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.     

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.     

Single-step granulation/tabletting of different grades of lactose: a comparison with high shear granulation and compression.

The influence of the particle size, particle morphology and crystallinity of lactose on the extrusion properties and on the quality of tablets were investigated using single-step granulation/tabletting as a tabletting technique. Results showed that particle size and type of lactose (alpha-lactose monohydrate, anhydrous beta-lactose and spray dried lactose) affected the powder feeding, the process performance as well as the process capacity. Different grades of lactose yielded tablets with similar tensile strength, but significantly different disintegration time. Single-step granulation/tabletting always yielded tablets with a significantly higher tensile strength and similar or significantly lower disintegration time compared to high shear granulation and compression. The tensile strength of alpha-lactose monohydrate tablets (without and with PVP) did not change during one year of storage at 60% RH-25 degrees C and at 75% RH-40 degrees C, whereas a significant increase in disintegration time was observed. It can be concluded that although the lactose grade affected the performance and the optimal parameters of single-step granulation/tabletting, all lactose grades can be efficiently processed using this technique.     

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.     

Measurement of lactose crystallinity using Raman spectroscopy

Raman spectroscopy (RS) was used to determine the crystallinity of lactose (a commonly used carrier in dry powder inhaler (DPI) formulations). Samples of alpha-lactose monohydrate and amorphous lactose were prepared using ethanol precipitation and lyophilisation respectively. The anomeric forms were confirmed using DSC at a rate of 10 degrees C/min and heated to 250 degrees C. The Raman spectra of both alpha-lactose monohydrate and amorphous lactose were obtained. Distinguishable differences were seen between the two spectra including peak areas and intensities. Depolarisation ratios (rho) of each form were then determined to identify the crystallinity of the lactose carrier samples. At the prominent Raman bands 865 and 1082 cm-1, significant differences in rho values were observed for crystalline (0.80+/-0.07, 0.89+/-0.06 respectively) and amorphous samples (0.44+/-0.07, 0.51+/-0.10).     

Electrostatic characterisation of inhaled powders: Effect of contact surface and relative humidity

Electrostatic charge accumulation on drug and excipient powders arising from interparticulate collisions or contacts between particles and other solid surfaces often leads to agglomeration and adhesion problems during the manufacture and use of dry powder inhaler (DPI) formulations. The aim of this work was to investigate the role of triboelectrification in particle interactions between micronised drug (salbutamol sulphate or ipratropium bromide monohydrate) and excipient (alpha-lactose monohydrate, 63-90 microm) during mixing in cylindrical vessels constructed from stainless steel, polypropylene and acetal under selected relative humidity (rh) conditions (0-86%). The charge was found to depend on both the nature of the powders and the mixing vessel surface. In addition, coating the vessels with drug or excipient removed the influence of the vessel material on charge generation, thus providing a technique to investigate interactions between the drug and excipient substances. A triboelectric series of all materials used, placed ipratropium at the positive end and polypropylene at the negative end. Micronised drug profoundly altered the charging properties of lactose in drug (1.46%, w/w)/lactose DPI formulations. An increase in rh in the range 0-86% produced a corresponding decrease in charge and adhesion values for each drug, lactose and DPI formulation during triboelectrification with each mixing vessel surface. The results provide increased knowledge of the role of electrostatics in DPI technology.     

Dry powder formulations for inhalation of fluticasone propionate and salmeterol xinafoate microcrystals

Direct crystallization of active pharmaceutical ingredient (API) particles in the inhalable size range of 1-6 microm may overcome surface energization resulting from micronization. The aerosolization of fluticasone propionate (FP) and salmeterol xinafoate (SX) microcrystals produced by aqueous crystallization from poly(ethylene glycol) solutions was investigated using a twin stage impinger following blending with lactose. Fine particle fractions from SX formulations ranged from 15.98 +/- 2.20% from SX crystallized from PEG 6000 to 26.26 +/- 1.51% for SX crystallized from PEG 400. The FPF of microcrystal formulations increased as the particle size of microcrystals was increased. The aerosolization of SX from DPI blends was equivalent for the microcrystals and the micronized material. FP microcrystals, which had a needlelike morphology, produced similar FPFs (PEG 400: 17.15 +/- 0.68% and PEG 6000: 15.46 +/- 0.97%) to micronized FP (mFP; 14.21 +/- 0.54). The highest FPF (25.66 +/- 1.51%) resulted from the formulation of FP microcrystals with the largest median diameter (FP PEG 400B: 6.14 +/- 0.17 microm). Microcrystallization of SX and FP from PEG solvents offers the potential for improving control of particulate solid state properties and was shown to represent a viable alternative to micronization for the production of particles for inclusion in dry powder inhalation formulations.     

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.     

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.     

Effects of particle size and adding sequence of fine lactose on the deposition of salbutamol sulphate from a dry powder formulation.

Ternary mixtures composed of coarse lactose (CL) (90.8 microm), salbutamol sulphate (SS) (5.8 microm) and either micronised lactose (ML) (5 microm) or intermediate sized lactose (IML) (15.9 microm) in a ratio of 66.5:1:1 w/w were prepared using different mixing sequences of the various components. In addition, a binary mixture composed of CL and SS (67.5:1 w/w) was also prepared as the control. The in vitro deposition of SS was measured using a twin stage impinger after aerosolisation at 60 and 90 l min-1 via a Rotahaler. The aerodynamic particle size distribution of both the aerosolised SS and lactose was further analysed using an Andersen cascade impactor at 60 l min-1. All ternary mixtures produced a significantly higher (analysis of variance, P<0.01) fine particle fraction (FPF) and fine particle dose (FPD) of SS than the control after aerosolisation at either 60 or 90 l min-1. Formulations containing the ML produced significantly (P<0.05) higher FPF and FPD of SS than those containing the IML at both aerosolisation flow rates. Different mixing sequences were also shown to result in different deposition profiles of both SS and lactose after aerosolisation of the ternary mixtures containing ML at 60 l min-1. The formulation prepared by first blending ML with CL before mixing with SS produced a higher FPF and FPD of SS but a lower FPF of lactose than the same formulation in terms of composition but prepared using different mixing orders of the three components. In contrast, the formulations containing IML produced a similar deposition profile to SS, regardless of the mixing sequences, and so did the formulations containing ML aerosolised at 90 l min-1. These results suggest that the effect of mixing sequences on drug deposition may become more prominent at lower aerosolisation flow rates and by reducing the size of any added fine lactose.     

Lactose as a carrier in dry powder formulations: the influence of surface characteristics on drug delivery.

The aim of the study was to investigate the interdependence of carrier particle size, surface treatment of the carrier, and inclusion of fines on the drug delivery from dry power inhaler formulations. Two size fractions (< 63 and 63-90 microm) of alpha-lactose monohydrate were subjected to treatment with 95% (v/v) ethanol to introduce small asperities or cavities onto the otherwise smooth surface without substantially changing the particle shape. After blending with albuterol sulfate [ALB; volume median diameter (VMD), 1.9 microm; geometric standard deviation (GSD), 1.5], the solvent-treated lactose produced a fine particle fraction (FPF; < 6.18 microm) and dispersibility of the drug that was significantly (ANOVA p < 0.01) lower than that which resulted from formulations containing untreated lactose of a similar size fraction, after aerosolization at 60 L min(-1) via a Rotahaler. The two size fractions of the treated lactose resulted in similar deposition profiles of ALB. The effects of such surface asperities or cavities of lactose were offset by introducing a small amount (5% w/w) of smaller-sized lactose (5-10 microm) to the powder formulations. The fine lactose increased the FPF and dispersibility of ALB to such a level that all lactose batches, regardless of particle size or whether solvent treated, produced a similar fraction of aerosolized ALB. The inclusion of recrystallized needle lactose (5-15 microm) was superior to micronized lactose in improving the aerosolization of ALB. The findings of this study indicate that the presence and characteristics of the finer fraction of lactose carrier particles dominate over the particle size and surface smoothness of the carrier particles in determining dispersion and deaggregation of drugs from dry powder formulations for inhalation.     

Assessing the re-crystallization behaviour of amorphous lactose using the RH-perfusion cell.

Many different reports have studied the crystallization behaviour of lactose, e.g., by exposing samples of amorphous lactose to different relative humidity at constant temperatures. However, only few reports are available investigating the formation of alpha-lactose monohydrate and beta-lactose during re-crystallization. Applying the static ampoule method in the microcalorimeter, the enthalpies of amorphous lactose were reported to be constantly 32 and 48 J/g, respectively, considering the mutarotation of lactose at 25 degrees C and 58% RH, 75% RH and 100% RH. In this study, an alternative microcalorimetric technique, the relative humidity-perfusion cell (RH-perfusion cell) was chosen. The RH-perfusion cell is able to deliver a constant and controlled flow of humidified air to the sample. Investigated compounds were purely amorphous lactose and different powder mixtures of lactose. They consisted of alpha-lactose monohydrate (Pharmatose 325M), beta-lactose (Pharmatose DCL21) or a combination (1:1) thereof as carriers, and different concentrations of amorphous lactose. The determination of the enthalpy of desorption of the just re-crystallization lactose by the RH-perfusion cell was used to discriminate whether the monohydrate or the anhydrous form of lactose was produced. Differences in the re-crystallization behaviour of lactose at 25 degrees C and 58-100% RH were found. At 60-80% RH purely amorphous lactose showed a high heat of desorption which can be attributed to a very high content of formed beta-lactose. Powder mixtures containing high contents of amorphous lactose (8% and 15%, respectively) blended with alpha-lactose monohydrate as a carrier resulted in similar results at the same RH ranges. The high amount of beta-lactose can be due to the equilibrium anomeric composition. Whereas powder mixtures containing beta-lactose as a carrier and amorphous lactose in a concentration of 1%, 8% and 15%, respectively, formed less beta-lactose than the mixtures containing alpha-lactose monohydrate as a carrier. At a relative humidity of 90% none of the powder mixtures showed desorption as to the fact that in all cases only alpha-lactose monohydrate was formed at the surface of the re-crystallized lactose. Furthermore, mixtures of alpha-lactose monohydrate and beta-lactose (1:1) and 8% amorphous lactose were investigated. An increase in formed alpha-lactose monohydrate by increasing RH was found. To consolidate the results, the same mixtures were re-crystallized at different RH in desiccators and subsequently investigated in the solution calorimeter. The results of the pre-mix were confirmed by the solution calorimeter. In summary, purely amorphous lactose and mixtures containing alpha-lactose monohydrate as a carrier show different re-crystallization behaviour compared to mixtures containing beta-lactose as a carrier.     

The influence of drug morphology on aerosolisation efficiency of dry powder inhaler formulations

The physicochemical properties of two forms of spray dried bovine serum albumin (BSA) have been investigated using particle sizing, surface energy measurement, atomic force microscopy (AFM) and colloid probe microscopy. The BSA powder had similar particle size distributions and surface energy but significantly different morphologies and roughness, classified as smooth and corrugated BSA. Adhesion forces between the corrugated BSA and alpha-lactose monohydrate indicated median adhesion forces were significantly less than for smooth/carrier interaction forces. These observations correlated well with aerosolisation from BSA/carrier blends, where the corrugated BSA particles gave a higher fine particle fraction than the smooth BSA, suggesting reduced BSA/carrier adhesion and increased drug liberation. The use of corrugated drug particle morphology in drug carrier DPI systems may lead to improved aerosol performance through reduced drug carrier contact area.     

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.     

Physico-chemical aspects of lactose for inhalation

A dry powder inhaler (DPI) is a dosage form that consists of a powder formulation in a device which is designed to deliver an active ingredient to the respiratory tract. It has been extensively investigated over the past years and several aspects relating to device and particulate delivery mechanisms have been the focal points for debate. DPI formulations may or may not contain carrier particles but whenever a carrier is included in a commercial formulation, it is almost invariably lactose monohydrate. Many physicochemical properties of the lactose carrier particles have been reported to affect the efficiency of a DPI. A number of preparation methods have been developed which have been claimed to produce lactose carriers with characteristics which lead to improved deposition. Alongside these developments, a number of characterization methods have been developed which have been reported to be useful in the measurement of key properties of the particulate ingredients. This review describes the various physicochemical characteristics of lactose, methods of manufacturing lactose particulates and their characterization.     

Formulation of inhalable lipid-based salbutamol sulfate microparticles by spray drying technique

Background

The aim of this work was to develop dry powder inhaler (DPI) formulations of salbutamol sulfate (SS) by the aid of solid lipid microparticles (SLmPs), composed of biocompatible phospholipids or cholesterol.

Methods

The SLmPs were prepared by using two different solvent systems (ethanol and water-ethanol) and lipid carriers (dipalmitoylphosphatidylcholine (DPPC) and cholesterol) with/without L-leucine in the spray drying process. The spray-dried microparticles were physically-mixed with coarse lactose monohydrate in order to make our final DPI formulations and were investigated in terms of physical characteristics as well as in vitro drug release profile and aerosolization behavior.

Results

We observed significant differences in the sizes, morphologies, and in vitro pulmonary depositions between the formulations. In particular, the SS-containing SLmPs prepared with water-ethanol (30:70 v/v) solution of DPPC and L-leucine which had then been blended with coarse lactose (1:9 w/w) exhibited the highest emitted dose (87.9%) and fine particle fraction (42.7%) among the formulations. In vitro drug release study indicated that despite of having a significant initial burst release for both cholesterol and DPPC-based microparticles, the remained drug released more slowly than the pure drug.

Conclusion

This study demonstrated the potential of using lipid carriers as well as L-leucine in DPI formulations of SS to improve its aerosolization behavior and retard the release profile of the drug.     

Alternative sugars as potential carriers for dry powder inhalations

Most dry powder inhaler (DPI) formulations rely on lactose monohydrate as a carrier in the drug powder blends. However, lactose cannot be used for compounds that interact with the reducing sugar function of the lactose, such as formoterol, budesonide or peptides and proteins. In this study, alternative carriers like mannitol, glucose, sorbitol, maltitol and xylitol have therefore been evaluated for their potential use in DPI formulations. Raw materials were characterised physico-chemically and blends with the model drug substance budesonide were tested with respect to the aerosolization behaviour of the powders.

It was found out that similarly to the problems known for lactose monohydrate, such as supplier variability, variability between different qualities of one supplier, the same difficulties apply to the alternative carriers investigated. Different sources and qualities of mannitol led to significant differences in the fine particle fraction (FPF), varying from 15 to 50% for two different qualities of mannitol. Similar observations were made for the other carrier materials studied. Also, the influence of conditioning the raw material at different relative humidity was found to have substantial influence on the performance of drug/carrier blends which is characterised by a strong decrease in the FPF. In summary, mannitol showed potential as a drug carrier to be used in DPIs whereas the more hygroscopic sugars only showed poor dispersibility.     

Characterisation and functionality of inhalation anhydrous lactose

The relationships between the physicochemical properties and functionality in dry powder inhaler (DPI) performance was investigated for inhalation grade anhydrous lactose and compared to monohydrate grades. The excipients were characterised using a range of techniques including particle size analysis, moisture sorption and powder rheometry. The inhalation anhydrous lactose grades were readily characterisable. The aerosolisation performance of capsule based DPI formulations containing budesonide (200 μg) and different grades of lactose evaluated using inertial impaction measurements produced fine particle doses of budesonide ranging from 24 to 49 μg. There were no apparent relationships between aerosolisation performance and excipient characteristics, such as particle size and powder density. However, formulations containing lactose grades which exhibit higher powder fluidisation energy values resulted in higher fine particle doses of budesonide.     

The Effect of Engineered Mannitol-Lactose Mixture on Dry Powder Inhaler Performance

Purpose

To co-crystallise mannitol and lactose with a view to obtaining crystals with more favourable morphological features than either lactose or mannitol alone, suitable for use as carriers in formulations for dry powder inhalers (DPIs) using simultaneous engineering of lactose-mannitol mixtures.

Methods

Mannitol and lactose individually and the two sugars with three different ratios were crystallised/co-crystallised using anti-solvent precipitation technique. Obtained crystals were sieved to separate 63?C90???m size fractions and then characterised by size, shape, density and in vitro aerosolisation performance. Solid state of crystallized samples was studied using FT-IR, XRPD and DSC.

Results

At unequal ratios of mannitol to lactose, the elongated shape dominated in the crystallisation process. However, lactose exerted an opposite effect to that of mannitol by reducing elongation ratio and increasing the crystals?? width and thickness. Crystallised ??-lactose showed different anomers compared to commercial lactose (??-lactose monohydrate). Crystallised ??-mannitol showed different polymorphic form compared to commercial mannitol (??-mannitol). Crystallised mannitol:lactose showed up to 5 transitions corresponding to ??-mannitol, ??-lactose monohydrate, ??-lactose, 5??-/3??-lactose and 4??-/1??-lactose. In vitro deposition assessments showed that crystallised carriers produced more efficient delivery of salbutamol sulphate compared to formulations containing commercial grade carriers.

Conclusion

The simultaneous crystallization of lactose-mannitol can be used as a new approach to improve the performance of DPI formulations.