Carrier-Free Inhalable Dry Microparticles of Celecoxib: Use of the Electrospraying Technique.

Upregulation of cyclooxygenase (COX-2) plays an important role in lung cancer pathogenesis. Celecoxib (CLX), a selective COX-2 inhibitor, may have beneficial effects in COVID-19-induced inflammatory storms. The current study aimed to develop carrier-free inhalable CLX microparticles by electrospraying as a dry powder formulation for inhalation (DPI). CLX microparticles were prepared through an electrospraying method using a suitable solvent mixture at two different drug concentrations. The obtained powders were characterized in terms of their morphology, solid state, dissolution behavior, and aerosolization performance. Electrosprayed particles obtained from the ethanol-acetone solvent mixture with a drug concentration of 3 % w/v exhibited the best in vitro aerosolization properties. The value of the fine particle fraction obtained for the engineered drug particles was 12-fold higher than that of the untreated CLX. When the concentration of CLX was increased, a remarkable reduction in FPF was obtained. The smallest median mass aerodynamic diameter was obtained from the electrosprayed CLX at a 3% concentration (2.82 µm) compared to 5% (3.25 µm) and untreated CLX (4.18 µm). DSC and FTIR experiments showed no change in drug crystallinity or structure of the prepared powders during the electrospraying process. The findings of this study suggest that electrospraying has potential applications in the preparation of DPI formulations.

Stability-Enhanced Ternary Solid Dispersions of Glyburide: Effect of Preparation Method on Physicochemical Properties.

Introduction: Limited aqueous solubility and subsequent poor absorption and low bioavailability are the main challenges in oral drug delivery. Solid dispersion is a widely used formulation strategy to overcome this problem. Despite their efficiency, drug crystallization tendency and poor physical stability limited their commercial use. To overcome this defect, ternary solid dispersions of glyburide: sodium lauryl sulfate (SLS) and polyethylene glycol 4000 (PEG), were developed using the fusion (F) and solvent evaporation (SE) techniques and subsequently evaluated and compared. Materials and Methods: Physicochemical and dissolution properties of the prepared ternary solid dispersions were evaluated using differential scanning calorimetry (DSC), infrared spectroscopy (FTIR), and dissolution test. Flow properties were also assessed using Carr's index and Hausner's ratio. The physical stability of the formulations was evaluated initially and after 12 months by comparing dissolution properties. Results: Formulations prepared by both methods similarly showed significant improvements in dissolution efficiency and mean dissolution time compared to the pure drug. However, formulations that were prepared by SE showed a greater dissolution rate during the initial phase of dissolution. Also, after a 12-month follow-up, no significant change was observed in the mentioned parameters. The results of the infrared spectroscopy indicated that there was no chemical interaction between the drug and the polymer. The absence of endotherms related to the pure drug from thermograms of the prepared formulations could be indicative of reduced crystallinity or the gradual dissolving of the drug in the molten polymer. Moreover, formulations prepared by the SE technique revealed superior flowability and compressibility in comparison with the pure drug and physical mixture (ANOVA, P < 0.05). Conclusion: Efficient ternary solid dispersions of glyburide were successfully prepared by F and SE methods. Solid dispersions prepared by SE, in addition to increasing the dissolution properties and the possibility of improving the bioavailability of the drug, showed acceptable long-term physical stability with remarkably improved flowability and compressibility features.

Solid-state characterization of ibuprofen-isonicotinamide cocrystals prepared by electrospraying and solvent evaporation.

Aim: Electrospraying (ELS) was used to prepare micronized ibuprofen-isonicotinamide cocrystal (IBU-INA-ELS) and its properties were compared with the solvent evaporated cocrystal (IBU-INA-SE). Methods: Solid-state characterization of crystalline phase, production yield, particle size, powder flow, wettability, solution mediated phase transformation (SMPT), and dissolution rate were measured. Results: The ELS produced phase pure particles of IBU-INA with a size of 1.46 µm and yield of 72.3%. This cocrystal improved the intrinsic dissolution rate and powder dissolution rate of IBU by 3.6- and 1.7-fold, respectively. Our experiments showed that the dissolution of IBU-INA was affected by particle size, solubility, SMPT and wettability. Conclusion: ELS produced micronized cocrystals for improving dissolution of ibuprofen with a high yield in a single step and mild conditions.

The intestinal absorption of ibuprofen is limited by low dissolution rate in the gastrointestinal fluids. This drug needs applied in an appropriate method to enhance its dissolution. One way to improve dissolution of ibuprofen is preparing micronized cocrystal of this drug and a water soluble compound, isonicotinamide. In this study, we prepared and characterized micronized particles of ibuprofen-isonicotinamide cocrystal by electrospraying, a single step and continuous method without need for any added material. Our experiments showed that the prepared micronized cocrystal could improve the dissolution of ibuprofen but the cocrystal is rapidly precipitated as ibuprofen crystals in contact with dissolution medium. This precipitation hampered the expected increase in dissolution. Therefore, solution mediated phase transformation should be considered in formulating micronized cocrystals.

Dissolution improvement of binary solid dispersions of erlotinib prepared by one-step electrospray method.

Erlotinib hydrochloride, a selective tyrosine kinase inhibitor approved for treatment of non-small cell lung cancer firstly. Erlotinib classified as class II drugs in the Biopharmaceutical Classification System (BCS), which characterized by low solubility and high permeability. The aim of this study was to enhance the dissolution rate of this drug. The binary solid dispersions of erlotinib: PVP prepared at different ratios (1:3, 1:5, and 1:8) by electrospray technique. The characterization of formulations performed using differential scanning calorimetery (DSC), Fourier transform infrared spectroscopy (FT-IR) and dissolution rate test. The dissolution results showed that the dissolution rate of erlotinib from binary solid dispersions improved in comparison to pure drug. FTIR spectrum results showed that all peaks of erlotinib functional groups are also observable in the prepared solid dispersions. The FTIR results demonstrated that there was no interaction between drug and polymer. DSC thermograms of the prepared solid dispersions showed no drug-related peak, which is probably related to reduced crystallinity and drug amorphization. Based on the obtained results, it can be concluded that the erlotinib solid dispersion systems displayed improved dissolution rate compared to the pure drug. This will likely lead to increased drug bioavailability.

Electrospun nanofibers as versatile platform in antimicrobial delivery: current state and perspectives.

Nanotechnology has attracted increasing interest in different aspects of biotechnology. The fabrication of electrospun nanofibers (NFs) containing antibacterial agents for antimicrobial applications has been significantly enhanced in recent years. In the current review, various electrospun NFs with antimicrobial properties were introduced and evaluated. The main focus was on the recent developments and applications of antimicrobial electrospun NFs incorporated with different antimicrobial agents, including metal nanoparticles (NPs), antibiotics, quaternized ammonium compounds, triclosan, herbal extracts, carbon nanomaterials, and antimicrobial biopolymers with inherent antimicrobial properties. The search results revealed that antimicrobial containing electrospun NFs had enhanced antimicrobial performance with various biomedical applications compared to the traditional antimicrobial materials. According to the reported results, most of the studies were of an investigative nature and were mostly based on in vitro tests. Hence, further examination on in vivo clinical performance of these antimicrobial NFs seems necessary. However, these antimicrobial NFs appear to have the potential to achieve clinical usefulness and commercial production in the near future.

Physicochemical characterization of atorvastatin calcium/ezetimibe amorphous nano-solid dispersions prepared by electrospraying method.

In the present study, electrospraying was applied as a novel method for the fabrication of amorphous nano-solid dispersions (N-SDs) of atorvastatin calcium (ATV), ezetimibe (EZT), and ATV/EZT combination as poorly water-soluble drugs. N-SDs were prepared using polyvinylpyrrolidone K30 as an amorphous carrier in 1:1 and 1:5 drug to polymer ratios and the total solid (including drug and polymer) concentrations of 10 and 20% (w/v). The prepared formulations were further investigated for their morphological, physicochemical, and dissolution properties. Scanning electron microscopy studies indicated that the morphology and diameter of the electrosprayed samples (ESs) were influenced by the solution concentration and drug:polymer ratio, so that an increase in the solution concentration resulted in fiber formation while an increase in the polymer ratio led to enhancement of the particle diameter. Differential scanning calorimetry and X-ray powder diffraction studies together with in vitro dissolution test revealed that the ESs were present in an amorphous form with improved dissolution properties. Infrared spectroscopic studies showed hydrogen-bonding interaction between the drug and polymer in ESs. Since the electrospraying method benefits from the both amorphization and nanosizing effect, this novel approach seems to be an efficient method for the fabrication of N-SDs of poorly water-soluble drugs.

Applications of electrospinning/electrospraying in drug delivery.

During recent years, nanoscaled materials have gained much attention because of their applications in the field of pharmaceutical and biomedical sciences. Electrospinning/electrospraying, as simple, effective and single-step methods, are used in the preparation of nanostructured materials (nanofibers and nanobeads). They offer an opportunity for direct encapsulation of the different types of drug molecules. The generated nanomaterials possess high surface area with porous characteristics, and the liberation of the loaded drugs follows a controlled-release pattern. Because of their wide applications in medical/pharmaceutical researches, the aim of this editorial is to highlight the importance of electrospinning/electrospraying technologies in drug delivery.

Evaluation of physicochemical properties and in vivo efficiency of atorvastatin calcium/ezetimibe solid dispersions.

Fixed-dose combination of atorvastatin calcium (ATV) and ezetimibe (EZT) provides a considerable advantage in the management of hyperlipidemia. However, both ATV and EZT suffer from the poor aqueous solubility, which can limit their oral bioavailability. The aim of the present study was to improve the in vitro performance and evaluate the in vivo efficiency of the improved (ATV/EZT) fixed-dose combination. The formulation was prepared through solid dispersion (SD)technique, using Polyvinylpyrrolidone K30 via solvent method. Solid-state analysis and the in vitro drug release of the prepared formulations were also assessed. In order to estimate the therapeutic efficiency of the prepared SDs, in vivo studies including measurement of serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were conducted. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) showed that the drugs crystallinity was notably decreased during the preparation process. All SDs showed enhanced release for both drugs compared to their binary mixture, drugs: polymer physical mixtures (PMs) and marketed product. Administration of ATV/EZT SD led to a remarkable decrease (P<0.05) in the serum levels of total cholesterol (TC) and LDL-C in the high fat diet-induced hyperlipidemic rats compared to the PM. Additionally, the histopathological examination of the liver tissue revealed the improved efficiency of the SDs on the liver steatosis. According to the obtained results, ATV/EZT SD with improved physicochemical characteristics, showed favorable effects on the serum lipid levels and liver steatosis.

Triamcinolone acetonide-Eudragit(®) RS100 nanofibers and nanobeads: Morphological and physicochemical characterization.

CONTEXT AND OBJECTIVE: The aim of the present research was to fabricate triamcinolone acetonide (TA)-Eudragit(®) RS100 nanostructures using the electrospraying method. MATERIALS AND METHODS: The physicochemical properties of the electrosprayed formulations as well as drug release patterns were assessed. The particle size and morphology were evaluated using scanning electron microscopy. X-ray crystallography and differential scanning calorimetry were also conducted to investigate the crystallinity and polymorphic alterations of the drug in the formulations. Probable chemical interactions between the drug and the carrier during the preparation process were analyzed using FT-IR spectroscopy. The drug release kinetic was also considered to predict the release mechanism. RESULTS AND DISCUSSION: Increasing the concentration of injected polymer solution resulted in the formation of more fibers and fewer beads, with the particle diameter ranging from 60 nm to a few micrometers based on the drug: polymer ratio. The drug crystallinity was notably decreased during the electrospraying process; however, no interaction between drug and polymer was detected. The electrosprayed formulations with 1:10 drug: polymer ratio showed an almost similar drug release rate compared to the pure drug, while those with 1:5 ratio revealed slower release profiles. The release data were best fitted to the Weibull model, so that the corresponding shape factor values of the Weibull model were less than 0.75, indicating the diffusion controlled release mechanism. CONCLUSION: Our findings revealed that TA loaded Eudragit(®) RS100 nanofibers and nanobeads were properly prepared by the electrospraying method, which is a simple, surfactant-free and cost effective technique for producing drug: polymer nanostructures.

Physicochemical characterization and pharmacological evaluation of ezetimibe-PVP K30 solid dispersions in hyperlipidemic rats.

The aim of this study was to improve the physicochemical properties as well as therapeutic efficacy of ezetimibe (EZT), through preparation of the solid dispersion (SD). SDs were formulated using polyvinylpyrrolidone K30 (PVP) via solvent method. The physicochemical properties along with in vitro drug release patterns of the prepared SDs were examined. To estimate the therapeutic efficiency of prepared SDs, in vivo studies including measurement of serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were performed. Differential scanning calorimetry (DSC) and powder X-ray diffractometery (PXRD) showed that the drug crystallinity was remarkably decreased during preparation process. Faster drug release pattern of SDs was proved by in vitro dissolution test. Administration the SD of EZT led to a significant decrease in serum total cholesterol (TC) and LDL-C level as well as liver index in hyperlipidemic rats (P<0.05) compared to the PM. Furthermore, histological analysis of the liver tissue confirmed the improved efficacy of the SDs on the liver steatosis. In the present study, we demonstrated that the SDs of EZT with improved physicochemical characteristics had favorable effects on liver steatosis, liver index and serum lipid levels in the high fat diet-induced hyperlipidemic rats.

Histopathological evaluation of caffeine-loaded solid lipid nanoparticles in efficient treatment of cellulite.

CONTEXT: Cellulite refers to dimpled appearance of the skin, usually located in the thighs and buttocks regions of most adult women. OBJECTIVE: The aim of this study was to formulate topically used caffeine-loaded solid lipid nanoparticle (SLN) for the treatment of cellulite. METHODS: SLNs were prepared by hot homogenization technique using Precirol® as lipid phase. The physical characterization and stability studies of SLNs as well as in vitro skin permeation and histological studies in rat skin were conducted. RESULTS: The mean particle size, encapsulation efficiency and loading efficiency percentages for optimized SLN formulation were 94 nm, 86 and 28%, respectively. In vitro drug release demonstrated that caffeine-loaded SLN incorporated into carbopol made hydrogel (caffeine-SLN-hydrogel) exhibited a sustained drug release compared to the caffeine hydrogel over 24 h. Caffeine-loaded SLNs showed a good stability during 12 months of storage at room temperature. The DSC and XRD results showed that caffeine was dispersed in SLN in an amorphous state. In vitro permeation studies illustrated higher drug accumulation in the skin with caffeine-SLN-hydrogel compared to caffeine hydrogel. The flux value of caffeine through rat skin in caffeine-SLN-hydrogel was 3.3 times less than caffeine hydrogel, representing lower systemic absorption. In contrast with caffeine hydrogel, the histological studies showed the complete lysis of adipocytes by administration of caffeine-SLN-hydrogel in the deeper skin layers. CONCLUSION: Results of this study indicated that SLNs are promising carrier for improvement of caffeine efficiency in the treatment of cellulite following topical application on the skin.

Application of electrospraying as a one-step method for the fabrication of triamcinolone acetonide-PLGA nanofibers and nanobeads.

The aim of the present project was to prepare triamcinolone acetonide nanofibers and nanobeads with prolonged anti-inflammatory activity. Triamcinolone acetonide-loaded PLGA nanoformulations were prepared by electrospraying method. The physicochemical and morphological properties of the fabricated nanoparticles were characterized as well. In vitro drug release of the prepared formulations was also studied. Differential scanning calorimetry and X-ray powder diffractometery showed that drug crystallinity was notably decreased during the electrospraying process. In vitro dissolution tests verified that the pure drug and physical mixtures had faster drug release pattern compared to the nanoformulations. Electrosprayed samples with the drug:polymer ratio of 1:10 revealed slower release profiles compared to those with a 1:5 ratio. Results obtained from SEM images of the prepared formulations indicated that polymer solution concentration was the critical parameter in the formation of fibers or beads; so that, fiber formation was increased proportionally with increasing polymer concentration. Moreover, the size of obtained nanostructures was also increased in order of polymer concentrations. As a final point, electrosprayed triamcinolone-loaded biodegradable micro/nanofibers and nanobeads with modified physicochemical characteristics and sustained drug release profiles were successfully prepared via simple, one-step and cost effective electrospraying technique.