3D printed dispersible efavirenz tablets: A strategy for nasogastric administration in children.

Enteral feeding tubes (EFTs) can be placed in children diagnosed with HIV which need nutritional support due to malnutrition. EFTs are the main route for medication administration in these patients, bringing up concerns about off label use of medicines, dose inaccuracy and tube clogging. Here we report for the first time the use of selective laser sintering (SLS) 3D printing to develop efavirenz (EFZ) dispersible printlets for patients with HIV that require EFT administration. Water soluble polymers Parteck® MXP and Kollidon® VA64 were used to obtain both 500 mg (P500 and K500) and 1000 mg printlets (P1000 and K1000) containing 200 mg of EFZ each. The use of SLS 3D printing obtained porous dosage forms with high drug content (20 % and 40 % w/w) and drug amorphization using both polymers. P500, K500 and K1000 printlets reached disintegration in under 230 s in 20 mL of water (25 ± 1 °C), whilst P1000 only partially disintegrated, possibly due to saturation of the polymer in the medium. As a result, the development of dispersible EFZ printlets using hydrophilic polymers can be explored as a potential strategy for drug delivery through EFTs in paediatrics with HIV, paving the way towards the exploration of more rapidly disintegrating polymers and excipients for SLS 3D printing.

A novel honeycomb-like 3D-printed device for rotating-disk sorptive extraction of organochlorine and organophosphorus pesticides from environmental water samples.

In this study, 3D-printing based on fused-deposition modeling (FDM) was employed as simple and cost-effective strategy to fabricate a novel format of rotating-disk sorptive devices. As proof-of-concept, twenty organochlorine and organophosphorus pesticides were determined in water samples through rotating-disk sorptive extraction (RDSE) using honeycomb-like 3D-printed disks followed by gas chromatography coupled to mass spectrometry (GC-MS). The devices that exhibited the best performance were comprised of polyamide + 15 % carbon fiber (PA + 15 % C) with the morphology being evaluated through X-ray microtomography. The optimized extraction conditions consisted of 120 min of extraction using 20 mL of sample at stirring speed of 1100 rpm. Additionally, liquid desorption using 800 µL of acetonitrile for 25 min at stirring speed of 1100 rpm provided the best response. Importantly, the methodology also exhibited high throughput since an extraction/desorption platform that permitted up to fifteen simultaneous extractions was employed. The method was validated, providing coefficients of determination higher than 0.9706 for all analytes; limits of detection (LODs) and limits of quantification (LOQs) ranged from 0.15 to 3.03 µg L-1 and from 0.5 to 10.0 µg L-1, respectively. Intraday precision ranged from 4.01 to 18.73 %, and interday precision varied from 4.83 to 20.00 %. Accuracy was examined through relative recoveries and ranged from 73.29 to 121.51 %. This method was successfully applied to analyze nine groundwater samples from monitoring wells of gas stations in São Paulo. Moreover, the greenness was assessed through AGREEprep metrics, and an overall score of 0.69 was obtained indicating that the method proposed can be considered sustainable.

Ivermectin-Loaded Mesoporous Silica and Polymeric Nanocapsules: Impact on Drug Loading, In Vitro Solubility Enhancement, and Release Performance.

Ivermectin (IVM), a widely used drug for parasitic infections, faces formulation and application challenges due to its poor water solubility and limited bioavailability. Pondering the impact of IVM's high partition coefficient value (log P) on its drug release performance, it is relevant to explore whether IVM nanoencapsulation in organic or inorganic nanoparticles would afford comparable enhanced aqueous solubility. To date, the use of inorganic nanoparticles remains an unexplored approach for delivering IVM. Therefore, here we loaded IVM in mesoporous silica particles (IVM-MCM), as inorganic nanomaterial, and in well-known poly(ε-caprolactone) nanocapsules (IVM-NC). IVM-MCM had a well-organized hexagonal mesoporous structure, reduced surface area, and high drug loading of 10% w/w. IVM-NC had a nanometric mean size (196 nm), high encapsulation efficiency (100%), physicochemical stability as an aqueous dispersion, and drug loading of 0.1% w/w. Despite differing characteristics, both nanoencapsulated forms enhance IVM's aqueous intrinsic solubility compared to a crystalline IVM: after 72 h, IVM-MCM and IVM-NC achieve 72% and 78% releases through a dialysis bag, whereas crystalline IVM dispersion achieves only 40% drug diffusion. These results show distinct controlled release profiles, where IVM-NC provides a deeper sustained controlled release over the whole experiment compared to the inorganic nanomaterial (IVM-MCM). Discussing differences, including drug loading and release kinetics, is crucial for optimizing IVM's therapeutic performance. The study design, combined with administration route plans and safety considerations for humans and animals, may expedite the rational optimization of IVM nanoformulations for swift clinical translation.

Pimobendan controlled release guar gum printlets: Tailoring drug doses for personalised veterinary medicines.

Treating chronic heart diseases in dogs is challenging due to variations in mass within and between species. Pimobendan (PBD), a veterinary drug only, is prescribed in specific cases of chronic heart disease in dogs and is available on the market in only a few different doses. Furthermore, the therapy itself is challenging due to the large size of the chewable tablets and the requirement for twice-daily administration. The development of customised and on-demand PBD medicines by three-dimensional (3D) printing has been proposed to circumvent these disadvantages. In this study, we designed controlled-release flavoured printlets containing PBD. We evaluated the use of two natural polymers, guar or xanthan gums, as the main component of the printing inks. Guar gum showed the better rheological behavior and printability by semisolid extrusion. The printlets were produced in three different shapes and sizes to allow dose customisation. Guar gum printlets showed a PBD controlled release profile, regardless of their shape or size. Therefore, we have demonstrated a novel approach for controlling PBD drug release and tailoring the dose by employing a natural polymer to produce 3D-printed tablets. This study represents a significant step towards the development of 3D-printed guar gum controlled-release formulations for veterinary applications.

Nanocellulose, the Green Biopolymer Trending in Pharmaceuticals: A Patent Review.

The use of nanocellulose in pharmaceutics is a trend that has emerged in recent years. Its inherently good mechanical properties, compared to different materials, such as its high tensile strength, high elastic modulus and high porosity, as well as its renewability and biodegradability are driving nanocellulose's industrial use and innovations. In this sense, this study aims to conduct a search of patents from 2011 to 2023, involving applications of nanocellulose in pharmaceuticals. A patent search was carried out, employing three different patent databases: Patentscope from World Intellectual Property Organization (WIPO); Espacenet; and LENS.ORG. Patents were separated into two main groups, (i) nanocellulose (NC) comprising all its variations and (ii) bacterial nanocellulose (BNC), and classified into five major areas, according to their application. A total of 215 documents was retrieved, of which 179 were referred to the NC group and 36 to the BNC group. The NC group depicted 49.7%, 15.6%, 16.2%, 8.9% and 9.5% of patents as belonging to design and manufacturing, cell culture systems, drug delivery, wound healing and tissue engineering clusters, respectively. The BNC group classified 44.5% of patents as design and manufacturing and 30.6% as drug delivery, as well as 5.6% and 19.4% of patents as wound healing and tissue engineering, respectively. In conclusion, this work compiled and classified patents addressing exclusively the use of nanocellulose in pharmaceuticals, providing information on its current status and trending advancements, considering environmental responsibility and sustainability in materials and products development for a greener upcoming future.

Poly(ɛ-caprolactone) and Eudragit E blends modulate the drug release profiles from FDM printlets.

Thermoplastic polymers have been used to produce filaments by hot melt extrusion (HME), which can be applied to obtain 3D printlets by fused deposition modelling (FDM). Poly(ε-caprolactone) (PCL) is a low melting point thermoplastic polymer that provides HME filaments with excellent mechanical and printability properties. However, due to the highly hydrophobic properties of PCL, they afford printlets with slow drug release behaviour. We hypothesized that blending a less hydrophobic polymer, the Eudragit E (EudE), with PCL could be an approach to increase the drug release rate from PCL 3D printlets. PCL and EudE were blended at different proportions, 50:50, 60:40, 70:30, and 80:20 (w/w), to produce HME filaments. They were produced with dexamethasone at 5 % (w/w) and were effectively extruded and printable by FDM, except that composed of 50:50 (w/w). Printlets had homogeneous distribution of their components. Their drug release behaviour was dependent on the ratio of the polymeric blends. The highest EudE ratio (60:40 w/w) afforded printlets showing the highest release rate. Therefore, adding up to 40 % (w/w) of EudE to PCL does not impair the mechanical and printability properties of its HME filaments. This innovative approach is proposed here to modulate the drug release behaviour from PCL printlets.

3D printed matrix solid forms: Can the drug solubility and dose customisation affect their controlled release behaviour?

The use of 3D printing in pharmaceutics has grown over the last years, along with the number of studies on the impact of the composition of these formulations on their pharmaceutical and biopharmaceutical properties. Recently, we reported the combined effect of the infill percentage and the presence of a pore former on the drug release behaviour of 3D printed matrix solid forms prepared by fused deposition modelling. However, there are some open questions about the effect of the drug solubility and the size of these dosage forms on their controlled release properties. Therefore, we produced poly(Ɛ-caprolactone) filaments containing different soluble forms of dexamethasone (free acid, DEX; acetate ester, DEX-A; and phosphate salt, DEX-P), which showed suitable mechanical properties and printability. 3D printed solid forms were produced in two different sizes. The formulations composed of DEX-P released about 50% of drug after 10 h, while those containing DEX or DEX-A released about 9%. The drug release profiles from the 3D printed forms containing the same drug form but with different sizes were almost completely overlapped. Therefore, these 3D printed matrix solid forms can have their drug content customised by adjusting their size, without changing their controlled release behaviour.

A critical review of traditional and advanced characterisation tools to drive formulators towards the rational development of 3D printed oral dosage forms.

The high degree of precision and control of 3D printing has given formulators the autonomy to engineer sophisticated and personalised medicines, starting a revolution in pharmaceutics. In addition, dosage forms with tailored drug release profile can be produced by changing some parameters of the 3D printing processes. Therefore, 3D printed medicines must be characterised in an orthogonal approach, to establish their physicochemical and biopharmaceutical features, and consequently to understand how these characteristics can be customised by changing the formulation and process parameters to ensure medicines' safety and efficacy. Given the recent regulation and commercialisation of 3D printed medicines, several methods and techniques have been transposed from official compendia; however, formulators must still make a critical assessment of their practical implications. A comprehensive review of the findings obtained by the characterisation of 3D printed oral dosage forms using traditional and advanced techniques is therefore presented here, to drive formulators towards a rational pharmaceutical development pathway. The characterisation methods have been classified in terms of their physicochemical or biopharmaceutical character. Interestingly, beyond the rise of modern characterisation techniques, the reassessment of data obtained by traditional methods has provided knowledge and a solid foundation to support the evolution of 3D printing techniques in pharmaceutics.

Ivermectin: recent approaches in the design of novel veterinary and human medicines.

Ivermectin (IVM) is a drug widely used in veterinary and human medicine for the management of parasitic diseases. Its repositioning potential has been recently considered for the treatment of different diseases, such as cancer and viral infections. However, IVM faces some limitations to its formulations due to its low water solubility and bioavailability, along with reports of drug resistance. In this sense, novel technological approaches have been explored to optimize its formulations and/or to develop innovative medicines. Therefore, this review discusses the strategies proposed in the last decade to improve the safety and efficacy of IVM and to explore its novel therapeutic applications. Among these technologies, the use of micro/nano-drug delivery systems is the most used approach, followed by long-acting formulations. In general, the development of these novel formulations seems to run side by side in veterinary and human health, showing a shared interface between the two areas. Although the technologies proposed indicate a promising future in the development of innovative dosage forms containing IVM, its safety and therapeutic targets must be further evaluated. Overall, these approaches comprise tailoring drug delivery profiles, decreasing the risks of developing drug resistance, and supporting the application of IVM for reaching different therapeutic targets.

Immediate release 3D printed oral dosage forms: How different polymers have been explored to reach suitable drug release behaviour.

Three-dimensional (3D) printing has been gaining attention as a new technological approach to obtain immediate release (IR) dosage forms. The versatility conferred by 3D printing techniques arises from the suitability of using different polymeric materials in the production of solids with different porosities, geometries, sizes, and infill patterns. The appropriate choice of polymer can facilitate in reaching IR specifications and afford other specific properties to 3D printed solid dosage forms. This review aims to provide an overview of the polymers that have been employed in the development of IR 3D printed dosage forms, mainly considering their in vitro drug release behaviour. The physicochemical and mechanical properties of the IR 3D printed dosage forms will also be discussed, together with the manufacturing process strategies. Up to now, methacrylic polymers, cellulosic polymers, vinyl derivatives, glycols and different polymeric blends have been explored to produce IR 3D printed dosage forms. Their effects on drug release profiles are critically discussed here, giving a complete overview to drive formulators towards a rational choice of polymeric material and thus contributing to future studies in 3D printing of pharmaceuticals.

Redispersible 3D printed nanomedicines: An original application of the semisolid extrusion technique.

Semisolid extrusion is a layer-by-layer 3D printing technique that produces objects from gels or pastes. This process can be carried out at room temperature, without using a light source, and has been explored in pharmaceutics in the last few years. In this regard, our group hypothesized its suitability for the production of three-dimensional (3D) printed nanomedicines containing drug-loaded organic nanocarriers. In this study, the original application of the semisolid extrusion was evaluated to produce redispersible 3D printed oral solid forms containing drug-loaded polymeric nanocapsules. A carboxymethyl cellulose hydrogel containing resveratrol and curcumin co-encapsulated in nanocapsules was prepared, and the nanocapsules did not change its complex viscosity and yield stress. Homogeneous and yellow cylindrical-shaped solid forms were printed, with a mean weight of 0.102 ± 0.015 g, a polyphenol content of approximately 160 µg/unit, disintegration time of <45 min, and recovery of the nanosized carriers. The polyphenols were completely released from the solid forms after 8 h, although part of them remained encapsulated in the nanocapsules. This study represents a proof of concept concerning the use of semisolid extrusion to produce 3D printed forms composed of polymeric nanocapsules in a one-step process. It proposes an original platform for the development of solid nanomedicines from liquid aqueous nanocapsule suspensions.

Drug-loaded mesoporous silica on carboxymethyl cellulose hydrogel: Development of innovative 3D printed hydrophilic films.

3D printing has been explored as an emerging technology for the development of versatile and printable materials for drug delivery. However, the alliance of 3D printing and nanomaterials has, to date, been little explored in pharmaceutics. Herein, a mesoporous silica with nanostructured pores, SBA-15, was used as a drug carrier for triamcinolone acetonide, a hydrophobic drug, with the aim of incorporating the drug formulation in a hydrophilic printable ink. The adsorption of the drug in the SBA-15 pores was confirmed by the decrease in its surface area and pore volume, along with an increase in the apparent aqueous solubility of triamcinolone acetonide, as shown by in vitro release studies. Thereafter, a hydrophilic ink composed of carboxymethyl cellulose containing drug-loaded SBA-15 was formulated and 3D printed as hydrophilic polymeric film using the semisolid extrusion technique (SSE). The 3D printed films showed complete drug release after 12 h, and the presence of the triamcinolone acetonide-loaded SBA-15 improved their in vitro mucoadhesion, suggesting their promising application in oral mucosa treatments. Besides representing an innovative platform to develop water-based mucoadhesive formulations containing a hydrophobic drug, this is the first report proposing the development of SSE 3D printed nanomedicines containing drug-loaded mesoporous silica.

Bioadhesive 3D-Printed Skin Drug Delivery Polymeric Films: From the Drug Loading in Mesoporous Silica to the Manufacturing Process.

The alliance between 3D printing and nanomaterials brings versatile properties to pharmaceuticals, but few studies have explored this approach in the development of skin delivery formulations. In this study, clobetasol propionate (CP) was loaded (about 25% w/w) in mesoporous silica nanomaterial (MSN) to formulate novel bioadhesive and hydrophilic skin delivery films composed of pectin (5% w/v) and carboxymethylcellulose (5% w/v) by 3D printing. As a hydrophobic model drug, CP was encapsulated in MSN at a 3:1 (w/w) ratio, resulting in a decrease of CP crystallinity and an increase of its dissolution efficiency after 72 h (65.70 ± 6.52%) as compared to CP dispersion (40.79 ± 4.75%), explained by its partial change to an amorphous form. The CP-loaded MSN was incorporated in an innovative hydrophilic 3D-printable ink composed of carboxymethylcellulose and pectin (1:1, w/w), which showed high tensile strength (3.613 ± 0.38 N, a homogenous drug dose (0.48 ± 0.032 mg/g per film) and complete CP release after 10 h. Moreover, the presence of pectin in the ink increased the skin adhesion of the films (work of adhesion of 782 ± 105 mN·mm). Therefore, the alliance between MSN and the novel printable ink composed of carboxymethylcellulose and pectin represents a new platform for the production of 3D-printed bioadhesive films, opening a new era in the development of skin delivery systems.

3D-Printed Products for Topical Skin Applications: From Personalized Dressings to Drug Delivery.

3D printing has been widely used for the personalization of therapies and on-demand production of complex pharmaceutical forms. Recently, 3D printing has been explored as a tool for the development of topical dosage forms and wound dressings. Thus, this review aims to present advances related to the use of 3D printing for the development of pharmaceutical and biomedical products for topical skin applications, covering plain dressing and products for the delivery of active ingredients to the skin. Based on the data acquired, the important growth in the number of publications over the last years confirms its interest. The semisolid extrusion technique has been the most reported one, probably because it allows the use of a broad range of polymers, creating the most diverse therapeutic approaches. 3D printing has been an excellent field for customizing dressings, according to individual needs. Studies discussed here imply the use of metals, nanoparticles, drugs, natural compounds and proteins and peptides for the treatment of wound healing, acne, pain relief, and anti-wrinkle, among others. The confluence of 3D printing and topical applications has undeniable advantages, and we would like to encourage the research groups to explore this field to improve the patient's life quality, adherence and treatment efficacy.

Eudragit®: A Versatile Family of Polymers for Hot Melt Extrusion and 3D Printing Processes in Pharmaceutics.

Eudragit® polymers are polymethacrylates highly used in pharmaceutics for the development of modified drug delivery systems. They are widely known due to their versatility with regards to chemical composition, solubility, and swelling properties. Moreover, Eudragit polymers are thermoplastic, and their use has been boosted in some production processes, such as hot melt extrusion (HME) and fused deposition modelling 3D printing, among other 3D printing techniques. Therefore, this review covers the studies using Eudragit polymers in the development of drug delivery systems produced by HME and 3D printing techniques over the last 10 years. Eudragit E has been the most used among them, mostly to formulate immediate release systems or as a taste-masker agent. On the other hand, Eudragit RS and Eudragit L100-55 have mainly been used to produce controlled and delayed release systems, respectively. The use of Eudragit polymers in these processes has frequently been devoted to producing solid dispersions and/or to prepare filaments to be 3D printed in different dosage forms. In this review, we highlight the countless possibilities offered by Eudragit polymers in HME and 3D printing, whether alone or in blends, discussing their prominence in the development of innovative modified drug release systems.

Multiple variable effects in the customisation of fused deposition modelling 3D-printed medicines: A design of experiments (DoE) approach.

Fused deposition modelling (FDM) is the most explored three-dimensional (3D) printing technique in pharmaceutics. However, there is still a lack of knowledge about the factors influencing the properties of the printed forms. Here, the main and combined effects of the presence of a pore former (mannitol, 0% or 10%), the infill percentage (50% or 100%) and the drug percentage (5% or 10%) on the pharmaceutical properties of 3D-printed forms were evaluated by a design of experiments (DoE) approach. Poly(Ɛ-caprolactone) filaments were produced by hot-melt extrusion and dexamethasone was used as a hydrophobic model drug. The 23 factorial design afforded eight formulations printed at 105 °C. The drug content ranged from 9.87 to 25.59 mg/unit, depending on the drug and infill percentages. The drug release profiles followed the Higuchi model. The infill percentage modulated the drug release rate, whereas the pore former had a combined effect on this parameter, depending on the drug and infill percentage levels. According to the DoE data, besides the changes in the infill percentage, the addition of a pore former can also tailor the drug release rate from 3D-printed solid forms. These findings may assist the development of personalised tumour implants by 3D printing.

Spray-dried raloxifene submicron particles for pulmonary delivery: Development and in vivo pharmacokinetic evaluation in rats.

Raloxifene hydrochloride (RH) is a selective oestrogen receptor modulator used for the treatment of osteoporosis. Even though 60% of an oral dose is quickly absorbed via the gastrointestinal tract, the absolute bioavailability of RH is only 2-3% in humans due to extensive first-pass metabolism. Various approaches to improve RH bioavailability have been reported over the past few years; however, none have focused on the development of products for pulmonary administration. Therefore, in this study, submicron particles containing RH were produced for pulmonary administration with the aim to limit first-pass metabolism. Powders were produced by vibrational atomisation spray drying with a high process yield (>80%). The drug content was between 440 and 890 mg·g-1, and powders had a high encapsulation efficiency (>95%), mean particle size of 400-700 nm, low residual moisture (<2%) and spherical shape. These powders showed an improved drug dissolution rate compared to the raw RH material. Moreover, they presented high dose uniformity (95-100%), a high in vitro respirable fraction (>55%) and adequate mass median aerodynamic diameter for pulmonary delivery (<5 µm). The pharmacokinetic study in male Wistar rats demonstrated an absolute bioavailability of 47.20% after pulmonary administration of the particles. Therefore, these submicron-sized powders are promising for pulmonary RH delivery as a dry powder medicine.

Phenytoin-loaded lipid-core nanocapsules improve the technological properties and in vivo performance of fluidised bed granules.

Lipid-core nanocapsules (LNCs) were recently reported by our group as a suitable binder system to produce fluidised bed granules. However, there is still a lack of knowledge about the influence of using these nanocarriers loaded with a drug on the properties of the granules and their in vivo performance. Therefore, this study was designed to produce innovative fluidised bed granules containing phenytoin-loaded LNCs (LNCPHT) as a strategy to evaluate the influence of the presence of the drug-loaded nanocarriers on their in vitro and in vivo properties. Granules were produced using a mixture of maltodextrin and phenytoin (1:0.004 w/w) as substrate. They were prepared by fluid bed granulation using water or LNCPHT as the liquid binder, affording good yields (73-82%) of granules with low moisture content (<5%). Granules prepared with LNCPHT had larger mean size (122 µm) compared to maltodextrin primary particles (50 µm) due to the formation of solid bridges. Moreover, the use of LNCPHT as the liquid binder improved their powder flow properties. The nanocarriers were recovered after aqueous dispersion (3.00 mg.mL-1 of PHT) with a redispersibility close to 90%. After reconstitution in water, granules containing LNCPHT showed an improved dissolution behaviour compared to those prepared without them. In addition, they showed a higher mucoadhesive effect due to a combined effect of the LNCPHT and maltodextrin in the interactions with porcine intestinal mucosa. Regarding the in vivo studies, granules containing the combination of non-encapsulated PHT and PHT-loaded lipid-core nanocapsules increased the latency to seizures compared to placebo granules, showing effective anticonvulsant effect in mice. In conclusion, the use of drug-loaded nanocapsules as binder is an encouraging approach to produce fluidised bed mucoadhesive granules with improved technological properties and in vivo performance.

Liquid chromatography method to assay tretinoin in skin layers: validation and application in skin penetration/retention studies.

A liquid chromatography (LC) method for the quantification of tretinoin (TTN) in different matrices (adhesive tape, cotton and porcine skin layers, stratum corneum, viable epidermis, and dermis) was validated and applied in in vitro porcine skin penetration/retention studies. This study proposes, for the first time, a method for assaying TTN in separated porcine skin layers (stratum corneum, viable epidermis, and dermis). The skin studies were carried out using tape stripping and cutaneous retention techniques. The procedures for the extraction of TTN from dermatological formulations (creams and gels) and biological and non-biological matrices used with the tape stripping and retention techniques were also evaluated. The LC method consisted of a mobile phase composed of a mixture of methanol, water, and glacial acetic acid (85:15:1, v/v); a C18 column used as the stationary phase; a flow rate of 1.0 mL min-1; an injection volume of 100 µL; and TTN detection at 342 nm. The method was linear in the range of 0.05-15.00 µg mL-1 (r = 0.9999), and it was precise and accurate. The limit of detection (LOD) and limit of quantification (LOQ) were 0.0165 µg mL-1 and 0.0495 µg mL-1, respectively. TTN was extracted from different matrices, showing good precision [relative standard deviation (RSD) of <5%] and accuracy (89.4-113.9%). This method was successfully applied in the evaluation of TTN skin retention/permeation from dermatological formulations (cream and gel). A higher penetration of TTN through the skin was achieved with the gel rather than the cream, showing the influence of the dosage form. Therefore, the developed method can easily be applied in porcine skin penetration/retention studies of dermatological formulations containing TTN, and it is able to discriminate the behaviours of the different formulations.

Redispersible Spray-Dried Powder Containing Nanoencapsulated Curcumin: the Drying Process Does Not Affect Neuroprotection In vitro.

A redispersible spray-dried formulation containing curcumin-loaded, lipid-core nanocapsules (LNC-C) was developed for oral administration. The neuroprotective activity of curcumin after the spray-drying process was evaluated in vitro. The spray-dried powder (SD-LNC-C) was produced using a drying adjuvant composed of a blend of maltodextrin and L-leucine (90:10 w/w). Acceptable process yield (~ 70%) and drug content (6.5 ± 0.2 mg g-1) were obtained. SD-LNC-C was formed by smooth, spherical-shaped particles, and confocal Raman analysis indicated the distribution of the LNC-C on the surface of the leucine/maltodextrin agglomerates. The surface of the agglomerates was formed by a combination of LNC-C and adjuvants, and laser diffraction showed that SD-LNC-C had adequate aqueous redispersion, with no loss of controlled drug release behaviour of LNC-C. The in vitro curcumin activity against the lipopolysaccharide (LPS)-induced proinflammatory response in organotypic hippocampal slice cultures was evaluated. Both formulations (LNC-C and SD-LNC-C) reduced TNF-α to similar levels. Therefore, neuroprotection of curcumin in vitro may be improved by nanoencapsulation followed by spray-drying, with no loss of this superior performance. Hence, the redispersible spray-dried powder proposed here represents a suitable approach for the development of innovative nanomedicines containing curcumin for the prevention/treatment of neurodegenerative diseases.