Preparation and characterization of co-processed starch/MCC/chitin hydrophilic polymers onto magnesium silicate

It was aimed to investigate the compressibility, compactibility, powder flow and tablet disintegration of a new excipient comprising magnesium (Mg) silicate co-processed (5%–85% w/w) onto chitin, microcrystalline cellulose (MCC) and starch as the hydrophilic polymers of interest. Initially, the mechanism of tablet disintegration was studied by measuring water infiltration rate, moisture sorption, swelling capacity and hydration ability. Moreover, the powders compression behavior was carried out by applying Kawakita model of compression analysis in addition to porosity and radial tensile strength measurements. In vitro drug release of compacts made of 400?mg ibuprofen and 300?mg of the hydrophilic polymers containing 30% w/w Mg silicate co-precipitate was investigated in phosphate buffer (pH 7.8). This work demonstrated that the incorporation of Mg silicate to the hydrophilic polymers lead to the improvement of powder flowability, compactibility, stability (with regard to storage conditions), compacts crushing strength, and disintegration time in addition to faster drug release. The overall findings are practically advantageous in the context of finding a low cost and multifunctional co-processed excipient of natural origins.     

Supercritical fluid impregnation of microcrystalline cellulose derived from the agricultural waste with ibuprofen

The present study was aimed to investigate the feasibility of loading microcrystalline cellulose derived from the agricultural waste with poorly water-soluble drug by using supercritical carbon dioxide as impregnation medium. Operating parameters of supercritical impregnation process (pressure, temperature and time) were varied to in order to maximize loading of ibuprofen used as a model drug into microcrystalline cellulose. The efficiency of ibuprofen loading using supercritical impregnation and release kinetics studies of microcrystalline cellulose in two pharmaceutical forms, powder and tablets, were investigated.The highest amount of ibuprofen was impregnated in microcrystalline cellulose powder by using supercritical impregnation at 25 MPa and 40 °C for 24 h (9.43%). Increasing pressure in the range of 10 MPa–25 MPa and time from 2 h to 24 h favours loading of ibuprofen into microcrystalline cellulose. A higher loading efficiency at the same impregnation conditions was observed for powdered microcrystalline cellulose. Temperature change in range of 40–60 °C had negligible influence on loading efficiency. FT-IR spectroscopy analysis showed no evidence of chemical modification of microcrystalline cellulose after processing. In vitro drug release study showed that impregnated powder formulations released the total amount of ibuprofen immediately, while the impregnation of microcrystalline cellulose powder in the form of tablets led to the achievement of the sustained release profile.     

Formation of physically stable amorphous phase of ibuprofen by solid state milling with kaolin.

Ibuprofen was milled in the solid state with kaolin (hydrated aluminium silicate) in different ratio to examine the extent of transformation from crystalline to amorphous state. The physical stability of the resultant drug was also investigated. X-ray powder diffractometry (XRD) and birefringence by Scanning Electron Microscopy (SEM) studies indicated almost complete amorphization of the drug on ball milling with kaolin at 1:2 ratio. Fourier transform infrared spectroscopy (FTIR) data showed a reduction in the absorbance of the free and the hydrogen-bonded acid carbonyl peak of carboxylic acid group accompanied by a corresponding increase in the absorbance of the carboxylate peak, indicating an acid-base reaction between the carboxylic acid containing ibuprofen and kaolin on milling. The extent of amorphization and reduction in the carbonyl peak and increase in carboxylate peak was a function of kaolin concentration in the milled powder. On storage of milled powder (at 40 degrees C and 75% RH for 10 weeks), XRD and birefringence of SEM study showed the absence of reversion to the crystalline state and FTIR data revealed continued reduction of carbonyl peak, whereas, ibuprofen converted from its crystalline acid form to amorphous salt form on milling with kaolin. Kaolin-bound state of ibuprofen was physically stable during storage. In-vitro dissolution studies revealed that percent release of ibuprofen from the kaolin co-milled powder is in the order: 1:2>1:1>1:0.5>1:0.1>milled alone ibuprofen>crystalline ibuprofen.     

Mg,Al layered double hydroxides with intercalated indomethacin: synthesis, characterization, and pharmacological study

Magnesium aluminium layered double hydroxides (LDH) with a molar Mg/Al ratio of 2.0 have been prepared with intercalated indomethacin following two routes: reconstruction from a previously calcined Mg(2)Al-CO(3) LDH, and coprecipitation from the corresponding chlorides. The solids have been characterized by powder X-ray diffraction, FTIR, and (13)C CP/MAS NMR spectroscopies and thermal stability (differential thermal analysis and thermogravimetric analysis). Intercalation of the drug is attained by both routes; however, while coprecipitation leads to a single layered structure, contamination with another layered MgAl-CO(3) phase occurs by the reconstruction method. The amount of drug intercalated, as well as the height of the gallery, are larger by the coprecipitation than by the reconstruction one. The data obtained support a somewhat tilted, upwards orientation of the drug molecules forming an interdigited bilayer, in the case of the sample prepared by coprecipitation, with the carboxylate groups pointing towards the hydroxyl layers. However, in the case of the sample prepared by reconstruction, the molecules are forming a tilted, upwards monolayer. The solids prepared are stable up to 250 degrees C. Pharmacological studies in vivo show that intercalation of the drug in the LDH reduces the ulcerating damage of the drug.     

Immobilization of ibuprofen and copper-ibuprofen drugs on layered double hydroxides

The immobilization of the NSAID ibuprofen (Hibp) and the Cu(II)-ibp compound on magnesium-aluminum layered double hydroxides (Mg3Al-LDH) is described. Ibuprofen was intercalated on LDHs by three routes (ion exchange, co-precipitation, and reconstruction). The organic drug and the Cu(II)-ibp were also immobilized by adsorption on LDH external surfaces. Materials were characterized by elemental analysis, UV/VIS, FTIR, and Raman spectroscopies, powder X-ray diffractometry (XRD), thermogravimetry, and electronic paramagnetic resonance (EPR). Mg3Al-(ibp)(cop) (30% w/w of drug/material) and Mg3Al-(ibp)(ie) (33%) materials exhibit bilayer arrangements of ibp anions intercalated between the host layers. Mg3Al-(ibp)(rec) and Mg3Al-(ibp)(ads) contain 13% and 6.2% of ibuprofenate, respectively. Mg3Al-(Cu-ibp)(ads) exhibits two Cu centers in different environments interacting with host layers. Pharmacological potential of materials are compared considering the amounts of immobilized drugs and their buffering properties. Mg3Al-(ibp)(ie) and Mg3Al-(ibp)(cop) exhibit poor buffering property, but contain high ibp amounts. Mg3Al-(ibp)(ads) despite having buffering property, contains low amount of ibuprofen. Mg3Al-(ibp)(rec) combines significant amount of immobilized ibp with good buffering property. Mg3Al-(Cu-ibp)(ads), due to the buffering property, may be an interesting new formulation aiming to decrease gastric irritation.     

Synthesis and study of controlled release of ibuprofen from the new acrylic type polymers

New acrylic type polymeric systems having degradable ester bonds linked to ibuprofen were synthesized and evaluated as materials for drug delivery. Methacryloyloxy(2-hydroxy)propyl-4-isobutyl-alpha-methylphenyl acetate (MOPE), a new methacrylic derivative of ibuprofen in which the drug is separated from the methacrylic backbone by an oxy(2-hydroxy)propylene spacer arm and hydrolytically labile ester bond, was synthesized from reaction of glycidyl methacrylate with ibuprofen. The resulting drug containing monomer was copolymerized with methacrylamide, 2-hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone or n-butyl methacrylate by free radical polymerization method in N,N-di-methylformamide (DMF) solution, utilizing azobisisobutyronitrile as initiator at the temperature range 65-70 degrees C. The obtained polymers were characterized by FT-IR, 1H NMR and 13C NMR spectroscopy. Gel permeation chromatography (GPC) was used for determination of average molecular weights of drug-polymer conjugates and showed that the polydispersity indices of the polymers are in the range of 1.9-2.3. Drug release studies were performed by hydrolysis in buffered solutions (pH 1 and 8) at 37 degrees C. Detection of hydrolysis by UV spectroscopy at selected interval showed that the drug can be released by selective hydrolysis of the ester bond at the side of drug moiety. The release profiles indicated that the hydrolytic behavior of polymeric prodrugs is strongly based on the hydrophilicity of polymer and the pH of the hydrolysis solution. The hydrophilic polymers containing ibuprofen were hydrolyzed in buffer solutions rather than the hydrophobic polymers.     

Comminution of ibuprofen to produce nano-particles for rapid dissolution

A critical problem associated with poorly soluble drugs is low and variable bioavailability derived from slow dissolution and erratic absorption. The preparation of nano-formulations has been identified as an approach to enhance the rate and extent of drug absorption for compounds demonstrating limited aqueous solubility. A new technology for the production of nano-particles using high speed, high efficiency processes that can rapidly generate nano-particles with rapid dissolution rate has been developed. Size reduction of a low melting ductile model compound was achieved in periods less than 1h. Particle size reduction of ibuprofen using this methodology resulted in production of crystalline particles with average diameter of approximately 270nm. Physical stability studies showed that the nano-suspension remained homogeneous with slight increases in mean particle size, when stored at room temperature and under refrigerated storage conditions 2-8°C for up to 2 days. Powder containing crystalline drug was prepared by spray-drying ibuprofen nano-suspensions with mannitol dissolved in the aqueous phase. Dissolution studies showed similar release rates for the nano-suspension and powder which were markedly improved compared to a commercially available drug product. Ibuprofen nano-particles could be produced rapidly with smaller sizes achieved at higher suspension concentrations. Particles produced in water with stabilisers demonstrated greatest physical stability, whilst rapid dissolution was observed for the nano-particles isolated in powder form.     

In vitro peptide release from liquid crystalline buccal delivery systems

Swelling and [D-Ala(2), D-Leu(5)]enkephalin (DADLE) release from the lamellar and cubic liquid crystalline phases of glyceryl monooleate (GMO) were studied using two in vitro methods, a total immersion method and a Franz cell method. The swelling of the lamellar phase and glyceryl monooleate (0% w/w water content) and DADLE release from the liquid crystalline phases were temperature dependent. The swelling ratio was greater at 20 degrees C than 37 degrees C while DADLE release increased at 37 degrees C compared to 20 degrees C for both the lamellar and cubic phases. The water uptake increased dramatically with decreasing initial water content of the liquid crystalline phases. However, DADLE release increased with increasing initial water content, which corresponded to increased viscosity. The swelling and DADLE release profiles obtained using a Franz cell method with a moist nylon membrane to mimic buccal drug release conditions were slower than the total immersion method. These results show that the swelling and DADLE release strongly depended on temperature, the initial water content of the liquid crystalline matrix and the methodology employed for determining the swelling and DADLE release.     

Intercalation compounds of hydrotalcite-like anionic clays with antiinflammatory agents--I. Intercalation and in vitro release of ibuprofen

Hydrotalcite-like compounds are layered solids having positively charged layers and interlayer charge-compensating anions. The synthetic Mg_0.67Al_0.33(OH)₂ Cl_0.33·0.6H₂O, which is biocompatible, has been used to intercalate a model drug, ibuprofen, in order to prepare a modified release formulation. The intercalation compound was prepared via ion-exchange starting from the chloride form of hydrotalcite and its composition, determined both by elemental microanalysis and thermogravimetric analysis, was Mg_0.67Al_0.33(OH)₂IBU_0.33·0.47H₂O, drug content 50% (w/w). As a consequence of the intercalation, the interlayer distance of the host increased from 0.78 nm (interlayer distance of chloride form) to 2.17 nm. The result of dissolution tests at pH 7.5 showed that the in vitro drug release was modified if compared with that obtained with comparative formulations. The mechanism of modified drug release has been interpreted on the basis of the ion exchange process of the ibuprofen anion intercalated in the lamellar host and phosphates contained in the intestinal fluid buffer.     

Effect of temperature-increase rate on drug release characteristics of dextran microspheres prepared by emulsion solvent evaporation process

Microspheres containing theophylline (TH) were prepared from a hydrophobic dextran derivative by an emulsion solvent evaporation process using an acetone/liquid paraffin system. The effects of solvent evaporation rate on particle properties and drug release characteristic of the microspheres were evaluated. The solvent evaporation rate was controlled by the rate of increase in temperature of the water bath, ranging 7.5-30 degrees C/h. Drug release from the microspheres was examined using JPXIV 2nd fluid (pH 6.8) containing 0.1% Tween 80, and was found to be greatly affected by the solvent evaporation rate. The percentage of drug released until 8h varied; from 28% to 84% for 30 and 7.5 degrees C, respectively. Differential scanning calorimetry and powder X-ray diffraction studies revealed that TH partially interacted with the polymer and drug crystallinity was maintained intact in the microspheres. According to scanning electron microscopy observations, all microspheres showed a well-formed spherical particle with a solid interior. The appearances of the microspheres were, however, extremely different. Microspheres prepared at 30 degrees C/h had a very smooth surface, while those prepared at 7.5-15 degrees C/h had a rough surface with large craters. These findings demonstrated that the surface morphology and drug release characteristic were controlled by the rate of increase of temperature.     

Influence of Dissolution Media and Presence of Alcohol on the In Vitro Performance of Pharmaceutical Products Containing an Insoluble Drug

The purpose of this investigation is to determine how the dissolution media may influence the release rate of an insoluble drug in in vitro conditions. Some oral dosage forms containing ibuprofen, a molecule that shows pH-dependent solubility, are tested. They are evaluated in different media to simulate the gastrointestinal transit at paddle rotation speeds of 50 and 100 rpm. Moreover, the potential effect of different ethanol concentrations on drug release is tested. The dissolution profiles of the tablets show a similar behavior in water (pH 1.0) and phosphate buffer (pH 4.5) where the 2 doses are not completely dissolved. The soft capsules show a different behavior: a certain amount of ibuprofen, which is in solution inside the capsule, reprecipitates in water and in the pH 4.5 buffer. Instead, ibuprofen dissolves rapidly in the pH 6.8 buffer from all the formulations. In the water-ethanol solutions, the dissolution curves show a valuable increase in the drug dissolved at higher ethanol concentrations.     

Preparation and characterisation of ibuprofen-poloxamer 188 granules obtained by melt granulation.

The aim of this study was to prepare, by melt granulation, granules containing ibuprofen as a poorly water soluble model drug in order to improve its dissolution rate and its availability; lactose as a diluent and poloxamer 188 (Lutrol F68), as a new meltable hydrophilic binder, were used. The granules were prepared in a laboratory-scale high-shear mixer, using a jacket temperature of 50 degrees C and an impeller speed of 500 rpm. The particle size analysis shows that the main fraction was between 200 and 500 microm, while the determination of drug content indicated that ibuprofen was quite uniformly distributed in all the fractions. Scanning Electron Microscopy (SEM), image and fractal analysis revealed that the granules did not have a perfect spherical shape and a rugged surface (D(s)=2.6475). The in vitro dissolution tests showed an increase in the dissolution rate of granules compared to pure drug and physical mixture. The characterisation of the samples, performed by Differential Scanning Calorimetry (DSC) and X-ray powder diffraction (XRD), suggests that the improvement of dissolution rate could be correlated to the formation of a eutectic mixture between the drug and the binder. Stability studies indicated that the granule properties do not change, at least after 1 year of storage at 25 degrees C. In conclusion, the results of this work suggest that the melt granulation technique is an easy and fast method to improve the dissolution rate of ibuprofen, using poloxamer 188 as a new hydrophilic meltable binder.     

Effect of milling conditions on the solid-state conversion of ranitidine hydrochloride form 1

Powder samples of ranitidine hydrochloride forms 1 and 2 were milled using a vibrational ball mill (Retsch MM301) for periods up to 240min at 4, 12 and 35 degrees C. X-ray powder diffraction (XRPD), diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), solid-state nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC) were used to monitor solid-state properties of the milled samples. Milling of form 1 at 4 degrees C led to a powder temperature of 36 degrees C in the milling chamber and produced only amorphous drug; at 12 degrees C (powder temperature 45 degrees C) and at 35 degrees C (powder temperature 62 degrees C) progressive transformation of form 1 via amorphous drug to form 2 occurred. DSC of the milled samples showed a glass transition at 13-30 degrees C and a crystallization exotherm (T(c)) between 30 and 65 degrees C if the sample contained amorphous drug. The behaviour of the solid was speculated to be influenced by the relationship between powder temperature and T(c); at powder temperatures below T(c), amorphous drug is formed but no crystallization of form 2 occurs; at temperatures close to T(c), amorphous content initially increases with transformation to form 2 on continued milling. At temperatures much higher than T(c), at intermediate stages, less amorphous drug but both form 1 and form 2 are recovered, but continued milling gives only form 2. Form 2 did not transform to form 1 under any conditions used in this study.     

Drug delivery from therapeutic self-assembled monolayers (T-SAMs) on 316L stainless steel

Delivery of therapeutic agents from self-assembled monolayers (SAMs) on 316L stainless steel (SS) has been demonstrated as a viable method to deliver drugs for localized coronary artery stent application. SAMs are highly-ordered, nano-sized molecular coatings, adding 1-10 nm thickness to a surface. Hydroxyl terminated alkanethiol SAMs of 11-mercapto-1-undecanol (-OH SAM) were formed on 316L SS with 48 hr immersion in ethanolic solutions. Attachment of ibuprofen (a model drug) to the functional SAMs was carried out in toluene for 5 hrs at 60 degrees C using Novozume-435 as a biocatalyst. SAM formation and subsequent attachment of ibuprofen was characterized collectively using X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and contact angle (CA) measure-ments. The quantitative in vitro release of ibuprofen into a "physiological" buffer solution was characterized using reverse phase HPLC. Drug release kinetics showed that 14.1 microg of ibuprofen eluted over a period of 35 days with 2.7microg being eluted in the first day and the remaining being eluted over a period of 35 days. The drug release kinetics showed an increase in ibuprofen elution that occurred during first 14 days (2.7microg in 1 day to 9.5 microg in 14 days), following which there was a decrease in the rate of elution. Thus, functional SAMs on 316L SS could be used as tethers for drug attachment and could serve as a drug delivery mechanism from stainless steel implants such as coronary artery stents.     

Preparation and characterisation of hydrocortisone particles using a supercritical fluids extraction process.

Crystallisation and subsequent milling of pharmaceutical powders by traditional methods often cause variations in physicochemical properties thereby influencing bioavailability of the formulation. Crystallisation of drug substances using supercritical fluids (SFs) offers some advantages over existing traditional methods in controlling particle characteristics. The novel particle formation method, solution enhanced dispersion by supercritical (SEDS) fluids was used for the preparation of hydrocortisone (HC) particles. The influence of processing conditions on the solid-state properties of the particles was studied. HC, an anti-inflammatory corticosteroid, particles were prepared from acetone and methanol solutions using the SEDS process. The solutions were dispersed with supercritical CO(2), acting as an anti-solvent, through a specially designed co-axial nozzle into a pressured vessel maintained at a specific constant temperature and pressure. The temperatures and pressures studied were 40-90 degrees C and 90-180 bar, respectively. The relative flow rates of drug solution to CO(2) were varied between 0.002 and 0.03. Solid-state characterisation of particles included differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), solubility studies and scanning electron microscopy (SEM) examination. The aerodynamic properties of SEDS prepared particles were determined by a multistage liquid impinger (MLI). Particles produced from acetone solutions were crystalline needles, melting at 221+/-2 degrees C. Their morphology was independent of processing conditions. With methanol solutions, particles were flakes or needles depending on the processing temperature and pressure. This material melted at 216+/-1 degrees C, indicating a different crystal structure from the original material, in agreement with observed differences in the position and intensity of the XRPD peaks. The simulated lung deposition, using the MLI, for HC powder was improved after SEDS processing. It was possible to produce and control the crystallinity, morphology, and aerodynamic properties of HC particles with the SEDS technique. This method may be useful for the processing of inhalation powders.     

Development of novel ibuprofen-loaded solid dispersion with improved bioavailability using aqueous solution

To develop a novel ibuprofen-loaded solid dispersion with enhanced bioavailability, various ibuprofen-loaded solid dispersions were prepared with water, HPMC and poloxamer. The effect of HPMC and poloxamer on aqueous solubility of ibuprofen was investigated. The dissolution and bioavailability of solid dispersion in rats were then evaluated compared to ibuprofen powder. When the amount of carrier increased with a decreased in HPMC/poloxamer ratio, the aqueous solubility of ibuprofen was elevated. The solid dispersion composed of ibuprofen/HPMC/poloxamer at the weight ratio of 10:3:2 improved the drug solubility approximately 4 fold. It gave significantly higher initial plasma concentration, AUC and Cmax of drug than did ibuprofen powder in rats. The solid dispersion improved the bioavailability of drug about 4-fold compared to ibuprofen powder. Thus, this ibuprofen-loaded solid dispersion with water, HPMC and poloxamer was a more effective oral dosage form for improving the bioavailability of poor water-soluble ibuprofen.     

Coprocessing via spray drying as a formulation platform to improve the compactability of various drugs

It was evaluated if coprocessing via spray drying can be used as a formulation platform to improve the compactability of formulations containing drug substance (acetaminophen, ibuprofen, cimetidine) and excipients (carbohydrates, disintegrant, glidant, surfactant). Experimental design was applied to optimise the drug concentration and solid content of the feed suspension. In addition, scaling-up of acetaminophen- and ibuprofen-containing formulations was performed on a production-scale spray dryer. Optimised acetaminophen (drug concentration: 70% w/w), ibuprofen (drug concentration: 75% w/w) and cimetidine (drug concentration: 70% w/w) powders were obtained via co-spray drying of aqueous suspensions with a high solid content of the feed (35% w/w) and the resulting powders were directly compressed. Scaling-up of optimised acetaminophen and ibuprofen formulations was performed successfully, resulting in a robust and reproducible manufacturing process. It can be concluded that a combination of mannitol, erythritol, Glucidex^® 9, Kollidon^® CL, colloidal silicon dioxide and polyoxyethylene 20 sorbitan monooleate allowed the spray drying of highly dosed drug substances (acetaminophen, ibuprofen, cimetidine) in order to obtain ‘ready-to-compress’ powder mixtures on lab-scale and production-scale equipment.     

Dry polymer powder coating and comparison with conventional liquid-based coatings for Eudragit) RS, ethylcellulose and shellac.

Drug-layered pellets were coated with micronized polymer powders (Eudragit) RS, ethylcellulose, and shellac) by a dry powder coating technique as an alternative to organic- and aqueous-based coatings (Eudragit) RS 30D, Aquacoat) ECD) were investigated. High plasticizer concentrations (40%) and a thermal after-treatment (curing) were necessary for the coalescence of the polymer particles and good film formation. Ethylcellulose required a higher curing temperature and time than Eudragit) RS because of its higher glass transition temperature (133 versus 58 degrees C). A smaller polymer particle size also promoted film formation. In general, pellets coated with polymer powders required higher coating levels to obtain similar drug release patterns as pellets coated with organic polymer solutions and aqueous polymer dispersions.     

The impact of drying method and formulation on the physical properties and stability of methionyl human growth hormone in the amorphous solid state

The objective of this work was to investigate the impact of drying method and formulation on the physical stability (aggregation) and selected important physical properties of dried methionyl human growth hormone (Met-hGH) formulations. Solutions of Met-hGH with different stabilizers were dried by different methods (freeze drying, spray drying, and film drying), with and without surfactant. Properties of the dried powders included powder morphology, specific surface area (SSA), protein surface coverage, thermal analysis, and protein secondary structure. Storage stability of Met-hGH in different formulations was also studied at 50 degrees C and at 60 degrees C for 3 months. The dried powders displayed different morphologies, depending mainly on the method of drying and on the presence or absence of surfactant. Film dried powders had the lowest SSA (approximately 0.03 m(2)/g) and the lowest total protein surface accumulation (approximately 0.003%). Surfactant caused a reduction in the SSA of both spray dried and freeze dried powders. Spray dried powders showed greater protein surface coverage and SSA relative to the same formulations dried by other means. Greater in-process perturbations of protein secondary structure were observed with polymer excipients. Formulation impacted physical stability. In general, low molecular weight stabilizers provided better stability. For example, the aggregation rate at 50 degrees C of Met-hGH in a freeze dried trehalose-based formulation was approximately four times smaller than the corresponding Ficoll-70-based formulation. Drying method also influenced physical stability. In general, the film dried preparations studied showed superior stability to preparations dried by other methods, especially those formulations employing low molecular weight stabilizers.     

Dry Powder Coating of Pellets with Micronized Eudragit® RS for Extended Drug Release

PURPOSE: To develop a novel powder coating technology for extended-release pellets based on the acrylic polymer, Eudragit RS. METHODS: A mixture of micronized Eudragit RS plus talc and a liquid feed (plasticizer plus binder solution) were sprayed separately onto propranolol hydrochloride-loaded pellets in a fluidized bed coater. The coated pellets were heat-cured under different conditions (40 degrees C to 60 degrees C, 2 h to 24 h). The coalescence (film formation) of the polymer particles was studied via the determination of the glass transition and the minimum polymer-softening temperatures (MST). The coated pellets were characterized with respect to their morphologic, release, and stability properties. RESULTS: The optimum plasticizer type and concentration and process temperatures could be identified by the determination of the MST. High concentrations of plasticizer (40% based on the polymer) and a thermal treatment were necessary to achieve complete film formation and extended drug release. Curing the pellets resulted in release profiles, which did not change during storage for 3 years. The coated pellets had a smooth, continuous surface and a dense film structure after curing. CONCLUSIONS: This novel coating technique avoids the use of organic polymer solutions or latex dispersions, has short processing times, and results in stable extended-release profiles.