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T Rades

Publications and source records attributed to T Rades.

36 records · Page 2Linked to original sources
PubMed2001

Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis.

The aim of this study was to determine the miscibility of drug and excipient to predict if glass solutions are likely to form when drug and excipient are melt extruded. Two poorly water-soluble drugs, indomethacin and lacidipine, were selected along with 11 excipients (polymeric and non-polymeric). Estimation of drug/excipient miscibility was performed using a combination of the Hoy and Hoftzyer/Van Krevelen methods for Hansen solubility parameter calculation. Miscibility was experimentally investigated with differential scanning calorimetry (DSC) and hot stage microscopy (HSM). Studies were performed at drug/excipient ratios, 1:4, 1:1 and 4:1. Analysis of the glass transition temperature (T(g)) was performed by quench cooling drug/excipient melts in the DSC. Differences in the drug/excipient solubility parameters of <7.0 MPa(1/2) were predicted to indicate significant miscibility and, therefore, glass solution formation on melt extrusion. In comparison, differences of >10 MPa(1/2) were expected to indicate a lack of miscibility and not form glass solutions when melt extruded. Experimentally, miscibility was shown by changes in drug/excipient melting endotherms and confirmed by HSM investigations. Experimental results were in agreement with solubility parameter predictions. In addition, drug/excipient combinations predicted to be largely immiscible often exhibited more than one T(g) upon reheating in the DSC. Melt extrusion of miscible components resulted in amorphous solid solution formation, whereas extrusion of an "immiscible" component led to amorphous drug dispersed in crystalline excipient. In conclusion, combining calculation of Hansen solubility parameters with thermal analysis of drug/excipient miscibility can be successfully applied to predict formation of glass solutions with melt extrusion.

Calorimetry, Differential Scanning↗
PubMed2001

Determination of polymorphic forms of ranitidine-HCl by DRIFTS and XRPD.

The identification, characterization and quantification of crystal forms are becoming increasingly important within the pharmaceutical industry. A combination of different physical analytical techniques is usually necessary for this task. In this work solid-state techniques, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and X-ray powder diffractometry (XRPD) were combined to analyze polymorphic purity of crystalline ranitidine-HCl, an antiulcer drug, H2 receptor antagonists. A series of 12 different mixtures of Form 1 and 2 was prepared by geometric mixing and their DRIFT spectra and XRD powder patterns were obtained and analyzed, either alone or combined together, using Artificial Neural Networks (ANNs). A standard feed-forward network, with back-propagation rule and with multi layer perceptron architecture (MPL) was chosen. A working range of 1.0-100% (w/w) of crystal Form 2 in Form 1 was established with a minimum quantifiable level (MQL) of 5.2% and limit of detection of 1.5% (w/w). The results demonstrate that DRIFTS combined with XRPD may be successfully used to distinguish between the ranitidine-HCl polymorphs and to quantify the composition of binary mixtures of the two.

Ranitidine↗
PubMed2001

Monitoring the intragastric distribution of a colloidal drug carrier model by magnetic resonance imaging460.

PURPOSE: Monitoring the distribution of drugs or drug delivery systems in the human gastrointestinal tract is an important prerequisite for the design of orally administered drugs. We investigated the intragastric distribution of a colloidal drug delivery system (liposomes containing the contrast agent Gd-DOTA) by magnetic resonance imaging. METHODS: Following ingestion of a liquid or a solid meal, gastric distribution of liposomes released from a capsule and the fat component of the solid meal were tracked in 7 healthy subjects for 90 min. Liposomes were identified in gastric content by the increased signal intensity provided by the encapsulated Gd-DOTA. RESULTS: With the liquid meal, liposomes initially formed a layer on the surface before distributing in 86 +/- 2% of gastric content (maximum distribution volume) within 42 +/- 6 min. With the solid meal, maximum distribution (7 +/- 1%, reached within 24 +/- 6 min) was confined to a small volume in the fundus without forming a layer, suggesting that distribution was related to the accessible liquid compartment. Fat distribution was inhomogeneous and concentrated in the fundus. CONCLUSIONS: Intragastric distribution of a colloidal drug carrier model, such as Gd-DOTA-filled liposomes, varies between meals of different composition. These differences can be monitored in three dimensions in humans by MRI.

Adult↗
PubMed2001

Fat digestion modulates gastrointestinal sensations induced by gastric distention and duodenal lipid in humans.

BACKGROUND AND AIMS: It is unclear whether fat digestion is required for the induction of gastrointestinal sensations and whether different fats have different effects. We investigated the effect of fat digestion and of medium-chain triglycerides (MCTs; C < 12) and long-chain triglycerides (LCTs; C > 16) on gastrointestinal sensations. METHODS: In a double-blind study, 15 healthy subjects were studied on 5 occasions during which LCT or MCT emulsions (2 kcal/min), with or without 120 mg tetrahydrolipstatin (THL, lipase inhibitor), or sucrose polyester (SPE, nondigestible fat) were infused intraduodenally in randomized order. After 30 minutes, the proximal stomach was distended in 1 mm Hg steps/min. Intensity of gastrointestinal sensations (on a 0-10 visual analog scale), plasma cholecystokinin (CCK) levels, and gastric volumes were assessed throughout. RESULTS: LCT and MCT increased gastric volume at baseline pressure compared with SPE, and LCT more than MCT. THL entirely abolished this effect (volumes [mL]: LCT, 213 +/- 19; LCT-THL, 39 +/- 3; MCT, 155 +/- 12; MCT-THL, 43 +/- 5; SPE, 44 +/- 5). Only LCT increased plasma CCK levels (pmol/L per 30 minutes: LCT, 21 +/- 2; LCT-THL, 9 +/- 1; MCT, 9 +/- 1; MCT-THL, 11 +/- 1; SPE, 9 +/- 1). During distentions, intragastric volumes were greater during infusion of LCT and MCT than during the respective THL conditions or SPE, but plasma CCK levels did not change. The intensity of sensations increased (hunger decreased) more with LCT than with MCT. During infusion of THL or SPE, the effects were smaller than during LCT or MCT. CONCLUSIONS: Fat digestion is required for the modulation of gastrointestinal sensations during gastric distention. The effects of fat depend on the fatty acid chain length and are not entirely explained by release of CCK.

Adult↗
PubMed2001

Characterizing colloidal structures of pseudoternary phase diagrams formed by oil/water/amphiphile systems.

Two pseudoternary phase diagrams were constructed using ethyl oleate, water, and a surfactant blend containing poly (oxyethylene 20) sorbitan monooleate and sorbitan monolaurate with or without the cosurfactant 1-butanol. Two colloidal regions were identified in the cosurfactant-free phase diagram; a microemulsion (ME) and a region containing lamellar liquid crystals (LC). The addition of 1-butanol increased the area in which systems formed microemulsions and eliminated the formation of any liquid crystalline phases. Samples that form the colloidal regions of both systems were investigated by freeze-fracture transmission electron microscopy and by viscosity and conductivity measurements. The three techniques were compared and evaluated as characterisation tools for such colloidal systems and also to identify transitions between the colloidal systems formed. A droplet ME was present at a low water volume fraction (phi w) in both systems (phi w < 0.15) as revealed by electron microscopy. At higher phi w values, LC structures were observed in micrographs of samples taken from the cosurfactant-free system while the structure of samples from the cosurfactant-containing system was that of a bicontinuous ME. The viscosity of both systems increased with increasing phi w to 0.15 and flow was Newtonian. However, formation of LC in the cosurfactant-free system resulted in a dramatic increase in viscosity that was dependent on phi w and a change to pseudoplastic flow. In contrast, the viscosity of the bicontinuous ME was independent of phi w. Three different methods were used to estimate the percolation threshold from the conductivity data for the cosurfactant-containing system. The use of nonlinear curve fitting was found to be most useful yielding a value close to 0.15 for the phi w.

Colloids↗
PubMed2001

The potential of small-scale fusion experiments and the Gordon-Taylor equation to predict the suitability of drug/polymer blends for melt extrusion.

The aim of this study was to investigate the use of small-scale fusion experiments and the Gordon-Taylor (GT) equation to predict whether melt extrusion of a drug with an amorphous polymer produces a stable amorphous dispersion with increased drug dissolution. Indomethacin, lacidipine, nifedipine, piroxicam, and tolbutamide were used as poorly soluble drugs. Drug/polyvinylpyrrolidone (PVP) blends were prepared at a 1:1 mass ratio. Small-scale fusion experiments were performed in a differential scanning calorimeter (DSC) and in stainless steel beakers. Extrusion was performed in a Brabender Plasti-corder. The glass transition temperatures Tg were determined by DSC. Taking an average Tg from the DSC melt, beaker melt, and GT equation accurately predicted the extrudate Tg. Physical stability of beaker melt and extrudate samples was tested by X-ray powder diffraction (XRPD) and DSC after storage at 30 degrees C (beaker melt) or 25 degrees C (extrudate) and less than 10%, 60%, and 75% relative humidity, (RH). Beaker melts were amorphous, apart from some residual crystallinity. Extrudates were amorphous after preparation. Except for indomethacin/PVP, which remained amorphous, the crystallinity of beaker melts and extrudates increased only at 75% RH. Recrystallization occurred even when the Tg of the sample was well above the storage temperature. Chemical stability of the beaker melts and extrudates was tested by capillary electrophoresis and high-performance liquid chromatography (HPLC). Stability was slightly improved in the extrudate compared to the beaker melt. In general, the order for rate of dissolution was crystalline drug was less than the physical mixture, which was less than the drug/PVP beaker melt, which was approximately equal to the extrudate. The use of beaker melts allows a conservative estimate of the potential to melt extrude a drug. To predict physical stability, analysis of the Tg must be combined with physical stability experiments.

Algorithms↗
PubMed2001

Characterization of glass solutions of poorly water-soluble drugs produced by melt extrusion with hydrophilic amorphous polymers.

Indomethacin, lacidipine, nifedipine and tolbutamide are poorly soluble in water and may show dissolution-related low oral bioavailability. This study describes the formulation and characterization of these drugs as glass solutions with the amorphous polymers polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone-co-vinyl acetate by melt extrusion. The extrudates were compared with physical mixtures of drug and polymer. X-ray powder diffraction, thermal analysis, infrared spectroscopy, scanning electron microscopy, HPLC, moisture analysis and dissolution were used to examine the physicochemical properties and chemical stability of the glass solutions prepared by melt extrusion at a 1:1 drug/polymer ratio. Depending on the temperature used, melt extrusion produced amorphous glass solutions, with markedly improved dissolution rates compared with crystalline drug. A significant physico-chemical interaction between drug and polymer was found for all extrudates. This interaction was caused by hydrogen bonding (H-bonding) between the carbonyl group of the pyrrole ring of the polymer and a H-donor group of the drug. Indomethacin also showed evidence of H-bonding when physical mixtures of amorphous drug and PVP were prepared. After storage of the extrudates for 4-8 weeks at 25 degrees C/75% relative humidity (RH) only indomethacin/polymer (1:1) extrudate remained totally amorphous. All extrudates remained amorphous when stored at 25 degrees C/< 10% RH. Differences in the physical stability of drug/polymer extrudates may be due to differences in H-bonding between the components.

Chemical Phenomena↗
PubMed2000

Hydration of lipid films with an aqueous solution of Quil A: a simple method for the preparation of immune-stimulating complexes.

Immune-stimulating complexes (ISCOMs) are stable colloidal complexes of the adjuvant Quil A, cholesterol and phospholipid, which are effective carriers for subunit vaccines. The techniques currently available for the preparation of ISCOMs from the constituent components are rather complex and are based on either centrifugation or dialysis. This note reports a new simple procedure for the preparation of ISCOM matrices based on hydration of a cholesterol/phospholipid film with an aqueous solution of Quil A. It is demonstrated that ISCOM matrices do not form in the absence of phospholipid when prepared by this method. Further, the ratio by weight of phospholipid to either cholesterol or Quil A must be greater than that required for preparation by either dialysis or centrifugation. Photon correlation spectroscopy, negative stain transmission electron microscopy and centrifugation through a sucrose gradient demonstrate that ISCOM matrices can be prepared from cholesterol/lipid films by hydration with an aqueous solution of Quil A when the ratio of phospholipid:cholesterol:Quil A by weight is 6:1:4, respectively. Lower ratios of phospholipid:cholesterol reduce the efficiency of ISCOM formation while higher ratios produce systems containing a mixture of ISCOMs together with liposomes.

Cholesterol↗
PubMed2000

Effects of alcohols and diols on the phase behaviour of quaternary systems.

The aim of the current study was to investigate the effect of different co-surfactants on the phase behaviour of the pseudoternary system water:ethyl oleate:nonionic surfactant blend (sorbitan monolaurate/polyoxyethylene 20 sorbitan mono-oleate). Four aliphatic alcohols (1-propanol, 1-butanol, 1-hexanol and 1-octanol) and four 1, 2-alkanediols (1,2-propanediol, 1,2-pentanediol, 1,2-hexanediol and 1,2-octanediol) were used. The co-surfactant-free system forms two different colloidal structures, a water-in-oil microemulsion (w/o ME) and lamellar liquid crystals (LC) and two coarse dispersions, water-in-oil (w/o EM) and oil-in-water (o/w EM) emulsions. Microemulsion region area (%ME), liquid crystalline region area (%LC), amount of amphiphile blend required to produce a balanced microemulsion (%AMPH) and amount of water solubilised (%W) were used as assessment criteria to evaluate the co-surfactants. Seven calculated physico-chemical descriptors were used to represent the different co-surfactants. 1-butanol, 1,2-hexanediol and 1, 2-octanediol produced balanced MEs capable of solubilising a high percentage of both oil and water. A similarity was observed between the descriptors attributed to 1-butanol and 1,2-hexanediol. The requirements of a co-surfactant molecule to produce a balanced microemulsion were: HLB value 7.0-8.0, a carbon backbone of 4-6 atoms, percentage carbon of 60-65%, percentage oxygen of 20-30%, logP value 0.2-0.9 and log 1/S (S: aqueous solubility) close to zero.

1-Butanol↗
PubMed2000

Direct detection of dissolution of 14C-labeled compounds into an oil phase by the fat scintillation proximity method.

Traditional analysis of the dissolution of lipophilic compounds from aqueous phase into oil is often hampered by the necessity to separate the receiver oil compartment from the aqueous phase. In order to avoid possible artefacts associated with additional separation methods, a procedure was developed to selectively detect the entry of a compound into the oil phase of a oil/water dispersion. When a combination of a primary and secondary scintillator was predissolved in the oil, and solid 14C-tetrahydrolipstatin was added, increasing signals from the same container were measured upon prolonged incubation. The data are consistent with the hypothesis that 14C-THL that has dissolved in the oil phase is essentially responsible for the measured signal. The obtained dissolution profiles of 14C-THL into oil match with parallel experiments using classical procedures.

Carbon Radioisotopes↗
PubMed2000

Ranitidine hydrochloride X-ray assay using a neural network.

A simple X-ray powder diffractometric (XRD) method with artificial neural networks (ANNs) for data modelling was developed to recognize and quantify two crystal modifications of ranitidine HCl in mixtures and thus, provide information about the solid state of the bulk drug. The method was also used to quantify ranitidine HCl from tablets in the presence of other components. An ANN consisting of three layers of neurons was trained by using a back-propagation learning rule. A sigmoid output function was used in the hidden layer to facilitate non-linear fitting. Unlike other techniques the ANN method described here employed pattern recognition on the entire XRD pattern. Correct classification was mainly influenced by the XRD pattern resolution. It was shown that data transformations improved the quantitative performance when the XRD patterns were not contaminated by other components. Only smoothed X-ray diffractograms were required to distinguish between the two crystalline forms in a mixture. In the case of ranitidine-HCl quantification from tablets, where significant interference with tablet excipients was present, better results were obtained without data transformations. The trained ANN perfectly quantified ranitidine HCI polymorphic forms from mixtures (mean sum of squared error was less than 0.02%) and ranitidine HCl form 1 from tablets (recovery = 98.65). Excellent quantification performance of the ANN analysis. demonstrated in this study, serves as an indication of the broad potential of neural networks in pattern analysis. While the system described has been developed to interpret XRD patterns, peak detection has implications in every chemical application where the recognition of peak-shaped signals in analytical data is important.

Anti-Ulcer Agents↗
PubMed2000

Preparation of biodegradable insulin nanocapsules from biocompatible microemulsions.

PURPOSE: To prepare poly(ethyl 2-cyanoacrylate) nanocapsules containing insulin by interfacial polymerization of spontaneously forming, biocompatible microemulsions. METHODS: A pseudo-ternary phase diagram of a mixture of medium chain glycerides (caprylic/capric triglycerides and mono-/diglycerides), a mixture of surfactants (polysorbate 80 and sorbitan mono-oleate) and water was constructed. Polarizing light microscopy was used to identify combinations forming microemulsions. Microemulsions were characterized by conductivity and viscosity to select systems suitable for the preparation of poly(ethyl 2-cyanoacrylate) nanocapsules by interfacial polymerization. Nanocapsules were prepared by addition of 100 mg of ethyl 2-cyanoacrylate to a stirred water-in-oil microemulsion containing 1 g of water, 7.6 g of oil, and 1.4 g of surfactant. The nanocapsules formed were characterized by photon correlation spectroscopy, freeze fracture transmission and scanning electron microscopy. Insulin nanocapsules were prepared by using an aqueous solution of insulin (100 units/ml) as the dispersed phase of the microemulsion. The entrapment and the release of insulin from the nanocapsules were determined. RESULTS: Three regions were identified in the pseudo-ternary phase diagram; a microemulsion region, a region in which liquid crystalline structures were present and a coarse emulsion region. All systems in the microemulsion region were water-in-oil dispersions. Poly(ethyl 2-cyanoacrylate) nanocapsules having a mean particle size of 150.9 nm were formed upon interfacial polymerization of the microemulsion. Nanocapsules were found to have a central cavity surrounded by a polymer wall. In excess of 80% of the insulin present in the microemulsion was encapsulated upon interfacial polymerization. CONCLUSIONS: Interfacial polymerization of spontaneously forming water-in-oil microemulsions represents a convenient method for the preparation of poly(alkylcyanoacrylate) nanocapsules suitable for the entrapment of bioactive peptides.

Absorbable Implants↗
PubMed2000

Stability of polymorphic forms of ranitidine hydrochloride.

Ranitidine-HCl can exist in two different polymorphic forms: form I (m.p. 134-140 degrees C) and form II (m.p. 140-144 degrees C). In the present study the stability of form I of ranitidine-HCl to a selection of powder pretreatments, to reflect conditions which might occur in manufacturing procedures, and also to a limited range of storage conditions was investigated. The original samples of form I and form II used were characterised by X-ray powder diffraction (XRPD), hot stage microscopy (HSM) and differential scanning calorimetry (DSC). A quantitative XRPD method for determining the fraction of form II in the presence of form I was used. XRPD data were analysed using regression techniques and artificial neural networks (ANN). The quantitative XRPD technique was then used to monitor the relative proportion of form II in each treated sample. Pretreatments of form I included (i) mixing with form II or with common excipients (ii) compression and grinding (iii) contact with solvents (followed by drying) before storage. Storage conditions involved three temperatures (20 degrees C, 30 degrees C, 42 degrees C) and three relative humidities (45% RH; 55% RH; 75% RH). Samples were stored for a period of 6 months. A limited factorial design was used. No increase in the form II:form I ratio was observed in the following pretreatment processes: introduction of form II nuclei into form I; introduction of excipients to form I; compression of form I powder at 5 and 15 tons; normal mixing and grinding processes; addition of isopropanol (IPA) or water/IPA mix followed by drying. In the pretreatment process where water was added to form I powder (with most or all of the powder dissolving), drying of the liquefied mass led to a mix of form I and form II. On storage at room temperature (20-30 degrees C), low relative humidity (45-55% RH), and in an air-tight container there was no increase in the form II:form I ratio. Storage of form I/form II mixes, particularly at high humidity, resulted in a preferential loss of form II (compared to form I). Loss was greater at 30 degrees C/75% RH than at 20 degrees C/75% RH. Form II was also preferentially lost under low humidity conditions created by a saturated solution of potassium carbonate (45% RH) at the elevated temperature of 42 degrees C. This environment was shown to be acidic.

Calorimetry, Differential Scanning↗
PubMed1999

Powder diffractometric assay of two polymorphic forms of ranitidine hydrochloride.

A simple X-ray powder diffractometric method was developed for the qualitative and quantitative assay of the two crystalline modifications of ranitidine-HCl. The main purpose of the present work was to investigate if artificial neural networks (ANNs) could be applied in quantitative X-ray diffractometric analyses. The ANN approach was compared with a conventional mixture design method. The results obtained by the ANN had a smaller standard deviation and relative error and a better precision at lower concentrations. ANNs provide a simple alternative to conventional statistical modelling methods to identify the non-linear relationship without complex equations.

Anti-Ulcer Agents↗
PubMed1999

Use of artificial neural networks to predict quaternery phase systems from limited experimental data.

The aim of the present work was to develop a method for predicting the phase behaviour of four component systems consisting of oil, water and two surfactants from a limited number of screening experiments. Investigations were conducted to asses the potential of artificial neural networks (ANNs) with back-propagation training algorithm to predict the phase behaviour of four component systems. Three inputs only (percentages of oil and water and HLB of the surfactant blend) and four outputs (oil in water emulsion, water in oil emulsion, microemulsion, and liquid crystals containing regions) were used. Samples used for training represented about 15% of the sampling space within the tetrahedron body. The network was trained by performing optimization of the number and size of the weights for neuron interconnections. The lowest error was obtained with 15 hidden neurons and after 4,500 training cycles. The trained ANN was tested on validation data and had an accuracy of 85.2-92.9%. In most cases the errors in the prediction were confined to points lying along the boundaries of regions and for the extrapolated predictions outside the ANNs 'experience'. This approach is shown to be highly successful and the ANNs have proven to be a useful tool for the prediction of the phase behaviour of quaternary systems with less experimental effort.

Hexoses↗
PubMed1998

Interactions between fenoprofen sodium and poly (ethylene oxide).

Interactions of the amphiphilic drug fenoprofen sodium (FNa) in solution below and above its critical micelle concentration with poly (ethylene oxide) (PEO) of different chain length (PEO 400 to PEO 20000) and between a liquid crystalline formulation of fenoprofen (FLC; containing FNa, fenoprofen acid and water) and PEO were investigated, using surface tension measurements, viscometry, cloud point temperature measurements, [1H]NMR, polarised light microscopy, transmission electron microscopy, and differential scanning calorimetry. Interaction between FNa solutions and PEO: the investigations suggest that an interaction starts below the critical micelle concentration (CMC) of FNa. This can be concluded from [1H]NMR experiments (an upfield shift of the PEO proton signal was found at FNa concentrations below the CMC of FNa), surface tension measurements (absence of a critical association concentration) and cloud point temperature determinations. The surfactant does not seem to bind quantitatively on the PEO molecules (a higher FNa concentration was needed to cause the same upfield shift of the PEO proton signal than for more lipophilic surfactants, and no plateau phase in the surface tension reduction isotherm could be determined). Interactions were found to be independent from the chain length of the PEO. Interactions between FLC and PEO/pluronics: partial or complete dissolution of the fenoprofen mesophase (detected by [1H]NMR, polarised light microscopy and transmission electron microscopy) occurred after addition of PEO at concentrations between 2 and 10% (w/w), independent from the molecular weight of the PEO. A comparable amount of water added to the liquid crystalline samples does not change the mesophase into a liquid crystalline dispersion or a micellar solution. The liquid crystalline particles in the dispersion formed by the addition of PEO, had a higher transition temperature into an isotropic phase (between 54 degrees C and 57 degrees C), than in liquid crystalline dispersions without polymer (40 degrees C). The interactions between FNa and PEO can be interpreted in terms of a hydrophobic interaction with an association of the drug molecules on the polymer, i.e. the interaction between FNa and PEO occurs at a molecular rather than a micellar level. The interaction leads to a dissolution of the fenoprofen liquid crystal and the formation of an isotropic phase. No phase separation of the oily, amorphous, practically water insoluble fenoprofen acid could be found. Addition of PEO also seems to affect the composition of the remaining mesophase.

Anti-Inflammatory Agents, Non-Steroidal↗
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↗