Preparation and evaluation of ethylcellulose microcapsules with bacampicillin

Ethylcelluloses of different types were used to microencapsulate bacampicillin. Polymer deposition from cyclohexane was performed by temperature change. As coacervation - inducing agent different polyisobutylenes (Oppanol B - 200, B - 100, B - 50, B -3) were used. Fine products with slower drug release were obtained. Average diameters of prepared microcapsules were determined with sieve analysis and it was shown that the particle size of the microcapsules follows log - normal distribution. Scanning electron microscopy was used to examine the shape and the surface characteristics of the microcapsules. HPLC method was developed for testing drug content and its dissolution. Drug content in the microcapsules was in all cases over 80% regarding the amount added. Dissolution of bacampicillin from microcapsules was retarded comparing to the dissolution of bacampicillin itself. The experimental values of dissolution were fitted with different model kinetics. To describe the dissolution profiles we suggested the combined zero and first order kinetics. The bitter taste was quite satisfactory disguised in all prepared microcapsules.     

Preparation and Evaluation of Eudragit E Microspheres Containing Bacampicillin

Abstract

Microspheres with bacampicillin were prepared by the solvent evaporation method using systems methanol, acetone and methyl acetate/liquid paraffin and Eudragit E as polymer. Sieve analysis showed that the particle size of the microspheres follows log - normal distribution with average size of 123, 206 and 300 μm, respectively. Scanning electron microscopy was used to prove that all chosen systems provided the particles of regular spherical shape without aggregation

HPLC method was developed for testing drug content, drug stability and dissolution. The results of HPLC analysis showed the exisistence of degradation products of bacampicillin in microspheres prepared by the use of all three solvents. The degree of degradation was the lowest in the case of methyl acetate. The experimental values of dissolution profiles fit well to 0. order and combined 0. and t^½ order. The comparison of dissolution profiles of microspheres and bacampicillin itself shows that microspheres produce retard effect and therefore bacampicillin is not expected to be released in saliva after peroral administration of microspheres     

Microencapsulation by Emulsion Non-Solvent Additicin Method

Abstract

Cellulose acetate butyrate microcapsules containing propranolol were prepared by emulsion non-solvent addition method. The effects on drug release of different polyethylene glycols (PEG), various concentrations of PEG 4000, and particle size of the drug to be encapsulated were investigated. In vitro dissolution of microcapsules in simulated intestinal fluid and buffers at different pH was also studied. PEGs were found to increase drug release for this system. The pH dissolution profiles of the microcapsules indicated that dissolution was slightly pH dependent during the first 8 hours of dissolution.     

A Study on the Manufacture and in Vitro Dissolution of Terbutaline Sulfate Microcapsules and their Tablets

Abstract

Microcapsules of terbutaline sulfate with cellulose acetate butyrate and ethylcellulose were prepared using an emulsion-solvent evaporation technique. The in vitro dissolution of terbutaline sulfate was studied using the USP rotating basket method. As the polymer to drug ratio increased, the microcapsule size distribution shifted to the smaller size and the release of terbutaline sulfate decreased. The release of terbutaline sulfate was independent of the dissolution medium pH for both polymers. The release kinetics from the microcapsules was dependent on the polymer type and polymer to drug ratio. The release of terbutaline sulfate from cellulose acetate butyrate and ethylcellulose microcapsules formulated with a 1:1 polymer to drug ratio was complex and could not be differentiated between the square-root of time and first-order release models. However, the square-root of time model was followed by microcapsules formulated with a 2:1 or a 3:1 cellulose acetate butyrate to drug ratio. When the ethylcellulose to drug ratio was increased to 2:1 the square-root of time model was followed. At an ethylcellulose to drug ratio of 3:1 the release kinetics could not be differentiated between the Hixon-Crowell and first-order release models. The T50% from ethylcellulose microcapsules was decreased when the microcapsules were compressed into tablets with the addition of Avicel^R/Emcompress^R (2:1) or Avicel^R.     

Controlled Release Kinetics of Captopril From Tableted Microcapsules

Abstract

Different viscosity grades ethylcellulose coated captopril microcapsules were prepared using temperature induced coacervation method from cyclohexane containing 2% Tween 80. Microcapsules were compressed directly into tablets. In vitro dissolution was carried out in 0.1 N HCl at 37°C using the rotating basket method. Release from tablets of all the batches was extensively prolonged in comparison to the respective microcapsules. The longest time for 70% drug release was shown by microcapsules (55min) and tablets (378 min) of the batch E-2. Release rate constants, correlation, determination and regression coefficients were calculated for the first-order, zero-order and Higuchi's equations. The best fit of release kinetics with the highest correlation and determination coefficients was achieved with the first-order followed by Higuchi's plot.     

Dissolution Characteristics of Polycaprolactone-Polylactide Microspheres of Chlorpromazine

Abstract

Studies were conducted on the preparation of controlled release polycaprolactone-polylactide microcapsules of chlorpromazine and on release of the drug from the microcapsules in pH 7.0 buffer medium. A wide range of release rates of the drug was obtained by simple change in the polymer system. Chlorpromazine was released from the microspheres in a biphasic manner consisting of an initial fast release phase followed by a slow-release phase. Increasing the drug content increased the initial drug release rate but no significant drug loading effect on the second stage dissolution rate was noted. There was no significant effect of particle size on the drug release rate from the microspheres. The swelling property of the microspheres and the agglomerate nature of the sieve fractions may complicate the drug release kinetics and obscure the particle size effect on dissolution rate.     

Gelatin-Acacia Complex Coacervation as a Method for Ketoprofen Microencapsulation

Abstract

Ketoprofen microcapsules were prepared by complex coacervation between gelatin and acacia, and dried with different methods: isopropanol addition, spray-drying, and freeze-drying, Successively, microparticles were analyzed by infrared thembalance, ultraviolet spectroscopy, optical and scanning electron microscopy, and sieves; and subjected to dissolution studies in order to examine parameters such as yield, moisture content, encapsulation percentage, morphology of solid particles, particle size, and dissolution behavior. Provided that encapsulation and drying methods did not affect ketoprofen dissolution profiles, the most appropriate drying method for industrial purposes was spray-drying.     

The Kinetics of Drug Release from Ethylcellulose Solid Dispersions

Abstract

Sulphadiazine - ethylcellulose (EC) solid dispersions with different drug: carrier ratios were prepared and fractionated. In vitro drug release followed an apparent zero-order kinetics rate constant being dependent on the thickness of the coat which was the rate controlling step in the process. Drug release was found to increase as the granule size was decreased. The amount of drug released was found to be pH dependent thus showing the existence of pores in the coat surrounding the drug particles. Inclusion of polyethylene glycol or sodium lauryl sulphate in the coat material or dissolution medium resulted in increased dissolution, an effect which was attributed to increase in porosity, reduction of interfacial tension and increase in wettability which was associated with the presence of these compounds.     

Effect of Different Binders on Release Characteristics of Theophylline from Compressed Microspheres

Abstract

Microspheres with 60% w/w drug loading were prepared by the solvent-evaporation method using cellulose acetate butyrate as the encapsulating polymer and micronized anhydrous theophylline as the core material. Four different binders - microcrystalline cellulose, glyceryl palmito-stearate, glyceryl stearate and glyceryl behenate were used to compress three different particle sizes of microspheres. Comparison of the in vitro drug dissolution profiles revealed that drug release was fastest from all the microspheres compressed with microcrystalline cellulose as the binder followed by those compressed with glyceryl palmitostearate, glyceryl stearate and glyceryl behenate.     

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 %.     

Clofibrate Microcapsules: III. Mechanism of Release

Abstract

The mechanism of release of clofibrate from microcapsules prepared in a gelatin-sodium sulfate system has been investigated. A theoretical model was developed to explain the release pattern of the drug from the microcapsules. It was shown that the release of the drug followed four stages giving individual zero-order profiles. The overall release from the thin-walled microcapsules showed greater deviation from the zero-order kinetics but followed the square-root of the time plots. Microcapsules having thicker walla approximated overall zero-order release but deviated from the square-root of time plots. The effect of hardening on the release profiles and possible explanations for the differences observed in the release of clofibrate from the thin-walled and thick-walled microcapsules are discussed.     

Release of Theophylline from Ethyl Cellulose Mecrocapsues Alone and in Conjuction with Fat Embedded (Precirol®) Granules and Hydroxypropyl Methycellulose

Abstract

Microcapsules of theophylline with ethyl cellulose were prepared by coacervation technique using cabosil® (silicon dioxide) as separant. Tablets were prepared from microcapsules, microcapsules + theophylline fat embedded granules, and microcapsules and hydroxypropyl methylcellulose 4000 (HPMC). Release was studied in vitro by the rotating basket method. Prolonged release of theophylline was observed from microcapsules with no drug dumping. The release from microcapsules was of first-order whereas that from all the tablet formulation was diffusion controlled according to the Higuchi model. Good correlation was found between release rate and core:wall ratio for all the systems. Decrease in hardness of tablets made from microcapsules alone decreased the release rate, indicating damage of microcapsules during compression. The tablets compressed from fat embedded granules, microcapsules with fat embedded granules, and microcapsules with HPMC gave a desired release for a 74 hour sustained release preparation.     

Sustained-Release Dosage Form of Nicardipine Hydrochloride: Application of Factorial Design and Effect of Surfactant on Release Kinetics

Abstract

Microcapsules of nicardipine hydrochloride with core:wall ratios of 1:1, 2:1, and 1:2 were prepared by the coacervation-phase separation method, using ethyl-cellulose as the coating material. Two batches of nicardipine hydrochloride microscapsules were divided into size fraction by using standard sieves ranging from 840 μm to 476 pn. Dissolution rate studies from microcapsules were performed using the USP XXII basket method. The kinetic model according to the Rosin-Rammler-Sperling-Bennet-Weibull (RRSBW) distribution was applied for the parametric representation of the dissolution curves. Preparation and dissolution rate studies on the nicardipine hydrochloride microcapsules were pellformed and the influence of particle size, core:wall ratio, and the amount of nicardipine hydrochloride on the release rate was examined by 2³ factorial design. The sign@cance of the observed effects was tested with the F test. A surface active substance was added in the dissolution medium to understand how this substance effects the release of drug from ideal microcapsule form which is found by the findings of the 2³ factorial design. Dissolution studies were repeated with this ideal formulation using different ratio of Tween 20.

The results of this study suggested that the solubility and bioavailability of the sustained-release dosage forms of nicardipine hydrochloride using sullface active substances could be increased.     

Effect of Temperature of Dissolution on The Release Kinetics of Phenobarbitone from Poly (Dl-Lactic Acid) Microcapsules: Calculation of Activation Energy.

Abstract

Poly (DL-lactic acid) [DL-PLA] microcapsules containing phenobarbitone (core:polymer, 1:2) were prepared using three different molecular weight polymers, 20,500, 13,300 and 5,200. Buffer pH 9 ware used to study dissolution rate at temperatures of 10°, 15°, 20°, 25°, 30° and 37°C. The release mechanism followed “Higuchi's” square root of time relationship at all these temperatures and allowed calculation of release rate from the straight line portion of release curve. These microcapsules showed an initial burst phase release followed by a lag phase; both of these phases are affected by the temperature of dissolution and polymer molecular weight. The normalized release rate [K_h2/SSA] was found to lower linearly with the lowering of temperature with all three polymers. Arrhenius plot of the normalized release rate allowed calculation of the activation energy (Ea) for the polymers. It was found to lower linearly with the increase in DL-PLA polymer molecular weight.     

Moment Analysis for the Evaluation of In Vitro Drug Release and In Vivo Bioavailability of Theophylline Microcapsules

Abstract

Statistical moment analysis has been used to establish an in vitro-in vivo correlation for five types of theophylline ethylcellulose microcapsules prepared by using various concentrations of ethylene-vinyl acetate (EVA) copolymer as a coacervation-inducing agent. The concentration of EVA copolymer was found to be played an important function in the controlled release of theophylline microcapsules. Correlations were found between the in vitro dissolution behavior, e.g., MDT _0→7, in vitro' and the rate of bioavailability, e.g., Cmax, Tmax, MDT _{in vivo} or MRT_0→2, although there was no valid correlation with the extent of bioavailability, e.g., AUC_0→27. Thus, moment analysis by studying the quantitative in vitro-in vivo correlations relating to drug release was validated.     

The Effect of Indomethacim Microcapsules on Intestinal Ulceration in the Rat

Abstract

The absorption of indomethacin in the rat was studied following a single oral dose of indomethacin in the form of the powdered drug or microcapsules.

Serum levels of unmetabolized drug were measured and gastrointestinal ulceration was assessed 72 hours after dosing by measuring the tensile strength of the intestine after its removal from the animal and by counting the number of ulcers present on the intestinal wall.

In vitro dissolution of the powdered drug and microcapsules was carried out in water, in Polyethylene Glycol solution and in 40mM sodium cholate solution for a comparison with the in vivo results.

Both in vitro and in vivo results for the microcapsules were similar to those of the powdered drug and therefore encapsulation of indomethacin offered no advantage over conventional dosage forms.     

Microencapsulation of Ibuprofen by A Coacervation Process Using Eudragit L100–55 as An Enteric Polymer

Abstract

Ibuprofen microcapsules were prepared using Eudragit as enteric coating material and a simple coacervation method as coating process. Preliminary experiments based on results published with cellulose acetate phthalate led to the formation of a precipitate rather than a coacervate. Adjusting the polarity of the solvent in the Eudragit system by the addition of cosolvents enabled the transformation of the precipitate into a coacervate. This behaviour was qualitatively explained using the solubility parameter approach. The coacervate phase obtained from a system containing 2-propanol as cosolvent was assayed quantitatively in the absence and in the presence of ibuprofen. Due to the increased solubility of the drug in the cosolvent containing system, the composition of the coacervate phase was significantly altered when compared to a system without drug. The surface morphology of the microcapsules was assessed by scanning electron microscopy. The enteric properties of the microcapsules were tested according to the USP XXII test procedures. The permeability of the wall was evaluated by a dissolution test performed at pH 4. During stability testing over a period of 6 months the quality of the ibuprofen microcapsules remained almost unchanged.     

A Study on the Manufacture and in Vitro Dissolution of Terbutaline Sulfate Microcapsules and their Tablets

Microcapsules of terbutaline sulfate with cellulose acetate butyrate and ethylcellulose were prepared using an emulsion-solvent evaporation technique. The in vitro dissolution of terbutaline sulfate was studied using the USP rotating basket method. As the polymer to drug ratio increased, the microcapsule size distribution shifted to the smaller size and the release of terbutaline sulfate decreased. The release of terbutaline sulfate was independent of the dissolution medium pH for both polymers. The release kinetics from the microcapsules was dependent on the polymer type and polymer to drug ratio. The release of terbutaline sulfate from cellulose acetate butyrate and ethylcellulose microcapsules formulated with a 1:1 polymer to drug ratio was complex and could not be differentiated between the square-root of time and first-order release models. However, the square-root of time model was followed by microcapsules formulated with a 2:1 or a 3:1 cellulose acetate butyrate to drug ratio. When the ethylcellulose to drug ratio was increased to 2:1 the square-root of time model was followed. At an ethylcellulose to drug ratio of 3:1 the release kinetics could not be differentiated between the Hixon-Crowell and first-order release models. The T50% from ethylcellulose microcapsules was decreased when the microcapsules were compressed into tablets with the addition of Avicel^R/Emcompress^R (2:1) or Avicel^R.     

Preparation and Evaluation of Controlled Release Indomethacin Microspheres

Abstract

Microspheres containing indomethacin were prepared with various combinations of polymers Eudragit RS and Eudragit L. The effects of different ratios of polymers, solvent-polymer ratio, polymer-drug ratio and evaporation temperature on the physical characteristics of the microspheres as well as the in vitro release rate of the drug were investigated. All the factors studied had an influence on the physical characteristics of the microspheres. In vitro dissolution results showed that all formulations gave prolonged release of indomethacin and the release followed apparent zero order kinetics until 80% of drug had been released.     

Design and characterization of enteric-coated controlled release mucoadhesive microcapsules of Rabeprazole sodium

The objectives of present work was to design and characterize the rabeprazole sodium loaded microcapsules prepared by solvent evaporation technique using ethyl cellulose (EC) based various mucoadhesive polymer, followed by a triple coating with Eudragit L100. The Box-behnken design (BBD) was applied for optimization of formulations containing EC, HPMCK100M and Eudragit L100 as factors for selected responses like entrapment efficiency, mucoadhesive property and drug release in 24 h. The prepared microcapsules were characterized for particle size, drug content, swelling index, mucoadhesive strength, and in vivo antiulcer activity. FT-IR studies revealed that there was no drug-polymer interaction. SEM studies revealed that microcapsules were non-aggregated, spherical shape and smooth appearance. In vitro drug release data from microcapsules was fitted to different kinetic models to explain release profiles. The correlation coefficient value (r²) indicated that the drug release followed Higuchi model. Analysis of variance (ANOVA) showed significant difference in the release of drug from all formulations at p < 0.05 level. Accelerated stability study of optimized formulation (F4) upto 6 months showed there was no change in drug content and release characteristics during storage. In vivo antiulcer activity showed that the optimized microcapsules were able to protect rat stomach against ulcer formation vis-à-vis aqueous solution of the drug showed only negligible and minimum effect.