prepared from formulas containing Aerosil® 200 VV and Cab-O-Sil® M-5P and showed consistent moisture permeability values during storage for up to 1 month at 25°C/0% relative humidity (RH). Scanning electron microscopy (SEM) imaging of pellets coated with a formulation containing Aerosil® 200 VV or Cab-O-Sil® M-5P demonstrated film structures that were homogenous, while those coated with a formulation containing Aeroperl® 300 produced heterogeneous films with large particles of the excipient present within the polymeric matrix of the film. Stability in the drug release rate exhibited by pellets coated with a formulation containing Eudragit® RS 30 D, 15% triethyl citrate (TEC), and 30% Aeroperl® 300 was attributed to the stabilization of the moisture vapor transmission rate of the acrylic films. Increasing the concentration of Aeroperl® 300 in the coating formulation increased the theophylline release rate from coated pellets.     

Influence of plasticizer type and level on the properties of Eudragit® S100 matrix pellets prepared by hot-melt extrusion

Matrix-type pellets with controlled-release properties may be prepared by hot-melt extrusion applying a single-step, continuous process. However, the manufacture of gastric-resistant pellets is challenging due to the high glass transition temperature of most enteric polymers and an unacceptably high, diffusion-controlled drug release from the matrix during the acidic phase. The objective was to investigate the influence of three plasticizers (triethyl citrate, methylparaben and polyethylene glycol 8000) at two levels (10% or 20%) on the properties of hot-melt extruded Eudragit® S100 matrix pellets. Extrusion experiments showed that all plasticizers produced similar reductions in polymer melt viscosity. Differential scanning calorimetry and powder X-ray diffraction demonstrated that the solid state plasticizers were present in the amorphous state. The drug release in acidic medium was influenced by the aqueous solubility of the plasticizer. Less than 10% drug was released after 2 h at pH 1.2 when triethyl citrate or methylparaben was used, independent of the plasticizer level. Drug release at pH 7.4 resulted from polymer dissolution and was not influenced by low levels of plasticizer, but increased significantly at the 20% level. Mechanical testing by diametral compression demonstrated the high tensile strength of the hot-melt extruded pellets that decreased when plasticizers were present.     

Solid-state plasticization of an acrylic polymer with chlorpheniramine maleate and triethyl citrate

The influence of in situ plasticization of chlorpheniramine maleate (CPM) on Eudragit RS PO from hot-melt extruded matrix tablets, and from compressed granules prepared by thermal processing was investigated. CPM was studied as both a model drug substance and as a solid-state plasticizer for the acrylic polymer. Triethyl citrate (TEC) was incorporated into the polymer blend as a liquid plasticizer for the polymer. The influence of TEC and CPM concentration on the dissolution properties of CPM tablets was investigated. The glass transition temperature (T(g)) of the samples was determined by modulated differential scanning calorimetry (MDSC). The morphologies of the granules formed by hot-melt extrusion and hot-melt granulation processes were investigated by scanning electron microscopy. The addition of 12% TEC to the polymer reduced the T(g) by 32.5 degrees C, while the reduction in the T(g) for the same level of CPM was 16.4 degrees C. The effect of TEC levels on drug release was dependent on the tablet preparation method. At high TEC levels, the release rate of CPM decreased in tablets prepared by direct compression and tablets made from compressed granules that had been prepared by high shear hot-melt granulation. However, the CPM release rate increased from hot-melt extruded tablets with increasing blends of plasticizer in the extruded tablets. An increase in the CPM content in the tablets resulted in an increase in the drug release rate. During high shear hot-melt granulation, the model drug adhered to the polymer to form a porous discontinuous structure. Following hot-melt extrusion, the drug was distributed at a molecular level in the continuous polymeric structure. The influence of both CPM and TEC levels on the drug release rate from these polymeric drug delivery systems was shown to be a function of whether the granules or tablets were formed by either hot-melt granulation or hot-melt extrusion, as well as the plasticization effects of both TEC and CPM on the acrylic polymer.     

Salmon calcitonin-loaded Eudragit® and Eudragit®-PLGA nanoparticles: in vitro and in vivo evaluation

The main objective of this study was to prepare salmon calcitonin (sCT)-loaded Eudragit®RSPO, Eudragit®L100 and Eudragit®-poly(lactic-co-glycolic acid) blend nanoparticles for in vitro and in vivo evaluation as an oral drug delivery system. The prepared nanoparticles ranged in size from 179.7 to 308.9?nm with a polydispersity index between 0.051 and 2.75, and had surface charges ? ?11 to +6?mV. Efficient sCT encapsulation and release was observed with all the nanoparticle formulations. The polymer type was an important factor that influenced the release characteristics and the in vivo hypocalcemic effect. Nanoparticle formulations were also prepared with sodium taurodeoxycholate (NaTDC) and characterized. No statistically significant difference was noted between the hypocalcemic effect of any of the nanoparticle formulations with and without NaTDC (p?>?0.05). The use of Eudragit®RSPO nanoparticles appears to be a potential approach for the oral delivery of sCT.     

Influence of thermal processing on the properties of chlorpheniramine maleate tablets containing an acrylic polymer

The purpose of this investigation was to determine the effects of thermal processing and post-processing thermal treatment on the release properties of chlorpheniramine maleate (CPM) from matrix tablets containing Eudragit RS PO and triethyl citrate (TEC). CPM tablets containing Eudragit RS PO with and without TEC were prepared by direct compression (DC), high shear hot-melt granulation (HMG), and hot-melt extrusion (HME). X-ray diffraction patterns showed that the CPM was distributed in Eudragit RS PO at the molecular level following HME. The thermogravimetry analysis (TGA) profiles of CPM, Eudragit RS PO, and TEC demonstrated that these materials were thermally stable during both the high shear HMG and HME processes. The tablets were subjected to post-processing thermal treatment by storing the tablets at 60 degrees C in open containers for 24 hr. Tablets prepared by DC showed the highest drug release rate constant of 36.2% hr-1/2. When 4% TEC was incorporated into the formulation, the drug release rate constant for the directly compressed tablets decreased to 32.4% hr-1/2. After high shear HMG and HME of the powder blend containing 4% TEC, the drug release rate constant decreased to 30.8 and 13.8% hr-1/2 for the respective processes. The drug release rate constants for all tablets decreased following post-processing thermal treatment. The reduction in release rate was due to an increase in the intermolecular binding and entanglement between drug molecules and polymer molecules that occurred during thermal processing. Post-processing thermal treatment of the hot-melt extrudates had a minimal effect on the drug release rate since the HME process enhanced the drug and polymer entanglement to a greater extent.     

Effect of Curing Conditions and Plasticizer Level on the Release of Highly Lipophilic Drug from Coated Multiparticulate Drug Delivery System

The study aimed to investigate the effect of triethyl citrate (TEC) plasticizer level (10, 15, and 20%), curing temperature (40, 50, and 60°C) and time (0 to 168h) on the release of a highly lipophilic drug bumetanide from pellets coated with methacrylate ester copolymer (Eudragit RS). Bumetanide was layered onto sugar pellets followed by coating with 6% Eudragit RS with and without hydroxypropyl methyl cellulose (HPMC) seal coat using Wurster Fluid Bed equipment. Coated pellets were stored for 3 months at room temperature and the release was tested in USP purified water. At 10% TEC level, increasing curing time and temperature lead to slower drug release. At 15 and 20% TEC levels, curing initially decreased drug release followed by increase in the release at longer curing time and higher temperature. Drug release from coated pellets plasticized with 15% TEC and completely cured followed zero order kinetic models. At plasticizer level of 20%, bumetanide release from the completely cured pellets was better modeled using the Higuchi's equation reflecting possible drug migration during curing. Storage led to an increase in drug release. The use of HPMC seal coat stabilized drug release after storage. It was concluded that bumetanide migration into Eudragit RS film coat was the main cause of the accelerated release after curing and storage. The drug migration during storage at room temperature was prevented by seal coating the pellets with HPMC.     

Eudragit® microparticles as a possible tool for ophthalmic administration of acyclovir

This paper describes the production and characterization of polyacrylic polymer (Eudragit® RL, RS and NE) microparticles by spray drying method. Microparticles were designed for ophthalmic administration of acyclovir. Microparticle morphology was characterized by optical and electron microscopy. The release kinetics of the drug from microspheres were determined by a dialysis method. The spray drying method described allows the production of microparticles with acceptable encapsulation efficiency and appropriate dimensional characteristics for ophthalmic administration. Release profile data indicate that acyclovir is released from microparticles in a controlled manner. In addition the release pattern of the drug is influenced by the type of Eudragit® used for microparticle production. Moreover the plaque reduction efficiency of acyclovir containing microparticles (except for RS/NE microspheres) is comparable to that displayed by the free drug. Finally our results suggest that acyclovir containing microparticles could represent an interesting system for the release of this antiviral drug at the eye site.     

Effect of curing conditions and plasticizer level on the release of highly lipophilic drug from coated multiparticulate drug delivery system

The study aimed to investigate the effect of triethyl citrate (TEC) plasticizer level (10, 15, and 20%), curing temperature (40, 50, and 60 degrees C) and time (0 to 168 h) on the release of a highly lipophilic drug bumetanide from pellets coated with methacrylate ester copolymer (Eudragit RS). Bumetanide was layered onto sugar pellets followed by coating with 6% Eudragit RS with and without hydroxypropyl methyl cellulose (HPMC) seal coat using Wurster Fluid Bed equipment. Coated pellets were stored for 3 months at room temperature and the release was tested in USP purified water. At 10% TEC level, increasing curing time and temperature lead to slower drug release. At 15 and 20% TEC levels, curing initially decreased drug release followed by increase in the release at longer curing time and higher temperature. Drug release from coated pellets plasticized with 15% TEC and completely cured followed zero order kinetic models. At plasticizer level of 20%, bumetanide release from the completely cured pellets was better modeled using the Higuchi's equation reflecting possible drug migration during curing. Storage led to an increase in drug release. The use of HPMC seal coat stabilized drug release after storage. It was concluded that bumetanide migration into Eudragit RS film coat was the main cause of the accelerated release after curing and storage. The drug migration during storage at room temperature was prevented by seal coating the pellets with HPMC.     

Piroxicam nanoparticles for ocular delivery: Physicochemical characterization and implementation in endotoxin-induced uveitis

To investigate the anti-inflammatory impacts of piroxicam nanosuspension, in the current investigation, piroxicam:Eudragit®RS100 nanoformulations were used to control inflammatory symptoms in the rabbits with endotoxin-induced uveitis (EIU). The nanoparticles of piroxicam:Eudragit®RS100 was formulated using the solvent evaporation/extraction technique. The morphological and physicochemical characteristics of nanoparticles were studied using particle size analysis, X-ray crystallography, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Drug release profiles were examined by fitting the data to the most common kinetic models. Selected nanosuspensions were used to assess the anti-inflammatory impacts of piroxicam nanoparticles in the rabbits with EIU. The major symptoms of EIU (i.e. inflammation and leukocytes numbers in the aqueous humor) were examined. All the prepared piroxicam formulations using Eudragit®RS100 resulted in a nano-range size particles and displayed spherical smooth morphology with positively charged surface, however, the formulated particles of drug alone using same methodology failed to manifest such characteristics. The Eudragit®RS100 containing nanoparticles displayed lower crystallinity than piroxicam with no chemical interactions between the drug and polymer molecules. Kinetically, the release profiles of piroxicam from nanoparticles appeared to fit best with the Weibull model and diffusion was the superior phenomenon. The in vivo examinations revealed that the inflammation can be inhibited by the drug:polymer nanosuspension more significantly than the microsuspension of drug alone in the rabbits with EIU. Upon these findings, we propose that the piroxicam:Eudragit®RS100 nanosuspensions may be considered as an improved ocular delivery system for locally inhibition of inflammation.     

Influence of methylparaben as a solid-state plasticizer on the physicochemical properties of Eudragit RS PO hot-melt extrudates.

The purpose of this study was to investigate the properties of methylparaben as a solid-state plasticizer for Eudragit RS PO during a hot-melt extrusion process. Extruded matrices containing different levels of methylparaben and Eudragit RS PO, were prepared by feeding the powder blend through a hot melt extruder. The melt viscosity of the polymer blends was assessed by torque rheometry using a Brabender Plasticorder. The physicochemical properties of the extruded methylparaben-containing polymer matrix were characterized by differential scanning calorimetry and X-ray diffraction. Solid state nuclear magnetic resonance spectroscopy (NMR) was used to study the possible interaction between methylparaben and Eudragit RS PO polymer. The results demonstrated that the glass transition temperature of the Eudragit RS PO decreased with increasing levels of methylparaben in the extrudate, due to an increase in the chain mobility of Eudragit RS PO. The crystallinity of methylparaben was absent following hot-melt processing. At increasing levels of methylparaben in the extrudates, a decrease in the melt viscosity was seen due to a plasticization of the polymer. Rheological properties of the extrudates containing methylparaben were compared with the extrudates containing conventional plasticizers. It was found that methylparaben was as effective as triethyl citrate (TEC) in reducing torque during the extrusion process. Solid state NMR spectra indicated a change in the chemical shift of Eudragit RS PO plasticized with methylparaben, which could be ascribed to an interaction between the hydroxyl group of the methylparaben and the ester group of the Eudragit RS PO polymer. The results of this study demonstrated that methylparaben could be used as a solid-state plasticizer for the Eudragit RS PO polymer when a hot melt extrusion technique was employed in the preparation of sustained release tablets.     

Formulation and Evaluation of Sustained Release Extrudes Prepared via Novel Hot Melt Extrusion Technique

The purpose of the present investigation is to emphasize the application of hot-melt extrusion technique (HMET) for the preparation of sustained release matrix formulation of highly dosed, freely soluble drugs. In this study, sustained release multiple unit dosage of venlafaxine hydrochloride (VH) was prepared by HMET. Custom design was used to screen the effect of four factors-type of polymer (ethylcellulose and eudragit RSPO) (X ₁), amount of polymer (X ₂), type of plasticizer (DBS, ATBC, TEC, and PEG) (X ₃), and plasticizer concentration (X ₄), on the drug release at 8 h (Y1) and machine torque (Y2). The experiments were carried out according to a four-factor 16-run statistical model and subjected to 12-h dissolution study in purified water. The significance of the model was indicated by ANOVA. Results of in vitro release study indicate that formulations prepared with higher amount of ethylcellulose and DBC show significant retardation at 8 h. The result shows that increase in concentration of polymer with the combination of water insoluble plasticizer (DBS and ATBC) has better sustained release while increasing concentration of TEC and PEG results faster in vitro release. Besides that increase in plasticizer concentration helps in reducing the melt temperature and machine torque. The in vivo study was performed, and formulations were compared using area under the plasma concentration-time curve (AUC_0-∞), time to reach peak plasma concentration (T_max), and peak plasma concentration (C_max). The drug release profiles of extrudes were found to fit both diffusion and surface erosion models. Further to this, scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction analysis of the hot-melt extrudates demonstrated that VH remained crystalline and was homogeneously dispersed throughout the polymer matrix.     

Influence of processing parameters and formulation factors on the drug release from tablets powder-coated with Eudragit L 100-55.

The aim of this study was to develop a dry powder coating process for chlorpheniramine maleate (CPM) tablets using Eudragit L 100-55 as the delayed release polymer. Powder coating, a water and organic solvent-free process, was investigated as a method to prevent the migration of an ionizable, highly water soluble model drug into the polymeric film during the coating process. Eudragit L 100-55 was pre-plasticized with triethyl citrate (TEC) using hot-melt extrusion at levels of 20%, 30%, and 40%, based on the polymer weight. The extrudate was subsequently cut into pellets and cryogenically ground into a fine powder. Talc was incorporated into the coating powder as an anti-tack agent. PEG 3350 was used as a primer for the powder coating of tablets with pre-plasticized Eudragit L 100-55. The addition of polyethylene glycol 3350 (PEG 3350) to the pre-plasticized Eudragit L 100-55 was necessary to enhance the adhesion of the coating powder to the tablet cores. PEG 3350 also improved film formation and coalescence of the polymeric particles due to its plasticization effects on the acrylic polymer. For comparison, theophylline tablets were also coated with pre-plasticized Eudragit L 100-55. Theophylline was selected as a less water soluble model drug. The powder coating process was performed in a modified laboratory scale spheronizer. The drug release rate was dependent both on TEC content and the coating level. The stability of the powder-coated CPM tablets was confirmed at 25 degrees C/60% RH over a storage time of 12 weeks.     

Effect of substitution of plasticizer dibutyl phthalate with dibutyl sebacate on Eudragit® RS30D drug release rate control

In the current study, the influence of type of plasticizer used with Eudragit^® RS 30D on the drug release was investigated in solid dosage form extrusion/spheronization, and film coating. The drug pellets were coated for controlling drug release with Eudragit^® RS 30D containing dibutyl phthalate and compared with dibutyl sebacate as an alternative plasticizer. To study the influence of pH of the dissolution medium on the drug release profile, capsules are tested for drug release profile at pH 1.2, 4.4, and 6.3. Additionally, the aging effect on the curing of Eudragit^® RS 30D is evaluated by exposing the capsules dosage form to room temperature (25?°C?±?2?°C/60%?±?5% RH) for time 0, 3, 6, and 9?months, accelerated temperature (40?°C?±?2?°C/75%?±?5% RH) for time 0, 3, and 6?months, and intermediate temperature (30?°C?±?2?°C/65%?±?5% RH) for time 0, 6, and 9?months. The replacement of dibutyl phthalate, with dibutyl sebacate for polymer coating system in similar concentration is comparable with respect to plasticization effect. The coalescence of the polymer particles is not changed and requires no additional processing parameter control or additional curing time.     

Microsphere-based once-daily modified release matrix tablets for oral administration in angina pectoris

The objective of this research was to develop microsphere-based once-daily modified release tablet formulations of diltiazem hydrochloride (DH), a potent calcium channel blocker used in angina pectoris. For this purpose, DH-loaded microspheres were prepared by the solvent evaporation technique using Eudragit®RS 100. The effect of variation in the drug/polymer ratio on the physical and release characteristics of the microspheres was investigated. After the selection of the suitable microspheres, tablets were compressed using Compritol®888 ATO, Ludipress® and Cellactose®80 as different direct tableting agents and excipients. As a result, modified release tablet formulations of DH-loaded microspheres were designed successfully for oral administration once rather than two or three times a day in angina pectoris.     

Novel application method of talcum powder to prevent sticking tendency and modify release of esomeprazole magnesium enteric-coated pellets

Actually, reflecting drug release from polymer-coated pellets remains a challenge. In this study, sticking of pellets caused by Eudragit®L30D-55 was observed during the release process, leading to change in drug release. Talcum powder (talc) was used in esomeprazole magnesium pellets to prevent sticking and modify release of pellets. Three methods including talc incorporated in enteric layer, physically mixed and coating resulted pellets were employed to prevent the sticking. The release of pellets was modified by addition talc into subcoat. The dispersion coefficient (F_d) and release profiles were determined in phosphate buffer solution (pH 6.8 and 6.0) and distilled water. It was found that the first manner made F_d increase to about 0.75, but the latter two methods could completely prevent sticking. Also, the second manner was more simple and readily scaled up. In addition, talc in subcoat significantly slowed the drug release in water, but the slowing release effect is less pronounced at pH 6.0 and 6.8. These different effects of talc were attributed to a different release mechanism in three media. The release profiles in water were fitted to Nuttanan model, and the K designated as “diffusive resistance constant” was linearly increased with talc levels in subcoat (R^2?=?0.9874).     

Influence of film additives on stabilizing drug release rates from pellets coated with acrylic polymers.

The objective of this study was to investigate the influence of talc and triethyl citrate (TEC) on stabilizing the drug release rates following curing and storage at elevated temperature of pellets coated with an aqueous acrylic polymeric dispersion. Core pellets containing anhydrous theophylline (20%), microcrystalline cellulose, and polyvinylpyrrolidone were prepared by extrusion-spheronization. The aqueous dispersions were prepared by adding up to 30% TEC as a plasticizer and talc up to 200% as an antiadherent to a mixture of Eudragit RS 30D/RL 30D (95:5). The theophylline pellets were coated in a fluidized-bed coating unit and then cured at elevated temperatures. Theophylline pellets were successfully coated with the Eudragit dispersions that contained up to 200% talc, based on the dry polymer weight, and the coating efficiency was greater than 93%. Our results demonstrated that the polymer, which was plasticized by TEC, was able to function as a film-forming agent for dispersions containing high levels of talc. No sticking of the coated pellets was observed during the coating process or during the curing or equilibrating phase, even with high levels of TEC in the film. The dissolution rate of theophylline from the coated pellets was delayed when the film coating dispersion contained high levels of talc. Additionally, the stability of the drug release profiles from the coated pellets after storage was significantly improved. Furthermore, a modified dissolution testing used to simulate mechanical stresses that may be encountered in vivo showed the film coated pellets would have sufficient strength. The results of this study demonstrated that high levels of film additives in the acrylic dispersion contributed to the stabilization of the drug release rates as well as the reproducibility of the coating process.     

Sustained-release solid dispersion of pelubiprofen using the blended mixture of aminoclay and pH independent polymers: preparation and in vitro/in vivo characterization

The present study aimed to develop the sustained-release oral dosage form of pelubiprofen (PEL) by using the blended mixture of 3-aminopropyl functionalized-magnesium phyllosilicate (aminoclay) and pH-independent polymers. The sustained-release solid dispersion (SRSD) was prepared by the solvent evaporation method and the optimal composition of SRSD was determined as the weight ratio of drug: Eudragit® RL PO: Eudragit® RS PO of 1:1:2 in the presence of 1% of aminoclay (SRSD(F6)). The dissolution profiles of SRSD(F6) were examined at different pHs and in the simulated intestinal fluids. The drug release from SRSD(F6) was limited at pH 1.2 and gradually increased at pH 6.8, resulting in the best fit to Higuchi equation. The sustained drug release from SRSD(F6) was also maintained in simulated intestinal fluid at fasted-state (FaSSIF) and fed-state (FeSSIF). The structural characteristics of SRSD(F6) were examined by using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), indicating the change of drug crystallinity to an amorphous form. After oral administration in rats, SRSD(F6) exhibited the prolonged drug exposure in plasma. For both PEL and PEL-transOH (active metabolite), once a day dosing of SRSD(F6) achieved oral exposure (AUC) comparable to those from the multiple dosing (3 times a day) of untreated drug. In addition, the in vivo absorption of SRSD(F6) was well-correlated with the in vitro dissolution data, establishing a good level A in vitro/in vivo correlation. These results suggest that SRSD(F6) should be promising for the sustained-release of PEL, thereby reducing the dosing frequency.     

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^® 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^® K30 or Carbopol^® 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_g) of Eudragit^® 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^® 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.     

Preparation and characterization of metformin hydrochloride loaded-Eudragit®RSPO and Eudragit®RSPO/PLGA nanoparticles

The aim of the present study was to develop and characterize metformin HCl-loaded nanoparticle formulations. Nanoparticles were prepared by the nanoprecipitation method using both a single polymer (Eudragit^®RSPO) and a polymer mixture (Eudragit/PLGA). The mean particle size ranged from 268.8 to 288?nm and the nanoparticle surface was positively charged (9.72 to 10.1 mV). The highest encapsulation efficiency was observed when Eudragit®RSPO was used. All formulations showed highly reproducible drug release profiles and the in vitro drug release in phosphate buffer (pH?=?6.8) ranged from 92 to 100% in 12?h. These results suggest that Eudragit^®RSPO or Eudragit/PLGA nanoparticles might represent a promising sustained-release oral formulation for metformin HCl, reducing the necessity of repeated administrations of high doses to maintain effective plasma concentrations, and thus, increasing patient compliance and reducing the incidence of side-effects.