Near-infrared spectroscopic analysis of the breaking force of extended-release matrix tablets prepared by roller-compaction: influence of plasticizer levels and sintering temperature

The aim of this study was to investigate the feasibility of near-infrared (NIR) spectroscopy for the determination of the influence of sintering temperature and plasticizer levels on the breaking force of extended-release matrix tablets prepared via roller-compaction. Six formulations using theophylline as a model drug, Eudragit® RL PO or Eudragit® RS PO as a matrix former and three levels of TEC (triethyl citrate) as a plasticizer were prepared. The powder blend was roller compacted using a fixed roll-gap of 1.5?mm, feed screw speed to roller speed ratio of 5:1 and roll pressure of 4?MPa. The granules, after removing fines, were compacted into tablets on a Stokes B2 rotary tablet press at a compression force of 7?kN. The tablets were thermally treated at different temperatures (Room Temperature, 50, 75 and 100?°C) for 5?h. These tablets were scanned in reflectance mode in the wavelength range of 400–2500?nm and were evaluated for breaking force. Tablet breaking force significantly increased with increasing plasticizer levels and with increases in the sintering temperature. An increase in tablet hardness produced an upward shift (increase in absorbance) in the NIR spectra. The principle component analysis (PCA) of the spectra was able to distinguish samples with different plasticizer levels and sintering temperatures. In addition, a 9-factor partial least squares (PLS) regression model for tablets containing Eudragit® RL PO had an r² of 0.9797, a standard error of calibration of 0.6255 and a standard error of cross validation (SECV) of 0.7594. Similar analysis of tablets containing Eudragit® RS PO showed an r² of 0.9831, a standard error of calibration of 0.9711 and an SECV of 1.192.     

Controlled Release of a Poorly Water-Soluble Drug from Hot-Melt Extrudates Containing Acrylic Polymers

ABSTRACT

Controlled release tablets containing a poorly water-soluble drug, indomethacin (IDM), acrylic polymers (Eudragit® RD 100, Eudragit® L 100, or Eudragit® S 100), and triethyl citrate (TEC) were prepared by hot-melt extrusion. The physicochemical and IDM release properties of the controlled release hot-melt extrudates were investigated. Indomethacin (IDM) was found to be both thermally and chemically stable following hot-melt extrusion processing and displayed a plasticizing effect on Eudragit® RL PO as demonstrated by a decrease in the glass transition temperatures of the polymer. The inclusion of either Pluronic® F68, Eudragit® L 100, or Eudragit® S 100 in the powder blend containing Eudragit® RD 100 prior to processing increased the rate of release of the IDM from the extrudates. An increase in the media pH and a decrease in the granule particle size also increased the rate of release of IDM. The inclusion of TEC up to 8% in the granule formulation or compressing the granules into tablets had no significant effect on the drug release rate. Indomethacin (IDM) was transformed from a crystalline Form I into an amorphous form in the Eudragit® RD 100 granules following hot-melt extrusion. The thermal processing facilitated the formation of a solid solution with a continuous matrix structure that was shown to control drug diffusion from the extrudates.     

The effects of plasticizers on the release of metoprolol tartrate from granules coated with a polymethacrylate film

For coating metoprolol tartrate granules, coating dispersions of Eudragit RS 30 D containing 6%, 12%, or 18% (based on polymer weight) of one of the following plasticizers were used: polyethylene glycol 400 (PEG400), propylene glycol (PG), tributyl citrate (TBC), and triethyl citrate (TEC). The release of metoprolol tartrate from these coated granules was determined at pH 1.2 and 7.4. Slower release resulted from the use of each plasticizer, being slower with increasing concentration of the plasticizer. Release was faster with the more water soluble PEG400 and PG than with TBC and TEC. pH-dependent release was observed with PEG400, PG, and TBC, while TEC gave pH-independent release of drug.     

Modifying the Release Properties of Eudragit® L30D

Abstract

The influence of various additives, namely, PEG, mannitol, and HPMCP 50 incorporated with Eudragit® L30D on drug release from pellets was investigated. Cores of a water soluble drug were prepared by the powder layering technique using the CF Granulator (CF 360) and coating was accomplished utilizing the Glatt GPCG3 machine. Drug release from pellets coated with Eudragit® L30D was found to be influenced by the type and the level of the additive incorporated with the copolymer. At pH 1.5, PEG, regardless of the molecular weight, did not have any significant effect on drug release. At pH 5.5, however, PEG significantly decreased drug release from coated pellets, and the decrease was more pronounced as the molecular weight of PEG was increased. Release of the drug from pellets coated with Eudragit® L30D containing mannitol was found to be dependent on mannitol concentration at pH 1.5, 3.5 and 4.5 but independent of mannitol concentration at pH 5.5. The release of drug through Eudragit® L30D:HPMCP 50 films was found to be dependent on the ratio of the polymers.     

Preparation and In-Vitro Evaluation of A Controlled Release Drug Delivery System of Theophylline Using An Aqueous Acrylic Resin Dispersion.

Abstract

Eudragit® E30D was utilized in conjunction with talc and xanthan gum to coat theophylline granules via a Wurster-type air suspension column. Since the resin is extremely tacky and cannot be used alone as a coating formulation, different amounts of talc and xanthan gum were incorporated into the Eudragit® E30D suspension to allow for coating of theophylline granules. The release profile of theophylline from the coated granules was found to be dependent on the ratio of the additives to the resin used in the coating suspension as well as on the coating level applied to the final product. A sample of theophylline granules coated with a film-coating suspension containing 1.5:1.0: :Talc: Eudragit® E30D resin (calculated on dry basis) exhibited a zero order release profile. However, the in-vitro release rates of this formulation decreased on storage. As the ratio of talc and Eudragit® E30D was changed to 1:1, the coated theophylline granules showed a release profile that remained unchanged even after exposure at room temperature, 30° C and 40° C for three months. A stable theophylline formulation was achieved by curing the coated product at 40°C for 24 hours.     

Time-Dependent Mechanical Properties of Polymeric Coatings Used in Rupturable Pulsatile Release Dosage Forms

Abstract

The mechanical properties of polymer films used in pharmaceutical coatings of pulsatile drug delivery systems were evaluated in the dry and the wet state by a newly developed puncture test, which allowed the time-dependent measurement of the mechanical properties on the same film specimen. Force, puncture strength, energy at break, modulus, and strain were investigated as a function of water exposure time with respect to the type of polymer and the type and concentration of plasticizer and pore former (hydroxypropyl methylcellulose, HPMC). Eudragit® RS films were very flexible, had a high strain, and broke upon puncture with only small cracks. In contrast, ethylcellulose films were more brittle with a lower strain and showed complete film rupture. Increased amounts of the hydrophilic pore former, HPMC, resulted in a reduced puncture strength and in an increase in water uptake and weight loss of the films. The puncture strength decreased with increasing plasticizer concentration and was lower with the lipophilic dibutyl sebacate than with the hydrophilic triethyl citrate.     

The Effect of Curing on Drug Release and Morphological Properties of Ethylcellulose Pseudolatex-Coated Beads

Abstract

Drug-containing nonpareil beads were coated in a fluidized bed with a commercial ethylcellulose pseudolatex, Aquacoat. The drug release was investigated as a function of curing conditions (curing time and temperature) for a hydrophilic and lipophilic drug (chlorpheniramine maleate and ibuprofen) at different levels of plasticizer (triethyl citrate). Curing of coated beads at elevated temperatures immediately after the coating process significantly changed the drug release pattern. Both a retardation and an enhancement in drug release were seen, with the extent being dependent on the type of drug and curing conditions. With chlorpheniramine maleate, a drug with low affinity for the ethylcellulose coating, a curing step was necessary at intermediate plasticizer levels to obtain good film formation and a limiting drug release pattern, while the use of higher plasticizer levels eliminated the need for a curing step. With ibuprofen, a lipophilic drug with high solubility in the ethylcellulose coating, drug crystals were apparent on the bead surface after curing. Curing of ibuprofen beads as a function of time initially decreased but then substantially increased the drug release as a result of drug diffusion across the ethylcellulose membrane with subsequent crystallization on the bead surface. An intermediate seal coat reduced the diffusion of the drug into the ethylcellulose coating.     

Preparation and Bioavailability of Sustained-Release Doxofylline Pellets in Beagle Dogs

The objective of this study was to develop doxofylline-loaded sustained-release pellets coated with Eudragit® NE30D alone (F1) or blend of Eudragit® RL30D/RS30D (F2) and further evaluate their in vitro release and in vivo absorption in beagle dogs. Doxofylline-loaded cores with a drug loading of 70% (w/w) were prepared by layering drug-MCC powder onto seed cores in a centrifugal granulator and then coating them with different kinds of polymethacrylates in a bottom-spray fluidized bed coater. Dissolution behaviour of these formulations was studied in vitro under various pH conditions (from pH 1.2 to pH 7.4) to evaluate the effect of pH on drug release profiles. It was found that F2 produced a better release profile than F1 did and two different release mechanisms were assumed for F1 and F2, respectively. The relative bioavailability of the sustained-release pellets was studied in six beagle dogs after oral administration in a fast state using a commercially available immediate release tablet as a reference. Coated with Eudragit® NE30D and a blend of Eudragit® RL30D/RS30D (1:12), at 5% and 8% coating level, respectively, the pellets acquired perfect sustained-release properties and good relative bioavailability, with small fluctuation of drug concentration in plasma. But combined use of mixed Eudragit® RL30D/RS30D polymers with proper features as coating materials produced a longer T_max, a lower C_max and a little higher bioavailability compared to F1 (coated with Eudragit® NE30D alone). The C_max, T_max and relative bioavailability of F1 and F2 coated pellets were 15.16 μg/ml, 4.17 h, 97.69% and 11.41 μg/ml, 5 h, 101.59%, respectively. Also a good linear correlation between in vivo absorption and in vitro release was established for F1 and F2, so from the dissolution test, formulations in vivo absorption can be properly predicted.     

Thermal,mechanical and drug release characteristics of an acrylic film using active pharmaceutical ingredient as non-traditional plasticizer

Abstract

The objective of this study was to investigate thermal and mechanical properties as well as in vitro drug release of Eudragit® RL (ERL) film using chlorpheniramine maleate (CPM) as either active pharmaceutical ingredient or non-traditional plasticizer. Differential scanning calorimeter was used to measure the glass transition temperature (T_g) of 0–100% w/w CPM in ERL physical mixture. Instron testing machine was used to investigate Young’s modulus, tensile stress and tensile strain (%) of ERL film containing 20–60% w/w CPM. Finally, a Franz diffusion cell was used to study drug release from ERL films obtained from four formulations, i.e. CRHP0/0, CRHP0/5, CRHP2/0 and CRHP2/5. The T_g of ERL was decreased when the weight percentage of CPM increased. The reduction of the T_g could be described by Kwei equation, indicating the interaction between CPM and ERL. Modulus and tensile stress decreased whereas tensile strain (%) increased when weight percentage of CPM increased. The change of mechanical properties was associated with the reduction of the T_g when weight percentage of CPM increased. ERL films obtained from four formulations could release the drug in no less than 10?h. Cumulative amount of drug release per unit area of ERL film containing only CPM (CRHP0/0) was lower than those obtained from the formulations containing traditional plasticizer (CRHP0/5), surfactant (CRHP2/0) or both of them (CRHP2/5). The increase of drug release was a result of the increase of drug permeability through ERL film and drug solubility based on traditional plasticizer and surfactant, respectively.     

Formulation studies for mirtazapine orally disintegrating tablets

Abstract

Objective: Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab).

Materials and methods: Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900?mL 0.1?N HCl medium, 900?mL pH 6.8 phosphate buffer or 900?mL pH 4.5 acetate buffer at 37?±?0.2?°C as dissolution medium.

Results: Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media.

Discussion: Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles.

Conclusion: Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.     

The MiniWiD-Coater. III. Effect of Application Temperature on the Dissolution Profile of Sustained-Release Theophylline Pellets Coated with Eudragit Rs 30 D

Abstract

Theophylline pellets were coated with Eudragit RS 30 D in a miniature fluid-bed pan coater called MiniWiD developed recently. The dispersions were plasticized with varying amounts of triethyl citrate (TEC), dibutyl phthalate (DBP), and polyethylene glycol 6000 (PEG) and applied at different temperatures ranging from 25 to 45 °C. Theophylline release was tested by dissolution using the USP Apparatus 2 (paddle) in 0.1 N hydrochloric acid under sink conditions over 6 hours.

At a coating level of 4 % (0.7 mg/cm²) sustained-release profiles were obtained from dispersions plasticized with TEC or DBP. By reducing the amount of plasticizer from 20 to 10%, films with higher permeabilities were obtained. This effect was compensated by tempering the pellets at 50 deg;C for 24 hours. The coating temperature had little effect on the dissolution profiles of TEC-plasticized films and no effect on films with DBP.

Coatings plasticized with 20% PEG were applied at temperatures ranging from 25 to 45 °C. These films required a coating level of about 18 % (3.3 mg/cm²) to provide comparable sustained-release properties. In contrast to DBP and TEC, a strong influence of the coating temperature on the release rates was observed in which higher temperatures led to slower release rates. This behavior can be explained by the minimum film-forming temperature (MFT). Since PEG does not lower the MFT of Eudragit RS 30 D, the application of these films below the MFT of 45 °C is associated with a lower degree of film formation.     

Optimization Studies on Floating Multiparticulate Gastroretentive Drug Delivery System of Famotidine

The objective of this study was to optimize floating microballoons of famotidine by the emulsion solvent diffusion technique using central composite design. Formulations F₁–F₁₅ were prepared using three independent variables (pH of medium, drug: Eudragit® S100 ratio and ethanol : dichloromethane ratio) and evaluated for dependent variables (shape, percentage buoyancy, and encapsulation). The optimized formulation F₉ was fractionated and a polymer combination of (Eudragit® S100 : Eudragit® L100-55, 9.5:0.5) resulted in microballoons that exhibited zero order release (94.73%) with 84.20% buoyancy at the end of the eighth hour when studied in the mesh-designed modified USP type II apparatus.     

The Effect of Curing on Drug Release and Morphological Properties of Ethylcellulose Pseudolatex-Coated Beads

Drug-containing nonpareil beads were coated in a fluidized bed with a commercial ethylcellulose pseudolatex, Aquacoat. The drug release was investigated as a function of curing conditions (curing time and temperature) for a hydrophilic and lipophilic drug (chlorpheniramine maleate and ibuprofen) at different levels of plasticizer (triethyl citrate). Curing of coated beads at elevated temperatures immediately after the coating process significantly changed the drug release pattern. Both a retardation and an enhancement in drug release were seen, with the extent being dependent on the type of drug and curing conditions. With chlorpheniramine maleate, a drug with low affinity for the ethylcellulose coating, a curing step was necessary at intermediate plasticizer levels to obtain good film formation and a limiting drug release pattern, while the use of higher plasticizer levels eliminated the need for a curing step. With ibuprofen, a lipophilic drug with high solubility in the ethylcellulose coating, drug crystals were apparent on the bead surface after curing. Curing of ibuprofen beads as a function of time initially decreased but then substantially increased the drug release as a result of drug diffusion across the ethylcellulose membrane with subsequent crystallization on the bead surface. An intermediate seal coat reduced the diffusion of the drug into the ethylcellulose coating.     

Eudragit® RS PO/RL PO as rate-controlling matrix-formers via roller compaction: Influence of formulation and process variables on functional attributes of granules and tablets

The influence of plasticizer level, roll pressure and sintering temperature was investigated on the granule properties, tablet breaking force and theophylline release from tablets. Nine formulations using theophylline as a model drug, Eudragit^® RL PO, Eudragit^® RS PO, or both as a matrix former and triethyl citrate (TEC) as a plasticizer were prepared. The formulations were roller compacted and the granules obtained were evaluated for particle size distribution and flowability. These granules were compacted into tablets at a compression force of 7?kN. The tablets were thermally treated at different temperatures (50 and 75°C) for 5?h and were evaluated for breaking force and dissolution. Increase in roll pressure and TEC levels resulted in a progressive increase in the mean particle size of the granules. The flowability of the granules also improved with increasing roll pressures and TEC levels. Tablet breaking force increased with an increase in TEC levels and sintering temperatures. But these effects were significant only at the highest level of plasticizer and sintering temperature respectively. For the tablets containing Eudragit^® RS PO, theophylline release decreased proportionately with increase in TEC levels and sintering temperatures. Tablets containing either Eudragit^® RL PO or a mixture of RS PO and RL PO failed to impart an extended-release property to the tablets at the studied variables i.e. roll pressure, TEC levels and sintering temperature. It was clearly demonstrated that with suitable optimization of these parameters, the release-rate of a water soluble drug from the matrix tablets prepared via roller compaction can be finely controlled.     

Controlled release formulation of ranitidine-containing montmorillonite and Eudragit® E-100

Aim: The objective of this work was to illustrate the suitability of montmorillonite (MMT) as a drug delivery carrier, by developing a new clay–drug composite of ranitidine hydrochloride (RT) intercalated in MMT. Methods: The MMT–RT composite was prepared by ion-exchange process. X-ray diffraction and Fourier transform infrared spectra were employed to confirm the intercalation of RT in the MMT interlayers. The prepared MMT–RT hybrid was coated with cationic polymer Eudragit® E-100 by oil-in-water solvent evaporation method. The release processes of RT from MMT–RT and MMT–RT/Eudragit® E-100 were monitored under in vitro condition in the gastric fluid. Results: X-ray diffraction and Fourier transform infrared spectra analysis indicated the intercalation of RT molecules within the clay lattice. The in vitro release studies showed that MMT–RT released RT in a controlled manner. In the case of MMT–RT/Eudragit® E-100, both the release rate and the release percentages noticeably increased in the presence of Eudragit® E-100, because of its effective exchange with intercalated RT molecules. The release kinetics followed parabolic diffusion mechanism. Conclusion: MMT has great potential as a drug delivery carrier with various scenarios. The dosage of the MMT–RT/Eudragit® E-100 can be in the tablet form. The hybrid material and polymer-coated hybrids are microparticles.     

The effect of inorganic salt type and concentration on hydrophilic drug loading into microspheres using the emulsion/solvent diffusion method

Aim: In order to avoid gastric irritation caused by tolmetin sodium (TS), gastro resistant Eudragit® S 100 microsphere formulations were prepared with the emulsion/solvent diffusion method.

Materials: Considering the high water solubility of the TS molecule, the effects of the presence of inorganic salt (NaCl, NaBr and KH₂PO₄; 0.1?M and 1.0?M) in external phase and external phase pH on the encapsulation efficiency were evaluated.

Results: Percentage yield value was found to vary between 55.8% and 72.1%. Improvement in encapsulation efficiency was determined by increasing concentrations of NaCl, NaBr and KH₂PO₄. The microspheres were observed to have a spherical shape and the measured particle size values varied between 52.1 and 81.5?µm. The released amounts of the drug were found to be low as the inorganic salt concentrations increased.

Conclusion: Conclusively, drug release in stomach pH was significantly prevented by the microspheres prepared using Eudragit® S 100 polymer, and these formulations are considered to be a model for other orally administered drugs with similar problems.     

Aqueous film coating to reduce recrystallization of guaifenesin from hot-melt extruded acrylic matrices

Objectives: This study investigated the effect of aqueous film coating on the recrystallization of guaifenesin from acrylic, hot-melt extruded matrix tablets. Methods: After hot-melt extrusion, matrix tablets were film-coated with either hypromellose or ethylcellulose. The effects of the coating polymer, curing and storage conditions, polymer weight gain, and core guaifenesin concentration on guaifenesin recrystallization were investigated. Results: The presence of either film coating on the guaifenesin-containing tablets was found to prolong the onset time of drug crystallization. The coating polymer was the most important factor determining the delay in the onset of crystallization, with the more hydrophilic polymer, hypromellose, having a higher solubilization potential for the guaifenesin and delaying crystallization for longer period (3 or 6 months in tablets stored at 40°C or 25°C, respectively) than the more hydrophobic ethylcellulose, which displayed a lower solubilization potential for guaifenesin (crystal growth on tablets cured for 2 hours at 60°C occurred within 3 weeks, whereas uncoated tablets displayed surface crystal growth after 30 minutes). Crystal morphology was also affected by the film coating. Elevated temperatures during both curing and storage, incomplete film coalescence, and high core drug concentrations all contributed to an earlier onset of crystal growth.     

Physicochemical characterization of spray-dried PLGA/PEG microspheres,and preliminary assessment of biological response

Context: The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection.

Objective: To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process.

Methods: Microspheres were prepared by spray-drying 0–20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry – DSC and thermogravimetric analysis – TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection.

Results: The spray dried particles were spherical, with a size range of about 2–3?µm and a yield of 16–60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59?°C (enthalpy: 170.61 J/g) and a degradation-onset of 180?°C for PEG 3350. PLGA 65:35 was amorphous, with a T_g of 43?°C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280?°C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation.

Conclusion: This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2–3?µm) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1–5% was optimal to maximize process yield, with minimal potential for immune detection.     

The MiniWiD-Coater. III. Effect of Application Temperature on the Dissolution Profile of Sustained-Release Theophylline Pellets Coated with Eudragit Rs 30 D

Theophylline pellets were coated with Eudragit RS 30 D in a miniature fluid-bed pan coater called MiniWiD developed recently. The dispersions were plasticized with varying amounts of triethyl citrate (TEC), dibutyl phthalate (DBP), and polyethylene glycol 6000 (PEG) and applied at different temperatures ranging from 25 to 45 °C. Theophylline release was tested by dissolution using the USP Apparatus 2 (paddle) in 0.1 N hydrochloric acid under sink conditions over 6 hours.

At a coating level of 4 % (0.7 mg/cm²) sustained-release profiles were obtained from dispersions plasticized with TEC or DBP. By reducing the amount of plasticizer from 20 to 10%, films with higher permeabilities were obtained. This effect was compensated by tempering the pellets at 50 deg;C for 24 hours. The coating temperature had little effect on the dissolution profiles of TEC-plasticized films and no effect on films with DBP.

Coatings plasticized with 20% PEG were applied at temperatures ranging from 25 to 45 °C. These films required a coating level of about 18 % (3.3 mg/cm²) to provide comparable sustained-release properties. In contrast to DBP and TEC, a strong influence of the coating temperature on the release rates was observed in which higher temperatures led to slower release rates. This behavior can be explained by the minimum film-forming temperature (MFT). Since PEG does not lower the MFT of Eudragit RS 30 D, the application of these films below the MFT of 45 °C is associated with a lower degree of film formation.     

Mechanistic Analysis of Drug Release from Theophylline Pellets Coated by Films Containing Pectin,Chitosan and Eudragit® RS

The objective of this study was to obtain detailed information on the mechanism of drug release from mixed-film of pectin-chitosan/Eudragit® RS. Pellets (710–840 μm in diameter) containing 60% theophylline and 40% microcrystalline cellulose were prepared by extrusion-spheronization method. Eudragit® L100-55 enteric coating capsules included film-coated pellets of theophylline in theoretical coating weight gains of 10, 15, and 20%, with pectin-chitosan complex contents of 5, 10, 15, and 20% for each level of weight gain were prepared and subjected to in vitro drug release. Drug release from this system showed a bimodal release profile characteristic with the drug release enhancement, being triggered (burst release) in the colonic medium. The reason for burst drug release may be due to the enzymatic degradation of pectin via pectinolytic enzymes in the simulated colonic medium. The mechanism of drug release from each formulation was evaluated in the terms of zero-order, first-order, Higuchi and Korsmeyer-Peppas models. It was observed that none of the enteric coating capsules showed any drug release in the simulated gastric medium (phase I). The analysis of release profiles showed that zero-order kinetics was found as the better fitting model for all formulations in the simulated small intestine (phase II) and it could be due to the pectin-chitosan swelling and subsequent formation of aqueous channels. In the colonic medium (phase III), due to degradation of pectin and its leaching from the mixed-film, there was a modification in drug release kinetics from swelling-controlled at phase II to anomalous at phase III. It also was found that both zero-order and Higuchi models contributed in colonic drug release from most of the formulations.