Impact of grinding balls on the size reduction of Aprepitant in wet ball milling procedure.

One of the widely used approaches for improving the dissolution of poorly water-soluble drugs is particle size reduction. Ball milling is a mechanical, top-down technique used to reduce particle size. The effect of ball number, ball size, and milling speed on the properties of milled Aprepitant is evaluated. A full factorial design was employed to investigate the influence of affecting factors on particle size reduction. The initial suspension was made by suspending the drug in distilled water using excipients followed by milling in a planetary ball mill. Ball size, ball number, and milling speed modulated particle size distribution of Aprepitant. Increasing the number of balls from minimum to maximum for each ball size led to approximately a 28% reduction in mean particle size, a 37% decrease in D90%, and a 25% decrease in the ratio of volume mean particle diameter to numeric mean particle diameter. On average, using 10 mm balls instead of 30 mm balls reduced mean particle size by 1.689 µm. As a result, ball size, ball number, and milling speed are three effective factors in the process of ball milling. By increasing the ball number and decreasing the ball size, efficient micronization of drug particles takes place and the particle size is more uniform.

Formulation and optimization of a single-layer coat for targeting budesonide pellets to the descending Colon.

The current budesonide formulations are inadequate for addressing left-sided colitis, and patients might hesitate to use an enema for a prolonged time. This study focuses on developing a single-layer coating for budesonide pellets targeting the descending colon. Pellets containing budesonide (1.5%w/w), PVP K30 (5%w/w), lactose monohydrate (25%w/w) and Avicel pH 102 (68.5%w/w) were prepared using extrusion spheronization technique. Coating formulations were designed using response surface methodology with pH and time-dependent Eudragits. Dissolution tests were conducted at different pH levels (1.2, 6.5, 6.8, and 7.2). Optimal coating formulation, considering coating level and the Eudragit (S + L) ratio to the total coating weight, was determined. Budesonide pellets were coated with the optimized composition and subjected to continuous dissolution testing simulating the gastrointestinal tract. The coating, with 48% S, 12% L, and 40% RS at a 10% coating level, demonstrated superior budesonide delivery to the descending colon. Coated pellets had a spherical shape with a uniform 30 µm thickness coating, exhibiting pH and time-dependent release. Notably, zero-order release kinetics was observed for the last 9 h in colonic conditions. The study suggests that an optimized single-layer coating, incorporating pH and time-dependent polymers, holds promise for consistently delivering budesonide to the descending colon.

Development of a PVA/PCL/CS-Based Nanofibrous Membrane for Guided Tissue Regeneration and Controlled Delivery of Doxycycline Hydrochloride in Management of Periodontitis: In Vivo Evaluation in Rats.

Antibiotic administration is an adjacent therapy to guided tissue regeneration (GTR) in the management of periodontitis. This is due to the major role of pathogen biofilm in aggravating periodontal defects. This study aimed to fabricate a GTR membrane for sustained delivery of doxycycline hydrochloride (DOX) while having a space-maintaining function. The membranes were prepared using a polymeric blend of polycaprolactone/polyvinyl alcohol/chitosan by the electrospinning technique. The obtained membranes were characterized in terms of physicochemical and biological properties. Nanofibers showed a mean diameter in the submicron range of < 450 nm while having uniform randomly aligned morphology. The obtained membranes showed high strength and flexibility. A prolonged in vitro release profile during 68 h was observed for manufactured formulations. The prepared membranes showed a cell viability of > 70% at different DOX concentrations. The formulations possessed antimicrobial efficacy against common pathogens responsible for periodontitis. In vivo evaluation also showed prolonged release of DOX for 14 days. The histopathological evaluation confirmed the biocompatibility of the GTR membrane. In conclusion, the developed nanofibrous DOX-loaded GTR membranes may have beneficial characteristics in favour of both sustained antibiotic delivery and periodontal regeneration by space-maintaining function without causing any irritation and tissue damage.

The effect of anionic Eudragit polymers on drug supersaturation and in vitro permeation improvement.

OBJECTIVES: In the present study, Cinnarizine was selected as a weakly basic drug with poor aqueous solubility to investigate the supersaturation maintaining the ability of different types of anionic Eudragit polymers (Eudragits L100-55, L100 and S100). Furthermore, the interplay between polymer-mediated supersaturation maintenance and in vitro permeation enhancement was studied. METHODS: The effect of Eudragit polymers on the pH-induced supersaturation of Cinnarizine was examined under different pHs (6.4, 6.8, and 7.8). Moreover, the effect of Eudragit polymers on the permeation of Cinnarizine through the Caco-2 membrane was investigated. RESULTS: The aggregate size of Eudragit polymers in solution was determined and it was found that the size of polymer aggregate was bigger when lower pH or more hydrophobic polymer was used, which corresponded strongly with improved drug supersaturation. Based on the findings, hydrophobic Cinnarizine-polymer interactions seemed to be essential in determining the impact of Eudragit polymers on maintaining the Cinnarizine supersaturation. The permeation study demonstrated that the rate of drug permeation through the Caco-2 membrane increased in the presence of Eudragit polymers, but their effect on maintaining supersaturation was more significant than their effect on the drug permeation rate. Moreover, the highest level of Cinnarizine supersaturation observed in a non-permeation condition did not correlate with the optimal absorption in a permeation condition. CONCLUSION: This study revealed that the integration of permeation and supersaturation assays is needed to reliably predict the impact of supersaturation maintenance by polymers on the absorption of poorly soluble drugs.

Inhalation phage therapy as a new approach to preventing secondary bacterial pneumonia in patients with moderate to severe COVID-19: A double-blind clinical trial study.

Inhalation phage therapy is proposed as a replacement approach for antibiotics in the treatment of pulmonary bacterial infections. This study investigates phage therapy on bacterial pneumonia in patients with moderate to severe COVID-19 via the inhalation route. In this double-blind clinical trial, 60 patients with positive COVID-19 hospitalized in three central Mazandaran hospitals were chosen and randomly divided into two intervention and control groups. Standard country protocol drugs plus 10 mL of phage suspension every 12 h with a mesh nebulizer was prescribed for 7 days in the intervention group. The two groups were compared in terms of O2Sat, survival rate, severe secondary pulmonary bacterial infection and duration of hospitalization. Comparing the results between the intervention and control group, in terms of the trend of O2Sat change, negative sputum culture, no fever, no dyspnea, duration of hospitalization, duration of intubation and under ventilation, showed that the difference between these two groups was statistically different (P value < 0.05). In conclusion, inhalation phage therapy may have a potential effect on secondary infection and in the outcome of COVID-19 patients. However, more clinical trials with control confounding factors are needed to further support this concept.

Development of Sustained Release Formulations Based on Lipid-Liquid Crystal to Control the Release of Deoxycholate: In Vitro and In Vivo Assessment.

Subcutaneous injections of phosphatidylcholine (PC), sodium deoxycholate (NADC), and a mixture of them were found to be an effective option for treating cellulite. However, it is noteworthy that the injection of NADC may result in inflammation as well as necrosis in the injection area. The preparation of a sustained release formulation based on lipid-liquid crystal that controls the release of NADC could be a potential solution to address the issue of inflammation and necrosis at the site of injection. To present a practical and validated approach for accurately determining the concentration of NADC in LLC formulations, spectrofluorimetry was used based on the International Council for Harmonization (ICH) Q2 guidelines. Based on the validation results, the fluorometric technique has been confirmed as a reliable, efficient, and economical analytical method for quantifying NADC concentrations. The method demonstrated favorable attributes of linearity, precision, and accuracy, with an r2 value of 0.999. Furthermore, it exhibited excellent interday and intraday repeatability, with RSD values below 4%. The recovery percentages ranged from 97 to 100%, indicating the method's ability to accurately measure NADC concentrations. The subcutaneous injection of the LLC-NADC demonstrated a reduction in inflammation and tissue necrosis in skin tissue, along with an increase in fat lysis within 30 days, when compared to the administration of only NADC solution. Moreover, the histopathological assessment confirmed that the use of the LLC formulation did not result in any detrimental side effects for kidney or heart tissue.

Nanohybrid Based on (Mn, Zn) Ferrite Nanoparticles Functionalized With Chitosan and Sodium Alginate for Loading of Curcumin Against Human Breast Cancer Cells.

This study reports on the synthesis of Mn1 - xZnxFe2O4 (Mn, Zn ferrite) magnetic nanoparticles (MNPs) as drug delivery carriers for effective therapeutic outcomes. The MNPs were prepared using the coprecipitation method, and their magnetic properties were investigated based on their composition. Among the compositions tested, Mn0.8Zn0.2Fe2O4 MNPs exhibited superparamagnetic properties with a saturation magnetization moment of 34.6 emu/g at room temperature (25°C). To enhance the water solubility of curcumin (Cur), known for its hydrophobic nature, it was successfully loaded onto alginate (Alg)/chitosan (Chit)@Mn0.8Zn0.2Fe2O4 nanoparticles (NPs). The nanocomposite was characterized by field emission scanning electron microscopy (FE-SEM) which revealed a particle size of approximately 20 nm. The crystalline structure of the NPs was analyzed using X-ray diffraction, while Fourier-transform infrared (FTIR), energy-dispersive X-ray, and map analysis techniques were employed for further characterization. In terms of drug release, there was an initial burst release of Cur (around 18%) within the first hour, followed by a slower release (approximately 61%) over the next 36 h. The anti-tumor properties of the Cur-loaded NPs were evaluated using the Methyl Thiazol Tetrazolium (MTT) assay and quantitative real-time polymerase chain reaction. The MTT assay confirmed a higher cytotoxic effect of Cur-loaded Alg/Chit@Mn0.8Zn0.2Fe2O4 NPs on the MCF-7 breast cancer cell line compared to free Cur, highlighting the significance of incorporating Cur into nano-sized carrier systems.

Supercritical CO2 versus water as an antisolvent in the crystallization process to enhance dissolution rate of curcumin.

Antisolvent crystallization approach using either water (in conventional crystallization process (WAS)), or supercritical CO2 (in supercritical anti-solvent crystallization (SCAS)), was employed in presence of hydroxypropyl methylcellulose (HPMC) to enhance the dissolution of curcumin. The impact of pressure, temperature and depressurization time on the SCAS process was studied using the Box-Behnken design to achieve the highest saturation solubility. A physical mixture of curcumin-HPMC was prepared for comparison purposes. Saturation solubility, scanning electron microscopy, differential scanning calorimetry, X-ray diffraction analysis and Fourier transform infrared spectroscopy were conducted to characterize the solid-state characteristics of the crystallized samples. Dissolution studies helped in ascertaining the effects of the crystallization techniques on the performance of the formulation. Curcumin crystalized by different antisolvent displayed varied shapes, sizes, saturation solubility's and dissolution properties. In SCAS process, the maximum saturation solubility (2.83 µg/mL) was obtained when the pressure, temperature and depressurization time were 275 bars, 55 °C, and 22 min respectively. The SCAS samples showed the highest dissolution (70%) in 30 min compared to WAS (27%), physical mixture (18%) and unprocessed curcumin (16%). The improved dissolution rate of SCAS sample originates from the development of sponge-like particles with augmented porosity, decreased crystallinity as well as increased solubility of curcumin.

Loading Pistacia atlantica essential oil in solid lipid nanoparticles and its effect on apoptosis of breast cancer cell line MDA-MB-231.

Pistacia atlantica has an anti-cancer effect due to its essential oil which is the major constituent of P. atlantica. Unfortunately, this essential oil evaporates easily and makes it less effective. The current research, therefore, aimed to improve the anti-cancer effect of P. atlantica essential oil (PAEO) in solid lipid nanoparticles (SLN). The chemical components of PAEO were assessed by gas chromatography. PAEO-SLNs were prepared by the probe-ultrasonication method, and their particle size, polydispersity index and zeta potential were determined. Encapsulation Efficiency (EE%) and Loading Capacity (LC%) of formulations was also calculated. Transmission electron microscopy was employed to determine the morphology of optimal formulation (PAEO-SLN4). Furthermore, the anticancer effects of PAEO-SLN4 against MDA-MB-231 cells were evaluated by cellular assays. The results showed that the type of surfactant and loading of the essential oil had a significant effect on size distribution, zeta potential and the polydispersity index. The encapsulation efficiency (EE%) and loading capacity for PAEO-SLN4 were 97.3% and 9.6%, respectively. The cellular assay demonstrates that PAEO-SLN4 could lead MDA-MB-231 cells to apoptosis. The findings also revealed that PAEO-SLN4 can stimulate apoptosis in MDA-MB-231 cells more than the placebo and free PAEO thereby indicating PAEO-SLN4 to be beneficial in breast cancer treatment.

Solid lipid nanoparticles and nanostructured lipid carriers: a review of the methods of manufacture and routes of administration.

The bioavailability of drugs is dependent on several factors such as solubility and the administration route. A drug with poor aqueous solubility, therefore, poses challenges with regards to its pharmaceutical advance and ultimately its biological usage. Lipid nanoparticles have been used in pharmaceutical science due to their importance in green chemistry. Their biochemical properties as 'green' materials and biochemical processes as 'green' processes mean they can be environmentally sustainable. Generally, lipid nanoparticles can be employed as carriers for both lipophilic and hydrophilic drugs. The proposed administration route for nanoparticles can present advantages and disadvantages which should be considered by a formulator. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are attractive delivery systems because of their ease of manufacture, biocompatibility, biodegradability, and scale-up capacity of formulation constituents. The easy and simple scalability of novel SLNs and nano lipid carriers, along with their various processing procedures, recent developments, limitation and toxicity, formulation optimization and approaches for the manufacture of lipid nanoparticles, lyophilization and drug release are comprehensively discussed in this review. This review also summarizes the research data related to the various preparation methods and excipients used for SLNs and NLCs in recent years.

Evaluation of Manufacturer-to-Manufacturer Variability of Croscarmellose Sodium: Influence on the Dissolution of Sitagliptin Tablets (Water-Soluble Drug) and Escitalopram Tablets (Sparingly Soluble Drug).

The present study aimed to investigate if the manufacturer variability of croscarmellose sodium, a superdisintegrant, could have an impact on the dissolution of sitagliptin phosphate (a highly water-soluble drug) and escitalopram oxalate (a sparingly soluble drug) from their tablets. Some of the physicochemical properties of croscarmellose sodium (CCS) powders obtained from four different manufacturers were studied. Tablets containing 25 mg sitagliptin phosphate and 10 mg escitalopram oxalate were prepared, and the effects of the source and varying concentration of CCS (0, 1, 3, and 5%w/w) on the disintegration time and dissolution rate of the mentioned drugs were investigated. The results of the following tests: degree of substitution, residue on ignition, loss on drying, content of water-soluble material, and pH, carried out according to the USP/NF CCS monograph, were within the acceptance criteria for all four products. However, considerable differences were found in the swelling behavior of CCS samples, differentiating them into two groups of highly swelling and low-swelling products. The disintegration times of the tablets containing different quantities of the various CCS samples were similar, which confirms the indiscriminatory nature of this test. However, the highly swelling CCSs resulted in tablets with superior dissolution profiles. While with the highly water-soluble drug, increasing the concentration of low-swelling CCSs to 3 or 5% could improve the dissolution profiles; in the case of sparingly soluble drug, this was not possible. Therefore, functional differences between CCSs produced by various manufacturers are affected by the drug solubility and the ratio of the disintegrant used in the formulations.

An Insight into Eudragit S100 Preserving Mechanism of Cinnarizine Supersaturation.

Generally, supersaturation of weakly basic drug solution in the gastrointestinal tract can be followed by precipitation, and this can compromise the bioavailability of drugs. The purpose of this study was to evaluate the effect of Eudragit® S100 on the pH-induced supersaturation of cinnarizine and to examine the preserving mechanism of cinnarizine supersaturation by Eudragit®. Variables, including pH of media, ionic strength, and degree of supersaturation, were studied to investigate the effects of these parameters on cinnarizine supersaturation in the presence and absence of Eudragit®. The size of the Eudragit® aggregate in solution using dynamic light scattering was determined. The effect of Eudragit® on the transport of cinnarizine through the Caco-2 membrane was also investigated. The particle size study of Eudragit® aggregates showed that the size of these aggregates become large when the pH was lowered. Supersaturation experiments also demonstrated that Eudragit® preserved higher cinnarizine supersaturation with increasing ionic strength of the solution. The phase separation behavior of cinnarizine solution as a function of the degree of the supersaturation could be readily explained by considering the drug amorphous solubility. In vitro permeation studies revealed that the rate of cinnarizine permeation across Caco-2 cells increased in the presence of Eudragit®. According to the obtained results, the aggregation status of Eudragit® and nonspecific hydrophobic cinnarizine-Eudragit® interactions seemed to be essential in determining the effect of Eudragit® on cinnarizine supersaturation.

Atorvastatin Entrapped Noisome (Atrosome): Green Preparation Approach for Wound Healing.

The present study aimed to formulate atorvastatin niosome (Atrosome) through an ultrasonic technique and to determine its contribution to the extent of wound healing in an animal model. The optimized Atrosome formulation (Atrosome-2) was stable at 4 °C for 3 months. Differential scanning calorimetry (DSC), ATR-Fourier transform infrared spectroscopy (ATR-FTIR), and powder X-ray diffraction (PXRD) analysis revealed that atorvastatin (ATR) was well encapsulated within the niosomes either in a stabilized amorphous form or a molecularly dispersed state. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscope (AFM) confirmed the spherical nature of the Atrosomes. The optimized formulation showed polydispersity index, particle size, drug encapsulation efficiency (EE%), and zeta potential of 0.457 ± 0.05, 196.33 ± 6.45 nm, 86.15 ± 0.58 %, and - 20.73 ± 0.98 mV, respectively. ATR release from the Atrosome gel followed the first-order kinetic model and showed no cytotoxicity in the in vitro cytotoxicity test. Cell viability (human foreskin fibroblast cell line) was nearly 99%. An excision wound model was also applied in male Wistar rats to examine the in vivo efficacy of the optimized formulation, followed by investigating malondialdehyde (MDA, an end-product of lipid peroxidation), superoxide dismutase (SOD, an endogenous antioxidant), hydroxyproline levels, and glutathione peroxidase (GPx) in skin tissue samples. MDA significantly decreased in the Atrosome gel group after 21 days, while GPx, SOD, and hydroxyproline levels demonstrated an increase. According to histological results, rats receiving Atrosomes were treated effectively faster when compared to the other formulation used.

Venlafaxine HCl Encapsulated in Niosome: Green and Eco-friendly Formulation for the Management of Pain.

The goal of this experimentation was to increase the cutaneous absorption of venlafaxine HCl (VFX) encapsulated in a niosome (venlasosme) produced by an ultrasonic approach. The impact of the cholesterol:surfactant (Chol:Surf) proportion was examined to modify the venlasosme properties. Photon correlation spectroscopy, powder X-ray diffraction (PXRD), SEM, DSC, and ATR-FTIR spectroscopy were utilized to investigate the solid-state and morphology of VFX in the venlasosme. The studies revealed that increasing the level of Chol in the venlasosme increased the size of the particles. Alterations in the Chol to surfactant ratios (when Chol decreased from 2.5 to 0%) caused the zeta potential enhancement from 7.37 ± 0.67 to 15.53 ± 1.47 mV. The venlasosme with the highest cholesterol concentration (2.5%) had the highest encapsulation efficiency (approximately 63%). PXRD results revealed that VFX in venlasosme was in the amorphous form. The levels of VFX in the cutaneous layers and the receiver compartment were higher for the venlasosme gel than for VFX simple gel in the cutaneous permeability study and showed no cutaneous irritancy in rats. Furthermore, the venlasosme gel demonstrated significant antinociceptive and anti-inflammatory responses when compared to the control groups (VFX simple gel and diclofenac gel). The topical administration of the venlasosme gel also considerably increased the tail-flick and hot-plate response time when compared to the VFX simple gel, control groups, and diclofenac gel (p < 0.05). These findings suggest that niosomes can improve VFX efficacy as an antinociceptive and anti-inflammatory substance by improving the medicaments delivery to the specified site.

The effect of some acrylic polymers on dissolution of celecoxib solid dispersion formulations.

OBJECTIVE: The purpose of the present study was firstly to identify the effectiveness of Eudragit® polymers (Eudragit® RL, RS, L100-55, L100, S100 and E100) in inhibition of celecoxib precipitation from buffer solutions (pH = 6.8). Furthermore, the influence of Eudragit® polymers on non-sink dissolution behavior of celecoxib from solid dispersions was investigated. METHODS: Solid dispersions were prepared by the rotary evaporation method. In vitro dissolution studies, FT-IR and differential scanning calorimetry were employed to characterize the formulations. RESULTS: The results revealed that Eudragit® E100, L100 and S100 inhibited precipitation of celecoxib efficiently. It is understood that crystallization during the dissolution of solid dispersions could happen through crystallization from solid matrix following contact with the dissolution medium or from the supersaturated solution produced following dissolution. The supersaturated drug concentrations attained from the dissolution of Eudragit®-celecoxib solid dispersions were almost similar, suggesting that crystallization from solid matrix did not occur readily. However, only solid dispersions containing efficient crystallization inhibitor polymers were able to maintain the supersaturated solution up to the end of the dissolution run. CONCLUSION: Results revealed that the principal mechanism of attaining supersaturated solution of celecoxib from solid dispersions was related to crystallization inhibition from solution not from solid matrix.

Liqui-Tablet: the Innovative Oral Dosage Form Using the Newly Developed Liqui-Mass Technology.

In this study, an attempt was made to produce Liqui-Tablets for the first time. This was carried out through the compaction of naproxen Liqui-Pellets. The incentive to convert the novel Liqui-Pellet into Liqui-Tablet was due to the array of inherent advantages of the popular and preferred tablet dosage form. The study showed that naproxen Liqui-Tablet could be successfully produced and the rapid drug release rate (100% drug release ~ 20 min) could be achieved under pH 1.2, where naproxen is insoluble. It was observed that the different pH of the dissolution medium affected the trend of drug release from formulations with varying amounts of liquid vehicle. The order of the fastest drug-releasing formulations was different depending on the pH used. The presence of Neusilin US2 showed considerable enhancement in the drug release rate as well as improving Liqui-Tablet robustness and hardness. Furthermore, images from X-ray micro-tomography displayed a uniform distribution of components in the Liqui-Tablet. The accelerated stability studies showed acceptable stability in terms of dissolution profile.

Polyvinyl Alcohol/Chitosan Single-Layered and Polyvinyl Alcohol/Chitosan/Eudragit RL100 Multi-layered Electrospun Nanofibers as an Ocular Matrix for the Controlled Release of Ofloxacin: an In Vitro and In Vivo Evaluation.

A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0-96 for the nanofibers was 9-20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.

Solubility Study of Acetylsalicylic Acid in Ethanol + Water Mixtures: Measurement, Mathematical Modeling, and Stability Discussion.

Solubility determination of poorly water-soluble drugs is pivotal for formulation scientists when they want to develop a liquid formulation. Performing such a test with different ratios of cosolvents with water is time-consuming and costly. The scarcity of solubility data for poorly water-soluble drugs increases the importance of developing correlation and prediction equations for these mixtures. Therefore, the aim of the current research is to determine the solubility of acetylsalicylic acid in binary mixtures of ethanol+water at 25 and 37°C. Acetylsalicylic acid is non-stable in aqueous solutions and readily hydrolyze to salicylic acid. So, the solubility of acetylsalicylic acid is measured in ethanolic mixtures by HPLC to follow the concentration of produced salicylic acid as well. Moreover, the solubility of acetylsalicylic acid is modeled using different cosolvency equations. The measured solubility data were also predicted using PC-SAFT EOS model. DSC results ruled out any changes in the polymorphic form of acetylsalicylic acid after the solubility test, whereas XRPD results showed some changes in crystallinity of the precipitated acetylsalicylic acid after the solubility test. Fitting the solubility data to the different cosolvency models showed that the mean relative deviation percentage for the Jouyban-Acree model was less than 10.0% showing that this equation is able to obtain accurate solubility data for acetylsalicylic acid in mixtures of ethanol and water. Also, the predicted data with an average mean relative deviation percentage (MRD%) of less than 29.65% show the capability of the PC-SAFT model for predicting solubility data. A brief comparison of the solubilities of structurally related solutes to acetylsalicylic acid was also provided.

3D printing for enhanced drug delivery: current state-of-the-art and challenges.

Three-dimensional (3D) printing has recently appeared as one of the most promising additive manufacturing techniques to fabricate 3D objects, with uses spanning from engineering prototyping to medicines and cell-laden models for biomedical applications. Regardless of the type and underlying theory, 3D printing techniques involve the deposition of materials such as thermoplastic polymers or hydrogel in sequential layers one onto another to produce a 3D object. 3D printing has recently gained momentum in developing various drug delivery systems for pharmaceutical applications which is reflected by the exponential rise in the number of published papers and patents in recent years. Whilst the future of 3D printing techniques is bright, various obstacles need to be overcome before it can be applied practically in commercial-scale production. This review article discusses current approaches of altering drug delivery when manufacturing 3D printed dosage forms that vary in their drug release profiles and characteristics. Such achievements correspond to developing and delivering patient-specific treatments. With each type of 3D printing application, there are great benefits, and these are highlighted, however, a critical discussion will underline the limitations and challenges associated with 3D printing.

Self-assembled peptide nanoparticles for efficient delivery of methotrexate into cancer cells.

The low cellular uptake of Methotrexate (MTX), a commonly used anticancer drug, is a big challenge for efficient cancer therapy. Self-assembled peptide nanoparticles (SAPNs) are one of the major classes of peptide vectors that have gained much attention toward novel drug delivery systems. In the present study, different sequences of cell-penetrating peptides including R2W4R2 and W3R4W3 and their SAPNs (R2W4R2-E12 and W3R4W3-E12) were designed for efficient delivery of MTX into MCF7 breast cancer cells. Based on electron microscopy results, the obtained SAPNs were in nano scale with spherical shape. There was a positive relationship between the free energy of water to octanol transferring and cellular penetration of designed nanostructures. The R2W4R2 possessed proper free energy and ability to form a spherical structure and hydrophobic-hydrophobic interactions, therefore, exhibited more cellular penetration than W3R4W3. The cellular uptake of obtained nanoparticles was examined by flow cytometry and fluorescence microscopy, in which, R2W4R2 and R2W4R2-E12 showed more appropriate penetration into MCF7 cells than W3R4W3 and W3R4W3-E12. The cytotoxicity of MTX-loaded peptides and SAPNs was examined by MTT assay. As a result, at higher concentrations, the R2W4R2 and R2W4R2-E12 showed higher cytotoxic behavior than their counterparts. Despite their enhanced cellular internalization, the cytotoxic behavior of MTX-loaded SAPNs at lower concentrations was relatively less than free MTX, which could be ascribed to the gradual nature of drug detachment from these conjugates. Therefore, R2W4R2 could be considered as an efficient choice to enhance the therapeutic efficiency of MTX in cancer treatments.