Comparing inhaled colistin with inhaled fosfomycin/tobramycin as an adjunctive treatment for ventilator-associated pneumonia: An open-label randomized controlled trial.

PURPOSE: Although investigations are limited, adjunctive aerosolized antibiotics have been advised in the setting of gram-negative ventilator-associated pneumonia (VAP). This study aimed to compare the efficiency of inhaled colistin with inhaled fosfomycin/tobramycin in treating VAP due to extensively drug-resistant (XDR) Acinetobacter baumannii. METHODS: This single center open-label randomized controlled trial included 60 patients who developed XDR A. bumannii VAP. Eligible participants were randomly assigned to two groups (no. 30). Regardless of the assignment, all participants received meropenem (2 g as a 3-h extended infusion every 8 h) plus intravenous colistin (a loading dose of 9 million IU and then 4.5 million IU every 12 h). The control group was given inhaled colistin (1 million IU every 8 h), and the case group received inhaled tobramycin/fosfomycin (300 mg every 12 h/80 mg every 12 h) as adjunctive therapy. The primary outcome was treatment duration, and the secondary outcomes were Clinical Pulmonary Infection Score (CPIS) trend and mortality rate in the groups. The decision to stop treatment was made by the treating physician. RESULTS: The mean treatment duration was 13.73 ± 3.22 days in the colistin group and 10.85 ± 2.84 days in the tobramycin/fosfomycin group; the mean treatment duration in the latter group was lower significantly (P = 0.001). CPIS was decreased in the groups significantly (P < 0.001), but the mean changes of CPIS were significantly different between the groups, and in the inhaled tobramycin/fosfomycin group, a greater reduction (P = 0.005) was observed. Two (6.67%) patients in the control group and three (10%) patients in the case group died. CONCLUSION: The use of inhaled tobramycin/fosfomycin in cases with XDR A. bumannii VAP was associated with a shorter treatment duration in this open-label trial.

Effect of motor skills development on psychological and social traits of students of mazandaran province during the covid-19 pandemics.

Nowadays, the covid 19 pandemics are challenging all students. The present study aimed to investigate whether motor skill development affects students' psychological and social traits during the covid 19 pandemics. The present study's population consisted of all students aged 9-17 years in the three grades of the elementary, middle, and high school in Mazandaran province in the academic year 2020-2021, which corresponded to approximately 534 thousand students. We used a simple random sampling to determine the sample size because Iranian schools were closed. In this study, we selected 15 individuals for each of the experimental and control groups. Due to some students dropping out or leaving the practice, the samples comprised 42 girls and 45 boys in the control group and 41 girls and 43 boys in the experimental group. To collect data, we used the Standard Student Social Skills Questionnaire by Garsham and Elliott (1990), Cooper-Smith Self-Esteem Questionnaire, and Children's Depression Scale Short Form (CDS-A). We conducted the experimental group for 36 sessions, i.e., three months and three sessions per week, and each session lasted 30-45 min, depending on the quarantine conditions on the 19th day. To analyze the data, we used a two-way analysis of variance and the Scheffe post hoc test. The results showed that all groups had lower scores in psychological traits than those in the pretest. However, no significant difference was found between groups (P. < 0.05), and this effect was not significant in social traits (05/0 < P.). We also suggest that school principals and health care professionals use this study to design guidelines for creating a healthy environment and developing health-oriented educational programs to improve students' quality of life and health.

Comparison of eating disorders symptoms and body image between individual and team sport adolescent athletes during the COVID-19 pandemic.

BACKGROUND: COVID-19 has significantly disrupted the routines of school sports for adolescent athletes, which can affect their usual eating behaviors and body image. Specific pressures of individual sports (which tend to emphasize "leanness" as a means to improving performance), versus team sports (which tend to not require "leanness" for an athlete to be competitive), may further increase the risk of disordered eating (DE), eating disorders (ED), and distorted body image. An additional factor to consider is the gender of the athletes, with participation in "lean" sports associated with increased DE and body dissatisfaction for male, but not female, athletes. METHODS: Participants of the study included 124 Iranian male adolescent athletes residing in Mazandaran province (one of the most affected areas of Iran during COVID-19), who played in 1 of 6 sports (3 individual, 3 team). ED symptoms were assessed by the Eating Attitudes Test-26 (EAT-26), and body image was assessed by the Body-Esteem Scale for Adolescents and Adults (BESAA). RESULTS: The individual athlete group (n = 62) had significantly higher EAT-26 subscale scores for Bulimia and Food Preoccupation (p = 0.019), as well as significantly higher BESAA subscale scores for Appearance (p = 0.001), Weight (p = 0.001), and Attribution (p = 0.001), compared to the team athlete group (n = 62). However, there were no significant differences between the two athlete groups on the EAT-26 Dieting and Oral Control subscales. CONCLUSIONS: COVID-19 presents specialized issues for adolescent athletes, particularly those at risk for, or experiencing, DE, ED, and distorted body image. While individual athletes had significantly higher scores than team athletes on most subscales, there were no differences between groups on subscales of dieting and oral control. Overall, the findings highlight the need for sport psychologists, coaches, and other sports professionals working with male adolescent athletes (individual and team) to monitor DE, ED, and distorted body image during COVID-19, in order to provide early intervention, and mitigate the risk of long-term consequences. COVID-19 has significantly disrupted the routines of school sports for adolescent athletes, which can affect their usual eating behaviors and body image. Specific pressures of individual sports (which tend to emphasize "leanness" as a means to improving performance), versus team sports (which tend to not require "leanness" for an athlete to be competitive), may further increase the risk of disordered eating (DE), eating disorders (ED), and distorted body image. An additional factor to consider is the gender of the athletes, with participation in "lean" sports associated with increased DE and body dissatisfaction for male, but not female, athletes. Participants of the study included 124 Iranian male adolescent athletes in Mazandaran province (one of the most affected areas of Iran during COVID-19), who played in 1 of 6 sports (3 individual, 3 team). The individual athlete group (62 participants) had significantly higher scores on measures of ED (Bulimia, Food Preoccupation), and body image (Appearance, Weight, Attribution), versus the team athlete group (62 participants). However, there were no significant differences between groups on other measures of ED (Dieting, Oral Control). Findings highlight the need for sport professionals working with adolescent athletes to monitor DE and body image during COVID-19 for early intervention.

Behavioral activation / inhibition systems and lifestyle as predictors of mental disorders in adolescent athletes during Covid19 pandemic.

BACKGROUND: The following study investigates the correlational relationship between behavioral activation/inhibition systems, lifestyle and mental disorders in Adolescent Athletes during the Covid-19 pandemic. METHODS: Research methods are descriptive and correlational; "Of the eligible participants who were available during a COVID-19 quarantine period from June through August 2020 (N = 180), the Krejcie and Morgan Sampling Method was used to simplify the process of determining the sample size for a finite population [46], resulting in a calculation of N = 130 sample participants. to respond to Carver & White's Behavioral activation/inhibition systems Scale (BIS/BAS), Mille's Lifestyle Questionnaire and Goldberg & Williams's General Health Questionnaire (GHQ-12). Data was analyzed using linear regression analysis and Pearson's correlation coefficient. RESULTS: Findings showed a positive correlation of statistical significance between behavioral inhibition systems (BIS) and mental disorders in Adolescent Athletes at the 0.01 level and a negative correlation of statistical significance between scaling components of the behavioral activation systems (BAS), lifestyle and mental disorders in Adolescent Athletes at the 0.05 level. CONCLUSIONS: Analyzing the data, it can thus be concluded that whilst behavioral inhibition and activation systems seem to work together to significantly predict mental disorders, lifestyle cannot.

The Effect of Plantago major Hydroalcoholic Extract on the Healing of Diabetic Foot and Pressure Ulcers: A Randomized Open-Label Controlled Clinical Trial.

Aims: Diabetic foot ulcer (DFU) and pressure ulcer (PU) both are common types of ulcers worldwide. The wound healing effect of Plantago major leaves has been shown in a few animal studies. This study aimed to evaluate the clinical efficacy of P. major hydroalcoholic extract on DFU and PU healing. Methods: In this clinical trial, patients with DFU or PU who met the inclusion criteria were randomly assigned to drug (P. major) or control groups. For patients in the drug group, Plantago extract 10% topical gel was applied on the wound once daily concurrent with dressing and routine wound care for two weeks, while for the control group, an appropriate novel dressing was used along with routine wound care for the same duration. The percentage of wound size reduction at the end of the seventh and 14th days of intervention was recorded and compared between the groups. Results: Fifty and 44 patients in drug and control groups, respectively, completed the interventions. Plantago extract gel significantly resulted in more reduction in the wound size compared to control at the end of the first (64.90 ± 29.75% vs. 33.11 ± 26.55%; P < 0.001) and second week (86.85 ± 24.34% vs. 52.87 ± 32.41%; P < 0.001). Furthermore, the number of patients with complete wound healing in the drug group (n = 32, 64%) was significantly more than the control group (n = 9, 20.45%; OR: 3.129, 95% CI: 1.685-5.809, P < 0.001). Conclusion: The use of 10% topical gel of P. major leaf extract results in the acceleration of DFU and PU healing. Key points: Application of P. major topical gel results in the acceleration of diabetic foot ulcer and pressure ulcer healing. - P. major extract helps reducing the wound's erythema.- P. major leaf extract assists decreasing the wound size.- The number of patients completing wound healing process is higher among whom undergoing P. major dressing.

The Effects of Berberis integerrima Fruit Extract on Glycemic Control Parameters in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Clinical Trial.

BACKGROUND: Berberis integerrima Bunge fruits have been utilized in traditional medicine to control diabetes mellitus (DM). However, no clinical survey has been done in this regard. This study was conducted to clinically evaluate the effects of fruit extract of this plant in improving glycemic control indices in patients with type 2 DM (T2DM). METHODS: In a randomized controlled clinical trial, patients with T2DM who met the inclusion criteria were randomly divided into two groups of drug (Berberis) and control to receive the extract solution 5 ml twice daily (equivalent to 1000 mg of dry extract) with standard treatment (metformin) or only standard treatment, respectively, for 8 weeks. Before and after the intervention, fasting blood sugar (FBS), serum glycosylated hemoglobin (HbA1c), serum insulin, the homeostasis assessment model for insulin resistance (HOMA-IR), body mass index (BMI), and systolic and diastolic blood pressure were determined and compared between the two groups. RESULTS: During the study, 30 and 35 patients in the drug and control groups, respectively, completed the study. Although no significant changes occurred in any parameter within each group, postintervention FBS (117.5 [107-128.8] versus 134 [120-142], P = 0.001) and HbA1c (7 [6.4-7.7] versus 7.5 [6.8-7.9], P = 0.045) were significantly lower in the drug group than in the control one. In terms of other parameters, there were no significant differences between the groups. CONCLUSION: Consumption of B. integerrima Bunge fruit extract at a dosage of 1000 mg daily decreases FBS and HbA1c but does not affect HOMA-IR in patients with type 2 diabetes mellitus.

Curcumin nanoparticles containing poloxamer or soluplus tailored by high pressure homogenization using antisolvent crystallization.

Curcumin is a natural active constituent of Curcuma longa from Zingiberaceae family that shows many different pharmacological effects such as anticancer, antioxidant, anti-inflammatory, antimicrobial and antiviral effect. However, its bioavailability is profoundly limited by its poor water solubility. In this study antisolvent crystallization followed by freeze drying was used for the preparation of curcumin nanoparticles. The presence of different ratios of hydrophilic polymers (poloxamer 188 & soluplus) on physicochemical properties of curcumin nanoparticles was also investigated. In addition, the effect of high pressure homogenization (HPH) on solubility and dissolution properties of curcumin was investigated. All nanoparticle formulations were examined to determine their particle size distribution, saturation solubility, morphology (SEM), solid state (DSC, XRPD and FT-IR) and dissolution behavior. It was observed that curcumin crystallized in the presence of polymers exhibited better solubility and dissolution rate in comparison with original curcumin. The results showed that the concentration of the stabilizer and the method used to prepare nanoparticles can control the dissolution of curcumin. The crystallized nanoparticles showed polymorph 2 curcumin with lower crystallinity and higher dissolution rate. Curcumin nanoparticles containing 50% soluplus prepared via HPH method presented 16-fold higher solubility than its original form. In conclusion, samples crystalized and proceed with HPH technique showed smaller particle size, better re-dispersibility, higher solubility and dissolution rate in water compared with a sample prepared using a simple antisolvent crystallization process.

Effect of high pressure homogenization on physicochemical properties of curcumin nanoparticles prepared by antisolvent crystallization using HPMC or PVP.

Dissolution enhancement of poorly water soluble drugs is a major challenge in pharmaceutical industry. The aim of this study is to fabricate curcumin nanoparticles by antisolvent crystallization in the presence of PVP-K30 or HPMC with various concentrations as a stabilizer. The effect of high pressure homogenization on properties of curcumin particles is also investigated in this study. The antisolvent crystallization method followed by freeze drying (CRS-FD) and also antisolvent crystallization and high pressure homogenization followed by freeze drying (HPH-FD) were employed to modify curcumin particles. Physical mixtures of the drug and additives were also prepared for comparison purposes. The solid state analysis (DSC, XRPD and FT-IR studies), particle size measurement, morphological analysis, saturation solubility and dissolution behavior of the samples were investigated. The curcumin crystallized without using stabilizer produced polymorph 2 curcumin with lower crystallinity and higher solubility. The samples obtained in the presence of stabilizers showed higher solubility compared to its physical mixtures counterpart. It was found that the stabilizers used in the current study were capable of inhibiting the crystal growth of particles during crystallization. High pressure homogenizer method generated smaller particles compared to those samples that were not subjected to high pressure homogenizer (for example, 2748 nm for 5% PVP CRS-FD sample and 706 nm for 5% PVP HPH-FD sample). Particles obtained via HPH showed better solubility and dissolution rate compared to those samples that HPH was not employed (for example, the saturated solubility of 25% PVP CRS-FD sample was near 2 µg/ml while this amount was approximately 4.3 µg/ml for 25% HPH-FD sample. The effect of high pressure homogenization on dissolution rate is more pronounced for samples with lower stabilizer ratio. The samples prepared with high pressure homogenizer using 50% PVP showed 25-fold higher solubility compared to untreated curcumin. Generally, it can be concluded that the method of preparation, selection of suitable stabilizer and concentration of stabilizer play a critical role on particle size and dissolution rate of curcumin.

Design, Optimization and Evaluation of Orally Disintegrating Tablet of Meloxicam Using Its Menthol Based Solid Dispersions.

BACKGROUND: Meloxicam (MLX) is classified as NSAID that is used for the treatment of rheumatoid arthritis and osteoarthritis. Poor water solubility of MLX leads to its slow oral absorption and slow onset. Preparation of solid dispersion (SD) could improve the water solubility of poorly water soluble drugs. It has been demonstrated that orally disintegrating tablets (ODTs) show faster onset of action and could be more appropriate for the treatment of acute pain. METHOD: The purpose of this study is to improve the solubility of MLX through the preparation of its SD and then decrease the onset of action by preparation of ODTs from prepared SD. MLX SDs were prepared by solvent evaporation method. MLX, polyvinylpyrrolidone k30 (PVP k30), crospovidone and sodium lauryl sulfate (SLS) with different ratios were dispersed in molten menthol as solvent. Menthol was separated by freeze drying. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis approved amorphous form of MLX in SDs. RESULT: The optimum SD with highest saturation solubility in water (12.60±1.2 microgram/ml) which consists of MLX, PVP, crospovidone and SLS in a ratio of 1:1:1:0.03 was used for the preparation of MLX ODTs. ODTs were prepared by direct compression method and optimized by 23 factorial design. The effect of the superdisintegrant concentration, mannitol/avicel ratio and the level of compression force was evaluated on the disintegration time, hardness and percent of dissolved MLX after 30 min of prepared MLX ODTs. The optimized ODT formulation contained 10% superdisintegrant, mannitol and avicel a ratio of 2:1 compressed using a high level of compression force. CONCLUSION: Optimized ODT showed hardness (48±4.3 N) and friability (0.81±0.07%). This formulation provided rapid disintegration in 19±2 seconds of which 77.8±5.1% of drug was released within 30 minutes. The present study demonstrated an effective method for the preparation of suitable dosage form of MLX with improved solubility and onset of action.

Anomalous dissolution behavior of celecoxib in PVP/Isomalt solid dispersions prepared using spray drier.

Celecoxib is a COX II inhibitor NSAID which is used for joint pains, rheumatoid arthritis and osteoarthritis, however due to its poor water solubility it shows very low oral bioavailability. Using solid dispersion formulations is one of the most promising strategies to increase solubility of poorly water soluble drugs. The purpose of this study is dissolution enhancement of celecoxib by preparation of solid dispersions via spray drying technique using PVP and Isomalt as hydrophilic carriers. Different ratios of celecoxib, Isomalt and PVP K30 (7:3:0, 5:5:0, 3:7:0, 1:9:0 and 3:5:2, 3:2:5) were prepared from 2% hydroalcoholic solutions (70:30 ethanol:water) using spray drier. Particle size analyzing, saturation solubility, SEM, DSC, FT-IR, XRPD and dissolution studies in 0.25% SDS and 0.04M Na3HPO4 mediums were performed. Stability of samples was also studied after a week and a month storage at 75% humidity condition. The results showed that the saturation solubility of celecoxib in solid dispersion samples is 20-30 folds higher than raw celecoxib. Similar results have been shown for dissolution studies. Solid state analyses showed glass solution state of celecoxib in PVP/Isomalt matrixes. FTIR studies exhibited the formation of hydrogen bonding between celecoxib and PVP in these samples. Spray dried celecoxib (amorphous celecoxib) without usage of carrier showed lower dissolution rate compare to its crystalline state (in 0.25% SDS dissolution medium) whilst these results is vise versa in Na3PO4 dissolution medium. Interestingly almost all samples exhibited higher dissolution rate (in 0.25% SDS) after storage in 75% humidity. XRPD analysis demonstrated the crystallization of amorphous celecoxib after 1month storage. In general using PVP K30 and Isomalt as hydrophilic carriers could increase solubility and dissolution rate of celecoxib in solid dispersion formulations.

Preparation and physicochemical characterization of meloxicam orally fast disintegration tablet using its solid dispersion

ABSTRACT Meloxicam (MLX) is a non-steroidal, anti-inflammatory drug that is prescribed in the treatment of rheumatoid arthritis and osteoarthritis. MLX is practically insoluble in water and exhibits a slow onset of action. In this study, MLX solid dispersions (MLX SDs) were prepared to improve the water solubility of this poorly water-soluble drug. Then orally disintegrating tablets (ODT) of MLX were developed using MLX SD to decrease the onset of action of this drug. MLX, poloxamer 188, and crospovidone of different ratios were melted in molten poloxamer 188 as a hydrophilic carrier. The optimum SD with the highest saturation solubility in water (13.09±0.34 microgram/mL) consisting of MLX: poloxamer 188: crospovidone in the ratio of 1:2:0 was used for the preparation of MLX ODTs. MLX ODTs were prepared by the direct compression method and optimized by the 23 factorial design. The effect of the superdisintegrant concentration, the mannitol-avicel ratio, and the level of compression force on the disintegration time, hardness, and percent of dissolved MLX from MLX ODTs after 30 min was evaluated. DSC and XRD analysis approved an amorphous form of MLX in SDs. The optimized ODT formulation containing 10% of superdisintegrant, and mannitol and avicel in the ratio of 4:1 respectively was compressed using a high level of compression force. The optimized ODT showed hardness (34.37±2.1 N) and friability (1.26±0.04%). This formulation showed a rapid disintegration in 12.66±2.5 seconds, which 82.66±5.1% of the MLX released within 30 min. MLX ODTs, prepared from MLX SD, could be introduced as a suitable dosage form of MLX with improved solubility and the onset of action.

Antisolvent precipitation technique: A very promising approach to crystallize curcumin in presence of polyvinyl pyrrolidon for solubility and dissolution enhancement.

Curcumin with a vast number of pharmacological activities is a poorly water soluble drug which its oral bioavailability is profoundly limited by its dissolution or solubility in GI tract. Curcumin could be a good anticancer drug if its solubility could be increased. Therefore, the aim of the present study was to increase the dissolution rate of curcumin by employing antisolvent crystallization technique and to investigate the effect of polyvinyl pyrrolidone K30 (PVP) as colloidal particles in crystallization medium on resultant particles. Curcumin was crystalized in the presence of different amounts of PVP by antisolvent crystallization method and their physical mixtures were prepared for comparison purposes. The samples were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FT-IR). The solubility and dissolution of the treated and untreated curcumin were also determined. Antisolvent crystallization of curcumin led to the formation of particles with no definite geometric shape. It was interesting to note that the DSC and XRPD studies indicated the formation of a new polymorph and less crystallinity for particles crystallized in the absence of PVP. However, the crystallized curcumin in the presence of PVP was completely amorphous. All crystalized curcumin samples showed much higher dissolution rate compared to untreated curcumin. The amount of curcumin dissolved within 10 for treated curcumin in the presence of PVP (1:1 curcumin:PVP) was 7 times higher than untreated curcumin and this enhancement in the dissolution for curcumin samples crystallized in the absence of PVP was around 5 times. Overall' the results of this study showed that antisolvent crystallization method in the absence or presence of small amounts of PVP is very efficient in increasing the dissolution rate of curcumin to achieve better efficiency for curcumin.

Preparation and characterization of celecoxib dispersions in soluplus(®): comparison of spray drying and conventional methods.

The present study deals with characterization of dispersions of a poorly water-soluble drug, celecoxib (CLX) in polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus(®) (SOL)) prepared by different techniques. Dispersions of CLX in SOL at different ratios (2:1, 1:1, 1:2, 1:4 and 1:6) were prepared by spray drying, conventional solvent evaporation and melting methods. The solid states of samples were characterized using particle size measurements, optical and scanning electron microscopy, XRPD, DSC and FT-IR. The Gordon-Taylor equation was used to predict the Tg of samples and the possibility of interaction between CLX and SOL. The solubility and dissolution rate of all samples were determined. Stability of samples was studied at ambient conditions for a period of 12 months. DSC and XRPD analyses confirmed amorphous state of drug in samples. Surprisingly dispersions of CLX:SOL with the ratio of 2:1 and 1:1 showed slower dissolution rate than CLX while other samples showed higher dissolution rate. At 1:2 ratio the spray dried samples exhibited higher dissolution rate than corresponding samples prepared by other methods. However at higher SOL content (1:4 and 1:6), samples prepared by different methods showed similar dissolution profiles. The stability studies showed that there were no remarkable changes in the dissolution profiles and solid state of the drug after 12 months storage at ambient conditions. It was concluded that SOL was a proper carrier to enhance the dissolution rate of CLX. At high SOL ratios the method of preparation of dispersed samples had no effect on dissolution rate, whilst at low SOL content spray drying was more efficient method.

Promising dissolution enhancement effect of soluplus on crystallized celecoxib obtained through antisolvent precipitation and high pressure homogenization techniques.

Poor solubility and dissolution of hydrophobic drugs have become a major challenge in pharmaceutical development. Drug nanoparticles have been widely accepted to overcome this problem. The aim of this study was to manufacture celecoxib nanoparticles using antisolvent precipitation and high pressure homogenization techniques in the presence of varying concentrations of soluplus(®) as a hydrophilic stabilizer. Antisolvent crystallization followed by freeze drying (CRS-FD) and antisolvent crystallization followed by high pressure homogenization and freeze drying (HPH-FD) were used to obtain celecoxib nanoparticles. The obtained nanoparticles were analyzed in terms of particle size, saturation solubility, morphology (optical and scanning electron microscopy), solid state (DSC, XRPD and FT-IR) and dissolution behavior. The results showed that celecoxib nanoparticle can be obtained when soluplus was added to the crystallization medium. In addition, the results showed that the concentration of soluplus and the method used to prepare nanoparticles can control the size and dissolution of celecoxib. Samples obtained in the presence of 5% soluplus through HPH technique showed an excellent dissolution (90%) within 4min. It is interesting to note that celecoxib samples with high crystallinity showed better dissolution than those celecoxib samples with high amorphous content, although they had the same concentration of soluplus. DSC and XRPD proved that samples obtained via HPH technique are more crystalline than the samples obtained through only antisolvent crystallization technique.

Preparation and characterization of celecoxib solid dispersions; comparison of poloxamer-188 and PVP-K30 as carriers.

OBJECTIVES: Solid dispersion formulation is the most promising strategy to improve oral bioavailability of poorly water soluble drugs. The aim of this study was to compare the effect of polyvinylpyrrolidone K30 (PVP) and poloxamer-188 (PLX) as carrier in solid dispersion formulations of celecoxib (CLX). MATERIALS AND METHODS: Solid dispersions of CLX:PVP or CLX:PLX were prepared at different ratios (2:1, 1:1, 1:2, 1:4, 1:6) by solvent evaporation and melting methods, respectively. The characterization of samples was performed using differential scanning calorimetery (DSC), X-Ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FT-IR). The Gordon-Taylor equation was used to estimate the Tg of solid dispersion systems and the possibility of the interaction between CLX and PVP. Also, the dissolution rate of all samples was determined. RESULTS: DSC and XRPD analyses confirmed the presence of amorphous state of drug in solid dispersion systems. FT-IR studies showed CLX could participate in hydrogen bonding with PVP whilst no specific interaction between CLX and PLX was observed. Both PVP and PLX enhanced the dissolution rate of drug in solid dispersion samples. The dissolution rate was dependent on the ratio of drug: carrier. Interestingly, the solid dispersion samples of PLX at 2:1 and 1:1 drug: carrier showed slower dissolution rate than pure CLX, whilst these results were not observed for PVP. CONCLUSION: The effect of PVP on dissolution rate enhancement was more pronounced compared to the other carrier. Having a higher Tg and more effect on dissolution rate, PVP could be considered as a more suitable carrier compared to PLX in solid dispersion formulation of CLX.

Comparing various techniques to produce micro/nanoparticles for enhancing the dissolution of celecoxib containing PVP.

One of the major challenges in pharmaceutical development is the poor dissolution performance of drugs. Celecoxib (CLX) is a poorly water soluble drug with its bioavailability being limited by its poor dissolution. In this study several particle engineering methods were employed on CLX using various ratios of CLX:PVP-K30. Micro/nanoparticles of CLX:PVP were prepared by using spray drying (SD), antisolvent crystallization followed by freeze drying (CRS-FD) and spray drying (CRS-SD) techniques. The suspension obtained through antisolvent crystallization was also subjected to high pressure homogenization followed by freeze drying (HPH-FD). Particle size measurements, saturation solubility, optical and scanning electron microscopy, DSC, XRPD, FT-IR and dissolution test were performed to characterize the physicochemical and pharmaceutical properties of the samples. The results showed that spray dried samples in the presence of (50%) PVP produced spherical particles and exhibited a high dissolution rate. Interestingly in the antisolvent crystallization technique, spherical nanoparticles of drug-PVP were obtained in the range of 291-442 nm. The average particle size was dependent on the concentration of the PVP used during the crystallization process. Solid state analysis showed that these particles were completely amorphous in nature. Also interesting to note was that at concentration of 5% PVP, when the suspension of nanoparticles was subjected to the high pressure homogenization process, the crystallinity of CLX increased. Despite the partial crystallinity of particles produced, they showed excellent dissolution behavior. It can thus be concluded that the method of preparation of CLX micro/nanoparticles had a big impact on the dissolution rate when the concentration of PVP was low (e.g., 5%). At high PVP concentration (e.g., 50%) all methods used to prepare engineered CLX particles showed better dissolution with no significant differences in their dissolution efficiency.

Improvement of Physico-mechanical Properties of Partially Amorphous Acetaminophen Developed from Hydroalcoholic Solution Using Spray Drying Technique.

OBJECTIVE(S): This study was performed aiming to investigate the effect of particle engineering via spray drying of hydroalcoholic solution on solid states and physico-mechanical properties of acetaminophen. MATERIALS AND METHODS: Spray drying of hydroalcoholic solution (25% v/v ethanol/water) of acetaminophen (5% w/v) in the presence of small amounts of polyninylpyrrolidone K30 (PVP) (0, 1.25, 2.5 and 5% w/w based on acetaminophen weight) was carried out. The properties of spray dried particles namely morphology, surface characteristics, particle size, crystallinity, dissolution rate and compactibility were evaluated. RESULTS: Spray drying process significantly changed the morphology of acetaminophen crystals from acicular (rod shape) to spherical microparticle. Differential scanning calorimetery (DSC) and x-ray powder diffraction (XRPD) studies ruled out any polymorphism in spray dried samples, however, a major reduction in crystallinity up to 65%, especially for those containing 5% w/w PVP was observed. Spray dried acetaminophen particles especially those obtained in the presence of PVP exhibited an obvious improvement of the dissolution and compaction properties. Tablets produced from spray dried samples exhibited excellent crushing strengths and no tendency to cap. CONCLUSIONS: The findings of this study revealed that spray drying of acetaminophen from hydroalcoholic solution in the presence of small amount of PVP produced partially amorphous particles with improved dissolution and excellent compaction properties.

Preparation, Characterization and Stability Studies of Glassy Solid Dispersions of Indomethacin using PVP and Isomalt as carriers.

OBJECTIVES: The purpose of the present study was to use the solid dispersion (SD) technique to improve the dissolution rates of indomethacin (IMC). MATERIALS AND METHODS: IMC solid dispersions in PVP K30 and isomalt (GALEN IQ 990) were prepared using the solvent evaporation technique and a hot melt method in weight ratios of 2, 10 and 30% (IMC:PVP). Solid dispersions and physical mixtures were characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and dissolution test. Physical stability tests were also performed at different temperatures and humidity conditions. RESULTS: The dissolution rates of all solid dispersions were faster than those of their physical mixtures. In samples containing 2% or 10% of IMC, there were no significant differences between the dissolution rates of IMC in PVP and isomalt solid dispersions, but in samples containing 30% of IMC, the dissolution rates were higher in isomalt dispersions. The XRPD analysis showed no crystalline peaks in solid dispersions, indicating that IMC was amorphous within the carrier. The DSC results showed that an interaction occurred between the drug and the carrier in PVP and isomalt dispersions. Physical stability tests at severe storage conditions showed that the dissolution rate of IMC in PVP solid dispersions decreased, while the dissolution profile of IMC in isomalt solid dispersions did not change significantly. CONCLUSION: It was shown that the dissolution rates of IMC in PVP and isomalt solid dispersions were substantially increased compared with their physical mixtures and pure IMC.