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.     

The apparent plasticizing effect of polyethylene glycol (PEG) on the crystallinity of spray dried lactose/PEG composites.

Aqueous solutions of lactose and polyethylene glycol (PEG) were spray dried in a Büchi Model 191 spray dryer with the aim to investigate the effect of PEG on the crystallinity of the composite. A PEG concentration of 10.7% by weight of solids was studied for PEG 200, 600, 1500, 4000 and 8000. For PEG 200 and 4000 additional concentrations from 1.5-19.3% to 1.5-32.4%, respectively, were investigated. The spray dried composites were analysed with X-ray powder diffraction and modulating differential scanning calorimetry. The crystallinity of lactose in the composites varied from 0% to 60%, dependent on the molecular weight and concentration of PEG. Apparently, lactose crystallinity is promoted by low molecular weight and high concentration of the PEG. PEG did not affect the lactose glass transition temperature. It is suggested that lactose and PEG are solidified separately during spray drying and that partial crystallization of lactose is associated with effects of PEG on the rate of drying.     

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.     

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.     

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.     

Investigation of the effects of pharmaceutical processing upon solid-state NMR relaxation times and implications to solid-state formulation stability

Crystalline lactose was subjected to various forms of pharmaceutical processing including compaction, lyophilization, spray drying, and cryogrinding. (13)C cross polarization and magic-angle spinning (CPMAS) NMR spectra were acquired for bulk crystalline lactose as well as the processed samples. Saturation recovery experiments to determine proton spin-lattice relaxation times ((1)H T(1)) showed that the alpha-monohydrate form had a (1)H T(1) of 243 s, while compaction resulted in a threefold reduction in T(1) (79 s), with little change in the spectrum. Lyophilization and spray drying both produced amorphous lactose, with relaxation times around 4 s. Cryogrinding for various times produced mixtures of crystalline and amorphous material, with the amount of amorphous material increasing with grinding time. Sixty minutes of grinding time produced mostly amorphous material, with some crystalline material remaining. The (1)H T(1) of this sample was 2.0 s. Reducing particle size, introducing crystal defect sites, and producing amorphous material all serve to reduce the T(1) by creating sites of high mobility. Spin diffusion to the high-energy sites creates a uniform (1)H T(1) across the sample. The result is shorter relaxation times for the high-energy mixtures. Relaxation measurements performed on dosage forms could potentially be used to predict stability of pharmaceutical formulations.     

Lactose modifications enhance its drug performance in the novel multiple dose Taifun DPI

Drug–carrier particle interactions greatly affect the detachment of drug from the carrier in inhalation powders. In this study, a novel multiple dose, reservoir-based Taifun^® was used as a dry powder inhaler, and the effects of carrier physical properties were evaluated on the pulmonary deposition of budesonide, along with physical stability of the inhalation powder. In this study, untreated commercial preparation of -lactose monohydrate, highly amorphous spray dried lactose, crystallized spray dried lactose, Flowlac-100^® and Flowlac-100^® mixed with crystalline micronized lactose were used as carriers. Dry powder formulations were prepared by the suspension method, where the budesonide–carrier ratio was 1:15.1 (w/w). Carriers and formulations were initially characterized, and again after 1 month’s storage at 40 °C/75% RH. The physical properties of the carriers strongly affected the pulmonary deposition of budesonide and the physical stability of the inhalation powder. Initially, amorphous contents of the carriers were 0–64%, but spontaneous crystallisation of the amorphous lactose occurred during storage and, thus all carriers were 100% crystalline after storage. When compared to an untreated -lactose monohydrate, the highly amorphous spray dried lactose and Flowlac-100^® did not improve aerosol performance of the inhalation powder. When crystalline spray dried lactose was used as a carrier, the highest RF% values were achieved, and RF % values did not alter during storage but the emitted budesonide dose was lower than the theoretical dose. When Flowlac-100^® mixed with crystalline micronized lactose was used as a carrier, the emitted budesonide dose was close to the theoretical dose, and high RF % values were achieved but these changed during storage.     

Solidification Studies of Polyethylene Glycols,Gelucire 44/14 or their Dispersions with Triamterene or Temazepam

The solidification of polyethylene glycols (PEG 1500, PEG 2000, PEG 4000, PEG 6000), gelucire 44/14 or their dispersions containing triamterene or temazepam were studied to assess the feasibility of using these dispersions to liquid-fill hard gelatin capsules. Solidification from melts, investigated by differential scanning calorimetry using cooling cycles, showed a tendency of the drugs, carriers or their dispersions to supercool. The degree of supercooling depended on the rate of cooling, the drug content and, for the PEGs, on the molecular weight. PEG 1500 and PEG 2000 gave one morphological form, irrespective of cooling rate; PEG 4000 and PEG 6000 solidified into at least two forms, depending on the cooling rate. Incorporation of drugs affected the morphology of the PEGs during solidification. The rate of crystal growth was, furthermore, influenced by the fusion temperature, molecular weight and the degree of supercooling. The degree of crystallinity, as measured by the enthalpies of solidification, decreased with increasing cooling rate. The results show that reducing the rate of solidification could lead to incomplete solidification, giving products that are liable to change on storage.     

An atomic force microscopy approach for assessment of particle density applied to single spray-dried carbohydrate particles

To evaluate an atomic force microscopy (AFM) approach for effective density analysis of single spray dried carbohydrate particles in order to investigate the internal structure of the particles. In addition, the AFM method was compared to an established technique, that is gas pycnometry. Resonant frequency AFM analysis was employed for determination of the mass of individual particles of spray-dried lactose, mannitol, and a mixture of sucrose/dextran (4:1). The effective particle density was calculated using the diameter of the spherical particles obtained from light microscopy. The apparent particle density was further analyzed with gas pycnometry. It was observed by microscopy that particles appeared either "solid" or "hollow." A solid appearance applied to an effective particle density close to the true density of the material, whereas a density around 1 g/cm(3) corresponded to a hollow appearance. However, carbohydrates, which crystallized during spray drying, for example, mannitol appeared solid but the average effective particle density was 0.95 g/cm(3), indicating a continuous but porous structure. AFM measurements of effective particle density corroborate the suggestion of differences in particle structure caused by the varying propensity of carbohydrates to crystallize during spray drying, resulting in mainly either amorphous hollow or crystalline porous particles.     

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.     

Structural effects caused by spray‐ and freeze‐drying of liposomes and bilayer disks

Cryo‐TEM and dynamic light scattering was used to investigate morphological changes induced by spray‐ and freeze‐drying of liposomes and nanosized bilayer disks composed of 1,2‐distearoyl‐sn‐glycero‐3‐phosphocholine (DSPC), cholesterol, and 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐[methoxy(polyethylene glycol)‐5000] (DSPE‐PEG) from lactose solution. Particular focus was put on the identification of structural alterations that risk influencing the performance of liposomes and bilayer disks as carriers for protein and peptide drugs. Significant changes in the lipid aggregate structure and/or size was noted upon dehydration. Uni‐lamellar liposomes tended to shrink in size and become bi‐lamellar as a consequence of the drying process. The same transformation was observed upon deliberate establishment of a lactose gradient over the membranes of liposomes in solution. A mechanism based on an osmotically driven invagination of the liposomes is proposed to explain the change from uni‐ to bi‐lamellar structures. PEGylation promoted formation of larger liposomes during spray‐drying, and had a similar, but less pronounced, effect also during freeze‐drying. The observed structural changes may have important consequences for the bioavailability of protein/peptide drugs bound to, or embedded in, the liposome membranes. The radius of bilayer disks increased upon both spray‐ and freeze‐drying, but the drying procedure did not change the open single‐bilayer structure of the disks. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2032–2048, 2010     

Moisture sorption, compressibility and caking of lactose polymorphs

The aim of this study was to conduct storage studies on the moisture sorption and caking properties of lactose powder containing different polymorphs (i.e. alpha-monohydrate, alpha-anhydrous unstable, alpha-anhydrous stable, beta-anhydrous) and spray-dried lactose. The dry sample was compacted using a texture analyzer in paper cylinders and stored at relative humidity (RH) of 33%, 43%, 57% and 75% (25 degrees C, for 3 months). The samples were monitored for weight gain, moisture content, alpha/beta balance and hardness. A simple new method of powder compression for measuring the degree of hardness of caked lactose was developed using a texture analyzer. Clear distinctions were found in the storage behavior of the five different samples. Storage at various RHs caused severe caking to beta-lactose anhydrous and spray-dried lactose. The beta-lactose anhydrous was hygroscopic at 75% RH. The spray-dried lactose, which contained some amorphous lactose, was hygroscopic at all RHs studied. Its moisture sorption behavior differed from that of its major component, alpha-lactose monohydrate, by initially absorbing moisture then desorbing. alpha-Lactose monohydrate was less hygroscopic at 75% RH and it formed friable cakes. The alpha-lactose anhydrous stable was hygroscopic at 75% RH and initially formed hard cakes which became friable during storage. The unstable form of anhydrous alpha-lactose was hygroscopic at all levels of RH studied but did not cake.     

Effect of Lipidic Excipients on the Particle Properties and Aerosol Performance of High Drug Load Spray Dried Particles for Inhalation

High drug load inhalable particles were prepared by co-spray drying a hydrophobic, crystalline, small molecule drug with various lipid or phospholipid excipients at a 9:1 molar ratio to understand the primary drivers of aerosol performance. The effect of excipient structure on solid-state, surface characteristics, and aerodynamic performance of the co-spray dried particles was studied while keeping the spray drying parameters constant. Spray drying of the drug with lipids produced crystalline drug particles, whereas phospholipids produced partially amorphous drug particles. All of the co-spray dried particles were nearly spherical with a smooth surface, except for the spray dried drug particles without excipients – which showed the presence of rough crystals on the surface. All co-spray dried particles showed surface enrichment of the excipient. The surface enrichment of the phospholipids was higher compared to the lipids. Co-spray dried particles that showed higher surface enrichment of excipients showed improved aerosol performance. In comparing all the excipients studied, distearyolphosphatidylcholine (DSPC) showed maximum enrichment on the particle surface and thereby significantly improved aerosol performance. This study demonstrated that the addition of small amounts of lipid excipients during spray drying can change surface morphology, composition, and cohesion, impacting aerosol performance of drugs.     

Development of Fully Redispersible Dried Nanocrystals by Using Sucrose Laurate as Stabilizer for Increasing Surface Area and Dissolution Rate of Poorly Water-Soluble Drugs

There is much interest in converting poorly water-soluble drugs into nanocrystals as they provide extremely high surface area that increases dissolution rate and oral bioavailability. However, nanocrystals are prepared as aqueous suspensions, and once the suspensions are dried for development of solid dosage forms, the nanocrystals agglomerate as large particles to reduce the excess surface energy. For successful development of drug products, it is essential that any agglomeration is reversible, and the dried nanocrystals regain original particle sizes after redispersion in aqueous media. We have established that sucrose laurate serves as a superb stabilizer to ensure complete redispersion of dried nanocrystals in aqueous media with mild agitation. Nanocrystals (150–300 nm) of three neutral drugs (fenofibrate, danazol and probucol) were produced with sucrose laurate by media milling, and suspensions were dried by tray drying under vacuum, spray drying, and lyophilization. Dried solids and their tablets redispersed into original particle sizes spontaneously. Preliminary studies showed that sucrose laurate can also redisperse acidic and basic drugs, indicating its versatile application. Fatty acid ester of another disaccharide, lactose laurate, also performed like sucrose laurate. Thus, we have developed a method of retaining high dissolution rate and, by implication, high bioavailability of nanocrystals from solid formulations.     

Particle formation of budesonide from alcohol-modified subcritical water solutions

Recently, subcritical water (SBCW: water that has been heated to a temperature between 100°C and 200°C at pressures of up to 70bar) has been used to dissolve several hydrophobic pharmaceutical compounds (Carr et al., 2010a). Furthermore, a number of active pharmaceutical ingredients (APIs) have been rapidly precipitated from SBCW solutions (Carr et al., 2010b,c). It is possible to alter the precipitate morphology by altering the processing variables; including the SBCW-API solution injection temperature and adding impurities (such as pharmaceutical excipients, e.g. lactose) to the precipitation chamber. The work presented in this article demonstrates that the morphology of pharmaceutical particles can be tuned by adding organic solvents (ethanol and methanol) to the SBCW-API solutions. Particle morphology has also been tuned by adding different pharmaceutical excipients (polyethylene glycol 400 and lactose) to the precipitation chamber. Different morphologies of pharmaceutical particles were produced, ranging from nanospheres of 60nm diameter to 5μm plate particles. Budesonide was used as the model API in this study. Two experimental products were spray dried to form dry powder products. The aerodynamic particle size of the powder was established by running the powder through an Andersen Cascade Impactor. It has been shown that the drug particles produced from the SBCW micronization process, when coupled with a spray drying process, are suitable for delivery to the lungs.     

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 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.     

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.     

Physicochemical characterization and in vivo properties of Zolpidem in solid dispersions with polyethylene glycol 4000 and 6000.

Solid dispersions and physical mixtures of Zolpidem in polyethylene glycol 4000 (PEG 4000) and 6000 (PEG 6000) were prepared with the aim to increase its aqueous solubility. These PEG based formulations of the drug were characterized in solid state by FT-IR spectroscopy, X-ray powder diffraction, and differential scanning calorimetry. By these physical determinations no drug-polymer interactions were evidenced. Both solubility and dissolution rate of the drug in these formulations were increased. Each individual dissolution profile of PEG based formulation fitted Baker-Lonsdale and first order kinetic models. Finally, significant differences in ataxic induction time were observed between Zolpidem orally administered as suspension of drug alone and as solid dispersion or physical mixture. These formulations, indeed, showed almost two- to three-fold longer ataxic induction times suggesting that, in the presence of PEG, the intestinal membrane permeability is probably the rate-limiting factor of the absorption process. Copyright