Studies on microcapsules

Summary Potentiometric titrations and electrophoretic mobility measurements were made on carboxylated polyphthalamide microcapsules prepared by the interfacial polycondensation method.The values of surface potential and zeta potential of the microcapsules were calculated by using a theoretical potentiometric equation and the simple Smoluchowski equation, respectively.The ionic strength of the medium was found to have no effect on the conformation of the polymer chains of the microcapsules.The negative surface potential obtained from potentiometric titration data rose first with increasing pH of the medium and then tended to level off as the pH approached 7 while the zeta potential as evaluated from electrophoresis data was found to change until the pH attained a value of 10.The cause for this difference in pH change between the surface potential and the zeta potential of the microcapsules was ascribed to the reason that potentiometric titration does not permit the detection of terminal amino groups of the polymer chains constituting the microcapsules, which are far smaller in number than the carboxyl groups, while electrophoresis can detect the presence of the terminal amino groups.

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Zusammenfassung Mit Poly(phthaloyl-l-lysin)-Mikrokapseln wurden potentiometrische Titrationen and elektrophoretische Messungen durchgeführt. Die Größen des Oberflächenpotentials and des Zeta-Potentials der Mikrokapseln wurden unter Verwendung einer theoretischen potentiometrischen Gleichung bzw. der Smoluchowskischen Gleichung berechnet. Es stellte sich heraus, daß die Ionenstärke keinen Einfluß auf die Konformation der Polymerketten der Mikrokapseln ausübt. Das negative Oberflächenpotential, welches aus den potentiometrischen Titrationsdaten erhalten wird, steigt mit dem pH-Wert des Medium bis pH = 7, während das aus den Elektrophoresedaten abgeleitete negative Zeta-Potential mit dem pH-Wert bis pH = 10 zunimmt.Dieser Unterschied zwischen dem Oberflächenpotential und dem Zeta-Potential der Mikrokapseln bei pH-Änderung wird dadurch erklärt, daß bei der potentiometrischen Titration terminale Aminogruppen in den Polymerketten nicht gefunden werden, während die Elektrophorese auf die Anwesenheit terminaler Aminogruppen anspricht.

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With 4 figures     

Studies on microcapsules

Summary The permeability of polyphthalamide microcapsules to various electrolytes was studied. The permeability constants were found to be of the order of 10^–8 cm/sec and almost temperature-independent. The surprisingly low permeation rate was ascribed to the formation of a stable diffusion layer of the electrolytes in the interior of microcapsules. The insignificant temperature effect was interpreted as being due to the presence of adsorbed Tween 20 molecules on the microcapsule membrane.

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Zusammenfassung Es wurde die Durchlässigkeit von Polyphthalamidmikrokapseln für verschiedene Elektrolyten untersucht. Die Durchlässigkeitskonstanten liegen in der Größenordnung von 10^–8 cm/sec und sind von der Temperatur fast unabhängig. Die unerwartet niedrige Permeationsgeschwindigkeit wurde der Bildung einer stabilen Diffusionsschicht des Elektrolyten innerhalb der Mikrokapseln zugeschrieben. Der geringe Temperatureffekt wurde auf die Existenz der an die Mikrokapselmembranen adsorbierten Moleküle von Tween 20 zurückgeführt.

     

Studies on microcapsules

Summary Electrophoretic mobilities were measured on sulfonated and carboxylated polyphthalamide microcapsules prepared by the interfacial polycondensation method in the presence of various cations. The zeta-potentials were then calculated using the mobility data by means of theHelmholtz-Smoluchowski equation.Different cations lowered the zeta-potential to different degrees. A modifiedGouy-Chapman equation was used to calculate the surface charge densities in the electrokinetic plane of shear from the zeta-potentials. The surface charge densities increased with increasing concentration of cations, suggesting the increase in the surface ionization.The use ofStern's adsorption theory made it possible to estimate the free energy of cation binding of the microcapsules from the surface charge density data. The values of free energy of cation binding thus obtained were comparable to those for carboxylic acid surface reported in the literature.The charge reversal spectra for the microcapsules were also obtained from the electrokinetic data.

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Zusammenfassung Die elektrophoretische Beweglichkeit in Gegenwart von verschiedenen Kationen wurde an sulfonierten und karboxylierten Polyphthalamid-Mikrokapseln gemessen, die durch Grenzflächenpolymerisation präpariert wurden.Das Zeta-Potential wurde aus der Beweglichkeit mittels derHelmholtz-Smoluchowskischen Gleichung berechnet. Der Zusammenhang zwischen Zeta-Potential und Kationkonzentration ist für jede Art Kationen verschieden. Die modifizierteGouy-Chapmansche Gleichung wurde verwendet, um die Flächenladungsdichte der elektrokinetischen Verschiebungsfläche aus dem Zeta-Potential zu berechnen. Die Flächenladungsdichte erhöht sich mit der Konzentration an Kationen, was auf Anwachsen an Ionisation in der Grenzfläche deutet.Der Gebrauch derSternschen Adsorptionstheorie ermöglicht die Berechnung der Freien Energie der Kationbindung auf den Mikrokapseln aus der Flächenladungsdichte. Die Werte der Freien Energie für die Kationbindung wurden mit denjenigen an einer Karbonsäureoberfläche verglichen, wie sie in der zitierten Literatur mitgeteilt ist. Die Umkehrspektra der elektrischen Ladung der Mikrokapseln wurden ebenfalls aus den elektrokinetischen Daten abgeleitet.

     

Biopharmaceutical evaluation of sustained-release ethylcellulose microcapsules containing amoxicillin using beagle dogs

A beta-lactam antibiotic, amoxicillin, was microencapsulated with ethylcellulose using a solvent evaporation process in liquid paraffin containing sorbitan tristearate as a dispersing agent, and the microcapsules obtained showed first-order drug release. Usage of the previous log-log relationship of cefadroxil between in vitro dissolution half-lives (T50) and the experimental release rate constants (k'r) of the drug in vivo, and the nomogram for the design of satisfactory sustained-release preparations resulted in the prediction that ethylcellulose microcapsules containing 60% amoxicillin would show the most effective sustained-release pattern. Prepared microcapsules containing various amounts of amoxicillin were administered to beagle dogs and it was found that above prediction was correct. In addition, a more precise log-log correlation concerning amoxicillin was also undertaken, good linearity was observed and the decline was very similar to that of cefadroxil.     

Influence of key parameters on the morphology of ethylcellulose microcapsules prepared via room-temperature spray drying

In this contribution, the morphology of ethylcellulose (EC) microspheres prepared with a room-temperature spray-drying technique is examined as a function of solution concentration, nozzle-to-target distance, and choice of solvent. Additionally, to determine the morphology of EC microspheres in the presence of an aqueous encapsulated material, a series of encapsulation measurements was conducted using hydrogen peroxide solution as the core component. It was observed that highly concentrated EC solutions lead to the formation of tail-like fibers adjacent to the sprayed microcapsules because of the high viscosity of solutions. Furthermore, when the solutions are sprayed from relatively short nozzle-to-target distances, porous EC films are formed on the target surface along with the EC microspheres. Three nozzle-to-target distances were tested (38, 69, and 115 cm), and the optimal one was found to be 115 cm. To determine how and to what extent the solvent used in room-temperature spray-drying experiments affects the morphology of resultant microspheres, EC was dissolved in either acetone or dichloromethane (DCM), and sprayed from the resultant solutions. While microcapsules prepared from the EC-in-DCM system exhibit even, but porous wall surfaces, microspheres prepared from the EC-in-acetone solution display irregular, but cavity-free wall-surfaces. Finally, as opposed to the pure EC capsules, the ones containing H₂O₂ solution exhibit very smooth wall surfaces; this effect was attributed to the plasticizing effect that the aqueous solution has on the ethylcellulose macromolecules.     

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules III. Effects of the dissolution condition on the release process

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the entire release properties. As the first step, the dissolution test under various conditions is selected for the in vitro test, and usually the results are analyzed following Drug Approval and Licensing Procedures. In this test, 3 time points for each release ratio, such as 0.2-0.4, 0.4-0.6, and over 0.7, respectively, should be selected in advance. These are analyzed as to whether their values are inside or outside the prescribed aims at each time point. This method is very simple and useful but the details of the release properties can not be clarified or confirmed. The validity of the dissolution test in analysis using a combination of the square-root time law and cube-root law equations to understand all the drug release properties was confirmed by comparing the simulated value with that measured in the previous papers. Dissolution tests under various conditions affecting drug release properties in the human body were then examined, and the results were analyzed by both methods to identify their strengths and weaknesses. Hereafter, the control of pharmaceutical preparation, the manufacturing process, and understanding the drug release properties will be more efficient. It is considered that analysis using the combination of the square-root time law and cube-root law equations is very useful and efficient. The accuracy of predicting drug release properties in the human body was improved and clarified.     

Magnetic microcapsules for targeted delivery of anticancer drugs

To achieve targeted distribution of anticancer drugs with sustained activity, ferromagnetic ethylcellulose microcapsules containing an anticancer drug, mitomycin C (FM-MMC-mc), were prepared by a method based on phase separation principles. Two prototypes of FM-MMC-mc were made: one with the drug as the core and zinc ferrite on its capsular surface (outer type); the other with both the drug and zinc ferrite as the core (inner type). Both preparations provided a sustained-release property and a sensitive response to conventional magnetic force, although certain differences in the release rate of drug, magnetic responsiveness, and particle size were found between the two dosage forms. Animal studies showed that the magnetic microcapsules could be magnetically controlled in the artery and urinary bladder. VX2 tumors in the rabbit hind limb and urinary bladder were successfully treated with magnetic control of FM-MMC-mc. Pharmacokinetic study revealed that the targeting of the microcapsules markedly enhanced the drug absorption into the surrounding tissues for a prolonged period of time. The results indicate the feasibility and effectiveness of the magnetic microcapsules as a targeted drug delivery system.     

Studies on the dissolution of carbide fuels

The dissolution of carbide fuels was tried with the aid of various oxidants like H₂O₂, NaBiO₃, (NH₄)₂Ce(NO₃)₆, (NH₄)₂S₂O₈, and AgO in nitric acid medium. During the dissolution, the carbon dioxide liberated has been measured. Among the oxidants studied, H₂O₂ and NaBiO₃ appeared to be more effective for dissolution of carbides. 200–300 mg of sintered uranium carbide sample dissolved within 15 minutes in the presence of oxidants H₂O₂ or NaBiO₃. Mixed carbide sample (70%) was dissolved within 30 min, whereas plutonium carbide required more than one hour. From the resulting solutions uranium and plutonium could be determined by conventional redox methods. More than 97% of plutonium could be recovered and purified from the resulting carbide solutions by conventionally used anion exchange method.     

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules V. Release properties of ethylcellulose layered matrix granules

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the release properties. In previous papers, a combination of the square-root time law and cube-root law equations was confirmed to be a useful equation for qualitative treatment. It was also confirmed that the combination equation could analyze the release properties of layered granules as well as matrix granules. The drug release property from layered granules is different from that of matrix granules. A time lag occurs before release, and the entire release property of layered granules was analyzed using the combination of the square-root time law and cube-root law equations. It is considered that the analysis method is very useful and efficient for both matrix and layered granules. Comparing the granulation methods, it is easier to control the manufacturing process by tumbling granulation (method B) than by tumbling-fluidized bed granulation (method C). Ethylcellulose (EC) layered granulation by a fluidized bed granulator might be convenient for the preparation of controlled release dosage forms as compared with a tumbling granulator, because the layered granules prepared by the fluidized bed granulator can granulate and dry at the same time. The time required for drying by the fluidized bed granulator is shorter than that by the tumbling granulator, so the fluidized bed granulator is convenient for preparation of granules in handling and shorter processing time than the tumbling granulator. It was also suggested that the EC layered granules prepared by the fluidized bed granulator were suitable for a controlled release system as well as the EC matrix granules.     

pH-dependent release from ethylcellulose microparticles containing alginate and calcium carbonate

Ethylcellulose microparticles containing alginate and calcium carbonate nanoparticles were prepared by spray drying water-in-oil emulsion. Alginate solution (3%) in distilled water was used as an aqueous phase, ethylcellulose solution (5%) in dichloromethane as an oil phase, and sorbitan sesquioleate as an emulsifier. The nanoparticles of calcium carbonate were dispersed into the emulsion. By spray-drying the emulsion, ethylcellulose microparticles containing alginate and calcium carbonate were obtained. When the ratios of alginate to calcium carbonate were 4:1 and 2:1, the pH dependency of the release was marked and the degree of release was suppressed in acidic conditions. When the ratio increased to 1:2, the degree of release increased while the pH-dependent release profiles were maintained. Cavities created by the dissolution of calcium carbonate could account for the increased release.