Biomedical subjects

C C Müller-Goymann

Publications and source records attributed to C C Müller-Goymann.

At least 37 records · Page 2Linked to original sources

PubMed2003

Characterization of solidified reverse micellar solutions (SRMS) and production development of SRMS-based nanosuspensions.

Solidified reverse micellar solutions (SRMS), i.e. binary mixtures of 30-60% (w/w) lecithin and two different hard fats, were investigated regarding their physicochemical properties and the influence of lecithin on solid lipids. For this purpose, the systems were characterized with X-ray and thermal analysis, transmission electron microscopy (TEM) and photon correlation spectroscopy. The melting point (m.p.) of the solid lipids, which is a crucial parameter of the solid state, was not altered up to a lecithin concentration of 50% whereas reverse micelles were likely to be frozen still in the solid state. In addition, solubilities of 17beta-oestradiol-hemihydrate, pilocarpine base and hydrochloride in the SRMS melt were studied for evaluation of the drug carrier potency. Drug solubilization in the SRMS melt increased linearly with rising amount of lecithin. SRMS-based nanosuspensions were developed with a given lecithin/hard fat ratio of 1:1 (w/w). High-pressure homogenization was applied on cold to avoid lecithin loss. Optimization of the systems in terms of a variation of the homogenizing parameters such as pressure, number of cycles and temperature resulted in nanoparticulate systems with a polysorbate 80/SRMS ratio of 1:5 (w/w), and a total amount of 5 and 15% (w/w) SRMS, respectively. Production temperatures near the lipid m.p. proved best to be maintained by varying the pressure, yielding small nanoparticles with a narrow particle size distribution. The solid lipid nanoparticles were characterized with X-ray and thermal analysis as well as TEM. The crystalline particles (beta modification) are of anisometrical shape and have transition temperatures far below the bulk m.p. due to the colloidal character of the systems.

Calorimetry, Differential Scanning↗

PubMed2002

Influence of different ceramides on the structure of in vitro model lipid systems of the stratum corneum lipid matrix.

Human stratum corneum (SC) consists of several layers of keratinized corneocytes embedded in a lipid matrix of ordered lamellar structure which is considered to constitute the major barrier to percutaneous penetration. Artificial mixtures of SC lipids are often used as model systems to mimic the skin barrier or to investigate the effects of substances on the phase behaviour of the models. In the present study a SC lipid model composed of cholesterol, fatty acids and ceramides was used to investigate the effect of three different commercially available ceramide types on the microstructure and the physicochemical behaviour of the lipids. Polarized light microscopy, transmission electron microscopy, small-angle X-ray diffraction, wide-angle X-ray diffraction and differential scanning calorimetry (DSC) were used for physicochemical characterization. The results revealed a lamellar structure for all models but showed differences with regard to the thermal and optical behaviour depending obviously on the composition of the ceramide mixtures. A model containing a mixture of Cer[AS] was comparable to human SC lipids.

Calorimetry, Differential Scanning↗

PubMed2002

Comparative permeation studies for delta-aminolevulinic acid and its n-butylester through stratum corneum and artificial skin constructs.

The improvement of the permeation properties through excised human stratum corneum and artificial skin constructs (ASC) of delta-aminolevulinic-n-butylester (ABE) compared with delta-aminolevulinic acid (ALA) was investigated. For this purpose the permeated amounts of each substance were determined depending on time in a Franz diffusion cell experiment with stratum corneum and ASC, respectively. Furthermore the barrier properties of ASC were compared with those of stratum corneum. Detection of both substances was performed by high-performance liquid chromatography (HPLC) analysis. For the determination of ABE a new HPLC method was developed. ABE could be determined with the new HPLC method with sufficient sensitivity (detection limit: 0.1 microg/ml) after derivatisation with o-phthalaldehyde (OPA). Stratum corneum and ASC were more permeable for ABE than for ALA. The permeation coefficient P of ABE through stratum corneum was nearly ten-fold higher than that of ALA. Using ASC as permeation barrier the permeation coefficient of ABE was about 22-fold higher than that of ALA. ABE and ALA permeated 142-fold and 64-fold, respectively, faster through ASC than through stratum corneum.

Aminolevulinic Acid↗

PubMed2001

[Development of an organotypic corneal construction as an in vitro model for permeability studies].

BACKGROUND: In vitro investigations of transcorneal permeation behaviour with new drugs in ophthalmology are mainly carried out using excised corneas taken from slaughtered or experimental animals. Analogous to previously used dermis models, an in vitro model was constructed from porcine corneal cell cultures and the permeation barrier properties were tested and compared with permeation data from excised corneas. METHODS: Epithelial, stroma and endothelial cells were successfully isolated by treatment with various enzymes and a corneal equivalent was created step-by-step which morphologically resembled the original tissue. Five different drug formulations were investigated and pilocarpine hydrochloride was chosen as the model drug. The permeation studies were made with a modified Franz cell and analysis was performed by high performance liquid chromatography. Permeation data from excised corneas and from the cornea construct were compared whereby data obtained with lipophilic preparations did not differ (factor of 1) and those obtained with aqueous formulations were relatively similar (factor of 3-4). RESULTS AND CONCLUSIONS: The results obtained show that the cornea construct can be used as an alternative to excised corneas for in vitro investigations of ophthalmic drug preparations.

Animals↗

PubMed2001

Reconstruction of an in vitro cornea and its use for drug permeation studies from different formulations containing pilocarpine hydrochloride.

The aim of the present contribution was to develop a functional three-dimensional tissue construct to study ocular permeation of pilocarpine hydrochloride from different formulations. The in vitro model was compared to excised bovine cornea. Modified Franz cells were used to study the transcorneal permeability. Analysis was performed by reversed-phase high-performance liquid chromatography. Comparisons of the permeation rates through excised bovine cornea and the in vitro model show the same rank order for the different formulations. The permeation coefficient, K(P), obtained with the cornea construct, is about 2-4-fold higher than that from excised bovine cornea. It is possible to reconstruct bovine cornea as an organotypic culture and also to use this construct as a substitute for excised bovine cornea in drug permeation studies in vitro.

Animals↗

PubMed2001

Solubilization of bromhexine hydrochloride in aqueous lecithin dispersions. Physicochemical characterization of interactions between drug and carrier.

In aqueous systems bromhexine hydrochloride (Br-HCl) has a poor solubility (4.54 mg/g) and displays no amphiphilic character e.g. self association. Therefore the drug is molecularly dispersed in water until the solubility product of Br-HCl is exceeded. Solubilization of Br-HCl is linearly increased on addition of lecithin; calculations show that 10 mg Phospholipon 90G (P 90G) enable solubilization of additional 1.25 mg Br-HCl after the solubility product of Br-HCl has been exceeded. This means that four to five phospholipid molecules are needed for the solubilization of one drug molecule. Ternary systems with P 90G concentrations up to 20% have a lamellar microstructure. The systems are multilamellar vesicle dispersions as polarisation microscopy, transmission electron microscopy and small-angle X-ray diffractometry suggest. Furthermore, Br-HCl solubilization leads to a significant reduction of the interlamellar distance d and increases the elastic properties of the systems. 31P NMR data provide evidence that Br-HCl is solubilized within the lipophilic part of the phospholipid bilayer.

Bromhexine↗

PubMed2000

Interactions during aqueous film coating of ibuprofen with aquacoat ECD.

During the development of a coated ibuprofen formulation a sticking tendency occurred when applying Aquacoat ECD. This interaction indicated the formation of a eutectic mixture. The compatibility of the components of Aquacoat ECD with ibuprofen was investigated by differential scanning calorimetry. Cetyl alcohol, a stabilizing excipient in Aquacoat, was found to form a eutectic system with ibuprofen. It was characterized by the construction of a phase diagram with 33 mol% ibuprofen and an onset temperature of 40.5 degrees C. Wide-angle X-ray diffraction was used to identify the polymorphic forms of cetyl alcohol. The results confirmed the amorphous state in the aqueous dispersion in contrast to the beta(0)- and gamma(4)-polymorphs of solid cetyl alcohol.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Controlled release of solid-reversed-micellar-solution (SRMS) suppositories containing metoclopramide-HCl.

The investigated drug delivery system is a solid-reversed-micellar-solution (SRMS). The composition of this solution is 70% Witepsol W35 and 30% (w/w) lecithin. 1% (w/w) metoclopramide-HCl (MCP) was solubilized in the SRMS. After melting and on contact with water or any physicological aqueous media the SRMS exhibits an application induced transformation into a semisolid system of liquid crystalline microstructure. The structure of the liquid crystal has been identified by polarized light microscopy as a lamellar mesophase. Due to a low coefficient of diffusion in this mesophase a controlled release of the drug may be possible. The release profiles of the in vitro experiments have shown zero order kinetics and a sustained release of the SRMS-suppositories (SRMS-supp.) in comparison with commercial suppositories (Gastrosil-supp.). To examine bioavailability an in vivo study with rabbits was carried out. Five SRMS-supp. (10 mg MCP) and five Gastrosil-supp. (10 mg MCP) were tested in a parallel-group study. These experiments have shown a five times longer mean residence time (parameter of sustained release) in comparison with Gastrosil-supp. In vitro and in vivo studies have shown that rectal application of SRMS-supp. provides an appropriate route for controlled release of MCP via application induced transformation into liquid crystals.

Administration, Rectal↗

PubMed2000

Solubilization of timolol maleate in reversed micellar systems. Measurement of particle size using SAXS and PCS.

Small angle X-ray scattering (SAXS) and photon correlation spectroscopy (PCS) are two methods to measure particle sizes in the order of 10 nm magnitude, which can be used to characterize reversed micellar systems, in this case reverse micelles consisting of lecithin and isopropyl myristate (IPM). In this study these micelles are loaded with different concentrations of the amphiphilic anti-glaucoma drug timolol maleate (TM). The PCS results are consistent with those yielded by SAXS, showing a decrease of particle size with higher TM concentration. In addition, SAXS is capable to give information about the particle shape. This kind of evaluation yields an ellipsoidal shape for micelles with low drug loads, which transform into nearly spherical micelles at higher drug concentrations.

Dose-Response Relationship, Drug↗

PubMed2000

Physicochemical characterization of a reverse micellar solution after loading with different drugs.

Diclofenac sodium (DS), timolol maleate (TM) and pilocarpine hydrochloride (PHCl) were solubilized in a reverse micellar solution (RMS) consisting of lecithin and middle-chain triglycerides (MCT). The influence of these drugs on the physicochemical parameters of the RMS was investigated. Although none of the drugs influenced the size of the associates, the micellar shapes varied considerably. While DS and PHCl increased the anisometry, reverse micelles with TM were spherical. The transformation of the RMS into a lamellar mesophase on contact with water was generally not prevented by any of the drugs but all drugs led to an increased number of defect structures in the liquid crystal. Furthermore the interlayer distance of the lamellar mesophase was reduced by a higher content of DS. In comparison with an RMS containing isopropylmyristate (IPM) instead of MCT, differences in the physicochemical properties of the drug-free RMS and in the influences of solubilized drugs were noticed.

Chemical Phenomena↗

PubMed1999

Modified water containing hydrophilic ointment with suspended hydrocortisone-21-acetate--the influence of the microstructure of the cream on the in vitro drug release and in vitro percutaneous penetration.

Water containing hydrophilic ointment DAB 1997 was modified by the incorporation of ethanol and the effects of ethanol on the evaporation, the drug liberation and the permeation through human excised stratum corneum were investigated. Creams with 10%, 20%, 30% (v/v) and without ethanol were produced. As a model drug 2% (w/w) hydrocortisone-21-acetate was suspended in the o/w cream. The evaporation of the creams decreased with an increasing amount of ethanol which was unexpected because the vapor pressure of ethanol is higher than that of water. From this result it was concluded that ethanol might be interlamellarly fixed in the mixed crystal of the polyhydrate of the emulsifier to a higher extent than it is distributed within the aqueous bulk phase. In context with the liberation studies, ethanol decreased the drug liberation from the cream. This is in accordance with the above hypothesis of the ethanol partitioning within the cream, because the solubility of the drug in ethanol is higher than that in water. Therefore the interlamellar drug concentration should be higher than the solubility of the drug in the bulk phase, with the assumption that the gel network of the emulsifier polyhydrate is finally responsible for the delay in drug liberation. The permeation through stratum corneum showed no significant differences between the alcohol-free and the alcohol-loaded formulations. Obviously the decrease in drug liberation by ethanol was compensated for by the penetration enhancing effect.

Administration, Topical↗

PubMed1998

Transformation of a liposomal dispersion containing ibuprofen lysinate and phospholipids into mixed micelles - physico-chemical characterization and influence on drug permeation through excised human stratum corneum.

Our study is meant as a contribution to the investigation of molecular association of phospholipids and amphiphilic substances like, e.g. non-steroidal anti-inflammatory drugs. Our research focused on physico-chemical characterization of ternary systems containing ibuprofen lysinate, lecithin and water. The influence of the resulting microstructures on drug release and permeation through excised human stratum corneum was also investigated. Depending on the mixing ratio different physical states (lamellar and hexagonal liquid crystals, micellar solutions, liposomal dispersions and biphasic systems) were determined by gross, polarizing microscopic and small angle-X-ray analysis. A special emphasis was laid upon the storage-induced transformation of liposomal dispersions into mixed micellar solutions and its influence on drug release and permeation. A model for the transformation process is presented. Drug release of the liposomal dispersion (Da=1.1x10-5 cm2/s) and of the identically composed mixed micellar solution (Da=2.9x10-5 cm2/s) was delayed compared with the data of the aqueous drug solution (Da=4.7x10-5 cm2/s). Because of the association of ibuprofen lysinate molecules with phospholipid molecules within the liposomal and the mixed micellar system the share of free ibuprofen lysinate monomers, which can pass through the dialysis membrane in the release experiment, is markedly reduced. The results of permeation experiments of these systems, however, did not correspond to the release data. The permeability of the mixed micellar solution rose after 6 weeks of storage (P=4.2x10-8 cm/s), and almost reached the permeation of the aqueous solution (P=3.9x10-8 cm/s), whereas the permeation of the liposomal dispersion was very slow (P=1.5x10-8 cm/s). The different colloidal microstructures of the formulations obviously resulted in divergent interactions with the permeation barrier - the stratum corneum - and subsequently in different permeation behavior.

Cell Membrane Permeability↗

PubMed1998

Comparative investigations to evaluate the use of organotypic cultures of transformed and native dermal and epidermal cells for permeation studies.

In a comparative study organotypic cultures of both transformed and native dermal and epidermal cells were used for permeation studies. In these organotypic cultures the dermal cells are incorporated into a contracted collagen gel, the epidermal cells are seeded on top of this gel and form a multilayered stratified epidermis when cultivated at the air-liquid interface. For permeation studies two different donor systems containing ibuprofen acid were used, Ibutop-Creme and Dolgit-Mikrogel. Studies using excised human stratum corneum showed differences in drug permeability for these two formulations which were also observed when the native organotypic cultures were used. In general, organotypic cultures show a higher permeability for topically applied drugs than excised human stratum corneum, the cultures consisting of transformed cells showed an increase in drug permeability for the Dolgit-Mikrogel compared with the native cultures which might be due to a higher sensitivity for the enhancer isopropanol in this formulation.

Administration, Topical↗

PubMed1998

Phase transformation of a liposomal dispersion into a micellar solution induced by drug-loading.

PURPOSE: Loading a liposomal dispersion with drug may cause a phase transformation into a micellar solution. The present contribution presents a detailed physicochemical characterization and an overall model which describes transformation due to the properties of any drug. METHODS: Characterization of liposomal dispersions was obtained by photon correlation spectroscopy (PCS) and small angle X-ray scattering (SAXS). Microstructure of colloidal solutions was analysed by 31P-NMR and SAXS. RESULTS: At weight ratios of phospholipid to drug from 16:1 to 2:1, liposomal dispersions of milky-white appearance and a mean particle size of about 200 nm were obtained. From a ratio of phospholipid to drug of 1:1 downwards, the systems became nearly transparent. The particle size decreased to a value below 25 nm. SAXS also revealed the change of the colloids. Down to a ratio of phospholipid to drug of 2:1 the systems were described as bilayer-structured. At and below the ratio of 1:1, a mixed micelle was indicated. In the 31P-NMR spectra, the transformation is emphasized by both appearance and disappearance of signals. A model based on the theory of self-assembly is presented which explains the phase transformation due to drug amphiphilicity. CONCLUSIONS: We predict that the model presented will hold in general only due to the amphiphilic properties of the drug.

Colloids↗

PubMed1997

Ketoprofen sodium: preparation and its formation of mixed crystals with ketoprofen.

A simple two-step process for the preparation of ketoprofen sodium was developed. The procedure involved dissolution of ketoprofen in ethanolic NaOH followed by evaporation of the solvent. The resulting amorphous solid was crystallized by controlled precipitation from 96% ethanol. The sodium salt proved to be stable for 4 years and its aqueous solutions for at least 1 year (investigated period). Ketoprofen sodium appears to be an alternative bulk form to ketoprofen acid for production of formulations after further characterization of the compound.

Antirheumatic Agents↗

PubMed1997

In vivo and in vitro diclofenac sodium evaluation after rectal application of soft gelatine capsules enabling application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) for controlled release.

PURPOSE: Reverse micellar solutions of diclofenac sodium were encapsulated in soft gelatine capsules. On contact with aqueous media they exhibited an application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) which slows down drug release. The aim of the present paper was to study in vitro and in vivo drug release from these systems after rectal application. METHODS: In vitro drug release was determined in a self-constructed dissolution apparatus to simulate rectal application. For in vivo bioavailability studies rabbits were used as animal models. In vitro release and in vivo bioavailability of the capsules was compared to Voltaren suppositories. RESULTS: The release profiles of the in vitro experiments show zero-order kinetics. The in vivo bioavailability studies show bioequivalence in terms of AUC for both formulations (capsules and Voltaren suppositories). The mean residence time (parameter of sustained release) of the capsules is three time longer in comparison to Voltaren suppositories. CONCLUSIONS: Rectal administration of capsules provides an appropriate route for controlled release via AIT-SSLC which could be clearly verified in rabbits.

Administration, Rectal↗

PubMed1997

Characterization of a commercial liposome spray.

The commercial liposome spray Heparin-pur-ratiopharm was physicochemically characterized. This preparation is said to result in a fine gel-film containing pure, concentrated liposomes (including drug) on the skin after application and evaporation of the water/ethanol-mixture of the system. As phospholipids tends to form lamellar structures at lower water concentrations the structural characteristics of Heparin-pur-ratiopharm were investigated in the original preparation and after a drying process, which should be comparable to application on skin. For the characterization several methods were used, e.g. photon correlation spectroscopy, electron and polarized light microscopy, small angle X-ray (SAX) scattering and SAX diffraction. The results of the present investigation indicate that there are no changes in the colloidal state of the phospholipids before and after drying and application of the spray. There seem to be only changes in the degree of dispersion of the liquid crystalline phase, i.e. from small uni- or oligolamellar liposomes in the original preparation via multilamellar vesicles to a lamellar mesophase during the drying process. Therefore, it seems that there are no differences for the application of heparin if a preparation containing small uni- or oligolamellar liposomes is used or if the phospholipids are structured differently. The major point of importance for drug application, therefore, seems to be the presence of phospholipids as they possibly work as enhancer for the uptake of the drug through the skin to achieve a quick effect.

Aerosols↗

PubMed1987

[Structure of cholesterol-containing creams].

The colloidal structure of a four-component system consisting of cholesterol, fatty alcohol, petrolatum and water was studied. Depending on the variation of temperature, chain length of the fatty alcohol and concentration of all components, creamy systems of w/o type could be prepared, which present different structural features. Liquid phases as well as crystalline and/or liquid crystalline phases participate in the structure of the creams. The liquid phases are represented by water and by liquid hydrocarbons of low molecular weight of petrolatum. Part of the surfactants is dissolved in this latter phase. The liquid crystalline phase is formed by cholesterol and fatty alcohol together. The characterization of the lamellar liquid crystalline phase was performed by polarized light microscopy and small angle x-ray diffraction. The formation of the lamellar liquid crystals is favoured in a certain molar concentration range of cholesterol and fatty alcohol. The liquid crystalline region is largest with tetradecanol. The lamellar liquid crystals swell with water up to a certain limit. This incorporation of water stabilizes the lamellar liquid crystals so that they are stable in a larger temperature range. The crystalline structures form a network consisting of solid hydrocarbons and the eutectic mixture of cholesterol and fatty alcohol. If water is present the surfactants crystallize as hydrates. A surplus of water can be dispersed as droplets mechanically. Referring to maximum capacity of water incorporation, systems with lowest crystalline amounts (only the network of petrolatum) were best. The surfactants should be completely dissolved.

Chemistry, Pharmaceutical↗