Papers by Hartwig Steckel
release properties Bone substitute materials delivering zoledronic acid : Physicochemical characterization , drug load , and
Calcium phosphate-like bone substitute materials have a long history of successful orthopedic app... more Calcium phosphate-like bone substitute materials have a long history of successful orthopedic applications such as bone void filling and augmentation. Based on the clinical indications, these materials may be loaded with active agents by adsorption offering a perspective for providing innovative drug-delivery systems. The highly effective bisphosphonate zoledronic acid (ZOL) demonstrated a strong affinity to biominerals and is known to significantly reduce osteoclastic activity. Support of early bone formation and reduction of bone resorption can be promoted after implantation of bioceramics releasing ZOL. The aim of this study was to develop an easy to handle approach to combine ZOL with bone substitutes by use of a dipping technique. The properties of three different materials were investigated by using a number of physicochemical methods such as light microscopy, scanning electron microscopy (SEM), dynamic vapor sorption (DVS), true density, and surface area measurement to evalua...
Rekristallisationsverhalten von teil-amorpher Laktose während und nach der Tablettierung
Pharmazeutische Industrie, 2010
The solid state properties of lactose, widely used as a pharmaceutical excipient, are of signific... more The solid state properties of lactose, widely used as a pharmaceutical excipient, are of significant importance for the processing and stability of solid oral dosage forms. Alterations to the solid state properties, i. e. the creation or recrystallization of amorphous parts affect tablet properties like disintegration time and tensile strength. In the following stu¬dy, the occurrence of phase transitions (solid-state transi¬tion from amorphous to crys¬talline and from crystalline to amorphous) have been inves¬tigated. The solid state pro¬perties of six different lactose qualities were investigated before and after direct compres¬sion. Fast Flo® 316 NF, FlowLac® 90, FlowLac® 100 as well as SuperTab® USD and SuperTab® 14SD were used as spray-dried lactose qualities and compared to Tablettose® 80 as an example for an agglomerated lactose quality. At first the amorphous content of powders of all lactose qualities was determined by microcalorimetry prior to compaction. Straight after dir...
[Treatment of bronchial asthma. Dosage forms for inhalational glucocorticoids]
Pharmazie in unserer Zeit, 2003
Calorimetric study on amorphous lactose during and after Re-crystallization at different relative humidity
α-Lactose monohydrate is the carrier of choice for dry powder inhaler formulations but problems d... more α-Lactose monohydrate is the carrier of choice for dry powder inhaler formulations but problems during dry powder inhalation development occur, mainly due to differences in the surface texture and surface energy of lactose received from different sources, but also due to batch-to-batch variability. It was the aim of this study to investigate the influence of the relative humidity during re-crystallization and the amount of amorphous material present on the physical form of the re-crystallized lactose. Spray-dried lactose and conditioned α-lactose monohydrate are used as reference materials for completely amorphous and fully crystalline lactose. Blends of these lactose qualities were re-crystallized in an isothermal microcalorimeter at different relative humidity (RH) and subsequently analysed by differential scanning calorimetry (DSC). It was found that the relative humidity during re-crystallization influences the physical form of the re-crystallized lactose. Re-crystallization at ...
Pharmaceutics, 2020
Oseltamivir phosphate (OP) is an antiviral drug available only as oral therapy for the treatment ... more Oseltamivir phosphate (OP) is an antiviral drug available only as oral therapy for the treatment of influenza and as a potential treatment option when in combination with other medication in the fight against the corona virus disease (COVID-19) pneumonia. In this study, OP was formulated as a dry powder for inhalation, which allows drug targeting to the site of action and potentially reduces the dose, aiming a more efficient therapy. Binary formulations were based on micronized excipient particles acting like diluents, which were blended with the drug OP. Different excipient types, excipient ratios, and excipient size distributions were prepared and examined. To investigate the feasibility of delivering high doses of OP in a single dose, 1:1, 1:3, and 3:1 drug/diluent blending ratios have been prepared. Subsequently, the aerosolization performance was evaluated for all prepared formulations by cascade impaction using a novel medium-resistance capsule-based inhaler (UNI-Haler). Formu...
The influence of high shear mixing on ternary dry powder inhaler formulations
International journal of pharmaceutics, Jan 20, 2017
The blending process is a key step in the production of dry powder inhaler formulations, but only... more The blending process is a key step in the production of dry powder inhaler formulations, but only little is known about the influence of process parameters. This is especially true for high shear blending of ternary formulations. For this reason, this study aims to investigate the influence of high shear mixing process parameters (mixing time and rotation speed) on the fine particle fraction (FPF) of ternary mixtures when using budesonide as model drug, two different carrier materials and two different mixing orders. Prolonged mixing time and higher rotation speeds led to lower FPFs, possibly due to higher press-on forces acting on the active pharmaceutical ingredients (API). In addition, a clear correlation between the energy consumption of the blender (the energy input into the blend) and the reduction of the FPF could be shown. Furthermore blending the carrier and the fines before adding the API was also found to be favorable.
Powder flow analysis: A simple method to indicate the ideal amount of lactose fines in dry powder inhaler formulations
International journal of pharmaceutics, Jan 15, 2018
Many efforts have been made in the past to understand the function of lactose fines which are giv... more Many efforts have been made in the past to understand the function of lactose fines which are given as a ternary component to carrier-based dry powder inhaler formulations. It is undisputed that fines can significantly improve the performance of such formulations, but choosing the right amount of fines is a crucial point, because too high concentrations can have negative effects on the dispersion performance. The aim of this study was to indicate the optimal concentration of fines with a simple test method. For this purpose, mixtures with salbutamol sulfate and two different lactose carriers were prepared with a high shear mixer, measured with a FT4 powder rheometer and tested for fine particle delivery with two different inhaler devices. A correlation between the fluidization energy, measured with the aeration test set up, and the fine particle fractions (FPF) could be proven. This also applied for the aeration ratio, as well as the permeability of the powder samples. In addition, ...
In vitro characterization of jet-milled and in-situ-micronized fluticasone-17-propionate
International Journal of Pharmaceutics, 2003
Particle properties are decisive for therapeutic efficiency of an inhaled pulmonary drug. Jet-mil... more Particle properties are decisive for therapeutic efficiency of an inhaled pulmonary drug. Jet-milling as the common way for micronization of inhaled powder drugs shows several disadvantages such as a non-homogeneous particle size distribution and unnatural, thermodynamically-activated particle surfaces causing a high agglomeration behavior. For pulmonary use in a dry powder inhaler (DPI) beside a small particle size, a good de-agglomeration activity is required. In this study, fluticasone-17-propionate (FP) is in-situ prepared in a respirable particle size by a controlled crystallization technique. First, the drug is dissolved in acetone and precipitated by a solvent change method in the presence of a cellulose ether (HPMC) as stabilizing hydrocolloid. By rapidly pouring the drug solution into the polymer-rich water phase, the previously molecularly dispersed drug is associated to small particles and stabilized against crystal growth simultaneously by the presence of the hydrophilic polymer. This dispersion was then spray-dried. The mean particle size of the drug was around 2 microm and consequently in the respirable range. The physico-chemical properties of the in-situ-micronized drug were compared to those of an unmilled and a jet-milled quality. Differences in the X-ray patterns and amorphous parts could be detected for the jet-milled but not for the in-situ-micronized drug. In addition, the aerodynamic behavior of the engineered and the jet-milled FP was analyzed using the FlowCaps inhaler as delivery device and compared to the commercial product Flutide Diskus. The fine particle fraction (FPF) (<5 microm) was increased four-fold from approximately 9% for the jet-milled drug to approximately 40% for the in-situ-micronized drug when the pure drug powder was dispersed with the FlowCaps device.
Nano- and Microstructured model carrier surfaces to alter dry powder inhaler performance
International Journal of Pharmaceutics, 2017
The present study investigates the effect of different carrier surface modifications on the aeros... more The present study investigates the effect of different carrier surface modifications on the aerosolisation performance and on the effective carrier payload of interactive blends for inhalation. Two different active pharmaceutical ingredients (APIs) were used: Formoterol fumarate dihydrate (FF) and budesonide (BUD). Blends were prepared with glass beads as model carriers which have been subjected to mechanical surface modifications in order to introduce surface roughness via treatment with hydrofluoric acid (HF) and/or milling with tungsten carbide (TC). As far as effective carrier payload, in this study expressed as true surface coverage (TSC), is concerned, surface modification had varying effects on blends containing BUD or FF. Aerodynamic characterisation in vitro showed a significant decrease in respirable fraction for glass beads treated with HF (40.2-50.1%), due to the presence of clefts and cavities, where drug particles were sheltered during inhalation. In contrast, grinding with TC leads to surface roughness on a nano scale, ultimately increasing aerodynamic performance up to 20.0-38.1%. These findings are true for both APIs, regardless of their chemical properties.
Micronizing of steroids for pulmonary delivery by supercritical carbon dioxide
International Journal of Pharmaceutics, 1997
The micronization of various drugs is beset with serious problems due to the insufficient brittle... more The micronization of various drugs is beset with serious problems due to the insufficient brittleness of crystals when using a jet mill. The purpose of this study was to investigate an alternative micronization technique using the aerosol solvent extraction system (ASES). ...
Neue Pulverinhalativa auf Basis modifizierter Laktosemischungen als Hilfsstoff New inhalation powders based on modified lactose mixtures as an adjuvant
Aufbau von Retardarzneimitteln Teilbarkeit und Sondengängigkeit von oralen Arzneiformen
Pz Prisma, 2011
Inhalation device and method for inhaling an active ingredient from a capsule
Novel Powder Inhalation Preparations Based on Modified Lactose Blends That Are Used as Adjuvants
Co-precipitation of Tobramycin into Hydroxyapatite Coatings
Device associated infections are a growing problem in the field of orthopaedics and dentistry. Ba... more Device associated infections are a growing problem in the field of orthopaedics and dentistry. Bacteria adhering to implant surfaces and subsequent biofilm formation are challenging to treat with systemic administered antibiotics. Functionalization of implant surfaces with therapeutic coatings that are capable of inhibiting bacterial adhesion are therefore considered as a straight forward strategy to treat and prevent implant related infections.In this thesis, the use of crystalline, arc deposited TiO2 and biomimetic hydroxyapatite (HA) coatings were evaluated with respect to their potential as antibacterial surface modifications for bone-anchored implants.UV light induced photocatalysis of anatase dominated TiO2 coated surfaces was shown to provide a bactericidal effect against S. epidermidis under clinically relevant illumination times and doses.Major parts of the drug release work carried out was based on biomimetic HA (HA-B) coated fixation pins. The analysis of the coating characteristics revealed that the nanoporous structure of HA-B coatings in addition to the chemical composition and surface charge are essential parameters that influence the drug carrier performance. Loading by adsorption was demonstrated to be a feasible approach to quickly incorporate antibiotics. The controlled release of antibiotics was shown to facilitate bactericidal effects against S. aureus over application-relevant time periods, even when exposed to biomechanical forces during insertion into bone model materials. Antibiotic incorporation during coating growth was shown to promote somewhat longer drug release time periods than those obtained using adsorption loading.In summary, functionalization of implant surfaces with bioactive and biocompatible coatings is a promising concept to impact the clinical success for bone-anchored applications. The additional feature of optional, on-demand antibacterial properties of these coatings through either on-site drug release or photocatalytic antibacterial treatment is advantageous for the prevention and effective treatment of devices-associated infections. Both strategies provide an immediate response to the implant contamination by bacteria and are believed to contribute towards minimizing the origin of post-surgical infections, while at the same time improving the interfacial stability between implant and bone.
Modifying Surfaces of Lactose Serving as an Auxiliary Agent to Be Used for Powder Inhalants
Biomechanical and antimicrobial properties of Tobramycin eluting fixation pins
Neue Pulverinhalativa auf Basis modifizierter Laktosemischungen als Hilfsstoff
Vorrichtung und Verfahren zur kontinuierlichen Herstellung von sph?rischen Pulveragglomeraten
Pharmaceutical composition for topical application of poorly soluble compounds
Uploads
Papers by Hartwig Steckel