Biomedical subjects

R Bodmeier

Publications and source records attributed to R Bodmeier.

At least 55 records · Page 3Linked to original sources

PubMed1997

Microencapsulation of antimicrobial ceftiofur drugs.

Polymeric microparticles containing two ceftiofur salts as antimicrobial agents for intramammary application in dry cows were prepared by modified o/w-solvent evaporation methods (dispersion or cosolvent method) or by a w/o/w-multiple emulsion solvent evaporation method. The microspheres were characterized with respect to drug loading, drug release, and morphological properties. The three methods resulted in high encapsulation efficiencies. The choice of organic solvent/solvent mixture strongly affected the structure of the microparticles; both matrix and reservoir-type structures with different porosities were obtained. Scaling up to larger batch sizes resulted in microspheres with a faster drug release. The addition of water-miscible cosolvents to the water-immiscible polymer solution allowed the preparation of microparticles from a drug solution rather than a drug dispersion. Microparticles prepared by the cosolvent method could be separated after shorter time intervals from the aqueous phase; the microspheres had a denser matrix with finely dispersed drug crystals and a slower drug release when compared with microspheres prepared by the dispersion method, which had a more porous structure with larger embedded drug crystals. The cosolvent and dispersion methods present a simple alternative to the w/o/w-solvent evaporation method for the encapsulation of water-soluble drugs with an external water phase.

Cephalosporins↗

PubMed1996

The influence of buffer species and strength on diltiazem HCl release from beads coated with the aqueous cationic polymer dispersions, Eudragit RS, RL 30D.

PURPOSE: Eudragit RL and RS 30D are pseudolatexes frequently used in the coating of solid dosage forms. They are based on cationic copolymers stabilized with quaternary ammonium groups (poly(ethylacrylate-methylmethacrylate-trimethylammonioethyl methacrylate chloride). A pH-independent drug release is expected because of the quaternary nature of the cationic groups. The objective was to explain a distinct "pH-dependent" drug release in various buffer media with coated diltiazem beads. METHODS: The diltiazem HCl release from and water uptake of Eudragit RS/RL-coated beads was determined in various buffers of different buffer species, pH or concentration. RESULTS: The drug release in the different buffer media was in the following order: pH 5.0 acetate > pH 3.5 formate > pH 7.4 phosphate buffer > 0.1M HCl). This "pH-dependent" drug release could be explained with an anion exchange process; the chloride counterions of the quaternary groups were exchanged with the anionic buffer species during the dissolution study. The water uptake of the coated beads correlated well with the drug release from the beads. Increasing the buffer strength (acetate buffer) first increased and then decreased the drug release, while increasing the ionic strength of different buffers with NaCl decreased the drug release and eliminated the observed buffer effects because of the excess of chloride ions. CONCLUSIONS: The anionic buffer species and not the pH had a significant effect on the hydration and hence on the drug release from beads coated with the cationic polymers, Eudragit RS and RL.

Acrylic Resins↗

PubMed1995

Polymeric microspheres prepared by spraying into compressed carbon dioxide.

PURPOSE: The objective was to prepare polymeric microparticles by atomizing organic polymer solutions into a spray chamber containing compressed CO2 (PCA-process) and to study the influence of various process parameters on their morphological characteristics. METHOD: The swelling of various pharmaceutically acceptable polymers [ethyl cellulose, poly(methyl methacrylate), poly(epsilon-caprolactone), poly(dl-lactide), poly(l-lactide) and poly(dl-lactide-glycolide) copolymers] in CO2 was investigated in order to find polymers which did not agglomerate during the spraying process. Poly(l-lactide) (L-PLA) microparticles were prepared by spraying the organic polymer solution into CO2 in a specially designed spraying apparatus. The effect of various process (pressure and temperature of the CO2 phase, flow rate) and formulation (polymer concentration) variables on the morphology and particle size of L-PLA-microparticles was investigated. RESULTS: Polymers with low glass transition temperatures agglomerated even at low temperatures. The formation of microparticles was favored at moderate temperatures, low polymer concentrations, high pressures and high flow rates of CO2. High polymer concentrations and low flow rates resulted in the formation of polymeric fibers. Colloidal L-PLA particles could also be prepared with this technique in a surfactant-free environment. Initial studies on the microencapsulation of drugs resulted in low encapsulation efficiencies. CONCLUSIONS: The PCA method is a promising technique for the preparation of drug-containing microparticles. Potential advantages of this method include the flexibility of preparing microparticles of different size and morphology, the elimination of surfactants, the minimization of residual organic solvents, low to moderate processing temperatures and the potential for scale-up.

Carbon Dioxide↗

PubMed1994

Mechanical properties of dry and wet cellulosic and acrylic films prepared from aqueous colloidal polymer dispersions used in the coating of solid dosage forms.

The mechanical properties of dry and wet polymeric films prepared from various aqueous polymeric dispersions were evaluated by a puncture test. They were studied with respect to type of polymer dispersion [cellulosic: Aquacoat and Surelease; acrylic: Eudragit NE, L, RS, and RL 30 D], plasticizer type (water-soluble or water-insoluble), drying or curing conditions, method of film preparation (pseudolatex-vs solvent casting) and ratio of Eudragit RS/RL 30 D in mixed Eudragit RS/RL films. Dry and wet mechanical strengths of the polymeric films depended primarily on the types of the colloidal polymer dispersion and the plasticizer. Films prepared from ethylcellulose dispersions resulted in very weak and brittle films when compared to the acrylic films. Pseudolatex-cast ethylcellulose films showed lower puncture strength and elongation values when compared to those of the solvent-cast films. Curing of the pseudolatex-cast ethylcellulose films had minimal effects on their mechanical properties. Eudragit L 30D, an enteric polymer dispersion, resulted in brittle films in the dry state, but in very flexible films in the wet state because of the plasticization effect of water. Wet Eudragit RS 30 D polymer films plasticized with water-insoluble plasticizers were significantly more flexible than the corresponding wet films plasticized with water-soluble plasticizers. The water-soluble plasticizers leached from the films during exposure to the aqueous medium, while the water-insoluble plasticizers were almost completely retained within the wet films. The low permeability of a water-soluble drug, chlorpheniramine maleate, and the weak mechanical properties of Aquacoat films could suggest osmotic driven/rupturing effects as the release mechanisms from Aquacoat-coated dosage forms.

Acrylates↗

PubMed1993

Microencapsulation of drugs with aqueous colloidal polymer dispersions.

Sustained-release polymer particles containing drugs with various solubility characteristics (ibuprofen, theophylline, guaifenesin, and pseudoephedrine HCl) were prepared with colloidal polymer dispersions in a completely aqueous environment as an alternative to conventional microencapsulation techniques, which use organic solvents. Spherical particles were prepared by spraying or dropping dilute sodium alginate solutions (0.67%, w/w) containing the dissolved or dispersed drug and colloidal polymer particles into calcium chloride solutions. The gelled particles, which formed by ionotropic gelation of the polysaccharide with calcium ions, were dried and cured at 60 degrees C to cause fusion of the colloidal polymer particles into a homogeneous matrix system. Actual drug contents close to 50% and encapsulation efficiencies of between 80 and 98% were achieved with all drugs. Guaifenesin and ibuprofen acted as plasticizers for the ethyl cellulose pseudolatex, whereas with theophylline and pseudoephedrine HCl, dibutyl sebacate had to be added as a plasticizer to yield a nondisintegrating polymer matrix. The stirring time before separation of the particles from the gelation medium had to be minimized with the water-soluble drugs to maximize drug loading; however, it was not critical with the water-insoluble drugs. Drug release was a function of the solubility of the drug, drug loading, and the type of polymer dispersion used.

Capsules↗

PubMed1991

Constant potassium chloride release from microporous membrane-coated tablets prepared with aqueous colloidal polymer dispersions.

To achieve constant drug release and to avoid the use of organic solvents, potassium chloride tablets were coated with aqueous latexes containing dispersed pore-formers with pH-dependent solubility characteristics. The pore-forming agent, dibasic calcium phosphate, was insoluble in the latex but soluble at low pH. Upon contact with simulated gastric fluids, it leached out rapidly to form a rate-controlling, microporous membrane. The release of potassium chloride was linear with time up to 75-80% drug released. It increased with increasing level of pore-former and decreasing membrane thickness but was independent of the degree of agitation and the pH of the dissolution medium after leaching of the pigments. Upon storage at different relative humidities, moisture uptake of the film coat and variations in the release profiles over time were minimal.

Chemistry, Pharmaceutical↗

PubMed1990

Drug release from laminated polymeric films prepared from aqueous latexes.

Laminated films comprised of a drug-containing reservoir layer and a drug-free, rate-controlling membrane were prepared from aqueous latexes and investigated as an alternative drug delivery system to polymeric films cast from organic solvents. The reservoir layer was prepared by casting and drying the latex [copolymer of poly(ethylacrylate-methylmethacrylate) esters - Eudragit NE 30D (NE 30D)] containing the dissolved drugs (chlorpheniramine maleate, propranolol HCl, or salicylic acid). Monolithic solutions (salicylic acid-NE 30D) or dispersions (chlorpheniramine maleate or propranolol HCl-NE 30D) were formed, depending on the solubility of the drug in the polymer matrix. Zero-order drug release was achieved by laminating a second, drug-free latex film onto the reservoir layer. The rate-controlling membrane was either attached to, or cast directly onto the reservoir. The release rate was independent of loading for the monolithic dispersions, but dependent on loading for the monolithic solution. Release rates were enhanced by the addition of a hydrophilic polymer, hydroxypropyl methylcellulose, to the rate-controlling membrane. An inverse relationship was observed between the release rate and membrane thickness. The rate-controlling membrane, cast from organic polymer solutions, had a denser structure, resulting in slower drug release when compared with latex-cast laminates.

Acrylic Resins↗

PubMed1990

Theophylline tablets coated with aqueous latexes containing dispersed pore formers.

Constant drug release was achieved from theophylline tablets coated with a multiporous membrane in an aqueous environment. The tablets were coated with an aqueous acrylic latex containing a dispersed pore-forming agent with pH-dependent solubility characteristics. The pore former, dibasic calcium phosphate, was insoluble in the latex but leached out rapidly in 0.1 M HCl. Theophylline was then released at a constant rate through the multiporous membrane. The drug release was a function of the level of the pore-forming agent and the membrane thickness, but independent of the pH of the dissolution medium and the degree of agitation.

Chemistry, Pharmaceutical↗

PubMed1989

Evaluation of biodegradable poly(lactide) pellets prepared by direct compression.

Biodegradable pellets intended for either parenteral or oral use were successfully prepared from low molecular weight poly(DL-lactide) (low MW PLA, MW' = 2000) or a relatively high molecular weight poly(L-lactide) (L-PLA, MW = 215,000) sample by a simple direct compression technique without the use of heat or organic solvents. The energy imparted during the compression step caused fusion of the low MW PLA particles. Pellets prepared from low MW PLA swelled considerably before eroding in pH 7.4 buffer, but acted as an enteric matrix in 0.1 M HCl. This was attributed to the high carboxyl endgroup:polymer chain ratio which increased with a decrease in molecular weight. Interactions between salts of basic drugs (quinidine sulfate or propranolol hydrochloride) and the polymeric carboxyl endgroups caused retardation in the drug release from low MW PLA pellets. The drug release from L-PLA pellets was independent of the pH of the dissolution media and drug-polymer interactions were absent. The drug release could be increased by admixing sodium chloride prior to compression, or reduced by dipping the pellets into methylene chloride for a short period of time.

Calorimetry, Differential Scanning↗

PubMed1989

Spherical agglomerates of water-insoluble drugs.

Spherical pellets of poorly soluble drugs (micronized griseofulvin, ibuprofen, indomethacin, sulfadiazine, or tolbutamide) were prepared by dispersing each drug in solutions of the ionic polysaccharides chitosan or sodium alginate, and then dropping these dispersions into solutions of the respective counterions tripolyphosphate or calcium chloride (CaCl2). The droplets instantaneously formed gelled spheres by inotropic gelation. Strong spherical beads with a narrow particle size distribution and low friability could be prepared with high yield and a drug content approaching 98%. The flow properties of micronized or needle-like drug crystals were significantly improved by this agglomeration technique when compared with nonagglomerated drug crystals. The ionic character of the polymers resulted in pH-dependent disintegration of the beads. Chitosan beads disintegrated in 0.1M HCl, while calcium alginate beads stayed intact in 0.1M HCl but rapidly disintegrated in simulated intestinal fluids. In addition to scanning electron microscopy, dissolution and disintegration tests were used to characterize the drug pellets.

Alginates↗

PubMed1989

Evaluation of drug-containing polymer films prepared from aqueous latexes.

Polymeric films containing salicylic acid or propranolol HCl were prepared by casting and drying a drug-containing, aqueous colloidal polymer dispersion (Eudragit NE 30D) as an alternative to films cast from organic polymer solutions. The drug was either dissolved (salicylic acid) or dissolved/dispersed (propranolol HCl) in the polymeric matrix. Incompatibilities (flocculation or coagulation) between salts of basic drugs and two ethylcellulose latexes were overcome by substituting the anionic surfactants with a nonionic surfactant (Pluronic P103). The drug release was studied as a function of drug loading, film thickness, amount of hydrophilic additive (hydroxypropyl methylcellulose), and storage humidity. The release of propranolol HCl (monolithic dispersion) was a combination of diffusion through the polymer and pores or channels; the extent of each release mechanism depended on the drug loading. On DSC thermograms, melting transitions were obtained with monolithic dispersions but not with monolithic solutions. The heat of fusion was linearly correlated to the amount of drug in the films. The amount of drug remaining in the film after the dissolution study was not detectable and corresponded to the drug dissolved in the polymer. The drug release increased with increased drug loading and increased amount of hydroxypropyl methylcellulose but was independent of film thickness and relatively insensitive to different storage humidities.

Chemistry, Pharmaceutical↗

PubMed1989

A novel approach to the oral delivery of micro- or nanoparticles.

A novel oral multiple-unit dosage form which overcame many of the problems commonly observed during the compression of microparticles into tablets was developed in this study. Micro- or nanoparticles were entrapped in beads formed by ionotropic gelation of the charged polysaccharide, chitosan or sodium alginate, in solutions of the counterion, tripolyphosphate (TPP) or calcium chloride (CaCl2), respectively. The described technique did not change the physical properties of the microparticles, and it allowed a high microparticle loading (up to 98%). The ionic character of the polymers allowed pH-dependent release of the microparticles. Chitosan beads disintegrated and released the microparticles in 0.1 N HCl, while calcium alginate beads stayed intact in 0.1 N HCl but rapidly disintegrated in simulated intestinal fluids. Coating the calcium alginate beads with cellulose acetate phthalate resulted in an enteric drug delivery system. Scanning electron microscopy and dissolution and disintegration tests were used to characterize the microparticle-containing beads. The disintegration time of the beads was studied as a function of the solution viscosity of the polysaccharide, gelation time, counterion concentration, and method of drying.

Alginates↗

PubMed1988

Preparation of biodegradable poly(+/-)lactide microparticles using a spray-drying technique.

Drug containing biodegradable poly(+/-)lactide microparticles were prepared by using a spray-drying technique. Formulations containing model drugs in either a dissolved (progesterone) or dispersed state (theophylline) were spray-dried. The spray-drying method was less dependent on the solubility characteristics of the drug when compared with traditional microencapsulation techniques such as phase separation or solvent evaporation techniques. Differential scanning calorimetry and scanning electron microscopy were used to characterize the microparticles. The drug release profiles were characterized by a rapid release phase (burst effect) followed by a slow release phase, the extent of each phase being dependent on the drug loading.

Biodegradation, Environmental↗

PubMed1987

The preparation and evaluation of drug-containing poly(dl-lactide) microspheres formed by the solvent evaporation method.

Several compounds such as caffeine, diazepam, hydrocortisone, progesterone, quinidine, quinidine hydrochloride, quinidine sulfate, and theophylline were evaluated for incorporation into poly(dl-lactide) (PLA) microspheres using the solvent evaporation technique. The process is generally limited to the entrapment of water-insoluble drugs. Adjustment of the pH of the aqueous phase to minimize drug solubility resulted in increased drug contents within the microspheres in the case of ionizable drugs. The release profile of quinidine from the microspheres was characterized by three different release phases, a lag time with no drug release, a burst effect of rapid drug release within a short period of time, and a slow release phase, respectively. The structure of the microsphere surface layer, which was a function of the pH of the aqueous phase at preparation, strongly influenced the rate and amount of drug released. Thermal analysis of quinidine-loaded microspheres revealed three thermal events, corresponding to the glass transition temperature of the polymer and to the recrystallization and melting of quinidine.

Drug Carriers↗

PubMedDate not supplied

Multiple unit gastroretentive drug delivery systems: a new preparation method for low density microparticles.

The aim of this study was to develop a new preparation method for low density foam-based, floating microparticles and to demonstrate the systems' performance in vitro. Major advantages of the novel preparation technique include: (i) short processing times, (ii) no exposure of the ingredients to high temperatures, (iii) the possibility to avoid toxic organic solvents, and (iv) high encapsulation efficiencies close to 100%. Floating microparticles consisting of polypropylene foam powder, model drug [chlorpheniramine maleate (CPM), diltiazem HCl, theophylline or verapamil HCl] and polymer [Eudragit RS or polymethyl methacrylate (PMMA)] were prepared by soaking the microporous foam carrier with an organic solution of drug and polymer and subsequent drying. The effects of various formulation and processing parameters on the resulting in vitro floating behaviour, internal and external particle morphology, drug loading, in vitro drug release and physical state of the incorporated drug were studied. Good in vitro floating behaviour was observed in most cases and a broad variety of drug release patterns could be achieved by varying the drug loading and type of polymer. Interestingly, PMMA-based microparticles showed incomplete drug release with verapamil HCl. This restriction could be overcome by forming the free base of the drug prior to microparticle preparation. In contrast to the salt, the free base acted as a plasticizer for PMMA, resulting in sufficiently high diffusion coefficients and, consequently, complete drug release. The low density microparticles were compressed into rapidly disintegrating tablets in order to provide an administrable oral dosage form.

Administration, Oral↗

PubMedDate not supplied

Microparticles prepared by grinding of polymeric films.

Microparticles were prepared by a film grinding method, whereby thin drug-containing ethylcellulose films were cryogenically ground into microparticles. The particle size and shape of the microparticles could be controlled by the thickness of the films and by the milling time. The encapsulation efficiency as well as the in vitro drug release depended on the physical state of the drug in the ethylcellulose matrix (dispersed vs dissolved). Increased drug loadings and decreased particle size and film thickness increased the drug release. Microparticles prepared from cast films were more dense and had a slower drug release compared to microparticles prepared from sprayed films or from films prepared from an aqueous colloidal ethylcellulose dispersion, Aquacoat ECD. Lamination of the drug-containing film with a drug-free polymer layer on both sides resulted in a reduced drug release. Hydrophilic plasticizers acted as pore-formers and accelerated drug release, while lipophilic plasticizers reduced the drug release. The solubility of the drug in the organic polymer solution was one of the main parameters to achieve high encapsulation efficiencies and extended drug release, while dispersed drug was released much faster. The drug release from microparticles prepared by film grinding was faster than from microparticles prepared by the solvent evaporation method. The faster release was attributed to the fractured surface of the ground particles. Grinding of microparticles, which were prepared by the solvent evaporation, also resulted in a faster release.

Biocompatible Materials↗

PubMedDate not supplied

Polylactic acid microspheres containing quinidine base and quinidine sulphate prepared by the solvent evaporation technique. I. Methods and morphology.

D,1-polylactic acid (PLA) microspheres containing the antiarrhythmic drug, quinidine, were prepared by the solvent evaporation method. The drug was present as either the base or as the sulphate salt. A slight modification in the process resulted in high yields of free-flowing, non-aggregated microspheres. The successful entrapment of drug within the microspheres was highly dependent on drug solubility in the aqueous phase. Diffusion and drug loss to the aqueous phase was minimized by adjusting the pH of the aqueous phase to minimal drug solubility. Saturation of the aqueous phase with drug further improved the payload of the microspheres. The appearance of the microsphere surface depended on the pH of the aqueous phase, the electrolyte concentration, and the type and amount of drug present. Structural changes and erosion of the polymer were observed at high pH-values.

Hydrogen-Ion Concentration↗

PubMedDate not supplied

Polylactic acid microspheres containing quinidine base and quinidine sulphate prepared by the solvent evaporation technique. II. Some process parameters influencing the preparation and properties of microspheres.

D,L-polylactic acid (PLA) microspheres containing quinidine base and quinidine sulphate were prepared by the solvent evaporation method. The present study was carried out to examine how various process parameters in the aqueous phase influenced the preparation and properties of PLA-microspheres. The amount of drug that could be incorporated into the microspheres depended primarily on the solubility of the drug in the aqueous phase and the precipitation of PLA at the droplet surface. The drug content was found to be influenced by the organic solvent: aqueous phase ratio, the temperature of the aqueous phase, and the amount of emulsifying agent. Time-dependent pH-change studies in the aqueous phase showed that polymer precipitation at the outer surface of the microspheres, and drug loss due to partitioning, occurred rapidly. A partition method for increasing the payload of drug in the microspheres was developed by incorporating drug in both the aqueous and the organic phases. Using this method, drug could be loaded into the microspheres independent of the pH of the aqueous media. The partition method circumvented the surface degradation observed with PLA microspheres prepared at high pH values of the aqueous phase. This method may prove useful for the entrapment of water-soluble drugs.

Hydrogen-Ion Concentration↗