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Spray drying is a well-established technology to produce inhalable dry powders. However, the amorphous nature of the particles typically obtained from the process can lead to physically and chemically unstable products. The purpose of this study was to investigate whether spray-drying could be used as a manufacturing method to produce co-amorphous drug amino acid powders with high physical stability and inhalable particulate properties. Budesonide (BUD), a compound for the treatment of lung inflammation, was co-spray-dried at a 1:1 M ratio with arginine (ARG) to produce co-amorphous powders. Two experimental factors, the solid concentration (0.85, 1.00 and 1.13%, w/v) and the ethanol concentration (55 and 75%, v/v) of the feed solution were varied to investigate the formation of co-amorphous BUD-ARG. X-ray powder diffraction (XRPD), modulated temperature differential scanning calorimetry (mDSC) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) were used for solid state characterization. The particle morphology, the median mass aerodynamic diameter and the aerodynamic properties of the resulting co-amorphous powders were investigated using scanning electron microscopy (SEM), an aerodynamic particle sizer (APS), and a next generation impactor (NGI), respectively. Furthermore, the physical stability of the obtained dry powder was examined. The co-spray-dried BUD-ARG samples prepared within the experimental range were predominantly amorphous. However, it was observed that while using the feed solution with both high solid and ethanol concentrations, some residual crystallinity related to budesonide was observed. The formation of co-amorphous BUD-ARG, rather than two separate amorphous phases, was confirmed by mDSC analyses. In addition, FTIR analyses indicated that hydrogen bonding occurs between the carbonyl groups of BUD and the amide groups of ARG in the co-amorphous BUD-ARG mixtures. The NGI results indicated that the particulate properties of the co-spray-dried co-amorphous BUD-ARG were at an inhalable range, with emitted doses >80%, and fine particle fractions >50%. In addition, the co-amorphous BUD-ARG was more physically stable than spray-dried BUD when stored at room temperature under dry conditions. This study demonstrated that spray drying is a useful manufacturing approach to produce physically stable co-amorphous dry powders for inhalation purposes.

Spray drying is one of the widely used manufacturing processes in pharmaceutical industry. While there are voluminous experimental studies pertaining to the impact of various process-formulation parameters on the quality attributes of spray dried powders such as particle size, morphology, density, and crystallinity, there is scant information available in the literature regarding process scale-up. Here, we first analyze salient features of scale-up attempts in literature. Then, spray drying process is analyzed considering the fundamental physical transformations involved, i.e., atomization, drying, and gas-solid separation. Each transformation is scrutinized from a scale-up perspective with non-dimensional parameters & multi-scale analysis, and comprehensively discussed in engineering context. Successful scale-up entails similar key response variables from each transformation across various scales. These variables are identified as droplet size distribution, outlet temperature, relative humidity, separator pressure loss coefficient, and collection efficiency. Instead of trial-and-error-based approaches, this review paper advocates the use of mechanistic models and scale-up rules for establishing design spaces for the process variables involved in each transformation of spray drying. While presenting a roadmap for process development and scale-up, the paper demonstrates how to bridge the current gap in spray drying scale-up via a rational understanding of the fundamental transformations.

Spray-dried pectin microparticles can potentially improve the oral bioavailability of peptides by virtue of their mucoadhesion. However, developing such formulations with desirable quality attributes is challenging due to the sensitivity of microparticle critical quality attributes towards changes in spray drying processing parameters. In this study, a central composite design approach was applied to investigate the influence of input temperature, aspirator rate, feed flow rate, polymer concentration and polymer feed weight on the yield and particle size of pectin microparticles prepared via spray drying. A mathematical model for the prediction of yield was statistically significant with good predictability. A maximum yield of 72.2% was achieved through optimizing the spray drying conditions. The particle size remained in a relatively narrow range (D50, 2.16-3.67 μm), and therefore was considered independent of the factors investigated. The model for yield prediction was further validated using octreotide acetate as a representative peptide. The presence of octreotide acetate in the pectin microparticles increased their surface roughness and decreased their melting enthalpy. In addition, it was determined that pectin with a high degree of esterification (72%, AU201) resulted in faster drug release compared to pectin with a lower degree of esterification (62%, CU401). Interestingly, the degree of esterification did not impact microparticle particle size, morphology or thermal properties. This study demonstrates the importance of DoE in optimization of the spray drying process for the development of pectin-based peptide microparticles. This is the first report using spray-dried pectin-based microparticles for octreotide delivery. The yield prediction model achieved using a central composite design may also be helpful for formulation development of similar drug products.

Many pharmaceuticals such as pills, capsules, or tablets are prepared in a dried and powdered form. In this field, spray drying plays a critical role to convert liquid pharmaceutical formulations into powders. In addition, in many cases it is necessary to encapsulate bioactive drugs into wall materials to protect them against harsh process and environmental conditions, as well as to deliver the drug to the right place and at the correct time within the body. Thus, spray drying is a common process used for encapsulation of pharmaceuticals. In view of the rapid progress of nanoencapsulation techniques in pharmaceutics, nano spray drying is used to improve drug formulation and delivery. The nano spray dryer developed in the recent years provides ultrafine powders at nanoscale and high product yields. In this paper, after explaining the concept of nano spray drying and understanding the key elements of the equipment, the influence of the process parameters on the final powders properties, like particle size, morphology, encapsulation efficiency, drug loading and release, will be discussed. Then, numerous application examples are reviewed for nano spray drying and encapsulation of various drugs in the early stages of product development along with a brief overview of the obtained results and characterization techniques.

High dose delivery of drugs to the lung using a dry powder inhaler (DPI) is an emerging approach to combat drug-resistant local infections. To achieve this, highly aerosolizable powders are required. We hypothesized that co-spray-drying kanamycin, a hydrophilic hygroscopic antibiotic, with rifampicin, a hydrophobic antibiotic, would produce inhalable particles with surfaces enriched in rifampicin. Such particles would have higher aerosolization than kanamycin alone, and minimise the mass of powder for inhalation avoiding use of non-active excipients. Kanamycin was co-spray-dried with rifampicin using a Buchi Mini Spray-dryer. All powders were inhalable in size (1.1–5.9 µm) and noncrystalline. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) showed the surface of the combination powder was enriched with rifampicin. In vitro aerosolization (fine particle fraction) determined by next generation impactor (NGI), dramatically improved from 29.5 ± 0.2% (kanamycin-only) to 78.2 ± 1.3% (kanamycin-rifampicin combination). The combination powder was flake-shaped in morphology, stable at 15% and 53% RH and 25 ± 2 °C during one-month storage in an open Petri dish, and non-toxic (up to 50 µg/mL) to human alveolar and bronchial cell-lines. Surface enrichment of kanamycin by hydrophobic rifampicin improves aerosolization, which may help to combat drug-resistant local infections by facilitating high dose delivery to deep lung. Refereed/Peer-reviewed

Spray drying is a well-established scale-up technique for the production of cocrystals. However, to the best of our knowledge, the effect of introducing a third component into the feed solution during the spray drying process has never been investigated. Cocrystal formation in the presence of a third component by a one-step spray drying process has the potential to reduce the number of unit operations which are required to produce a final pharmaceutical product (e.g. by eliminating blending with excipient). Sulfadimidine (SDM), a poorly water soluble active pharmaceutical ingredient (API), and 4-aminosalicylic acid (4ASA), a hydrophilic molecule, were used as model drug and coformer respectively to form cocrystals by spray drying in the presence of a third component (excipient). The solubility of the cocrystal in the excipient was measured using a thermal analysis approach. Trends in measured solubility were in agreement with those determined by calculated Hansen Solubility Parameter (HSP) values. The ratio of cocrystal components to excipient was altered and cocrystal formation at different weight ratios was assessed. Cocrystal integrity was preserved when the cocrystal components were immiscible with the excipient, based on the difference in Hansen Solubility Parameters (HSP). For immiscible systems (difference in HSP > 9.6 MPa0.5), cocrystal formation occurred even when the proportion of excipient was high (90% w/w). When the excipient was partly miscible with the cocrystal components, cocrystal formation was observed post spray drying, but crystalline API and coformer were also recovered in the processed powder. An amorphous dispersion was formed when the excipient was miscible with the cocrystal components even when the proportion of excipient used as low (10% w/w excipient). For selected spray dried cocrystal-excipient systems an improvement in tableting characteristics was observed, relative to equivalent physical mixtures.

Spray-drying is an extensively used technology for engineering inhalable particles. Important technical hurdles are however experienced when lipid-based excipients (LBEs) are spray-dried. Stickiness, extensive wall deposition, or simply inability to yield a solid product have been associated to the low melting points of LBEs. In this work, solutions containing polyglycerol esters of behenic acid (PGFA-behenates), or other high melting point LBEs, were spray-dried to produce ibuprofen (IBU)-loaded inhalable lipid-microparticles. Prior to spray-drying, rational boundaries for the outlet temperature of the process were defined using LBE-IBU phase diagrams. Despite spray-drying the solutions at outlet temperatures below the boundaries, process performance and yield among LBEs were entirely different. Lipid crystallization into polymorphs or multi-phases negatively impacted the yield (10–47%), associated to liquid fractions unable to recrystallize at the surrounding gas temperature in the spray-dryer. The highest yields (76–82%), ascribed to PGFA-behenates, resulted from monophasic crystallization and absence of polymorphism. Lipid-microparticles, composed of a PGFA-behenate, were characterized by a volume mean diameter of 6.586 µm, tap density of 0.389 g/cm3 and corrugated surface. Application as carrier-free dry powder for inhalation resulted in high emitted fraction (90.9%), median mass aerodynamic diameter of 3.568 µm, fine particle fraction of 45.6% and modified release in simulated lung fluid.

Co-amorphous drug-amino acid mixtures have shown potential for improving the solid-state stability and dissolution behavior of amorphous drugs. In previous studies, however these mixtures have been produced mainly with small-scale preparation methods, or with methods that have required the use of organic solvents or other dissolution enhancers. In the present study, co-amorphous ibuprofen-arginine and indomethacin-arginine mixtures were spray dried from water. The mixtures were prepared at two drug-arginine molar ratios (1:1 and 1:2). The properties of the prepared mixtures were investigated with differential scanning calorimetry, X-ray powder diffractometry, Fourier-transform infrared spectroscopy and a 24 h, non-sink, dissolution study. All mixtures exhibited a single glass transition temperature (Tg), evidence of the formation of homogenous single-phase systems. Fourier transform infrared spectroscopy revealed strong interactions (mainly salt formation) that account for the positive deviation between measured and estimated Tg values. No crystallization was observed during a 1-year stability study in either 1:1 or 1:2 mixtures, but in the presence of moisture, handling difficulties were encountered. The formation of co-amorphous salts led to improved dissolution characteristics when compared to the corresponding physical mixtures or to pure crystalline drugs., final draft, peerReviewed

This study investigates drug-excipient interactions in amorphous solid dispersions (ASDs) of the model basic compound lumefantrine (LMN), with five acidic polymers. X-ray photoelectron spectroscopy (XPS) was used to measure the extent of the protonation of the tertiary amine in LMN by the five acidic polymers. The extent/efficiency of protonation of the ASDs was assessed a function of polymer type, manufacturing process (hot-melt extrusion vs. spray drying), and drug loading (DL). The most strongly acidic polymer, polystyrene sulfonic acid (PSSA) was found to be the most efficient polymer in protonating LMN, independently of manufacturing method and DL. The rank order for the protonation extent of LMN by each polymer is roughtly the same for both manufacturing processes. However, protonation efficiency of polymers of similar acidic strength ranged from ∼0% to 75% (HPMCAS and Eudragit L100-55, respectively), suggesting an important role of molecular/mixing effects. For some polymers, including Eudragit L100 55 and HPMCP, spray-drying resulted in higher protonation efficiency compared to hot-melt extrusion. This result is attributable to a more favorable encounter between acid and base groups, when exposed to each other in solution phase. Increasing DL led to decreased protonation efficiency in most cases, particularly for polyacrylic acid, despite having the highest content of acidic groups per unit mass. These results indicate that the combined effects of acid strength and mixing phenomena regulate the efficiency of acid-base interactions in the ASDs.

In this study, a novel solvent-evaporation based technology to manufacture amorphous solid dispersions (ASDs) called vacuum drum drying (VDD) was assessed in comparison to the conventional technologies hot-melt extrusion (HME) and spray drying (SD). Ritonavir (15%w/w) embedded in copovidone/sorbitan monolaurate was used to investigate the impact on the ASD quality, material properties and in-vitro dissolution. All ASDs met the critical quality criteria: absence of drug substance related crystallinity, residual solvents below ICH limit (SD, VDD) and degradation products within specification limits. Clear differences in material properties such as particle morphology and size distribution, powder densities and flowability properties were observed. Overall, the milled extrudate showed superior material properties in terms of downstream processability. The VDD intermediate performed slightly better in terms of flowability and electrostatic behavior compared to the spray dried while showing comparably unfavorable densities. However, the dissolution data suggested no significant difference between the ASDs prepared by HME, SD, and VDD and thus, no change in bioavailability is expected. In conclusion, the VDD technology might be a viable alternative to manufacture ASDs - especially for thermosensitive and shear-sensitive compounds with potential to process formulations with high solid loads and viscosities while exhibiting higher throughputs at a lower footprint.

We have produced a thermally stable recombinant human type 5 adenoviral vector (AdHu5) through spray drying with three excipient formulations (l-leucine, lactose/trehalose and mannitol/dextran). Spray drying leads to immobilization of the viral vector which is believed to prevent viral protein unfolding, aggregation and inactivation. The spray dried powders were characterized by scanning electron microscopy, differential scanning calorimetry, Karl Fischer titrations, and X-ray diffraction to identify the effects of temperature and atmospheric moisture on the immobilizing matrix. Thermal stability of the viral vector was confirmed in vitro by infection of A549 lung epithelial cells. Mannitol/dextran powders showed the greatest improvement in thermal stability with almost no viral activity loss after storage at 20°C for 90days (0.7±0.3 log TCID50) which is a significant improvement over the current -80°C storage protocol. Furthermore, viral activity was retained over short term exposure (72h) to temperatures as high as 55°C. Conversely, all powders exhibited activity loss when subjected to moisture due to amplified molecular motion of the matrix. Overall, a straightforward method ideal for the production of thermally stable vaccines has been demonstrated through spray drying AdHu5 with a blend of mannitol and dextran and storing the powder under low humidity conditions. NSERC/CIHR

The present study was conducted to harness spray drying technology as a novel method of producing Ciprofloxacin nanocrystals inside liposomes (CNL) for inhalation delivery. Liposomal ciprofloxacin dispersions were spray dried with sucrose as a lyoprotectant in different mass ratios (0.5:1, 1:1 and 2:1 sucrose to lipids), along with 2% w/w magnesium stearate and 5% w/w isoleucine as aerosolization enhancers. Spray drying conditions were: inlet air temperature 50 °C, outlet air temperature 33-35 °C, atomizer rate 742 L/h and aspirator 35 m3/h. After spray drying, the formation of ciprofloxacin nanocrystals inside the liposomes was confirmed by cryo- transmission electron microscopy. The physiochemical characteristics of the spray dried powder (particle size, morphology, crystallinity, moisture content, drug encapsulation efficiency (EE), in vitro aerosolization performance and drug release) were determined. The EE of the liposomes was found to vary between 44 and 87% w/w as the sucrose content was increased from 25 to 57% w/w. The powders contained partially crystalline particles with a volume median diameter of ~ 1 μm. The powders had low water content (~2 % wt.) and were stable at high relative humidity. Aerosol delivery using the Osmohaler® inhaler at a flow rate of 100 L/min produced an aerosol fine particle fraction (% wt. < 5 μm) of 58 - 64%. The formulation with the highest sucrose content (2:1 w/w sucrose to lipid) demonstrated extended ciprofloxacin release from liposomes (80% released within 7 hours) in comparison to the original liquid formulation (80% released within 2 hours). In conclusion, a stable and inhalable CNL powder with controlled drug release was successfully prepared by spray drying.

The study considered different fat content cow milks to deliver theophylline orally. Powders were obtained by spray drying theophylline dispersed in fresh milk according to a full factorial design of experiments. The correlation of the independent (milk fat content, skimmed to whole milk, theophylline fraction, and drying temperature) with the dependent (yield of the process and residual moisture content of the powder, particle size and distribution, density, surface polarity and theophylline content) variables enabled the construction of a mathematical model and a desirability function to predict the optimized levels of the variables. Good predictability was achieved for density, fairly good for yield, moisture content, surface polarity and yield whereas theophylline content and particle size were poorly predicted. Powders with up to 60% theophylline presented spherical (3.7 µm) and narrow sized distribution particles, with high density (1.6 g/cm−3) in high yields (>70%), stable for 6 month (25 °C/65%RH) in a closed container and for no longer than 2 day, after reconstitution in water due to bacteria growth (no pathogens) without signs of crystallinity. Preparations obtained with low fat milk were less stable than high fat content milk. Therefore, fresh milk can be transformed into stable powder compositions to prepare oral solid/liquid dosage forms to deliver individualized doses of theophylline.

The novel process of crystallo-co-spray drying of paracetamol and α-lactose monohydrate was investigated by varying the spray dryer inlet temperature and inlet feed solvent composition. A crystalline agglomerate was obtained with no change to the physical structure of either component throughout both investigations and with possible interactions between the hydroxyl groups of the α-lactose monohydrate and the amide and hydroxyl groups of the paracetamol detected. The percentage soluble fraction of the components in the inlet feed had the largest influence on the morphology of the final dried agglomerate. Low excipient soluble fraction resulted in an increase in paracetamol surface coating and high excipient soluble fraction produced agglomerates of highly mixed components. The use of crystallo-co-spray drying can serve as a method of producing an agglomerated blend of crystalline co-spray dried components leading to possible opportunities for process intensification with the reduction of process steps such as blending, agglomeration, drying and milling into one single stage.

This work demonstrates that an HSV-2 candidate vaccine can be thermostabilized by spray drying to reduce cold chain demands. This work is also to optimize the process responses by varying spray dry parameters for pre-screened suitable excipients; and to determine the validity of current prescreening techniques. Vaccine activity losses were measured by in vitro plaque forming assay with Vero cell line. An accelerated storage condition of 45 °C for 10 days was used to determine spray dried sample stability. Prescreening studies demonstrated that trehalose and sucrose were superior to other tested excipients spray dry thermal stabilization of HSV-2. Subsequent optimization by design of experiments (DOE) of activity responses to spray dry parameter changes demonstrated significant differences between trehalose and sucrose for stability of the viral vaccine. Model parameters included the drying conditions inlet temperature, spray gas flow rate, and solids concentration for the model responses of vaccine stabilization. Trehalose was an effective and robust stabilizing excipient for spray drying HSV-2 vaccine. In contrast, stabilization by sucrose was greatly dependent on the spray dry process parameters. These DOE differences indicated inadequate excipient selection by prescreening methods and the variability demonstrated current prescreening techniques may not be adequate for determining optimal excipients.

Currently, most of the approved protein and peptide-based medicines are delivered via conventional parenteral injection (intramuscular, subcutaneous or intravenous). A frequent dosing regimen is often necessary because of their short plasma half-lives, causing poor patient compliance (e.g. pain, abscess, etc.), side effects owing to typical peak-valley plasma concentration time profiles, and increased costs. Among many sustained-release formulations poly lactic-co-glycolic acid (PLGA)-based depot microparticle systems may represent one of the most promising approaches to provide protein and peptide drugs with a steady pharmacokinetic/pharmacodynamic profile maintained for a long period. However, the development of PLGA-based microparticle systems is still impeded by lack of easy, fast, effective manufacturing technologies. The aim of this paper is to review recent advances in spray drying, a one-step, continuous microencapsulation process, for manufacturing of PLGA-based depot microparticle systems with a focus on the recent efforts on understanding of the role of nozzle design in the microencapsulation of proteins/peptides, and the effect of critical solvent properties and process parameters on the critical quality attributes of the spray-dried microparticles.

Three solvent based methods: spray drying (SD), electrospinning (ES) and air-assisted electrospinning (electroblowing; EB) were used to prepare solid dispersions of itraconazole and Eudragit E. Samples with the same API/polymer ratios were prepared in order to make the three technologies comparable. The structure and morphology of solid dispersions were identified by scanning electron microscopy and solid phase analytical methods such as, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Raman chemical mapping. Moreover, the residual organic solvents of the solid products were determined by static headspace-gas chromatography/mass spectroscopy measurements and the wettability of samples was characterized by contact angle measurement. The pharmaceutical performance of the three dispersion type, evaluated by dissolution tests, proved to be very similar. According to XRPD and DSC analyses, made after the production, all the solid dispersions were free of any API crystal clusters but about 10 wt% drug crystallinity was observed after three months of storage in the case of the SD samples in contrast to the samples produced by ES and EB in which the polymer matrix preserved the API in amorphous state.

A central composite design approach was applied to study the effect of polymer concentration, inlet temperature and air flow rate on the spray drying process of the Büchi B-90 nano spray dryer (B-90). Hypromellose acetate succinate-LF was used for the Design of Experiment (DoE) study. Statistically significant models to predict the yield, spray rate, and drying efficiency were generated from the study. The spray drying conditions were optimized according to the models to maximize the yield and efficiency of the process. The models were further validated using a poorly water-soluble investigational compound (BI064) from Boehringer Ingelheim Pharmaceuticals. The polymer/drug ratio ranged from 1/1 to 3/1w/w. The spray dried formulations were amorphous determined by differential scanning calorimetry and X-ray powder diffraction. The particle size of the spray dried formulations was 2-10 μm under polarized light microscopy. All the formulations were physically stable for at least 3h when suspended in an aqueous vehicle composed of 1% methyl cellulose. This study demonstrates that DoE is a useful tool to optimize the spray drying process, and the B-90 can be used to efficiently produce amorphous solid dispersions with a limited quantity of drug substance available during drug discovery stages.

The inactivation of catalase during spray-drying over a range of outlet gas temperatures could be closely represented by the Arrhenius equation. From this an activation energy for damage to the catalase could be calculated. The close fit to Arrhenius suggests that the thermally-induced part of inactivation of the catalase during the complex drying and particle-formation processes takes place at constant temperature. These processes are rapid compared with the residence time of the powder in the collecting vessel of the cyclone where dried catalase is exposed to a constant temperature equal to approximately the drying gas outlet temperature. A lower activation energy after spray drying with the ultrasonic nozzle was found than with the 2-fluid nozzle under otherwise identical spray drying conditions. It is feasible that the ultrasonic nozzle when mounted in the lid of the spray dryer heats up toward the drying gas inlet temperature much more that the air-cooled 2-fluid nozzle. Calculation of the Arrhenius activation energy also showed how the stabilizing efficacy of trehalose and mannitol on the catalase varies in strength across the range of drying gas inlet and outlet temperatures examined.

The present study focuses on the ability of excipients to induce the crystallization of a specific polymorphic form of pyrazinamide (PZA) and more interestingly, to block the irreversible solid–solid transition of the metastable forms of the PZA to the stable form at room temperature. We outline an experimental protocol for the production of a structurally pure γ form of PZA by means of spray drying. Without any particular treatment, phase transition to δ form was detected after 14 days of storage under ambient conditions. In order to prevent this irreversible phase transition, different excipients were co-spray dried with PZA. By co-spray drying 5% in mass of 1,3-dimethylurea (DMU) with PZA, we noticed its ability in preventing phase transitions and thus to maintain PZA under its γ form up to 12 months of storage at room temperature. Raman spectroscopy evidenced how DMU crystals surround particles of γ PZA which suggest that DMU might interact with the surface of PZA particles, thus blocking the phase transition. On the other hand, the co-spray drying of PZA with the polymerpolyvinylpyrrolidone (PVP) resulted in the crystallization of δ form of PZA. The physical mixture was intact over 12 months of storage at room temperature.

Utilization of sugars (e.g. lactose, sucrose) as matrix formers for spray drying of drug nanosuspensions is associated with two drawbacks: (1) sugars are incapable of preventing agglomeration of drug nanoparticles (NPs) in the suspension state; and (2) the spray-dried sugars are usually amorphous and hygroscopic. This work aimed to apply a clay, montmorillonite (MMT) as an alternative matrix former for spray drying of drug nanosuspensions with fenofibrate (feno) as a model compound. Drug nanosuspensions were synthesized by liquid antisolvent precipitation with different amount of MMT followed by spray drying. It is found that MMT is able to reduce the agglomeration of drug nanoparticles in the suspension state, as observed from the gradual alleviation of the clogging with the increased clay during the spray drying. The spray-dried feno NPs/MMT powders exhibited a much lower moisture sorption than spray-dried feno NPs/lactose powders as evidenced by the dynamic vapor sorption (DVS) analysis. The dissolution within 5 min for the spray-dried feno NPs/MMT powders at drug:MMT weight ratio of 1:3 was 81.4 ± 1.8% and the total dissolution within 60 min was 93.4 ± 0.9%. Our results demonstrate that MMT is a useful matrix former for preservation of the high dissolution rate of nanosized drug particles after drying.

Quality by Design (QbD) principles were explored to understand spray drying process for the conversion of liquid nanosuspensions into solid nano-crystalline dry powders using indomethacin as a model drug. The effects of critical process variables: inlet temperature, flow and aspiration rates on critical quality attributes (CQAs): particle size, moisture content, percent yield and crystallinity were investigated employing a full factorial design. A central cubic design was employed to generate the response surface for particle size and percent yield. Multiple linear regression analysis and ANOVA were employed to identify and estimate the effect of critical parameters, establish their relationship with CQAs, create design space and model the spray drying process. Inlet temperature was identified as the only significant factor (p value

Biologicals are often formulated as solids in an effort to preserve stability which generally requires stabilising excipients for proper drying. The purpose of this study was to screen amino acids and their combinations for their stabilising effect on proteins during spray drying. Catalase, as model protein, was spray dried in 1+1 or 1+2 ratios with amino acids. Some amino acids namely arginine, glycine and histidine showed good retention of catalase functionality after spray drying and subsequent storage stress. A 1+1 combination of arginine and glycine in a 1+2 ratio with catalase resulted in a tremendously good stabilising effect. Storage at high temperature/humidity also showed beneficial effects of this combination. To evaluate whether this was a general principle, these findings were transferred to an antigenic protein of comparable size and supramolecular structure (haemagglutinin) as well as to a smaller enzyme (lysozyme). Upon spray drying with the combination of amino acids it could be shown that both proteins remain more stable especially after storage compared to the unprotected protein. The combination of arginine and glycine is tailored to the needs of protein stabilisation during spray drying and may hence be utilised in dry powder formulation of biomolecules with superior stability characteristics.