Friedrich Moll

Antibiotic in vivo/in vitro release, histocompatibility and biodegradation of gentamicin implants based on lactic acid polymers and copolymers

Abstract Biodegradable implants containing 10 mg of gentamicin each were prepared by compressing the polymer-drug mixture. The liberation of gentamicin from the implants and the biodegradation of the implants were investigated by following in vitro and in vivo experiments. Implants based on pure poly( l -lactic acid) (L-PLA) released the incorporated antibiotic throughout 30 days with a decreasing delivery rate. During the first 24 h L-PLA implants released a total amount of 3600 μg gentamicin. Within 14 days the release rate had decreased to about 12 μg/day. The release profile of implants based on dl -lactic acid-glycolic acid copolymer (RG 502) was completely different. About 1900 μg were released from the copolymer implants during the first 24 h. Release rate decreased to a value of about 3 μg/day 15 days after implantation. In a second phase, starting 20 days after implantation, drug delivery increased again to reach values of about 100 μg/day at the end of the experiment, i.e. 28 days after implantation. Very good tissue compatibility arises from the absence of inflammatory reactions throughout the entire time of implantation as shown by microscopy examinations. The developed implants based on biodegradable polymers are suited for the treatment of acute and chronic bone and tissue infections due to their specific release profiles, their excellent histocompatibility and their biodegradability.

In vitro pulsatile and continuous transdermal delivery of buserelin by iontophoresis

Abstract Transdermal delivery of buserelin, a nonapeptide, from hydroxyethylcellulose hydrogel through isolated human stratum comeum was studied. In vitro studies were carried out in a drug release apparatus (DAB 10/USP XII) using self designed rotary disk cells equipped with platinum electrodes. Different forms of current were examined. A pulsatile application of continuous current resulted in a step-like permeation profile. Different on/off ratios (5 min/55 min; 10 min/50 min; 15 min/45 min)) were studied. When continuous non-interrupted current with different current densities (0.1–0.3 mA·cm −2 ) was applied, linear dependence of the final cumulative amount of buserelin on current duration and density was observed. Passive permeation of buserelin through human stratum comeum was not detectable either before current flow or after a current period of 4 h (0.2 mA·cm −2 ). A comparison of iontophoretic release and passive release of buserelin from hydroxyethylcellulose hydrogel through a cellulose membrane showed matrix release for both. Iontophoretic enhancement was also significant for release behavior. In aqueous solution significant electrolysis was observed. Electrolysis of buserelin in hydrogel occurred less and was dependent on current density. The pH-shift in donor medium after electrically assisted permeation was examined for different current densities, current duration and ionic strength of buffer. The influence of donor pH and ionic strength on permeation was studied. Pulsed (2000 Hz; 0.1 mA·cm −2 ; square wave form) and continuous (0.1 mA·cm −2 ; 0.2 mA·cm −2 ) direct current were compared.

The effect of ultrasound on in vitro liberation and in vivo penetration of benzyl nicotinate

Abstract The effect of ultrasound on the in vitro liberation of benzyl nicotinate from polyacrylate gel and the in vivo penetration of benzyl nicotinate solution through the skin was investigated. An ultrasonic apparatus used in medical therapy was employed for ultrasonic treatment. Sonication of the gels accelerates the liberation and enhances the apparent diffusion coefficient of benzyl nicotinate. The liberation can be described by the square root law. The influence of ultrasound on the percutaneous absorption of benzyl nicotinate was investigated in healthy volunteers in a blind placebo-controlled crossover trial. In our experiments, ultrasonic treatment alone does not result in reddening of the skin. For recording the reddening of the skin on application of benzyl nicotinate a reflection photometry method was used. The parameters determined, i.e., lag time and intensity of redness, indicate a behaviour dependent on the concentration of benzyl nicotinate. Increasing concentrations reduce the lag time and increase the intensity of redness, both parameters tending towards a limit. Ultrasonic treatment of the skin in ther-apeutic doses of 0.2, 0.5 and 1.0 W/cm 2 reduces the lag time as a function of power after application of the benzyl nicotinate. Repetitions of the ultrasonic treatment confirm the reversibility of the changes in skin permeability. Thus, phonophoresis of benzyl nicotinate gels has two effects; acceleration of nicotinate liberation from gel and enhancement of percutaneous nicotinate permeation.

Iontophoretic in vitro release of antimycotics from hydrogels

A new in vitro model for iontophoretic release from hydrogels was developed. It represents a modification of the rotary disk cell developed by Moll/Bender and can be used in a normal dissolution tester. The iontophoretic release from antimycotic hydrogels through an artificial membrane was investigated and different types of antimycotics were tested. The influence of current density, drug concentration and vehicle was determined.

Controlled iontophoretic release of glucocorticoids through epithelial cell monolayers

In the present study the iontophoretic transdermal delivery of three different glucocorticoids through a confluent monolayer of MDCK cells, mimicking biological barriers, was studied. For this experiment an in vitro model with platinum electrodes for iontophoresis and MDCK cells was developed. With this model investigations concerning the biocompatibility of the cells depending on different current densities and the iontophoretic permeation of the three glucocorticoids through the cell monolayer were carried out. The permeation behavior of this living biological barrier should be very similar to the non-living barrier, human stratum corneum. Different current densities (12.74-38.22 microA/cm2) and a pulsatile application of continuous current to the cell monolayer were investigated. The pulsatile application of the current resulted in a step-like permeation profile. In all cases the electric current induced an reversible increase of the porosity of the cell monolayer demonstrated by transepithelial electrical resistance measurements and by sodium fluorescein assay.