Dynamic and static curing of ethylcellulose:PVA-PEG graft copolymer film coatings

When using aqueous polymer dispersions for the preparation of controlled-release film coatings, instability during long-term storage can be a crucial concern. Generally, a thermal after treatment is required to assure sufficient polymer particle coalescence. This curing step is often performed under static conditions in an oven, which is a time-consuming and rather cumbersome process. Dynamic curing in the fluidized bed presents an attractive alternative. However, yet little is known on the required conditions, in particular: temperature, time, and relative humidity, to provide stable film structures. The aim of this study was to better understand the importance of these key factors and to evaluate the potential of dynamic curing compared with that of static curing. Recently proposed ethylcellulose:poly(vinyl alcohol)-poly(ethylene glycol) graft copolymer (PVA-PEG graft copolymer) dispersions were coated on theophylline and metoprolol succinate-loaded starter cores, exhibiting different osmotic activity. Importantly, processing times as short as 2 h were found to be sufficient to provide long-term stable films, even upon open storage under stress conditions. For instance, 2-h dynamic curing at 57 °C and 15% relative humidity are assuring stable film structures in the case of theophylline matrix cores coated with 15% ethylcellulose:PVA-PEG graft copolymer 85:15. Importantly, the approach is also applicable to other types of drugs and starter cores, and the underlying drug release mechanisms remain unaltered.     

Evaluation of the drug release patterns and long term stability of aqueous and organic coated pellets by using blends of enteric and gastrointestinal insoluble polymers

The major aim of this study was to identify an efficient tool to adjust drug release patterns from aqueous and organic ethylcellulose (a gastrointestinal insoluble polymer) coated pellets and to evaluate the long term stability of the film coatings. Drug release was monitored during open and closed storage at 25 °C/60% RH (ambient conditions) and 40 °C/75% RH (stress conditions) for up to 24 months. Release of vatalanib succinate, a poorly soluble drug that demonstrates pH-dependent solubility, from pure ethylcellulose coated pellets was slow irrespectively of the type of coating and release medium. By addition of the enteric polymer methacrylic acid/ethyl acrylate copolymer (applied as aqueous Kollicoat MAE 30 DP dispersion or organic solution of Kollicoat MAE 100 P) to ethylcellulose broad ranges of drug release patterns could be achieved. For aqueous film coatings the addition of Kollicoat MAE 30 DP to ethylcellulose dispersions resulted in unaltered drug release kinetics during closed storage at ambient and stress conditions. The storage stabilizing effect of the added enteric polymer might be explained by the more hydrophilic nature of Kollicoat MAE 30 DP compared to ethylcellulose trapping water during film formation and improving polymer particle coalescence. However, during open storage of aqueous coated ethylcellulose:Kollicoat MAE 30 DP pellets at stress conditions drug release decreased due to further gradual polymer particle coalescence. In contrast, drug release rates from organic coated ethylcellulose:Kollicoat MAE 100 P pellets stored at ambient and stress conditions did not change which could be explained by differences in the film formation process. This clearly indicates that the presented concept of the addition of methacrylic acid/ethyl acrylate copolymer to ethylcellulose film coatings in combination with an organic coating process is able to achieve broad ranges of drug release patterns and to overcome storage instability.     

Ethanol-resistant ethylcellulose/guar gum coatings – Importance of formulation parameters

Recently, ethylcellulose/guar gum blends have been reported to provide ethanol-resistant drug release kinetics from coated dosage forms. This is because the ethanol insoluble guar gum effectively avoids undesired ethylcellulose dissolution in ethanol-rich bulk fluids. However, so far the importance of crucial formulation parameters, including the minimum amount of guar gum to be incorporated and the minimum required guar gum viscosity, remains unclear. The aim of this study was to identify the most important film coating properties, determining whether or not the resulting drug release kinetics is ethanol-resistant. Theophylline matrix cores were coated in a fluid bed with blends of the aqueous ethylcellulose dispersion “Aquacoat® ECD 30” and guar gum. The polymer blend ratio, guar gum viscosity, and degree of dilution of the final coating dispersion were varied. Importantly, it was found that more than 5% guar gum (referred to the total polymer content) must be incorporated in the film coating and that the apparent viscosity of a 1% aqueous guar gum solution must be greater than 150 cP to provide ethanol-resistance. In contrast, the investigated degree of coating dispersion dilution was not found to be decisive for the ethanol sensitivity. Furthermore, all investigated formulations were long term stable, even upon open storage under stress conditions for 6 months.     

Enteric polymers as acidifiers for the pH-independent sustained delivery of a weakly basic drug salt from coated pellets

Weakly basic drugs and their salts exhibit a decrease in aqueous solubility at higher pH, which can result in pH-dependent or even incomplete release of these drugs from extended release formulations. The objective of this study was to evaluate strategies to set-off the very strong pH-dependent solubility (solubility: 80 mg/ml at pH 2 and 0.02 mg/ml at pH 7.5, factor 4000) of a mesylate salt of weakly basic model drug (pK_a 6.5), in order to obtain pH-independent extended drug release. Three approaches for pH-independent release were investigated: (1) organic acid addition in the core, (2) enteric polymer addition to the extended release coating and (3) an enteric polymer subcoating below the extended release coating. The layering of aspartic acid onto drug cores as well as the coating of drug cores with an ethylcellulose/Eudragit L (enteric polymer) blend were not effective to avoid the formation of the free base at pH 7.5 and thus failed to significantly improve the completeness of the release compared to standard ethylcellulose/hydroxypropyl cellulose (EC/HPC)-coated drug pellets. Interestingly, the incorporation of an enteric polymer layer underneath the EC/HPC coating decreased the free base formation at pH 7.5 and thus resulted in a more complete release of up to 90% of the drug loading over 18 h. The release enhancing effect was attributed to an extended acidification through the enteric polymer layer. Flexible release patterns with approximately pH-independent characteristics were successfully achieved.     

Enzymatically degraded Eurylon 6 HP-PG: ethylcellulose film coatings for colon targeting in inflammatory bowel disease patients

Objectives Film coatings based on blends of Eurylon 6 HP‐PG (a hydroxypropylated and pregelatinized high amylose starch) and ethylcellulose were to be evaluated as promising coating materials for site‐specific drug delivery to the colon of patients suffering from inflammatory bowel diseases. Methods Pellet starter cores containing 60% 5‐aminosalicylic acid were prepared by extrusion/spheronization and coated with different Eurylon 6 HP‐PG : ethylcellulose blends at various coating levels. Drug release was measured in media simulating the contents of the upper gastrointestinal tract (in the presence and absence of enzymes) as well as in media simulating the contents of the colon. Key findings 5‐Aminosalicylic acid release could effectively be suppressed in 0.1 N HCl and phosphate buffer pH 6.8, optionally containing pepsin or pancreatin, but occurred as soon as the pellets came into contact with culture medium inoculated with faecal samples from inflammatory bowel disease patients. This can be attributed to the partial degradation of the starch derivative by enzymes secreted by bacteria present in the colon of these patients. Conclusions The presented drug delivery system is adapted to the pathophysiological conditions in inflammatory bowel disease patients. Furthermore, drug release remained unaltered upon 1 year open storage.     

Aqueous HPMCAS coatings: effects of formulation and processing parameters on drug release and mass transport mechanisms.

The major aim of the present work was to study the effects of various formulation and processing parameters on the resulting drug release kinetics from theophylline matrix pellets coated with aqueous hydroxypropyl methylcellulose acetate succinate (HPMCAS) dispersions. The plasticizer content, coating level and curing conditions significantly affected the release patterns in 0.1 M HCl, whereas no major effects were observed in phosphate buffer, pH 7.4. Due to the significant size of the HPMCAS particles (being in the micrometer range), their coalescence was particularly crucial and not complete upon coating. Consequently, at low coating levels continuous water-filled channels connected the bead cores with the release medium through which the drug could rapidly diffuse, resulting in high release rates even at low pH. In contrast, at high coating levels such continuous connections did not exist (due to the increased number of polymer particle layers), and drug release was controlled by diffusion through the macromolecular network resulting in much lower release rates in 0.1 M HCl. Importantly, pellet curing at elevated temperature and ambient relative humidity or exposure to elevated relative humidity at room temperature did not significantly alter the microstructure of the coatings, leading to only slightly decreased drug release rates. In contrast, pellet curing at elevated temperature combined with elevated relative humidity induced significant further polymer particle coalescence, resulting in a change of the underlying drug release mechanism and significantly reduced drug release rates.     

Influence of Plasticization Time,Curing Conditions,Storage Time,and Core Properties on the Drug Release from Aquacoat-Coated Pellets

Theophylline or chlorpheniramine maleate pellets were coated with an aqueous ethylcellulose dispersion, Aquacoat. The influence of the plasticization time, curing conditions, storage time, and core properties on the drug release were investigated. The plasticization time (time between plasticizer addition to the polymer dispersion and the spraying process) did not affect the drug release, when the water-soluble plasticizer, triethyl citrate, was used because of its rapid uptake by the colloidal polymer particles. In contrast, with the water-insoluble plasticizer, acetyltributyl citrate (ATBC), plasticization time (1/2 h vs 24 h) influenced the drug release, the longer plasticization time resulted in a slower drug release because of a more complete plasticizer uptake prior to the coating step. However, a thermal aftertreatment of the coated pellets at elevated temperatures (curing step) reduced/eliminated the effect of the plasticization time with ATBC. In general, curing reduced the drug release and resulted in stable drug release profiles. The time period between the coating and the curing step was not critical when the pellets were cured for a longer time. The structure of the pellet core (high dose matrix vs low dose layered pellet) strongly affected the drug release. A slow, zero-order drug release was obtained with high dose theophylline pellets, while a more rapid, first-order release pattern was obtained with low dose theophylline-layered nonpareil pellets.     

Influence of plasticization time, curing conditions, storage time, and core properties on the drug release from Aquacoat-coated pellets

Theophylline or chlorpheniramine maleate pellets were coated with an aqueous ethylcellulose dispersion, Aquacoat. The influence of the plasticization time, curing conditions, storage time, and core properties on the drug release were investigated. The plasticization time (time between plasticizer addition to the polymer dispersion and the spraying process) did not affect the drug release, when the water-soluble plasticizer triethyl citrate, was used because of its rapid uptake by the colloidal polymer particles. In contrast, with the water-insoluble plasticizer acetyltributyl citrate (ATBC), plasticization time (1/2 h vs 24 h) influenced the drug release, the longer plasticization time resulted in a slower drug release because of a more complete plasticizer uptake prior to the coating step. However a thermal aftertreatment of the coated pellets at eleylated temperatures (curing step) reduced/eliminated the effect of the plasticization time with ATBC. In general, curing reduced the drug release and resulted in stable drug release profiles. The time period between the coating and the curing step was not critical when the pellets were cured for a longer time. The structure of the pellet core (high dose matrix vs low dose layered pellet) strongly affected the drug release. A slow, zero-order drug release was obtained with high dose theophylline pellets, while a more rapid, first-order release pattern was obtained with low dose theophylline-layered nonpareil pellets.     

Improved drug delivery to the lower intestinal tract with tablets compression-coated with enteric/nonenteric polymer powder blends

The objective of this study was to develop pH-erosion-controlled compression-coated tablets for potential colonic drug delivery with improved gastric resistance and pulsatile release based on compression-coatings of powder blends of the enteric polymer Eudragit® L100-55 and the extended release polymer ethylcellulose. Tablet cores containing model drugs of varying solubilities (acetaminophen, carbamazepine and chlorpheniramine maleate) were compression-coated with different ratios of Eudragit® L100-55:ethylcellulose 10cP FP at different compression forces and tablet core:compression-coat ratios. The compression-coated tablets were characterized by drug release, media uptake, erosion behaviour and wettability. All drugs were released in a pulsatile fashion in higher pH-media after a lag time, which was controlled by the erosion properties of the Eudragit L:ethylcellulose compression-coating. The addition of ethylcellulose avoided premature drug release in lower pH-media and significantly increased the lag time in higher pH-media because of a reduction in wettability, media uptake and erosion of the compression-coatings. Importantly, ethylcellulose also reduced the pH-dependency of the erosion process between pH 5.5 and 7.4. The lag time could also be increased by increasing the compression force and decreasing the core:compression-coat ratio. In conclusion, tablets compression-coated with blends of Eudragit L and ethylcellulose resulted in excellent release properties for potential targeting to the lower intestinal tract with no release in lower pH-media and rapid release after a controllable lag time in higher pH-media.     

Evaluation of Drug-Containing Polymer Films Prepared from Aqueous Latexes

Polymeric films containing salicylic acid or propranolol HC1 were prepared by casting and drying a drug-containing, aqueous colloidal polymer dispersion (Eudragit NE 30D) as an alternative to films cast from organic polymer solutions. The drug was either dissolved (salicylic acid) or dissolved/ dispersed (propranolol HC1) in the polymeric matrix. Incompatibilities (flocculation or coagulation) between salts of basic drugs and two ethylcellulose latexes were overcome by substituting the anionic surfactants with a nonionic surfactant (Pluronic P103). The drug release was studied as a function of drug loading, film thickness, amount of hydrophilic additive (hydroxypropyl methylcellulose), and storage humidity. The release of propranolol HC1 (monolithic dispersion) was a combination of diffusion through the polymer and pores or channels; the extent of each release mechanism depended on the drug loading. On DSC thermograms, melting transitions were obtained with monolithic dispersions but not with monolithic solutions. The heat of fusion was linearly correlated to the amount of drug in the films. The amount of drug remaining in the film after the dissolution study was not detectable and corresponded to the drug dissolved in the polymer. The drug release increased with increased drug loading and increased amount of hydroxypropyl methylcellulose but was independent of film thickness and relatively insensitive to different storage humidities.     

Physicochemical properties of film-coated melt-extruded pellets

The purpose of this study was to investigate the physicochemical properties of poly(ethylene oxide) (PEO) and guaifenesin containing beads prepared by a melt-extrusion process and film-coated with a methacrylic acid copolymer. Solubility parameter calculations, thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), modulated differential scanning calorimetry (MDSC), X-ray powder diffraction (XRPD) and high performance liquid chromatography (HPLC) were used to determine drug/polymer miscibility and/or the thermal processibility of the systems. Powder blends of guaifenesin, PEO and functional excipients were processed using a melt-extrusion and spheronization technique and then film-coated in a fluidized bed apparatus. Solubility parameter calculations were used to predict miscibility between PEO and guaifenesin, and miscibility was confirmed by SEM and observation of a single melting point for extruded drug/polymer blends during MDSC investigations. The drug was stable following melt-extrusion as determined by TGA and HPLC; however, drug release rate from pellets decreased upon storage in sealed HDPE containers with silica desiccants at 40 degrees C/75% RH. The weight loss on drying, porosity and tortuosity determinations were not influenced by storage. Recrystallization of guaifenesin and PEO was confirmed by SEM and XRPD. Additionally, the pellets exhibited a change in adhesion behaviour during dissolution testing. The addition of ethylcellulose to the extruded powder blend decreased and stabilized the drug release rate from the thermally processed pellets. The current study also demonstrated film-coating to be an efficient process for providing melt-extruded beads with pH-dependent drug release properties that were stable upon storage at accelerated conditions.     

Drug release mechanisms from Kollicoat SR:Eudragit NE coated pellets

Thin, free films based on Kollicoat SR:Eudragit NE blends were prepared by casting or spraying aqueous dispersions of these polymers, and were thoroughly characterized with respect to their water uptake behavior, water permeability, dry mass loss kinetics, mechanical properties and drug release patterns. A mechanistic mathematical model based on Fick's law of diffusion was used to quantify the experimentally measured release of metoprolol succinate from various types of systems. With increasing Eudragit NE content the films became more hydrophobic, resulting in decreased water permeability as well as water uptake rates and extents. In addition, the dry mass loss upon exposure to the release medium decreased. Consequently, the films' permeability for the drug decreased. Importantly, metoprolol succinate release from thin films was mainly controlled by pure diffusion, allowing for the determination of the apparent diffusion coefficient of the drug in the different polymeric systems. Knowing these values, drug release from coated pellets could be quantitatively predicted, assuming intact film coatings throughout the observation period. Comparison with independent experimental results showed that crack formation set on very rapidly in the polymeric membranes upon exposure to the release medium in the case of sugar starter cores, irrespective of the polymer:polymer blend ratio and investigated coating level. In contrast, the onset of crack formation was delayed as a function of the blend ratio and coating thickness in the case of microcrystalline cellulose starter cores, attracting less water into the pellets core. The obtained new insight into the underlying drug release mechanisms can be very helpful during device optimization and improve the safety of this type of advanced drug delivery systems.     

Model prodrugs designed for the intestinal peptide transporter. A synthetic approach for coupling of hydroxy-containing compounds to dipeptides.

The human peptide transporter, hPepT1, situated in the small intestine, may be exploited to increase absorption of drugs or model drugs by attaching them to a dipeptide, which is recognised by hPepT1. A synthetic protocol for this kind of model prodrugs was developed, in which model drugs containing a hydroxy group were attached to enzymatically stable dipeptides by hydrolysable ester linkages. Furthermore, a number of benzyl alcohols with various substituents in the 4-position of the phenyl ring were coupled to D-Asp-Ala and D-Glu-Ala. Ideally, a prodrug should be stable in the upper small intestine and be converted to the parent drug during or after transport into the blood circulation. Therefore, we investigated the influence of the electronegativity of the substituent in the 4-position of the phenyl ring on stability in aqueous solution at pH 6.0 and 7.4, corresponding to pH in jejunum and blood, respectively. In addition, the influence of the electronegativity of the substituent on stability upon storage was examined. Model prodrugs containing electron donating substituents in the 4-position of the phenyl ring decomposed upon storage, while model prodrugs containing no substituents or electron withdrawing substituents in the 4-position were stable. In aqueous solution (pH 6.0 and 7.4), electron withdrawing substituents in the 4-position decreased the half-life of the model prodrug. These data provide important information on stability of this kind of model prodrugs upon storage and under aqueous conditions. The results may be applied in the rational design of oligopeptide ester prodrugs to obtain prodrugs, which are stable upon storage and have an optimal release profile of the drug.     

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.     

pH-Sensitive Polymer Blends Used as Coating Materials to Control Drug Release from Spherical Beads: Elucidation of the Underlying Mass Transport Mechanisms

Purpose To elucidate the drug release mechanisms from pellets coated with pH-sensitive polymer blends.Methods Verapamil hydrochloride-loaded beads were coated with various blends of a water-insoluble and an enteric polymer, ethylcellulose:Eudragit L and Eudragit NE:Eudragit L, respectively. Both experimental and theoretical techniques were used to characterize the systems before and upon exposure to 0.1 M HCl and phosphate buffer (pH 7.4).Results Using analytical solutions of Fick’s second law of diffusion, optical and scanning electron microscopy, and mechanical and gravimetric analysis, new insight into the underlying drug release mechanisms could be gained. More importantly, the latter can be effectively altered by varying the type of polymer blend and blend ratio. For example, at low pH drug release is primarily controlled by diffusion through the intact film coatings in Eudragit NE:Eudragit L blends, whereas crack formation is of major importance in ethylcellulose:Eudragit L-coated systems. At high pH, the (partial) leaching of the enteric polymer out of the coatings plays an important role. In all cases, the observed drug release profiles could be explained based on the occurring mass transport processes.Conclusions The obtained new knowledge can be used to effectively adjust desired drug release mechanisms and, thus, release patterns.     

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.     

Pectin/Ethylcellulose Film Coating Formulations for Colonic Drug Delivery

Purpose. The purpose of the study was to investigate the potential of pectin, ethylcellulose combinations as a practical film coating for colonic delivery. Methods. Combinations of pectin and ethylcellulose, in the form of an aqueous dispersion, were used as coating formulations. Paracetamol cores were used as the substrate. The coatings were assessed by a flow through dissolution system simulating in vivo conditions by changes in pH and residence time. Pectinolytic enzymes were used to simulate the bacterial flora of the colon. Results. Drug release was controlled by the ratio of ethylcellulose to pectin in the film coat. Increasing the proportion of ethylcellulose and increasing the coat weight reduced drug release in pHl and pH7.4 media. The addition of pectinolytic enzymes to pH6 media increased the release of drug. Conclusions. Combinations of ethylcellulose and pectin can provide protection to a drug in the upper g.i. tract while allowing enzymatic breakdown and drug release in the colon.     

Ibuprofen-loaded ethylcellulose/polystyrene microspheres: an approach to get prolonged drug release with reduced burst effect and low ethylcellulose content

The aim of this study was to develop ethylcellulose microspheres for prolonged drug delivery with reduced burst effect. Ethylcellulose microspheres loaded with ibuprofen were prepared with and without polystyrene, which was used to retard drug release from ethylcellulose microspheres. Ibuprofen-loaded ethylcellulose microspheres with a polystyrene content of 0-25% were prepared by the solvent evaporation technique and characterized by drug loading, infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy. The in vitro release studies were performed to study the influence of polystyrene on ibuprofen release from ethylcellulose microspheres. The microspheres showed 28-46% of drug loading and 80-92% of entrapment, depending on polymer/drug ratio. The infrared spectrum and thermogram showed stable character of ibuprofen in the microspheres and revealed an absence of drug polymer interaction. The prepared microspheres were spherical in shape and had a size range of 0.1-4 microm. Ethylcellulose/polystyrene microspheres showed prolonged drug release and less burst effect when compared to microspheres prepared with ethylcellulose alone. Microspheres prepared with an ethylcellulose/polystyrene ratio of 80:20 gave a required release pattern for oral drug delivery. The presence of polystyrene above this ratio gave release over 24 h. To find out the mechanism of drug release from ethylcellulose/polystyrene microspheres, the data obtained from in vitro release were fitted in various kinetic models. High correlation was obtained in Higuchi and Korsmeyer-Peppas models. The drug release from ethylcellulose/polystyrene microspheres was found to be diffusion controlled.     

Development of sustained release fast-disintegrating tablets using various polymer-coated ion-exchange resin complexes

Complex formation between drugs and ion-exchange resins was investigated and the effects of coating by various aqueous polymeric dispersions on the complexes were evaluated for developing new sustained-release fast-disintegrating tablets (FDTs). Complexes of ion-exchange resin and dextromethorphan, a model drug, were prepared using different particle sizes of the resins. Aqueous colloidal dispersions of ethylcellulose (EC) and poly(vinyl acetate) (Kollicoat SR30D) were used for fluid-bed coating. Based on drug loading, release profiles, and scanning electron microscopy (SEM) images, the coated particles were granulated with suitable tablet excipients and then compressed into the tablets. Drug release profiles and SEM pictures were compared before and after the manufacturing processes. As the particle size of resins increased, the drug loading and release rate decreased due to the reduced effective diffusion coefficient and surface area. Higher coating level decreased the release rate further. In contrast to EC, Kollicoat SR30D coated particles could be compressed into tablets without any rupture or cracks on the coating since the mechanical properties of the polymer was more resistant to the manufacturing processes. This resulted in no significant changes in release rates. SEM showed the mechanical strength of the polymers affected the morphological change after compression. When the drug release profiles were applied into Boyd model and Higuchi equation, the linear relationship was observed, indicating that the diffusion within the resin matrix is the rate-controlling step.     

Exploiting gastrointestinal bacteria to target drugs to the colon: an in vitro study using amylose coated tablets

The bacterial substrate amorphous amylose, in the form of a film coating, provides a means of delivering drugs to the colon. This coating has traditionally been applied to multi-unit systems, in part because of the small size and divided nature of this type of dosage form, which provides a large surface area for enzymatic attack and drug release. The present study was conducted to explore the utility of the coating for colonic targeting of single unit tablet systems. Amylose was combined with the water-insoluble polymer ethylcellulose, which acts as a structuring agent, in different proportions to produce film coatings of various thicknesses for application to mesalazine (mesalamine or 5-aminosalicylic acid)-containing tablets. Drug release from the coated products was assessed under pH dissolution conditions resembling the stomach and small intestine, and also in conditions simulating the colon using a batch culture fermenter inoculated with human faecal bacteria. The rate and extent of drug release was related to the ratio of amylose to ethylcellulose in the film and the thickness of the coating. Increasing the proportion of ethylcellulose in the film and/or the thickness of the coating depressed the rate of drug release in the conditions of the upper gastrointestinal tract. Drug release from the coated products was accelerated in the fermentation environment of the colon. This is attributed to bacterial digestion of the amylose component of the film coat producing pores for drug diffusion. This work indicates that amylose coated tablet formulations are promising vehicles for drug delivery to the colon.