The Release Rate of Indomethacin from Solid Dispersions with Eudragite

Abstract

The coprecipitates were prepared by a solvent technique using Eudragit E as carrier and indomethacin as a model drug.

X-Ray diffractometry, differential scanning calorimetry (DSC) and wettability tests were employed to investigate the physical state of the studied formulations. Up to 50% of indomethacin can be dispersed in an amorphous state in Eudragit E.

The influence of the pH on the in vitro release of solid dispersions has been evaluated. Because of the good solubility of Eudragit E at pH 1.2 a fast dissolution rate of the drug was observed while a marked delay was noticed at pH 7.5 where the polymer is only permeable to water. At pH 5.8 the kinetics of drug release can be modulated by the drug/polymer ratio. The dissolution rate of the drug can be increased by decreasing its amount in the coevaporate.     

The Release Rate of Indomethacin from Solid Dispersions with Eudragite

The coprecipitates were prepared by a solvent technique using Eudragit E as carrier and indomethacin as a model drug.

X-Ray diffractometry, differential scanning calorimetry (DSC) and wettability tests were employed to investigate the physical state of the studied formulations. Up to 50% of indomethacin can be dispersed in an amorphous state in Eudragit E.

The influence of the pH on the in vitro release of solid dispersions has been evaluated. Because of the good solubility of Eudragit E at pH 1.2 a fast dissolution rate of the drug was observed while a marked delay was noticed at pH 7.5 where the polymer is only permeable to water. At pH 5.8 the kinetics of drug release can be modulated by the drug/polymer ratio. The dissolution rate of the drug can be increased by decreasing its amount in the coevaporate.     

Drug Release Kinetics from Tablet Matrices Based Upon Ethylcellulose Ether-Derivatives: A Comparison Between Different Formulations

ABSTRACT

The present study involved the preparation of ibuprofen-containing controlled release tablets formulated from either the established granular product, Ethocel®Standard Premium, or the novel finely-milled product, Ethocel®Standard FP Premium. The tablets were prepared by either direct compression or wet granulation. The aim was to explore the influence of different parameters on the kinetics and mechanisms of ibuprofen release from the tablets. These parameters were; polymer particle size, polymer molecular weight, drug : polymer ratio, preparation methodology and partial replacement of lactose with the coexcipient—hydroxypropyl methylcellulose (HPMC). The derived drug release data were analyzed with reference to various established mathematical models while the f₂-metric technique was used in order to determine profile equivalency. It was found that drug release was mostly modulated by several interactive factors apparently exhibiting crosstalk. Nevertheless, it was possible to identify some simple rules. Incorporation of Ethocel® FP polymers and application of the wet granulation technique facilitated greater efficiency in controlling ibuprofen release behavior from the matrices. Furthermore, drug release profiles could be modulated by partial substitution of the primary excipient with HPMC. Polymer concentrations and particle sizes, rather than viscosity grade, were found to be decisive factors in controlling drug release rates.     

Mechanisms of Drug Release from Matrices Prepared with Aqueous Dispersion of Ethylcellulose

The objective of this study was to investigate the mechanism of acetaminophen (APAP) release from tablets prepared by the wet granulation method using an aqueous polymeric dispersion (Surelease) as a granulating agent. Tablets compressed from granules containing 10% w/w acetaminophen and 13.44% w/w total solids from Surelease released only 52.4% w/w drug after 120 min of dissolution testing, while controlled tablets without Surelease released 94.1% w/w drug. In order to prepare control tablets of 6.8 Kp hardness value, the upper compressional force recorded was 15.87 kN while tablets containing 13.44% w/w of total solids from Surelease had a recorded force of 6.28 kN. The drug release from tablets prepared with Surelease as a granulating liquid followed the diffusion-controlled model for an inert porous matrix     

Mechanisms of Dissolution of Fast Release Solid Dispersions

Abstract

Drug dissolution from a solid dispersion is dependent on the technology employed to prepare the dispersion and on the proportion and properties of the carrier used. The diffusion models describing dissolution from multi-component solids seem to adequately describe drug release from non-disintegrating systems in the weight fraction range where the drug phase is expected to control dissolution. When solid dispersions have higher dissolution rates than corresponding mechanical mixtures, solid state changes during the formation of the dispersion are indicated. These increases in rate may result from the formation of higher energy phases of either component or from interactions between the components. The carrier may play an important role in the formation of these phases and in stabilizing them during subsequent dissolution. When a large relative solubility difference exists between the carrier and the drug, deviations from theory can be expected to occur at high carrier weight fractions. The model fails because insufficient drug phase is present to form a viable surface drug layer. Drug release then becomes controlled by dissolution of the carrier. In polymer based systems the presence of drug retards dissolution of the carrier, possibly through effects on binding and polymer swelling. These effects need to be quantified in order to allow prediction of drug release from high carrier weight fraction systems.     

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.     

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.     

Studies on Drug Release Kinetics from Carbomer Matrices

The objective of this study is to gain a mechanistic understanding of drug release kinetics from directly compressed tablets containing Carbopol 934P and 974P resins. Carbopol resins belong to a family of carbomers which are synthetic, high molecular weight, non-linear polymers of acrylic acid, crosslinked with polyalkenyl polyether. They are currently being used as polymeric matrices for controlling drug release in pharmaceutical tablets. This investigation focuses on the influence of the type of drug and the pH of the dissolution media, along with other factors on the drug release kinetics from carbomer matrices. Directly compressed tablets were prepared using a Stokes single station laboratory press and blends of polymers and lactose with drugs like theophylline, norephedrine HCI, and chlorpheniramine maleate. In vitro. drug release studies from the tablets were performed according to USP method II. Drug release rates were obtained by plotting the fraction released versus time and data fitted to the equation:     

Studies on Drug Release Kinetics from Carbomer Matrices

The objective of this study is to gain a mechanistic understanding of drug release kinetics from directly compressed tablets containing Carbopol 934P and 974P resins. Carbopol resins belong to a family of carbomers which are synthetic, high molecular weight, non-linear polymers of acrylic acid, crosslinked with polyalkenyl polyether. They are currently being used as polymeric matrices for controlling drug release in pharmaceutical tablets. This investigation focuses on the influence of the type of drug and the pH of the dissolution media, along with other factors on the drug release kinetics from carbomer matrices. Directly compressed tablets were prepared using a Stokes single station laboratory press and blends of polymers and lactose with drugs like theophylline, norephedrine HCI, and chlorpheniramine maleate. In vitro. drug release studies from the tablets were performed according to USP method II. Drug release rates were obtained by plotting the fraction released versus time and data fitted to the equation:     

Controlled Drug Release from a Compressed Heterogeneous Polymeric Matrix: Kinetics of Release

A physical model of a new matrix-type system is presented where constant drug release can be maintained irrespective of the extent of the tortuosity and receding drug boundary. Theophylline base was dispersed as discrete crystals and fine particles in a matrix formed by the cross-linking of polymeric mixtures consisting of PEG, acrylic resins and ethyl cellulose. DSC analysis was performed to identify any solid state inactivation of the drug. Concave tablets at specified pressures were prepared in order to achieve a wide range of release rates and patterns of release. It was found that the patterns of release could be controlled by the formulation components and the manufacturing procedures. Drug release rates were determined spectrophotometrically under sink conditions and the flux of drug release, dQ/dt, from these matrix-type delivery systems was almost constant over 15 hours, during which time about 85% of the active drug was released. The release rate was devoid of any hydrodynamic boundary effect and environmental pH. The cumulative amount of drug released was found to be in accordance with zero-order kinetics. The system can be modified within broad limits and have flexibility as well as a wide spectrum of applicability with respect to different types of drugs.     

Controlled Drug Release from a Compressed Heterogeneous Polymeric Matrix: Kinetics of Release

A physical model of a new matrix-type system is presented where constant drug release can be maintained irrespective of the extent of the tortuosity and receding drug boundary. Theophylline base was dispersed as discrete crystals and fine particles in a matrix formed by the cross-linking of polymeric mixtures consisting of PEG, acrylic resins and ethyl cellulose. DSC analysis was performed to identify any solid state inactivation of the drug. Concave tablets at specified pressures were prepared in order to achieve a wide range of release rates and patterns of release. It was found that the patterns of release could be controlled by the formulation components and the manufacturing procedures. Drug release rates were determined spectrophotometrically under sink conditions and the flux of drug release, dQ/dt, from these matrix-type delivery systems was almost constant over 15 hours, during which time about 85% of the active drug was released. The release rate was devoid of any hydrodynamic boundary effect and environmental pH. The cumulative amount of drug released was found to be in accordance with zero-order kinetics. The system can be modified within broad limits and have flexibility as well as a wide spectrum of applicability with respect to different types of drugs.     

Mechanistical Analysis of Release Kinetics for Lipophilic Drug from Matrix-Type Drug Delivery Devices

Abstract

The release kinetics of lipophilic drug from hydrophobic polymer-based matrix-type drug delivery system was studied. Using the “intrinsic formula”, several experimental problems can be analyzed and solved. The results reveal that intrinsic release, calculated from the model, shows the true properties of the drug delivery system, which might have been disguised by the boundary layer effect. The results also demonstrated the needs of maintaining sink condition and uniform distribution of dispersed phase in studying the matrix diffusion-controlled drug release.     

Mechanistical Analysis of Release Kinetics for Lipophilic Drug from Matrix-Type Drug Delivery Devices

The release kinetics of lipophilic drug from hydrophobic polymer-based matrix-type drug delivery system was studied. Using the “intrinsic formula”, several experimental problems can be analyzed and solved. The results reveal that intrinsic release, calculated from the model, shows the true properties of the drug delivery system, which might have been disguised by the boundary layer effect. The results also demonstrated the needs of maintaining sink condition and uniform distribution of dispersed phase in studying the matrix diffusion-controlled drug release.     

Effect of Simulated Gastrointestinal Conditions on Drug Release from Pectin/Ethylcellulose as Film Coating for Drug Delivery to the Colon

The aim of this work was to investigate the effect of acidic pH representative of gastric fluid on the release of 5-aminosalicylic acid from beads coated with pectin/ethylcellulose as film coating intended for drug delivery to the colon, in media mimicking the lower gastrointestinal (GI) tract and representative of colonic conditions. In this work, the in vitro incubation of the beads in acid medium was found to influence the hydration and the swelling characteristics of pectin after transfer into simulated intestinal fluid and simulated cecal fluid containing pectinolytic enzymes. Moreover, the drug release profiles from the beads in simulated intestinal fluid after incubation for 2 h or 30 min in simulated gastric fluid vs. no acid incubation were found to be very different. The in vitro degradation of pectin in the coat by pectinolytic enzymes in simulated cecal fluid depended on whether the beads were placed in simulated gastric fluid prior to testing in simulated intestinal fluid. The percentage drug release also depended on the ratio of pectin to ethylcellulose in the coat.     

Tailoring the Release Rates of Fluconazole Using Solid Dispersions in Polymer Blends

Formulations of the drug Fluconazole with different release characteristics were prepared by dispersing the active pharmaceutical ingredient (API) in various polymeric carriers, and especially in polymer blends. Fluconazole was tested as a model drug with low solubility in water. First solid dispersions in pure polymers were studied. Use of pure polyvinylpyrrolidone (PVP) as carrier even for high drug load (30 wt%) resulted in rapid release. The drug release rates decreased by increasing the API content. The dissolution rate enhancement was attributed to drug amorphization, particle size reduction, and possible improvement of the drug wetting characteristics. Hydroxypropyl methylcellulose (HPMC) gave solid dispersions, from which the release rates of the drug varied from immediate to sustaining. As the drug amount increased, the rates became higher. Similar behavior also was found when Chitosan was used as carrier, with much more controlled rates close to those for sustained release. These differences were mainly attributed to the limited solubility and swelling of HPMC and Chitosan in aquatic media. To study the effectiveness of polymer blends in adjusting the release rates of the drug, solid dispersions in PVP/HPMC and PVP/Chitosan miscible blends were studied. The release rates of Fluconazole were adequately adjusted by differentiating the weight ratio of the polymers in the blends. PVP/HPMC blends with high PVP content can be used for immediate release formulations but PVP/Chitosan blends are inappropriate for such formulations and can only be used for controlled release.     

Effect of Simulated Gastrointestinal Conditions on Drug Release from Pectin/Ethylcellulose as Film Coating for Drug Delivery to the Colon

The aim of this work was to investigate the effect of acidic pH representative of gastric fluid on the release of 5-aminosalicylic acid from beads coated with pectin/ethylcellulose as film coating intended for drug delivery to the colon, in media mimicking the lower gastrointestinal (GI) tract and representative of colonic conditions. In this work, the in vitro incubation of the beads in acid medium was found to influence the hydration and the swelling characteristics of pectin after transfer into simulated intestinal fluid and simulated cecal fluid containing pectinolytic enzymes. Moreover, the drug release profiles from the beads in simulated intestinal fluid after incubation for 2 h or 30 min in simulated gastric fluid vs. no acid incubation were found to be very different. The in vitro degradation of pectin in the coat by pectinolytic enzymes in simulated cecal fluid depended on whether the beads were placed in simulated gastric fluid prior to testing in simulated intestinal fluid. The percentage drug release also depended on the ratio of pectin to ethylcellulose in the coat.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^-2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Abstract

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^?2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Effects of Surfactant on Release Characteristics of Clonidine Hydrochloride from Ethylcellulose Film

The effects of Tween 80 (polysorbate 80) and Span 80 (sorbitan monooleate) surfactants on release characteristics of clonidine hydrochloride from ethylcellulose 10 and 20 cps matrix films containing castor oil as a plasticizer were investigated. The release rates of drug from these films in water at 37°C were found to increase with the addition of surfactant, which was highest for the film prepared from ethylcellulose 20 cps with Tween 80. The experimental values of the cumulative amount of drug released were found to conform to the solution matrix model. The calculated values of the cumulative amount of clonidine hydrochloride released using the experimentally determined diffusion coefficients were also found to be in good agreement with the observed values.     

Drug Release Properties of the Microcapsules of Adriamycin Hydrochloride with Ethylcellulose Prepared by a Phase Separation Technique

Abstract

Adriamycin hydrochloride was microencapsulated with ethylcellulose by a phase separation method to develop a prolonged release dosage form. Polyisobutylene (PIB) was used as a coacervation-inducing agent to control the particle size and drug release rate of the resultant microcapsules. With increasing the concentration of PIB (1 to 3 %) the average diameter of the microcapsules decreased, due to the fact that the microcapsules were discreted to a single microcapsule. At low concentration of PIB, the resultant microcapsules were agglomerated, which resulted in increasing the size. The microcapsules prepared with PIB 2 % prolonged desirably the drug release from the microcapsules. A little size effects of the microcapsules on the drug release rate was found for the microcapsules with PIB 2 % and 3 %.