The effect of spray drying solutions of polyethylene glycol (PEG) and lactose/PEG on their physicochemical properties

The effect of spray drying polyethylene glycol (PEG) 4000 and lactose/PEG solutions was investigated. Micro-spherical PEG particles were successfully prepared from ethanol, which allowed lower outlet temperatures than water. The product was crystalline and consisted of rough spheres or rod like particles. In the case of lactose/PEG composites, spray dried from water, the crystallinity of both components was reduced on spray drying, the extent being dependent on the starting composition. Spray dried lactose/PEG with PEG present as 10% by weight was found to be the most amorphous of the systems prepared. Conversion to more crystalline products occurred over time, the rates of conversion being dependent on temperature and humidity. On storage at low humidity (31-34%) amorphous lactose in lactose/PEG spray dried systems converts to anhydrous crystalline lactose while at high humidity (75% RH) the monohydrate is formed. The rate of transformation of amorphous lactose to the crystalline monohydrate form, at high relative humidity, was quantified using the Avrami equation applied both to X-ray diffraction (XRD) peak intensity and heat of fusion data. Crystallisation of lactose appeared to be retarded at low PEG concentrations, where PEG was present predominantly in a non-crystalline state, but was accelerated at higher PEG contents.     

Predicting the physical state of spray dried composites: salbutamol sulphate/lactose and salbutamol sulphate/polyethylene glycol co-spray dried systems

The effect of spray drying salbutamol sulphate, salbutamol sulphate/lactose and salbutamol sulphate/polyethylene glycol (PEG) solutions was investigated. Co-spray drying salbutamol sulphate with lactose, which is amorphous when spray dried alone, resulted in amorphous composites. Co-spray drying salbutamol sulphate with PEG 4000 and PEG 20,000, which do not form amorphous systems when spray dried alone, resulted in systems of varying crystallinity, the crystallinity depending on the weight ratio of polymer to drug. Examination of the physical properties of these salbutamol sulphate co-spray dried systems and those of bendroflumethiazide/PEG and lactose/PEG composites suggested that the formation and physical stability of amorphous composites prepared by spray drying is dependent on whether the glass transition temperature, Tg, of one of the two components is high enough to result in a Tg of the composite sufficiently high that the Kauzmann temperature of the mix is greater than the temperature of storage. The modified Gordon-Taylor equation proved to be useful in predicting the likelihood that a two-component composite will be amorphous on spray drying. Furthermore, the Gordon-Taylor equation was also useful in predicting the likely physical stability of amorphous two component composites and predicted that even polymers with apparently low Tgs, such as PEGs, may be stabilised in an amorphous composite by a suitable additive having a sufficiently high Tg.     

The effect of co-spray drying with polyethylene glycol 4000 on the crystallinity and physical form of lactose

The effect of spray drying lactose alone and in the presence of polyethylene glycol 4000 was investigated. Lactose was added to distilled water to give concentrations of 10, 20, 30 and 40g/100ml at room temperature and each spray dried in turn. Identical samples were prepared to which polyethylene glycol (PEG) 4000 was added (12% by weight of lactose) prior to spray drying. Microcalorimetric and X-ray diffraction studies showed that spray drying lactose solutions produced completely amorphous material due to rapid solidification during the spray drying process, whereas lactose suspensions yielded partially crystalline products due to crystalline material that remained in suspension. However, all the PEG/lactose (12%w/w) co-spray dried products were found to be crystalline. It can be inferred that the solidification rates of the lactose in the presence of PEG must have been slower than that of lactose alone which allowed PEG and lactose to crystallize. The PEG/lactose products that were spray dried from solution consisted of alpha-anhydrous, alpha-monohydrate, beta-lactose and PEG extended chain polymorph, whereas those formed from suspension PEG/lactose samples consisted of only alpha-anhydrous, alpha-monohydrate and extended chain PEG crystals. PEG probably caused the more concentrated lactose suspensions to crystallize slowly due to the strong hydrogen bonding between PEG and water, which allowed growth on the alpha-lactose seed crystals.     

The effect of spray drying solutions of bendroflumethiazide/polyethylene glycol on the physicochemical properties of the resultant materials

The physicochemical properties of co-spray dried bendroflumethiazide (BFMT)/polyethylene glycol (PEG) 4000 composites were investigated. The co-spray dried composites produced from all BFMT/polymer solutions were amorphous. BFMT/PEG 4000 10 and 20% systems consisted of smooth spherical particles approximately 0.5-4mm in diameter. Spray drying resulted in no significant production of the main BFMT degradant, 5-trifluoromethyl-2,4-disulphamoylaniline (TFSA), and for composites consisting of 90% PEG 4000 by weight of total solids, spray drying appeared a superior method of production than the melt method which resulted in significant BFMT degradation. All BFMT/PEG compressed discs showed initial increased release of BFMT compared to discs of micronised BFMT alone, with the spray dried BFMT/PEG 4000 10% system showing initial rates two to three times that of BFMT alone. The physical stability of amorphous BFMT was reduced on inclusion of PEG 4000, recrystallisation occurring more quickly with increasing amount of PEG 4000 in the composites. PEG in the co-spray dried systems appeared to degrade on storage and recrystallised samples failed to show the presence of PEG by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) or GPC. DSC results were consistent with BFMT/PEG forming a eutectic combination rather than a monotectic system.     

Physicochemical and in vitro deposition properties of salbutamol sulphate/ipratropium bromide and salbutamol sulphate/excipient spray dried mixtures for use in dry powder inhalers

The physicochemical and aerodynamic properties of spray dried powders of the drug/drug mixture salbutamol sulphate/ipratropium bromide were investigated. The in vitro deposition properties of spray dried salbutamol sulphate and the spray dried drug/excipient mixtures salbutamol sulphate/lactose and salbutamol sulphate/PEG were also determined. Spray drying ipratropium bromide monohydrate resulted in a crystalline material from both aqueous and ethanolic solution. The product spray dried from aqueous solution consisted mainly of ipratropium bromide anhydrous. There was evidence of the presence of another polymorphic form of ipratropium bromide. When spray dried from ethanolic solution the physicochemical characterisation suggested the presence of an ipratropium bromide solvate with some anhydrous ipratropium bromide. Co-spray drying salbutamol sulphate with ipratropium bromide resulted in amorphous composites, regardless of solvent used. Particles were spherical and of a size suitable for inhalation. Twin impinger studies showed an increase in the fine particle fraction (FPF) of spray dried salbutamol sulphate compared to micronised salbutamol sulphate. Co-spray dried salbutamol sulphate:ipratropium bromide 10:1 and 5:1 systems also showed an increase in FPF compared to micronised salbutamol sulphate. Most co-spray dried salbutamol sulphate/excipient systems investigated demonstrated FPFs greater than that of micronised drug alone. The exceptions to this were systems containing PEG 4000 20% or PEG 20,000 40% both of which had FPFs not significantly different from micronised salbutamol sulphate. These two systems were crystalline unlike most of the other spray dried composites examined which were amorphous in nature.     

Aerosolisation of beclomethasone dipropionate using spray dried lactose/polyethylene glycol carriers.

The aim of this study was to characterize the physical properties of spray dried lactose in the presence of different polyethylene glycols (PEG 400, PEG 3000 and PEG 6000) and to evaluate their performance as carriers for dry powder inhaler (DPI) formulations. The efficiency of spray dried lactose/PEG carriers in aerosolisation of beclomethasone dipropionate (BD), a model hydrophobic drug, was compared to Pharmatose 325 M (L325), spray dried lactose alone (SDL), and also a sieved (< 38 microm) fraction of alpha-lactose monohydrate (SL). In vitro deposition analysis was performed using a twin stage liquid impinger at a flow rate of 60 l/min through a Spinhaler. The deposition profiles of the drug from binary formulations composed of BD and spray dried lactose/PEG carriers were also compared to ternary formulations containing large and fine lactose carriers. Differential scanning calorimetry and X-ray diffraction data showed the presence of alpha-anhydrous lactose in spray dried lactose/PEG crystalline powders. Spray drying of lactose in the presence of PEG 400 resulted in the production of a powder (SDL-PEG400) with lower alpha-lactose monohydrate content, and also smaller particle size distribution than those obtained in the presence of PEG 3000 (SDL-PEG3000) or PEG 6000 (SDL-PEG6000). All formulations showed different deposition profiles, except those containing SDL-PEG3000 or SDL-PEG6000 which exhibited similar data. The fine particle fraction of aerosolised BD varied from 6.26 +/- 1.07 (for L325) to 25.87 +/- 5.33 (for SDL-PEG3000). All deposition profiles of BD aerosolised from SDL-PEG3000 were significantly higher (P < 0.01) than those produced by binary and ternary formulations containing L325, a coarse lactose commercially available for DPI formulations. The differences observed in deposition data for various carriers were interpreted according to their physical properties. It was concluded that particle size distribution, morphology and specific surface texture of SDL-PEG3000 and SDL-PEG6000 were important factors influencing their efficiency as small carriers for DPI formulations.     

Characterization and aerodynamic evaluation of spray dried recombinant human growth hormone using protein stabilizing agents

The effect of the protein stabilizers on the stability and aerosol performance of spray dried recombinant human growth hormone (SD rhGH) was investigated. rhGH solution was spray dried alone, with polysorbate 20 (at three concentrations of 0.05%, 0.01%, and 0.005%), Zn(2+) (by Zn(2+):rhGH molar ratio of 2:1 and 4:1), and/or lactose (by lactose:rhGH weight ratio of 2:1). Size exclusion chromatography (SEC) analysis of spray dried powders demonstrated that of all the potential protein stabilizers, the combination of polysorbate 20 (0.05%), Zn(2+) (Zn(2+):rhGH molar ratio of 2:1) and lactose (lactose:rhGH weight ratio of 2:1) was the most effective at protecting rhGH against aggregation during spray drying. The results of circular dichroism (CD) analysis revealed that using of polysorbate 20 (in all concentrations) and Zn(2+) (by Zn(2+):rhGH molar ratio of 2:1) together in the formulations would preserve rhGH conformational stability during the process. The particle size distribution data obtained by laser diffraction method showed all SD rhGH formulations had volume median diameter and mean diameter below 5mum. The characterization of the aerosol performance of the spray dried powders by Andersen cascade impactor (ACI) showed that by increasing the concentration of polysorbate 20 in the formulations the aerodynamic efficiency of the resultant particles was reduced. In conclusion, the optimum amounts of polysorbate 20, Zn(2+) and lactose satisfied both physical stability during spray drying process (2.37% aggregation) and good aerosol performance (fine particle fraction; FPF=38.52%).     

Characterization of ternary solid dispersions of itraconazole, PEG 6000, and HPMC 2910 E5

In order to reduce the crystallinity of PEG 6000, blends were prepared by spray drying and extrusion with the following polymers; PVP K25, PVPVA 64, and HPMC 2910 E5. The maximal reduction of crystallinity in PEG 6000 was obtained by co-spray drying with HPMC 2910 E5. In the next step the model drug Itraconazole was added to the blend and the resulting ternary solid dispersions were characterized. The results of this study show that the addition of PEG 6000 to the Itraconazole/HPMC 2910 E5 system leads to phase separation that in most cases gives rise to recrystallization of either PEG 6000 or Itraconazole. For all ternary dispersions containing 20% of Itraconazole the drug was highly amorphous and the dissolution was improved compared to the binary 20/80 w/w Itraconazole/HPMC 2910 E5 solid dispersion. For all ternary dispersions containing 40% of Itraconazole, the drug was partially crystalline and the dissolution was lower than the dissolution of the binary 40/60 w/w Itraconazole/HPMC 2910 E5 dispersion. These results show that provided Itraconazole is highly amorphous the addition of PEG 6000 to HPMC 2910 E5 leads to an increase in drug release.     

Studies on the spray dried lactose as carrier for dry powder inhalation

The purpose of this study was to investigate the spray dried lactose as carrier for dry powder inhalation (DPI). The lactose particles were prepared by spray drying, then the particle size, shape and crystal form were characterized by laser diffraction, scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The spray dried lactose particles were spherical and amorphous, but would transfer to crystal form when storage humidity was above 32%. Thus, the humidity of the storage environment should be controlled below 30% strictly in order to maintain the amorphous nature of spray dried lactose which is a great benefit to DPI development.     

Effect of Moisture Sorption on Tabletting Characteristics of Spray Dried (15% Amorphous) Lactose

Spray dried (15% amorphous) lactose absorbs moisture when exposed to humidity. At 57% relative humidity (RH), the moisture uptake was 1.5%. It is suggested that the moisture is preferentially taken up in the amorphous regions, thereby increasing the actual moisture content in the amorphous parts up to 10%. The moisture uptake reduced the glass transition temperature below the operating temperature and thereby transformed the amorphous regions from a glassy to a rubbery state, setting up conditions for crystallisation of the lactose. Compaction of dry spray dried lactose led to a relatively low initial tablet strength. However, when pre-exposed to 57% RH for a short time period (2 to 4 hours) before compaction, the initial tablet strength increased markedly. This was due to moisture uptake which resulted in a higher molecular mobility of the amorphous spray dried lactose, and to an increase in plastic flow. Post compaction storage of tablets containing amorphous regions of spray dried lactose at 57% RH resulted in an increased tablet strength after 4 hours due to crystallisation. Spray dried lactose exposed to 57% RH for more than 6 hours before compaction led to the lowest initial tablet strength. Crystallisation of the amorphous regions of the spray dried lactose occurred before tabletting. No increase in tablet strength was noted on post compaction storage for these tablets.     

Particle engineering using sonocrystallization: salbutamol sulphate for pulmonary delivery

The aim of present work was to produce fine elongated crystals of salbutamol sulphate (SS) by sonocrystallization for pulmonary delivery and compare with micronized and spray dried SS (SDSS) for in vitro aerosolization behavior. Application of ultrasound during anti-solvent crystallization resulted in fine elongated crystals (sonocrystallized SS; SCSS) compared to aggregates of large irregular crystals obtained without sonication. Higher sonication amplitude, time, concentration and lower processing temperatures favored formation of smaller crystals with narrow particle size distribution (PSD). SCSS was separated from dispersion by spray drying in the form of loose aggregates (SD-SCSS). The fine particle fraction (FPF) of formulations with coarse lactose carrier in cascade impactor increased from 16.66% for micronized SS to 31.12% for SDSS (obtained by spray drying aqueous SS solution) and 44.21% for SD-SCSS, due to reduced cohesive/adhesive forces and aerodynamic size by virtue of elongated shape of crystals. SD-SCSS was stable without any change in crystallinity and aerodynamic behavior for 3 months at 40 degrees C/75% RH, but amorphous SDSS showed recrystallization with poor aerosolization performance on storage. Sonocrystallization, a rapid and simple technique is reported for production of SS crystals suitable for inhalation delivery.     

The effect of water to ethanol feed ratio on physical properties and aerosolization behavior of spray dried cromolyn sodium particles

Cromolyn sodium (CS) was spray dried under constant operation conditions from different water to ethanol feed ratios (50:50-0:100). The spray dried CS samples were characterized for their physicochemical properties including crystallinity, particle size distribution, morphology, density, and water/ethanol content. To determine quantitatively the crystallinity of the powders, an X-ray diffraction (XRD) method was developed using samples with different crystallinity prepared by physical mixing of 100% amorphous and 100% crystalline CS materials. The aerodynamic behavior of the CS samples was determined using an Andersen Cascade Impactor (ACI) with a Spinhaler at an air flow of 60 L/min. Binary mixtures of each spray dried CS powder and Pharmatose 325, a commercial alpha-lactose monohydrate available for DPI formulations, were prepared and in vitro aerosol deposition of the drug from the mixtures was analyzed using ACI to evaluate the effect of carrier on deposition profiles of the spray dried samples. CS spray dried from absolute ethanol exhibited XRD pattern characteristic for crystalline materials and different from patterns of the other samples. The crystallinity of spray dried CS obtained in the presence of water varied from 0% to 28.37%, depending on the ratio of water to ethanol in the feed suspensions. All samples presented different particle size, water/ethanol content, and bulk density values. CS particles spray dried from absolute ethanol presented uniform elongated shape whereas the other samples consisted mainly of particles with irregular shape. Overall, fine particle fraction increased significantly (p < 0.01) with decreasing d50% and water and ethanol content of spray dried CS samples. Significant difference (p < 0.01) in deposition profiles of the drug were observed between corresponding carrier free and carrier blended formulations. The difference in deposition profiles of CS aerosolized from various spray dried samples were described according to the particle size, shape, and water/ethanol contents of the powders. The results of this study indicate that enhanced aerosol performance of CS can be obtained by spray drying of the drug from suspensions containing > or = 87.5% v/v ethanol.     

The effect of process variables on the degradation and physical properties of spray dried insulin intended for inhalation

The aim of this study was to investigate the effect of process variables on the degradation and physical properties of spray dried insulin intended for inhalation. A 2(4) full factorial experimentally designed study was performed to investigate the influence of the following independent spray drying variables: feed flow rate, nozzle gas flow rate, inlet air temperature and aspirator capacity (drying gas flow rate). Human insulin (biosynthetic and Ph.Eur. quality) was dissolved in distilled water to concentrations of 5 mg/ml. The solutions were spray dried in a Mini Spray Dryer Büchi and the dry powders produced were characterized by high performance liquid chromatography, size exclusion chromatography, laser diffraction, thermo gravimetric analysis, scanning electron microscopy and weighing. The degradation of insulin was found to be affected mainly by the process variables that determine the outlet air temperature, i.e.: inlet air temperature, aspirator capacity and feed flow rate. The outlet air temperature should be kept below 120 degrees C to avoid degradation. A statistical optimization of the spray drying variables was performed, and found to recommend an experiment with an outlet air temperature of 61+/-4 degrees C. This experiment ought to generate a yield of 54+/-7% by weight of particles with a mass median diameter 2.9+/-0.4 microm, moisture content 3.9+/-0.5% by weight, content of high molecular weight proteins 0.3+/-0.1% by area, A-21 desamido insulin 0.3+/-0.05% by area and other insulin related compounds 0.3+/-0.1% by area.     

Droplet and particle size relationship and shell thickness of inhalable lactose particles during spray drying

To find means of controlling the size and density of particles intended for inhalation the relationship between droplet and particle size during spray drying was investigated. Lactose solutions were atomized with a two-fluid nozzle and dried in a laboratory spray drier. The effects of nozzle orifice diameter, atomization airflow and feed concentration on droplet and particle size were examined. Mass median diameter of both droplets and particles were analyzed with laser diffraction. In addition, scanning electron microscopy and transmission electron microscopy were used for studies of particle shape and morphology. It was demonstrated that nozzle orifice diameter and airflow, but not feed concentration controlled the droplet size during atomization. Increasing droplet size increased particle size but the effect was also influenced by feed concentration. Particles from solutions of a low concentration (1% w/w) were smaller than those from higher concentrations (5-20% w/w). This may be partly explained by lower yields at higher feed concentrations, but may also be related to differences in drying rate. Spray-dried lactose solutions formed hollow particles, and it was suggested that the shell thickness of the particles increased with increasing feed concentration.     

The impact of drying method and formulation on the physical properties and stability of methionyl human growth hormone in the amorphous solid state

The objective of this work was to investigate the impact of drying method and formulation on the physical stability (aggregation) and selected important physical properties of dried methionyl human growth hormone (Met-hGH) formulations. Solutions of Met-hGH with different stabilizers were dried by different methods (freeze drying, spray drying, and film drying), with and without surfactant. Properties of the dried powders included powder morphology, specific surface area (SSA), protein surface coverage, thermal analysis, and protein secondary structure. Storage stability of Met-hGH in different formulations was also studied at 50 degrees C and at 60 degrees C for 3 months. The dried powders displayed different morphologies, depending mainly on the method of drying and on the presence or absence of surfactant. Film dried powders had the lowest SSA (approximately 0.03 m(2)/g) and the lowest total protein surface accumulation (approximately 0.003%). Surfactant caused a reduction in the SSA of both spray dried and freeze dried powders. Spray dried powders showed greater protein surface coverage and SSA relative to the same formulations dried by other means. Greater in-process perturbations of protein secondary structure were observed with polymer excipients. Formulation impacted physical stability. In general, low molecular weight stabilizers provided better stability. For example, the aggregation rate at 50 degrees C of Met-hGH in a freeze dried trehalose-based formulation was approximately four times smaller than the corresponding Ficoll-70-based formulation. Drying method also influenced physical stability. In general, the film dried preparations studied showed superior stability to preparations dried by other methods, especially those formulations employing low molecular weight stabilizers.     

Quantitative determination of crystallinity of alpha-lactose monohydrate by Near Infrared Spectroscopy (NIRS)

The purpose of this study was to determine quantitatively the crystallinity in crystalline/amorphous powder mixtures of lactose, to asses the capability of Near Infrared Spectroscopy (NIRS) for quantitative determination of crystallinity and to compare the accuracy of the NIRS method with that of conventional X-ray powder diffraction (XRPD). Amorphous lactose was prepared by spray drying. Samples with different crystallinity were prepared by physical mixing of 100% amorphous and 100% crystalline materials. The samples were characterized by XRPD and NIRS. Analysis was performed on the data sets by multiple linear regression (MLR). There is a close correlation between the predicted and the actual crystallinity of physical mixtures of crystalline and amorphous lactose, determined by NIRS (R(2)=0.9994). NIRS results were compared to the XRPD using the same sample sets. The correlation coefficients was 0.9981. The results showed that NIRS is an useful method for accurately determining low quantities of the crystalline lactose in a physical mixture. Therefore, NIRS can be used for the quantitative determination of crystallinity of materials during pharmaceutical procedures.     

Spray-dried insulin particles retain biological activity in rapid in-vitro assay.

The purpose of this study was to rapidly determine, without the use of extensive animal studies, whether biological activity is retained after spray drying insulin with two excipients, lactose and xanthan gum. This was achieved by the detection of protein kinase B (PKB), which is activated by phosphorylation in response to insulin binding to cellular receptors. A myeloid cell line was cultured and stimulated with the reconstituted insulin powders. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was then utilised to allow in-vitro detection of phosphorylated PKB using an anti-phospho-PKB antibody. A single band specific to phosphorylated PKB was found on the Western blots, indicating that the active conformation of insulin was retained when spray dried in combination with lactose and with xanthan gum over the spray-drying inlet temperature range of 110-170 degrees C. Evidence of inactivation/denaturation was observed when insulin was spray dried at an inlet temperature of 200 degrees C. The assay may be of use as a more rapid and economic means to screen insulin formulations for inhalation and other purposes as opposed to conventional monitoring of blood glucose levels in animals.     

The properties of solid dispersions of indomethacin or phenylbutazone in polyethylene glycol

The effects of molecular weight of polyethylene glyeols (PEGs) on the dissolution rates and crystallinity of its solid dispersions with indoniethacin and phenylbutazone have been examined. The dissolution rates of both solid-dispersed drugs decreased as the molecular weight of PEG increased. The indoniethacin dissolution profiles were essentially linear using constant surface area disc methodology and a limiting dissolution rate of about 10.6 mg · min⁻¹ was observed. The phenylbutazone dissolution profiles were. however, generally linear-curvic usually giving lower release rates than the comparative indomethacin weight fractions. A limiting dissolution rate for the linear portions of the profiles was about 1.8 mg · min⁻¹. Infra-red spectra indicated that the differences between the two drugs could partly be explained on the basis of PEG crystallinity. Generally bands in the ranges 1100–1130 and 1200–1400 cm⁻¹ were poorly differentiated in indomethacin dispersions (PEG 1500, PEG 4000 and PEG 6000) but were better differentiated in phenylbutazone dispersions (PEG 4000, PEG 6000 and PEG 20,000). A greater proportion of amorphousness within the PEG moiety was predicted in indomethacin dispersions by the appearance of a new weak band at 1326 cm⁻¹ and by a decrease in intensity of the band at 845 cm⁻¹ at the expense of the peak at 960 cm⁻¹. The evidence was supported by differential scanning calorimetry. The heats of fusion were 44.7, 46.4, 47.2 and 39.5 cal · g⁻¹ for PEG 1500, PEG 4000, PEG 6000 and PEG 20.000 respectively. Heats of fusion for indomethacin dispersions (2, 5 and 10% drug) were generally lower than for the corresponding values for phenylbutazone dispersions-with the exception of PEG 20,000 dispersions. For example, values were obtained of 30.6 and 37.9 cal · g⁻¹ for PEG 1500 dispersions containing 10% indomethacin and phenylbutazone, respectively.     

The use of inverse phase gas chromatography to study the change of surface energy of amorphous lactose as a function of relative humidity and the processes of collapse and crystallisation

The purpose of this study was to assess the effect of relative humidity (RH) on the surface energy of amorphous lactose. Two samples of amorphous lactose were investigated; a spray dried 100% amorphous material and a ball milled sample of crystalline lactose. The milled sample had less than 1% amorphous content by mass, but on investigation at 0% RH, yielded surface energies comparable to those obtained from the 100% amorphous material, indicating that the surface was amorphous. The effect of increasing humidity was to reduce the dispersive surface energy of the two samples from 36.0 +/- 0.14 and 41.6 +/- 1.4 mJ m(-2) at 0% RH for the spray dried and milled samples respectively, to a value comparable to that obtained for the crystalline alpha-lactose monohydrate of 31.3 +/- 0.41 mJ m(-2). The change in surface energy due to water sorption was only reversible up to 20% RH; after exposure to higher RH values subsequent drying did not result in a return to the original surface energy of the amorphous form. This shows that the surface is reorganising as the glass transition temperature (Tg) is reduced, even though the sample has not collapsed or crystallised. It was possible to follow the collapse behaviour in the column with ease, using a number of different methods.     

The effect of PEG concentration on the release rate of cisplatin from PEG-modified silica xerogels

Cisplatin—an antineoplastic medicine—was incorporated into a polyethylene glycol (PEG)-modified silica xerogels received by the sol-gel method. The influence of PEG concentration and drying temperature on the release of cisplatin was studied. From our results we may state that addition of PEG (M_W 600) and drying of silica xerogels at 80 °C augmented the release of cisplatin. The release of cisplatin from the matrices grows with the increase of PEG volume in xerogel (up to 74-97% within 7 days), whereas application of thermal drying resulted in both increased speed and amount of the drug released up to 91-97% within 2 days.