Structural Characteristics and Permeability of Ethyl Cellulose Films Containing Different Plasticizers

The effect of different type of plasticizers was investigated in ethyl cellulose as coating polymer for manufacturing coated pellets of modified release containing a water soluble model drug. Scanning electron microscopic image analysis (SEM), differential scanning calorimetry (DSC), X-ray photoelectron spectroscopic chemical surface analysis (XPS) were used to study the films, and the dissolution profiles of coated pellets were evaluated. The effect of the different plasticizers and coating levels on the first order dissolution rate constant is determined by statistical experimental design. Correlation was found between the dissolution rate constant and the structural characteristics of the coating layer containing different plasticizers. Partial segregation of the plasticizers was detected especially on the surface of the films, which is in correlation with the differences in the glass transition temperatures. PEG 400 is found to be compatible enough to form continuous, durable EC coating at 5% concentration level, which gave the slowest dissolution.     

A controlled porosity osmotic pump system with biphasic release of theophylline

A controlled porosity osmotic pump system with biphasic release of theophylline was developed for the nocturnal therapy of asthma. The developed system was composed of a tablet-in-tablet (TNT) core and a controlled porosity coating membrane. Release pattern of the developed system was influenced by amount of pore former (18.2-45.5%, w/w of polymer), weight gain (16-26 mg per tablet) of the coating membrane and osmotic agents used in inner layer of the TNT core. When sodium phosphate and sodium chloride were selected as the osmotic agents in inner and outer layer of the TNT core respectively, target release profile was obtained with coating solution cellulose acetate-polyethylene glycol 400-diethyl phthalate (54.5-36.4-9.1%, w/w) at a weight gain of 16-22 mg per tablet. To examine the mechanism of drug release, release profiles of osmotic agents, micro-environmental osmotic pressure and micro-environmental pH of the formulation during dissolution were studied. Micro-environmental osmotic pressure decreased and micro-environmental pH increased continuously during the whole dissolution process, theophylline release was dominated by the successive dissolution of sodium chloride and sodium phosphate. Theophylline solubility increased as environmental pH exceeded 10.8. At the last stage of the biphasic release, micro-environmental pH in the developed formulation reached 10.9, and theophylline release was promoted by its elevated solubility despite of the decrease of micro-environmental osmotic pressure in the developed formulaiton.     

电场纺丝法制备药物缓释乙基纤维素纤维的研究

通过把四环素均匀分散在乙基纤维素溶液里,利用电场纺丝法制备了含有四环素的乙基纤维素超细纤维,并运用紫外-可见光分光度计测定了含四环素的乙基纤维素纤维在水中的释放曲线.发现用电场纺丝法制备的含四环素的纤维有良好的药物缓释作用,可以有效避免血液中药物浓度的“峰谷”现象的出现.纤维的直径以及药物在纤维中的浓度都会对四环素的释放效果产生影响,平均直径大的纤维的四环素的释放曲线增长的更为平稳,四环素含量高的纤维的释放曲线浓度高.     

Zero-order drug release cellulose acetate nanofibers prepared using coaxial electrospinning

Novel drug-loaded cellulose acetate (CA) nanofibres were prepared by a modified coaxial electrospinning process, after which their zero-order drug release profiles were determined. Using 2 % (w/v) unspinnable CA solution as a sheath fluid, coaxial electrospinning can be conducted smoothly to generate ketoprofen (KET)-loaded CA nanofibres coated with a thin layer of blank CA. Scanning electron microscopy images demonstrated that nanofibres obtained from the modified coaxial process have a smaller average diameter, a narrower size distribution, more uniform structures, and smoother surface morphologies than those generated from single-fluid electrospinning. Transmission electron microscopy observations demonstrated that the nanofibres have a thin coating layer of blank CA on their surface with a thickness of ca. 15 nm. X-ray diffraction and differential scanning calorimetry verified that KET molecules in all of the nanofibres presented an amorphous state. Fourier transform infrared spectra demonstrated that CA has good compatibility with KET, which is brought about by hydrogen bonding. In vitro dissolution tests showed that the nanofibres coated with blank CA have no initial burst release effects and can provide a zero-order drug release profile over 96 h via a diffusion mechanism. The modified coaxial electrospinning method can provide new approaches in developing cellulose-based nano products with definite structural characteristics and improved functional performance.     

Multiparticulate chitosan-dispersed system for drug delivery

A multiparticulate chitosan-dispersed system (CDS), which is composed of the drug reservoir and the drug release-regulating layer, was developed for drug delivery. The drug release-regulating layer is a mixture of water-insoluble polymer and chitosan powder. The drug is released from CDS pellets in all regions of the gastrointestinal tract (from the stomach to the colon). CDS pellets containing chitosan powder were designed to dissolve chitosan powder partly in the release-regulating layer in the stomach and release part of drug. After passing through the stomach, the drug is released from CDS pellets at a constant speed in the small intestine. In the large intestine, CDS pellets were designed to disintegrate the remaining chitosan powder at an accelerated speed and the remaining drug in CDS pellets is released. The drug release rate can be controlled with the thickness of the chitosan-dispersed water-insoluble layer. Furthermore, for colon-specific drug delivery, an additional outer enteric coating is necessary to prevent drug release from CDS pellets in the stomach, because the chitosan-dispersed water-insoluble layer dissolves gradually under acidic conditions. The resulting enteric-coated CDS (E-CDS) pellets were found to permit colon-specific drug delivery. In this study, the multiparticulate CDS was adopted not only for colon-specific drug delivery but also for sustained drug release.     

Bilayer tablets of atorvastatin calcium and nicotinic acid: formulation and evaluation

The objective of the study is to formulate bilayer tablets consisting of atorvastatin calcium (AT) as an immediate release layer and nicotinic acid (NA) as an extended release layer. The immediate release layer was prepared using super disintegrant croscarmellose sodium and extended release layer using hydroxypropylmethyl cellulose (HPMC K100M). Both the matrix and bilayer tablets were evaluated for hardness, friability, weight variation, thickness, and drug content uniformity and subjected to in vitro drug release studies. The amount of AT and NA released at different time intervals were estimated by HPLC method. The bilayer tablets showed no significant change either in physical appearance, drug content or in dissolution pattern after storing at 40 degrees C/75% relative humiding (RH) for 3 months. The release of the drug from the tablet was influenced by the polymer content and it was much evident from thermogravimetry/differential thermal analysis (TG/DTA) analysis. The results indicated that the bilayer tablets could be a potential dosage form for delivering AT and NA.     

The effect of additives on naltrexone hydrochloride release and solvent removal rate from an injectable in situ forming PLGA implant

Biodegradable in situ forming drug delivery systems for naltrexone release are promising for post‐treatment of drug addicts. The effect of two different additives, glycerol and ethyl heptanoate, on the naltrexone hydrochloride release and solvent removal from a poly(DL ‐lactide‐co‐glycolide) (PLGA) injectable implant is presented in this article. The experimental results showed that the in vitro initial release of the drug was decreased in the presence of these additives. Ethyl heptanoate was, however, more effective than glycerol and increasing the amount of additives in PLGA solution up to 5% (w/w) resulted in a decrease of initial naltrexone release rate up to 50%. The morphological evaluation of implants using scanning electron microscopy indicated that the additives generated a less porous structure together with a finger‐like to sponge‐like transition. The solvent removal profiles of injectable implants, which can be well described by thermogravimetric and morphological analysis, were in good agreement with drug release profiles. Copyright © 2006 John Wiley & Sons, Ltd.     

Hydroxypropyl chitosan bearing beta-cyclodextrin cavities: synthesis and slow release of its inclusion complex with a model hydrophobic drug

Hydroxypropyl chitosan-graft-carboxymethyl beta-cyclodextrin (HPCH-g-CM beta-CD) was synthesized by grafting CM beta-CD onto HPCH using water soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as the condensing agent. Due to the presence of hydrophobic beta-CD rings onto the HPCH backbone, this polymer can be used as a matrix for controlled drug release. The adsorption of a hydrophobic model drug, ketoprofen, by HPCH-g-CM beta-CD microparticles (using tripolyphosphate as an ionic crosslinking agent) fitted well in the Langmuir isotherm equation. The drug dissolution profile showed that HPCH-g-CM beta-CD microparticles provided a slower release of the entrapped ketoprofen than chitosan, and the release behavior was influenced by the pH value of the medium. These results suggest that beta-CD grafted with chitosan derivatives may become a potential biodegradable delivery system to control the release of hydrophobic drugs with pH-responsive capability.     

Starch cellulose acetate co-acrylate (SCAA) polymer as a drug carrier

The present study aims to create a controlled-release system through the preparation and characterization of starch cellulose acetate co-acrylate (SCAA) polymer for application as a carrier for cancer drugs. SCA was prepared from maize starch and different ratios of cellulose acetate. The obtained product SCA was reacted with acrylic acid monomer to give cellulose acetate co-acrylate. The best ratio of starch to cellulose acetate was found to be 90:10, giving a stable product with acrylic acid. The cancer drug 8-(2-methoxyphenyl)-3,4-dioxo-6-thioxo-3,4,6,7-tetrahydro-2h-pyrimido[6,1-c]-[1,2,4]triazine-9-carbonitrile was dissolved in dimethylformamide then added gradually at the end of the previous reaction under stirring for 15 min. The prepared polymers with and without the drug were characterized by Fourier-transform infrared spectroscopy. Cuboids discs of the prepared polymer/drug were subjected to drug release in aqueous media at different pH values. The release was measured spectrophotometrically. It was found that the release rate depends on the pH of the aqueous medium as well as on the concentration of the drug loaded onto the polymer carrier. Above pH 12, the polymer containing the drug degraded completely within 1 h after being subjected to alkaline media. Sustained release of drug extended to about 20 days. The amount released depended on the pH of the media in the following order: basic media > acidic media > neutral. According to Higuch’s equation, the diffusion coefficient was found to be 4.2 × 10^?8 and 5.5 × 10^?8 cm s^?1 for the two evaluated concentrations (1.5 and 2 %) of active organic compound (drug).     

In situ photopolymerization-coated pellets for pH-dependent drug delivery

An in situ photopolymerization-coating technique was applied to wrap the pellets surface with a pH-sensitive hydrogel layer made from acrylic acid and hydrophobic acrylate monomers. Powdered cellulose (Elcema^® P100) and poly(vinylpyrrolidone) (Kollidon^® 30) pellets containing theophylline were prepared by extrusion-spheronization, sprayed with an ethanol:water 50:50 v/v solution of the monomers, the cross-linker (N,N′-methylenebis(acrylamide)) and the initiator (Irgacure^® 2959), and immediately irradiated at 366 nm. The composition of coating mixture and the time of irradiation were optimized using oscillatory rheometry and analyzing the swelling and the drug release behaviour of the resultant hydrogels. When acrylic acid:lauryl acrylate 88:12 molar ratio was used, the coating did not significantly change the shape, size, or friability of the pellets, but remarkably modified theophylline release profiles. The thicker the coating layer, the better the pH-dependent control of drug release.     

Pelletization of needle-shaped phenylbutazone crystals

The flowability of needle- or plate-shaped crystals is very poor and the direct compression of these crystals is difficult. Commercial phenylbutazone consists of needle crystals and it has three polymorphs.The aim of this work was to investigate the solid-state thermal stability of phenylbutazone at condition of the pelletization process (40°C; 60 min). The other aim was the preparation of phenylbutazone pellets with centrifugal granulator.Based non the flowability and the other parameters of, the pellets, they are suitable for capsule filling or tabletting. The centrifugal granulation and the conditions were favourable for the preparation of pellets from phenylbutazone in the form of needle crystals.This revised version was published online in November 2005 with corrections to the Cover Date.     

Modulation of Tenoxicam release from hydrophilic matrix: modulator membrane versus rate-controlling membrane

This paper describes the preparation of two layered device comprising of tenoxicam containing layer and a drug free membrane layer based on Geomatrix Technology. Our device based on bilaminated films which produced by a casting/solvent evaporation technique. The drug-hydroxypropyl methylcellulose (HPMC) layer was covered by drug free membrane layer composed of a mixture of different ratios of HPMC and ethyl cellulose (EC). The prepared devices were evaluated for thickness, weight, drug content uniformity, water absorption capacity and in-vitro drug release. The films were also evaluated for appearance, smoothness and transparency. The influence of drug free membrane layer composition and thickness on the drug release pattern was studied on 12 devices (D1 to D12). The results indicate that, the release of drug from HPMC matrixes without the drug free membrane layer was fast and follows diffusion controlled mechanism. The release of drug from the devices D1, D4, D9 and D12 follow the same mechanism, while the release of drug from other devices become linear with time (zero order) and extended for long time especially when thickness and the ratio of EC was increased in the drug free membrane layer. From this study it is concluded that, changing the geometry of drug layer by addition of drug free membrane layer and changing its composition and thickness plays an important role in determining whether the drug free membrane layer is rate-controlling or modulator membrane. Hence it can facilitate the development of different pharmaceutical products with different release pattern.     

Statistical optimization of tamsulosin hydrochloride controlled release pellets coated with the blend of HPMCP and HPMC

The objective of the present study was to evaluate three coating parameters for the application of a blend of HPMCP and HPMC in ethylcellulose aqueous dispersions (Surelease) in order to obtain controlled release of tamsulosin hydrochloride. The selected independent variables, HPMCP content (X1), HPMC content (X2) and coating level (X(3)), were optimized with a three-factor, three-level Box-Behnken design. The selected dependent variables were the cumulative percentage values of tamsulosin hydrochloride that had dissolved after 2, 3 and 5 h. Various dissolution profiles of the drug from controlled release pellets were obtained. Optimization was performed for X1, X2 and X3 using the following target ranges; 15% < or = Y1 < or= 30%; 50% < or = Y2 < or = 65%; 80% < or = Y3 < or = 95%. Results of the optimization procedure indicated that the optimized levels of HPMCP content (X1), HPMC content (X2) and coating level (X3) were 30%, 15% and 25%, respectively. Controlled release pellets coated with the optimized formulation provided a release profile that was close to predicted values. In addition, the dissolution profiles of the controlled release pellets coated with the optimized formulation were similar to those of the commercial product Harunal capsule (f1 = 4.6, f2 = 78.7).     

Preparation and properties of silicon- and titanium-containing hybrid nanocomposite films based on ethyl cellulose

Nanocomposite hybrid films containing silicon and titanium compounds in the polymer matrix are prepared through the sol-gel method via the hydrolytic polycondensation of Si and Ti alkoxides (tetraethoxysilane and titanium tetrabutoxide) in the THF solution of a hydrophobic polymer, ethyl cellulose. Their structure and properties are studied with the use of a complex of physicochemical methods. During the hydrolysis of tetraethoxysilane and the subsequent polycondensation of the reaction products, silicon atoms are incorporated into the polymer and form -O-Si-O-bonds involving hydroxyl groups of ethyl cellulose. In the sol-gel method, titanium alkoxide yields nanosized particles of titanium dioxide that play the role of fillers in the polymer matrix. Titanium-containing films show solubility in THF and, after prolonged contact with the solvent, precipitate titanium dioxide from the solution. Hybrid films containing silicon are insoluble owing to the formation of a chemical network between polymer molecules and Si-OH groups of the products of hydrolysis of silicon alkoxide, as confirmed by the IR data. It is shown that the amounts and types of alkoxides and the diameters of the structures formed in the polymer matrix via the sol-gel procedure affect the hydrophilicity levels of ethyl cellulose hybrid films and their abilities to swell in water and aqueous solutions of organic dyes (brilliant blue and methylene blue). Ethyl cellulose hybrid films are hydrophilic, and they facilitate the removal of dye molecules from aqueous solutions. The best properties are featured by the films containing nanosized particles of titanium dioxide in the polymer matrix.     

Spray coating of cellulose aerogel particles in a miniaturized spouted bed

Cellulose - Aim of this work is to apply protective and homogeneous shellac coating layers on the surface of hydrophilic open-pore cellulose aerogel particles with low...     

Functional delivery vehicle of organic nanoparticles in inorganic crystals

This work has developed a functional delivery vehicle of an organic-inorganic hybrid consisted of organic nanoparticles in inorganic crystals, which greatly improves the stability of the bioactive and implements a unique pH-triggered release.     

Hydroxypropyl methylcellulose based cephalexin extended release tablets: influence of tablet formulation,hardness and storage on in vitro release kinetics

The object of this study was to develop hydroxypropyl methylcellulose (HPMC) based cephalexin extended release tablet, which can release the drug for six hours in predetermined rate. Twenty-one batches of cephalexin tablets were prepared by changing various physical and chemical parameters, in order to get required theoretical release profile. The influences of HPMC, microcrystalline cellulose powder (MCCP), granulation technique, wetting agent and tablet hardness on cephalexin release from HPMC based extended release tablets were studied. The formulated tablets were also characterized by physical and chemical parameters. The dissolution results showed that a higher amount of HPMC in tablet composition resulted in reduced drug release. Addition of MCCP resulted in faster drug release. Tablets prepared by dry granulation was released the drug slowly than the same prepared with a wet granulation technique. Addition of wetting agent in the tablets prepared with dry granulation technique showed slower release. An increase in tablet hardness resulted in faster drug release. Tablets prepared with a wet granulation technique and having a composition of 9.3% w/w HPMC with a hardness of 10-12 kg/cm(2) gave predicted release for 6 h. The in vitro release data was well fit in to Higuchi and Korsmeyer-Peppas model. Physical and chemical parameters of all formulated tablets were within acceptable limits. One batch among formulated twenty-one batches was successful and showed required theoretical release. The effect of storage on in vitro release and physicochemical parameters of successful batch was studied and was found to be in acceptable limits.     

Biodegradation of ldpe/cellulose blends by common fungi

We have developed a cellulose-polyethylene blend polymer film for degradative susceptibility to brown rot or cellulasic fungi. Paxon low-density polyethylene (LDPE) polymer pellets were melt-blended with 8855 cellulose. A pure polyethylene sample was melted, pressed and used as the control. Naturally occurring fungi were harvested from decaying wood and cultured on full nutrient agar until individual phenotypes developed. The discrete fungal colonies were isolated and transferred to bacteriological agar with carboxymethylcellulose as the only carbon source. Surviving fungi were subjected to an indirect cellulase assay to confirm cellulolytic properties. Trichoderma viride showed 100% surface area growth on low-density polyethylene (LDPE) blended with 8% (w/w) cellulose in 90 days. Growth coverage by Gliomastix on LDPE blended with 8% cellulose reached 100 % in 150 days, and up to 72% growth activity on blends with 1.5% cellulose, 1% cellulose, and the control LDPE.     

Functional delivery vehicle of organic nanoparticles in inorganic crystals

Encapsulation of bioactive substances for extended shelf life and controlled, targeted release is critical for their applications in food and drug delivery. Here, a new method has been developed to encapsulate bioactive molecules in the crystal composites, showing greatly enhanced stability and unique pH-triggered response. Chlorophyll, a model bioactive, is first loaded in shellac nanoparticles via co-precipitation with a high encapsulation efficiency, and then the chlorophyll-loaded nanoparticles are incorporated into calcite crystals grown from a gel media containing the nanoparticles. Under the protection of shellac nanoparticles and calcite crystals, chlorophyll shows excellent stability even under light. Encapsulated chlorophyll could only be released by first dissolving the calcite crystals under acidic condition and then dissolving the shellac nanoparticles under alkaline condition. The unique pH-triggered release mimics the pH change from acidic in the stomach to alkaline in the intestine and is thus well suited for controlled, targeted intestinal release. This work suggests that the crystal composites are an ideal delivery vehicle for the functional design of bioactive molecules.     

Improved skin delivery and validation of novel stability-indicating HPLC method for ketoprofen nanoemulsion

Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) widely used to treat rheumatoid arthritis and other inflammatory diseases. Normally used by oral route, this drug presents numerous side effects related to this administration route, such as nausea, dyspepsia, diarrhea, constipation and even renal complications. To avoid that, topical administration of ketoprofen represents a good alternative, since this drug has both partition coefficient and aqueous solubility suitable for skin application, compared to other NSAIDs. In this study, we describe the production of a nanoemulsion containing ketoprofen, its skin permeation and in vitro release study and a novel validation method to analyze this drug in the permeation samples and a forced degradation study using skin and nanoemulsion samples. The new HPLC method was validated, with all specifications in accordance with validation parameters and with an easy chromatographic condition. Forced degradation study revealed that ketoprofen is sensitive to acid and basic hydrolysis, developing degradation peaks after exposure to these factors. Concerning in vitro release from the nanoemulsion, release curves presented first order profile and were not similar to each other. After 8 h, 85% of ketoprofen was release from the nanoemulsion matrix while 49% was release from control group. In skin permeation study, nanoemulsion enabled ketoprofen to pass through the skin and enhanced retention in the epidermis and stratum corneum, layer on which the formulation presented statistically different values compared to the control group.