Optimization of tamoxifen solubility in carbon dioxide supercritical fluid and investigating other molecular targets using advanced artificial intelligence models.

Particle size, shape and morphology can be considered as the most significant functional parameters, their effects on increasing the performance of oral solid dosage formulation are indisputable. Supercritical Carbon dioxide fluid (SCCO2) technology is an effective approach to control the above-mentioned parameters in oral solid dosage formulation. In this study, drug solubility measuring is investigated based on artificial intelligence model using carbon dioxide as a common supercritical solvent, at different pressure and temperature, 120-400 bar, 308-338 K. The results indicate that pressure has a strong effect on drug solubility. In this investigation, Decision Tree (DT), Adaptive Boosted Decision Trees (ADA-DT), and Nu-SVR regression models are used for the first time as a novel model on the available data, which have two inputs, including pressure, X1 = P(bar) and temperature, X2 = T(K). Also, output is Y = solubility. With an R-squared score, DT, ADA-DT, and Nu-SVR showed results of 0.836, 0.921, and 0.813. Also, in terms of MAE, they showed error rates of 4.30E-06, 1.95E-06, and 3.45E-06. Another metric is RMSE, in which DT, ADA-DT, and Nu-SVR showed error rates of 4.96E-06, 2.34E-06, and 5.26E-06, respectively. Due to the analysis outputs, ADA-DT selected as the best and novel model and the find optimal outputs can be shown via vector: (x1 = 309, x2 = 317.39, Y1 = 7.03e-05).

Computational simulation and target prediction studies of solubility optimization of decitabine through supercritical solvent.

Computational analysis of drug solubility was carried out using machine learning approach. The solubility of Decitabine as model drug in supercritical CO2 was studied as function of pressure and temperature to assess the feasibility of that for production of nanomedicine to enhance the solubility. The data was collected for solubility optimization of Decitabine at the temperature 308-338 K, and pressure 120-400 bar used as the inputs to the machine learning models. A dataset of 32 data points and two inputs (P and T) have been applied to optimize the solubility. The only output is Y = solubility, which is Decitabine mole fraction solubility in the solvent. The developed models are three models including Kernel Ridge Regression (KRR), Decision tree Regression (DTR), and Gaussian process (GPR), which are used for the first time as a novel model. These models are optimized using their hyper-parameters tuning and then assessed using standard metrics, which shows R2-score, KRR, DTR, and GPR equal to 0.806, 0.891, and 0.998. Also, the MAE metric shows 1.08E-04, 7.40E-05, and 9.73E-06 error rates in the same order. The other metric is MAPE, in which the KRR error rate is 4.64E-01, DTR shows an error rate equal to 1.63E-01, and GPR as the best mode illustrates 5.06E-02. Finally, analysis using the best model (GPR) reveals that increasing both inputs results in an increase in the solubility of Decitabine. The optimal values are (P = 400, T = 3.38E + 02, Y = 1.07E-03).

Application of CO2 Supercritical Fluid to Optimize the Solubility of Oxaprozin: Development of Novel Machine Learning Predictive Models.

Over the last years, extensive motivation has emerged towards the application of supercritical carbon dioxide (SCCO2) for particle engineering. SCCO2 has great potential for application as a green and eco-friendly technique to reach small crystalline particles with narrow particle size distribution. In this paper, an artificial intelligence (AI) method has been used as an efficient and versatile tool to predict and consequently optimize the solubility of oxaprozin in SCCO2 systems. Three learning methods, including multi-layer perceptron (MLP), Kriging or Gaussian process regression (GPR), and k-nearest neighbors (KNN) are selected to make models on the tiny dataset. The dataset includes 32 data points with two input parameters (temperature and pressure) and one output (solubility). The optimized models were tested with standard metrics. MLP, GPR, and KNN have error rates of 2.079 × 10-8, 2.173 × 10-9, and 1.372 × 10-8, respectively, using MSE metrics. Additionally, in terms of R-squared, they have scores of 0.868, 0.997, and 0.999, respectively. The optimal inputs are the same as the maximum possible values and are paired with a solubility of 1.26 × 10-3 as an output.

Amphotericin B-PEG Conjugates of ZnO Nanoparticles: Enhancement Antifungal Activity with Minimal Toxicity.

Amphotericin B (AMB) is commonly used to treat life-threatening systemic fungal infections. AMB formulations that are more efficient and less nephrotoxic are currently unmet needs. In the current study, new ZnO-PEGylated AMB (ZnO-AMB-PEG) nanoparticles (NPs) were synthesized and their antifungal effects on the Candida spp. were investigated. The size and zeta potential values of AMB-PEG and ZnO-AMB-PEG NPs were 216.2 ± 26.9 to 662.3 ± 24.7 nm and -11.8 ± 2.02 to -14.2 ± 0.94 mV, respectively. The FTIR, XRD, and EDX spectra indicated that the PEG-enclosed AMB was capped by ZnO, and SEM images revealed the ZnO distribution on the surface NPs. In comparison to ZnO-AMB NPs and free AMB against C.albicans and C.neoformans, ZnO-AMB-PEG NPs significantly reduced the MIC and MFC. After a week of single and multiple dosage, the toxicity was investigated utilizing in vitro blood hemolysis, in vivo nephrotoxicity, and hepatic functions. ZnO-AMB-PEG significantly lowered WBC count and hematocrit concentrations when compared to AMB and ZnO-AMB. RBC count and hemoglobulin content, on the other hand, were unaltered. ZnO-AMB-PEG considerably lowered creatinine and blood urea nitrogen (BUN) levels when compared to AMB and ZnO-AMB. The difference in liver function indicators was determined to be minor by all formulae. These findings imply that ZnO-AMB-PEG could be utilized in the clinic with little nephrotoxicity, although more research is needed to determine the formulation's in vivo efficacy.

Development and optimization of oral nanoemulsion of rutin for enhancing its dissolution rate, permeability, and oral bioavailability.

Rutin-loaded nanoemulsion (NE-RU) formulation is the core research work in this report. Labrafil® M 1944 CS was used as the oil phase, Tween 80 as the surfactant, and Transcutol P as the co-surfactant in the preparation of nanoemulsion. By utilizing a three-level central composite design (CCD), the composition was optimized. The optimized formulation showed a droplet size of 98.53 ± 3.22 nm, zeta potential -46.70 ± 4.78 mV, and drug loading 92.34 ± 3.87%. The results of dissolution, permeability, and oral bioavailability showed about 25.55 folds, 1.98 folds, and 33.68 folds, respectively, in the case of NE-RU as compared to its naïve form. The response of fresh and aged NE was non-significantly different in terms of particle size, zeta potential, and drug loading, indicating that the formulation was stable. The successful development of NE-RU with an improved bioavailability profile suggested that this formulation might be used to examine the pharmacodynamics of oxidative stress-related metabolic disorders.

Preparation and Characterization of a Novel Mucoadhesive Carvedilol Nanosponge: A Promising Platform for Buccal Anti-Hypertensive Delivery.

Carvedilol (CRV) is a non-selective third generation beta-blocker used to treat hypertension, congestive heart failure and angina pectoris. Oral administration of CRV showed poor bioavailability (25%), which might be ascribed to its extensive first-pass metabolism. Buccal delivery is known to boost drugs bioavailability. The aim of this study is to investigate the efficacy of bilosomes-based mucoadhesive carvedilol nanosponge for enhancing the oral bioavailability of CRV. The bilosomes were prepared, optimized and characterized for particle size, surface morphology, encapsulation efficiency and ex-vivo permeation studies. Then, the optimized formula was incorporated into a carboxymethyl cellulose/hydroxypropyl cellulose (CMC/HPC) composite mixture to obtain buccal nanosponge enriched with CRV bilosomes. The optimized bilosome formula (BLS9), showing minimum vesicle size, maximum entrapment, and highest cumulative in vitro release, exhibited a spherical shape with 217.2 nm in diameter, 87.13% entrapment efficiency, and sustained drug release for up to 24 h. In addition, ex-vivo drug permeation across sheep buccal mucosa revealed enhanced drug permeation with bilosomal formulations, compared to aqueous drug suspension. Consecutively, BLS9 was incorporated in a CMC/HPC gel and lyophilized for 24 h to obtain bilosomal nanosponge to enhance CRV buccal delivery. Morphological analysis of the prepared nanosponge revealed improved swelling with a porosity of 67.58%. The in vivo assessment of rats indicated that CRV-loaded nanosponge efficiently enhanced systolic/diastolic blood pressure, decreased elevated oxidative stress, improved lipid profile and exhibited a potent cardio-protective effect. Collectively, bilosomal nanosponge might represent a plausible nanovehicle for buccal delivery of CRV for effective management of hypertension.

Optimization and Characterization of Cuscuta reflexa Extract Loaded Phytosomes by the Box-Behnken Design to Improve the Oral Bioavailability.

The purpose of this study is to determine whether the complexing hydroalcoholic extract of Cuscuta reflexa (HECR) with phosphatidyl choline increases its bioavailability. As a result, a novel phytosomal delivery system for the HECR-soya lecithin complex was developed (HECR-phytosome). The HECR-phytosome complex was synthesized and characterized as phytovesicles. The formulation was prepared using a variable concentration of soya lecithin (1:1-1:3 percent w/v), a temperature range of (45-65°C), and sonication time (4-8 min). Optimization of HECR-loaded phytosomal formulations was performed using Design Expert software. A three-factor, three-level Box-Behnken design was used to optimize this HECR delivery system, as dependent variables, vesicular size and entrapment efficiency were evaluated using a Box Behnken factorial design. Further characterization of the optimized formulation included vesicle size, PDI, zeta potential, entrapment efficiency, FTIR, DSC, TEM, and in vitro release. Vesicle sizes ranged from 173.5±6.17 nm to 215.9±6.53 nm, and response rates for entrapment efficiency ranged from 52.9±1.65 to 77.2±1.1%. The uniform structure and spherical shape were demonstrated by transmission electron microscopy. Among the drug release kinetic models, the formulation followed the Higuchi model (R2 = 0.9978), releasing 96.3±3.7% of the polyphenol and flavonoids phytoconstituents from HECR-loaded phytosomes in 12 hours, compared to 49.3±2.5% in the plain extract. In addition, the optimized formulation passes the stability test. Therefore, the results demonstrated that phytosomal nanocarriers have the potential to increase the bioavailability of Cuscuta reflexa extract.

Formulation of Chitosan-Coated Brigatinib Nanospanlastics: Optimization, Characterization, Stability Assessment and In-Vitro Cytotoxicity Activity against H-1975 Cell Lines.

The purpose of the current study was to develop Brigatinib (BGT)-loaded nanospanlastics (BGT-loaded NSPs) (S1-S13) containing Span 60 with different edge activators (Tween 80 and Pluronic F127) and optimized based on the vesicle size, zeta potential (ZP), and percent entrapment efficiency (%EE) using Design-Expert® software. The optimum formula was recommended with desirability of 0.819 and composed of Span-60:Tween 80 at a ratio of 4:1 and 10 min as a sonication time (S13). It showed predicted EE% (81.58%), vesicle size (386.55 nm), and ZP (-29.51 mv). The optimized nanospanlastics (S13) was further coated with chitosan and further evaluated for Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), in vitro release, Transmission Electron Microscopy (TEM), stability and in-vitro cytotoxicity studies against H-1975 lung cancer cell lines. The DSC and XRD revealed complete encapsulation of the drug. TEM imagery revealed spherical nanovesicles with a smooth surface. Also, the coated formula showed high stability for three months in two different conditions. Moreover, it resulted in improved and sustained drug release than free BGT suspension and exhibited Higuchi kinetic release mechanism. The cytotoxic activity of BGT-loaded SPs (S13) was enhanced three times in comparison to free the BGT drug against the H-1975 cell lines. Overall, these results confirmed that BGT-loaded SPs could be a promising nanocarrier to improve the anticancer efficacy of BGT.

Journey of Alpinia galanga from kitchen spice to nutraceutical to folk medicine to nanomedicine.

ETHANOPHARMACOLOGICAL IMPORTANCE: Alpinia galanga (L.) Willd (AG), belonging to Zingiberaceae family is used as a spice and condiment in various culinary preparations of Indonesia, Thailand and Malaysia. It has been also used as a key ingredient in various traditional systems of medicine for the treatment of throat infection, asthma, urinary ailments, inflammation and rheumatism amongst other conditions. AG is widely used as a functional food and included in various preparations to obtain its nutraceutical and pharmacological benefits of its phytoconstituents such as phenyl propanoids, flavonoids and terpenoids. Over the past decades, several researchers have carried out systematic investigation on various parts of AG. Numerous studies on AG rhizomes have shown positive pharmacological effects such as anti-inflammatory, anticancer, antipsoriasis, antiallergic, neuroprotective and thermogenesis. Till date, no comprehensive review summarizing the exploitation of AG into nanomedicine has been published. AIM OF THE REVIEW: This comprehensive review aims to briefly discuss cultivation methods, propagation techniques, extraction processes for AG. The ethnopharmacological uses and pharmacological activities of AG extracts and its isolates are discussed in detail which may contribute well in further development of novel drug delivery system (NDDS) i.e. future nanomedicine. MATERIALS AND METHODS: Information about AG was collected using search engine tools such as Google, Google Scholar, PubMed, Google Patent, Web of Science and bibliographic databases of previously published peer-reviewed review articles and research works were explored. The obtained data sets were sequentially arranged for better understanding of AG's potential. RESULTS: More advanced genetic engineering techniques have been utilized in cultivation and propagation of AG for obtaining better yield. Extraction, isolation and characterization techniques have reported numerous phytoconstituents which are chemically phenolic compounds (phenyl propanoids, flavonoids, chalcones, lignans) and terpenes. Ethnopharmacological uses and pharmacological activity of AG are explored in numerous ailments, their mechanism of action and its further potential to explore into novel drug delivery system are also highlighted. CONCLUSIONS: The review highlights the importance of plant tissue culture in increasing the production of AG plantlets and rhizomes. It was understood from the review that AG and its phytoconstituents possess numerous pharmacological activities and have been explored for the treatment of cancer, microbial infection, gastrointestinal disorders, neuroprotective effects, obesity and skin disorders. However, the use of AG as alternative medicine is limited owing to poor solubility of its bioactive components and their instability. To overcome these challenges, novel drug delivery systems (NDDS) have been utilized and found good success in overcoming its aforementioned challenges. Furthermore, efforts are required towards development of scalable, non-toxic and stable NDDS of AG and/or its bioactives.

Efficacy of SPG-ODN 1826 Nanovehicles in Inducing M1 Phenotype through TLR-9 Activation in Murine Alveolar J774A.1 Cells: Plausible Nano-Immunotherapy for Lung Carcinoma.

Alveolar macrophages are the first line of defense against intruding pathogens and play a critical role in cancer immunology. The Toll-like receptor (TLR) family mediates an important role in recognizing and mounting an immune response against intruding microbes. TLR-9 is a member of the intracellular TLR family, which recognizes unmethylated CG motifs from the prokaryotic genome. Upon its activation, TLR-9 triggers downstream of the MyD-88-dependent transcriptional activation of NF-κB, and subsequently results in abundant inflammatory cytokines expression that induces a profound inflammatory milieu. The present exploratory investigation aimed at elucidating the potency of schizophyllan for entrapping ODN 1826 (SPG-ODN 1826)-mediated stimulation of TLR-9 in provoking an inflammatory-type response in murine alveolar macrophages. Schizophyllan (SPG), a representative of the ß-glucan family, was used in the present study as a nanovehicle for endosomal trafficking of CpG ODN 1826. TEM analysis of SPG-ODN 1826 nanovehicles revealed that the prepared nanovehicles are spherical and have an average size of about 100 nm. Interestingly, SPG-ODN 1826 nanovehicles were competent in delivering their therapeutic payload within endosomes of murine alveolar macrophage (J774A.1) cells. Exposure of these nanovehicles within LPS stimulated J774A.1, resulted in a significant provocation of reactive oxygen species (ROS) (p < 0.01) in comparison to CpG ODN 1826 alone. Moreover, the formulated nanovehicles succeeded in generating a profound Th1-based cytokine profile constituted by enhanced expression of IFN-γ (p < 0.001) and IL-1ß (p < 0.001) inflammatory cytokines. These findings clearly indicated the immunostimulatory potential of SPG-ODN 1826 nanovehicles for inducing the Th1-type phenotype, which would certainly assist in skewing M2 phenotype into the much-desired M1 type during lung cancer.

Synthesis of Gold Nanoparticles by Using Green Machinery: Characterization and In Vitro Toxicity.

Green synthesis of gold nanoparticles (GNPs) with plant extracts has gained considerable interest in the field of biomedicine. Recently, the bioreduction nature of herbal extracts has helped to synthesize spherical GNPs of different potential from gold salt. In this study, a fast ecofriendly method was adopted for the synthesis of GNPs using fresh peel (aqueous) extracts of Benincasa hispida, which acted as reducing and stabilizing agents. The biosynthesized GNPs were characterized by UV-VIS and Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering. In addition, the in vitro antibacterial and anticancer activities of synthesized GNPs were investigated. The formation of gold nanoparticles was confirmed by the existence of a sharp absorption peak at 520 nm, corresponding to the surface plasmon resonance (SPR) band of the GNPs. TEM analysis revealed that the prepared GNPs were spherical in shape and had an average particle size of 22.18 ± 2 nm. Most importantly, the synthesized GNPs exhibited considerable antibacterial activity against different Gram-positive and Gram-negative bacteria. Furthermore, the biosynthesized GNPs exerted remarkable in vitro cytotoxicity against human cervical cancer cell line, while sparing normal human primary osteoblast cells. Such cytotoxic effect was attributed to the increased production of reactive oxygen species (ROS) that contributed to the damage of HeLa cells. Collectively, peel extracts of B. hispida can be efficiently used for the synthesis of GNPs, which can be adopted as a natural source of antimicrobial and anticancer agent.

Osteochondral fracture of the patella without soft tissue injury and with no dislocation: A case report.

INTRODUCTION: Osteochondral fracture of the patella is a fairly common pathology, but almost always associated with a spectrum of soft tissue injuries including anterior cruciate ligament (ACL) rupture. We present a rare case of an osteochondral fracture of the patella in the absence of ligament or soft tissue injuries and with no dislocation of the patella in a pediatric patient. PRESENTATION OF CASE: An 11-year-old male presented to the orthopedic clinic on crutches following a football injury. The patient had pain in his left knee with flexion deformity. Plain film radiography of the left knee was taken, and an osteochondral fracture of the patella was suspected. Further imaging studies were conducted including computed tomography (CT) and magnetic resonance imaging (MRI) which revealed an isolated osteochondral fracture of the patella with no other associated injuries. Open reduction and internal fixation of the displaced fragment was successfully preformed with favorable outcomes. During follow-up, almost full range of motion was regained, and plain film radiography revealed healed fracture with a normal appearance of the patella. DISCUSSION: Traumatic osteochondral fracture of the patella is a common injury and most of these injuries are commonly accompanied by an acute dislocation of the patella or soft tissue injuries such as rupture of the anterior cruciate ligament (ACL) and almost half of all patellar dislocations incidence are associated with osteochondral fractures of the patella. This case had an isolated osteochondral fracture of patella. CONCLUSION: As demonstrated in this case, osteochondral fractures are common among younger population and patients need to be thoroughly evaluated. Advanced Imaging such as MRI and CT are essential to exclude soft tissue injuries. Although management is highly variable, the importance of open reduction and early fixation should be emphasized for optimal outcomes.

Enhancing the Poor Flow and Tableting Problems of High Drug-Loading Formulation of Canagliflozin Using Continuous Green Granulation Process and Design-of-Experiment Approach.

Maximization of drug-loading can significantly reduce the size of dosage form and consequently decrease the cost of manufacture. In this research, two challenges were addressed: poor flow and tableting problems of high-drug loading (>70%) formulation of canagliflozin (CNG), by adopting the moisture-activated dry granulation (MADG) process. In this method, heating and drying steps were omitted so, called green granulation process. A 32 full-factorial design was performed for optimization of key process variables, namely the granulation fluid level (X1) and the wet massing time (X2). Granulation of CNG was carried out in the presence of polyvinylpyrrolidone, and the prepared granules were compressed into tablets. Regression analysis demonstrated the significant (p ≤ 0.05) effect of X1 and X2 on properties of granules and corresponding tablets, with pronounced impact of X1. Additionally, marked improvement of granules' properties and tableting of CNG were observed. Furthermore, the optimized process conditions that produced good flow properties of granules and acceptable tablets were high level of granulation fluid (3.41% w/w) and short wet massing time (1.0 min). Finally, the MADG process gives the opportunity to ameliorate the poor flow and tableting problems of CNG with lower amounts of excipients, which are important for successful development of uniform dosage unit.

Recurrence Rate in a Patient Treated with Colon Resection Followed by Chemotherapy in Comparison to a Patient Treated with Colon Resection without Chemotherapy.

Given that colon cancer is one of the most prevalent cancers worldwide, it is essential to employ strategies to try to reduce its incidence and recurrence rate. Though colon cancer is a sporadic disease in the vast majority of cases, multiple risk factors are linked to this disease, namely, obesity and cigarette smoking. Additionally, not many studies have been done in Saudi Arabia studying the recurrence rate of colon cancer. Therefore, we conducted a retrospective cohort study at King Khalid Hospital, King Abdulaziz Medical City, National Guard Health Affairs (NGHA), Jeddah, Saudi Arabia to investigate the recurrence rate of colon cancer in patients treated with complete colon resection followed by chemotherapy versus patients treated with colon resection alone via electronic and paper medical records. A total of 120 patients were included in this study; 61 were males (50.8%) and 59 were females (49.2%). According to our findings, the recurrence rate in patients who underwent surgical resection with adjuvant chemotherapy was 15.6% (n = 10), while the recurrence rate in patients with surgery alone was 21.4% (n = 12). Cancer recurrence is associated with significant morbidity and mortality. Therefore, further studies should be done to investigate the recurrence rate in patients with risk factors to identify and deal with the causes of recurrence.

Sustained release and enhanced oral bioavailability of rivaroxaban by PLGA nanoparticles with no food effect.

The purpose of the currents study was to enhance bioavailability of rivaroxaban (RXB) and reduce the food effect. RXB loaded PLGA nanoparticles (RXB-PLGA-NPs) were prepared by emulsion solvent evaporation method and optimized using central composite design (CDD). The optimized RXB-PLGA-NPs (F8) with composition, PLGA (125 mg), PVA (0.5%w/w) and RXB (20 mg) was found optimum with particle size (496 ± 8.5 nm), PDI (0.607), ZP (- 18.41 ± 3.14 mV), %EE (87.9 ± 8.6) and %DL (9.5 ± 1.6). The optimized NPs (F8) was further evaluated in vitro for DSC, FTIR, SEM and in vitro release studies. A comparative pharmacokinetic studies with commercial tablet (XARELTO®) were conducted on fasted and fed state rats. Compared to commercial tablet (XARELTO®), the RXB-PLGA-NPs (F8) exhibited a significant enhancement of bioavailability in both fasted and fed state. In addition, the bioavailability of RXB from NPs (F8) was found unaffected in the presence of food.

Development of spray-dried amorphous solid dispersions of tadalafil using glycyrrhizin for enhanced dissolution and aphrodisiac activity in male rats.

Tadalafil (TDL) is a phosphodiesterase-5 inhibitor (PDE5I), indicated for erectile dysfunction (ED). However, TDL exhibits poor aqueous solubility and dissolution rate, which may limit its application. This study aims to prepare amorphous solid dispersion (ASD) by spray-drying, using glycyrrhizin-a natural drug carrier. Particle and physicochemical characterizations were performed by particle size, polydispersity index measurement, yield, drug content estimation, Fourier Transformed Infrared (FTIR) spectroscopy, Differential scanning calorimetry (DSC), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and dissolution study. In order to evaluate the aphrodisiac activity of the prepared ASD, sexual behavior study was performed in male rats. It is further considered for the stability study. Our results revealed that TDL-GLZ spray-dried dispersion was a successful drug-carrier binary mixture. XRD and SEM showed that ASD of TDL with GLZ presented in the amorphous state and dented-spherical shape, unlike the drug indicating crystalline and spiked shaped. The optimized ASD3 formulation with particle size (1.92 µm), PDI (0.32), yield (97.78%) and drug content (85.00%) showed 4.07 folds' increase in dissolution rate compared to pure TDL. The results obtained from the in vivo study exhibit significantly improved aphrodisiac activity with ASD3. The stability study revealed that the prepared ASD3 did not show any remarkable changes in the dissolution and drug content for 1 month storage at room temperature.

Design and in vitro/in vivo evaluations of a multiple-drug-containing gingiva disc for periodontotherapy.

In the current work, we set out to develop and evaluate a gingiva disc of cellulose acetate phthalate and poloxamer F-127 for the simultaneous delivery of multiple drugs, namely minocycline, celecoxib, doxycycline hyclate, and simvastatin, to abolish infection, impede inflammation, avert collagen destruction, and promote alveolar bone regeneration, respectively. In vitro release studies revealed the sustained release profiles of the drugs for 12 h and that they were active against Staphylococcus aureus, Escherichia coli and Streptococcus mutans. The in vivo bioactivity levels of these drugs were assessed by comparing the number of colony forming units during different phases of a study on Wistar rats, and the results showed a reduction in the number of bacterial colonies with the applied formulation. A mucosal irritation study conducted on Wistar rat gingiva confirmed the non-irritancy of the optimal gingiva disc. Hence, this customized, non-invasive polymeric gingiva disc displaying a sustained release of drugs can be a useful tool to treat acute to moderate stages of periodontitis.

Estimating the Solubility, Solution Thermodynamics, and Molecular Interaction of Aliskiren Hemifumarate in Alkylimidazolium Based Ionic Liquids.

Estimating the solubility and solution thermodynamics parameters of aliskiren hemifumarate (AHF) in three different room temperature ionic liquids (RTILs), Transcutol-HP (THP) and water are interesting as there is no solubility data available in the literature. In the current study, the solubility and solution thermodynamics of AHF in three different RTILs, THP and water at the temperature range from 298.2 to 318.2 K under air pressure 0.1 MP were evaluated. The solid phase evaluation by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction (PXRD) indicated no conversion of AHF into polymorph. The mole fraction solubility of AHF was found to be highest in 1-hexyl-3-methylimidazolium hexafluorophosphate (HMMHFP) ionic liquid (7.46 × 10-2) at 318.2 K. The obtained solubility values of AHF was regressed by the Apelblat and van't Hoff models with overall root mean square deviations (RMSD) of 0.62% and 1.42%, respectively. The ideal solubility of AHF was higher compared to experimental solubility values at different temperatures. The lowest activity coefficient was found in HMMHFP, which confirmed highest molecular interaction between AHF-HMMHFP. The estimated thermodynamic parameters confirmed endothermic and entropy driven dissolution of AHF in different RTILs, THP, and water.

Nano-encapsulation and characterization of baricitinib using poly-lactic-glycolic acid co-polymer.

Baricitinib is a recently approved anti-rheumatic drug having very poor aqueous solubility and hence its performance suffers from low or inconsistent oral bioavailability. The purpose of the study was to develop and evaluate poly lactic-co-glycolic acid (PLGA) nanoparticles of baricitinib in order to enhance in vitro dissolution and performance. Nano-suspension of baricitinib with or without PLGA, a biodegradable, FDA approved semi-synthetic polymer, was developed by nanoprecipitation method. Research methodology employed a quantitative research utilizing experimental design wherein effect of independent variables such as amount of polymer, drug: polymer ratio, types of solvent, and solvent: anti-solvent ratio were evaluated over the size and size distribution of nanoparticles along with entrapment efficiencies. Among the several organic phases evaluated, acetone was found to be suitable solvent for drug and polymer. The aqueous phase (anti-solvent) was deionized water containing 1% w/v pluronic 127 as the stabilizer of nanoparticle suspension. The optimized nanoparticles had particle size less than 100 nm (91 nm ±â€¯6.23) with a very narrow size distribution (0.169 ±â€¯0.003), high zeta potential (-12.5 mV ±â€¯5.46) and entrapment efficiency (88.0%). The optimized nanoparticles were characterized by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, infrared spectroscopy and in vitro dissolution studies. In-vitro dissolution study of PLGA nanoparticles exhibited sustained release with approximately 93% release of baricitinib during 24-h period.