Pure Suspension Research Articles

Broad-spectrum solar conversion towards photothermal catalytic reforming hydrogen production with in-situ thermal regulation over core-shell nanocomposites

Photothermal catalytic hydrogen production is regarded as an effective conversion of solar energy into clean energy carrier. However, the uncontrollable in-situ photo-thermal effect would cause overheating of the catalytic site, thereby reducing the electron transfer efficiency, and the vast amount of energy contained in the near-infrared thermal effect has not been fully utilized. In this study, an Au/TiO2 nanorod catalyst and n-eicosane were employed to establish a core-shell structure to enhance solar energy conversion and regulating in-situ temperature rise during the photothermal catalytic process. The results revealed that the core-shell structure offered an efficient reaction area and high dispersion stability, while the amount of photothermal catalyst loaded also influenced the photothermal catalytic performance. Also, the in-situ overheating is effectively regulated to help enhance efficient electron transfer for hydrogen production. The core-shell structures with Au/TiO2 loading amounts of 9.3%, 14.5%, and 20.2% enhanced hydrogen yields by 30.3%, 42.2%, and 53.8%, respectively, compared to that of pure photothermal catalyst suspension. Meanwhile, the photothermal conversion efficiencies were 33.3%, 64.5% and 88.1% higher than those of 10 vol% glycerol solution. Thus, the photothermal effect has been shown to be effective for improving the performance of photothermal glycerol reforming for hydrogen production, and photothermal catalyst-phase change material composite structures can provide a new idea for promoting solar energy into thermal and chemical energy.

Development of Diphenyl carbonate-Crosslinked Cyclodextrin Based Nanosponges for Oral Delivery of Baricitinib: Formulation, Characterization and Pharmacokinetic Studies.

The aim of the present investigation is to prepare baricitinib (BAR)-loaded diphenyl carbonate (DPC) β-cyclodextrin (βCD) based nanosponges (NSs) to improve the oral bioavailability. BAR-loaded DPC-crosslinked βCD NSs (B-DCNs) were prepared prepared by varying the molar ratio of βCD: DPC (1:1.5 to 1:6). The developed B-DCNs loaded with BAR were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), % yield and percent entrapment efficiency (%EE). Based on the above evaluations, BAR-loaded DPC βCD NSs (B-CDN3) was optimized with mean size (345.8±4.7 nm), PDI (0.335±0.005), Yield (91.46±7.4%) and EE (79.1±1.6%). The optimized NSs (B-CDN3) was further confirmed by SEM, spectral analysis, BET analysis, in vitro release and pharmacokinetic studies. The optimized NSs (B-CDN3) showed 2.13 times enhancement in bioavailability in comparison to pure BAR suspension. It could be anticipated that NSs loaded with BAR as a promising tool for release and bioavailability for the treatment of rheumatic arthritis and Covid-19.

Stability and Tribological Performance of Nanostructured 2D Turbostratic Graphite and Functionalised Graphene as Low-Viscosity Oil Additives

The dispersion stability of carbon-based solid lubricants/lubricating oils remains a challenge to overcome. Recently, novel processing routes were developed to obtain 2D turbostratic graphite particles via solid-state reactions between B4C and Cr3C2 (GBC) and between SiC and Fe (GSF) that present outstanding tribological properties in a dry scenario, as well as functionalized graphene (GNH). This work investigated the suspension stability of GBC and GSF particles (0.05 wt.%) dispersed in a low-viscosity polyol ester lubricating oil and their tribological performance. Ammonia-functionalized graphene (GNH) particles were also used as a reference. In order to evaluate the dispersion stability, in addition to the classical digital image technique, a much more assertive, reliable, quantitative and rarely reported in the literature technique was used, i.e., the STEPTM (Space and Time-resolved Extinction Profiles) technology. Reciprocating sphere-on-flat tribological tests were carried out, in which before contact, 0.2 μL of pure oil and suspension (POE + 0.05 wt.% of solid lubricant) was applied on a flat surface. The results showed that the GBC particles remained remarkably stable and reduced the sphere wear rate by 61.8%. From the tribosystem point of view, the presence of GBC and GSF reduced the wear rate by 18.4% and 2.2%, respectively, with respect to the pure oil, while the GNH particles increased the wear rate by 4.2%. Furthermore, the wear rate was improved due to the highly disordered carbon tribolayer formation identified on both surfaces.

Use of eggshell waste: A green and effective method for the synthesis of pure calcium hydroxide suspensions

This paper presents a rapid method to obtain pure suspensions of Ca(OH)2 dispersed in 2-propanol. To this aim eggshell wastes (CaCO3) were decarbonated to calcium oxide (CaO) followed by sonication-assisted hydrolysis in water/2-propanol to form calcium hydroxide (Ca(OH)2). An important advantage of the method is that it does not require chemical reagents due to the high purity of eggshell in CaCO3. Moreover, CaO is fully converted into Ca(OH)2 which means that purification steps are not needed, as occurs in conventional routes of synthesis. To assess the reliability of the synthetic procedure, the purity and amount of Ca(OH)2 were studied by X-ray diffraction (XRD), infrared spectroscopy (FTIR) and thermal analysis (TG). In addition, the morphology and crystallite size were examined by transmission electron microscopy (TEM) and X-ray diffraction (XRD) using Rietveld refinement method. It was found that sonicated Ca(OH)2 suspensions (5 g/L) were composed of particles that ranged in size from several nanometers to few micrometers. Finally, the suitability of Ca(OH)2 from eggshell to reinforce architectural stone was also studied by microscopy examination, colour change tests, surface hardness and surface erosion measurements. All tests confirmed the consolidation effectiveness was comparable to conventional nanolime treatments and surface erosion was visibly reduced.

Disulfide Bridged Nanoparticles of Thiolated Sodium Alginate and Eudragit RS100 for Oral Delivery of Paclitaxel: In Vitro and In Vivo Evaluation.

Most biopharmaceutics classification system (BCS) class IV drugs have limited oral bioavailability due to poor solubility and poorer permeability. This work aims to investigate the possibility of utilizing disulfide bridged nanoparticles to improve BCS IV drug solubility and oral absorption. Disulfide bridged nanoparticles were made using thiolated sodium alginate (TSA) and thiolated eudragit RS100 (TERS100). This study used paclitaxel (PTL) as a model drug to create PTL-loaded nanoparticles using the air oxidation approach. PTL-loaded nanoparticles boosted the solubility of PTL by over 11 times (∼59 μg/mL). The nanoparticles had particle sizes of 103 nm, polydispersity indices of 0.034, and zeta potentials of -21 mV, respectively. Nanoparticles demonstrated 75.34% and 89.18% entrapment and loading efficiency of PTL, respectively. The PTL release data from nanoparticles had good sustained release properties. The effective permeability of PTL from nanoparticles was 2.19-fold higher than that of pure PTL suspension. The relative bioavailability of PTL with disulfide bridged nanoparticles was 237.11%, which was much higher than that of PTL suspension, according to the pharmacokinetic data. These results show that disulfide bridged nanoparticles have a wide range of clinical applications.

Engineering of Lurasidone Hydrochloride Loaded Niosomes for Enhancing the Antipsychotic Potential for Nasal Administration

Background: Drugs having high first-pass metabolism or that are susceptible to enzymatic degradation can be administered through the nasal route to avoid their degradation. Lurasidone exhibits less toxicity and side effects as compared to its sister drugs like risperidone, ziprasidone, clozapine, etc. Objectives: The present study aimed to develop Lurasidone loaded niosomes for nasal delivery. Methods: Lurasidone niosomes were developed by adapting the ether injection method and optimized using a central composite design. In vitro and in vivo studies were conducted using optimized formulation. Results: The findings showed that the optimized formulation exhibited a particle size of 159.02 ± 0.58 nm and an entrapment efficiency of 91.6 ± 1.6%. The findings from the nasal histopathological analysis revealed that the optimized formulation was non-irritant and non-toxic for nasal mucosa. The findings from in vitro studies revealed 94.61 ± 0.27% of drug release from optimized formulation F7 throughout 24 hrs. The findings of in vivo (Albino Wistar rats) studies demonstrated that various pharmacokinetic parameters (Cmax, Tmax, AUC(0-24), T1/2, Vd and Cl) and pharmcodynamic parameters (conditioned avoidance response, biochemical estimation using oxidative markers such as superoxide dismutase, malondialdehyde and glutathione) were significantly improved compared to marketed tablets (Lurasid® 40 mg) and pure drug suspension. Optimized formulation F-7 exhibited 4.9 times more bioavailability than that of pure drug suspension following intranasal administration. Conclusion: These findings indicate that nasal niosomal formulation of Lurasidone HCl is a promising nanoplatform for enhancing the overall performance of Lurasidone. These results could open new avenues into the future of nanomedicine.

Polydopamine-encapsulated cap-like mesoporous silica based delivery system for responsive pesticide release and high retention

Nanopesticides formulation has been applied in modern agriculture, but the effective deposition of pesticides on plant surfaces is still a critical challenge. Here, we developed a cap-like mesoporous silica (C-mSiO2) carrier for pesticide delivery. The C-mSiO2 carriers with surface amino groups present uniform cap-like shape and have an mean diameter of 300 nm and width of 100 nm. This structure would reduce the rolling and bouncing of carriers on plant leaves, leading to improving the foliage deposition and retention. After loading dinotefuran (DIN), polydopamine (PDA) was used to encapsulate the pesticide (DIN@C-mSiO2@PDA). The C-mSiO2 carriers exhibit high drug loading efficiency (24.7%) and benign biocompatibility on bacteria and seed. Except for pH/NIR response release, the DIN@C-mSiO2@PDA exhibited excellent photostability under UV irradiation. Moreover, the insecticidal activity of DIN@C-mSiO2@PDA was comparable to that of pure DIN and DIN commercial suspension (CS-DIN). This carrier system has the potential for improving the foliage retention and utilization of pesticides.

Optimization and In Vitro Characterization of Telmisartan Loaded Sodium Alginate Beads and Its In Vivo Efficacy Investigation in Hypertensive Induced Animal Model.

Antihypertensive drug telmisartan (TEL) belongs to BCS class II, which is characterized by low water solubility and, consequently, low oral bioavailability. Gastroretentive systems may overcome the problems associated with low solubility of TEL and incomplete absorption by localizing the drug release in the stomach. The purpose of this study was to prepare TEL-loaded, oil-entrapped, floating alginate beads with the intent of enhancing the oral bioavailability of TEL for the treatment of hypertension. For the formulation and optimization of seventeen formulations of TEL-loaded oil-entrapped floating alginate beads, a central composite design was utilized. The concentration of sodium alginate (X1), the concentration of cross-linker (X2), and the concentration of sesame oil (X3) served as independent variables, whereas the entrapment efficiency (Y1), in vitro buoyancy (Y2), and drug release Q6h (Y3) served as dependent variables. Using the emulsion gelation method and calcium chloride as the cross-linking agent, different formulations of TEL alginate beads were produced. All formulations were evaluated for their entrapment efficiency percentage, in vitro buoyancy, and in vitro drug release. The optimal formulation of TEL alginate beads was prepared with and without oil and evaluated for entrapment efficiency percentage, in vitro buoyancy, swelling ratio, average size, and in vitro drug release. Using scanning electron microscopes, the surface morphology was determined. Using IR spectroscopy, the compatibility between the ingredients was determined. In vivo evaluation of the optimized formulation in comparison to the free TEL was done in hypertension-induced rats, and the systolic blood pressure and all pharmacokinetic parameters were measured. The prepared beads exhibited a high entrapment efficiency percentage, in vitro buoyancy, and prolonged drug release. TEL was compatible with other ingredients, as approved by IR spectroscopy. The prepared TEL beads were spherical, as shown by the SEM. The relative bioavailability of TEL-loaded oil-entrapped beads was 222.52%, which was higher than that of the pure TEL suspension. The prepared TEL beads formulation exhibited a higher antihypertensive effect for a prolonged time compared to pure TEL suspension. It can be concluded that this innovative delivery method of TEL-loaded oil-entrapped beads is a promising tool for enhancing drug solubility and, thus, oral bioavailability and therapeutic efficacy, resulting in enhanced patient compliance. Furthermore, the in vivo study confirmed the formulation's extended anti-hypertensive activity in animal models.

Enhancing the biopharmaceutical attributes of atorvastatin calcium using polymeric and lipid-polymer hybrid nanoparticles: An approach for atherosclerosis treatment

Atherosclerosis is associated with inflammation in the arteries, a significant cause of heart attacks and strokes. Although statin therapy can reduce the chances of atherosclerotic plaque formation, they need to be administered in high doses due to low systemic bioavailability and encountered with side effects. To overcome these challenges, we developed nanoparticles using biocompatible and biodegradable lipids and polymers for improving systemic drug absorption and therapeutic response. The polymeric nanoparticles were prepared using PLGA and PVA, while hybrid nanoparticles were prepared using PLGA and Phospholipon 90 G. Both nanoparticles were systematically optimized by I-optimal response surface design. The optimum formulation composition exhibited particle size of less than 250 nm, polydispersity index of less than 0.3, entrapment efficiency of more than 70%, and sustained drug release up to 6 h. In vivo pharmacokinetic evaluation in rats indicated multi-fold improvement in the extent of drug absorption (Cmax and AUCtotal) for atorvastatin from the nanoparticles vis-à-vis the pure drug suspension. In vivo pharmacodynamic studies also indicated the excellent ability of nanoparticles to lower the elevated levels of lipids (total cholesterol, triglycerides, and low-density lipoproteins) and increase the level of high-density lipoproteins as compared to that of the pure drug suspension.

Formulation development, optimization and characterization of Pemigatinib-loaded supersaturable self-nanoemulsifying drug delivery systems

BackgroundPemigatinib is a small molecule tyrosine kinase inhibitor of fibroblast growth factor receptor inhibitors. The oral bioavailability of Pemigatinib is constricted due to its limited solubility at physiological pH. It is essential to develop a novel formulation of Pemigatinib to improve the intrinsic solubility and to reduce the pharmacokinetic variability. Self-nanoemulsifying drug delivery system is an effective, smart and more adequate formulation approach for poorly soluble drugs. Different from conventional self-nanoemulsifying drug delivery system, a supersaturable self-nanoemulsifying drug delivery system of Pemigatinib was prepared by using a supersaturation promoter.ResultsAmong all the oils, Captex® 300 have shown maximum solubility of Pemigatinib. Considering the solubilization potential and emulsification ability Kolliphor®RH 40 was selected as surfactant. Transcutol®HP was selected as co-surfactant. The composition of oil, surfactant and co-surfactant was identified using phase diagrams and further adjusted by simplex-lattice design. HPMC K4M as precipitation inhibitor at 5% concentration resulted in effective supersaturating with increased self-emulsification time. The droplet of sSNEDDS ranges from 166.78 ± 3.14 to 178.86 ± 1.24 nm with PDI 0.212 – 0.256, which is significantly smaller than that observed with plain SNEDDS. TEM images revealed the spherical shape of the nanodroplets. The final optimized formulation formed spontaneous nanoemulsion within 15 secs when added to physiological fluids. The percent transmittance of the diluted formulation was found to be 99.12 ± 0.46. The viscosity was found to be 574 ± 26 centipoises indicating the good flow ability. FTIR and DSC studies indicated the amorphization of the drug. The dissolution profile of sSNEDDS indicated the faster release of drug compared to both pure drug suspension and SNEDDS formulation. The drug release rate is directly proportional to the concentration of the drug. The drug release from the insoluble matrix is a square root of time-dependent Fickian diffusion process. The formulation was found to be stable and transparent at all pH values and the percent transmittance was more than 95%. Any kind of separation or precipitation was not observed at different temperatures cycles. No significant difference was observed with all the samples exposed at different storage conditions.ConclusionsThis study demonstrated the feasibility of stabilizing and improving the in-vitro performance of self-nanoemulsifying drug delivery systems of Pemigatinib by incorporating HPMC K4M as precipitation inhibitor.

Design, Development and In vivo Evaluation of Core in Cup Tablets of Budesonide

Budesonide is widely used drug for treatment of active inflammatory bowel disease (IBD). Core in-cup tablets were prepared to achieve a prolonged release of Budesonide and for alleviating the symptoms of inflammatory bowel disease. The objective of this study was to investigate differences in the pharmacokinetic patterns between an optimized core in cup tablet formulation and pure Budesonide suspension. In-vivo evaluation studies were performed based on the uniform and reliable results of in-vitro drug release studies. Various pharmacokinetic parameters were compared to obtain mean plasma drug concentration curve versus time. The pure drug suspension and Core-in-cup tablets formulation of Budesonide were administered to two groups of white New Zealand rabbits (n=6) through the oral route following cross over design pattern. The drug concentration in plasma samples were measured using LC-MS/MS method. Pharmacokinetic parameters were determined for each formulation. The comparison of the plasma time curves of the dosage forms showed that each dosage form caused significant differences in the drug plasma levels. The optimized core in cup tablet formulation shown some lag phase initially before releasing the drug. The mean residence time of core in cup tablet formulation was found to be more than the pure drug suspension formulation. The oral administration of Budesonide resulted in a low and quite variable AUC of 154.1±1.44 ng/ml/hr., whereas the optimized core-in-cup tablets resulted in AUC of 918.2±3.11 ng/ml/hr. The bioavailability of optimized formulation was enhanced six times compared with pure drug suspension. From the above results, it can be concluded that the prepared core in cup tablet can be considered as one of the promising formulation techniques for chronotherapeutic management of inflammatory bowel disease.

Silver and zinc oxide nanoparticles disrupt essential parasitism, neuropeptidergic, and expansion-like proteins genes in Meloidogyneincognita

Meloidogyne incognita leads to considerable losses in crop productivity. In this study, the impact of silver nanoparticles (AgNPs) and zinc oxide nanoparticles (ZnONPs) in 100, 200, or 300 ppm concentrations were investigated on some essential genes of M. incognita in vitro. For this purpose, AgNPs and ZnONPs were synthesized and characterized for their physicochemical properties. Thereafter, second-stage Juveniles (J2) of M. incognita were exposed to AgNPs and ZnONPs solution for 24 h. The LC50, LC90, and mortality rates were calculated for both nanoparticles. Finally, the expression of parasitism genes (Xyl-1; msp-20; 16D10), neuropeptidergic gene (Ace-2), expansion-like proteins (MAP-1), and oxidative stress gene (GSTS-1) was analyzed. The results showed a successful preparation of nanoparticles to obtain a pure, well-dispersed, and stable suspension, as revealed by physicochemical properties. ZnONPs showed LC50 and LC90 values of 63.56 and 208.5 ppm, respectively, while AgNPs recorded 11.78 and 28.59 ppm, respectively. AgNPs at concentrations 100, 200, and 300 ppm showed mortality rate 66%, 84%, and 100%, respectively, whereas ZnONPs at the same concentrations caused a 58%, 78%, and 91% mortality rate, respectively. Analysis of gene expression showed dose-dependent downregulation of each parasitism gene Xyl-1, 16D10, and msp-20 genes, neuropeptidergic gene (Ace-2), and expansion-like proteins MAP-1 after treatment with either AgNPs or ZnONPs. On the other hand, the oxidative stress response gene GSTS-1 showed upregulation with all concentrations of AgNPs and ZnONPs. The study concluded that the AgNPs and ZnONPs have efficient nematocidal activity and can be used in Meloidogyne incognita control.

Formulation and Evaluation of Zolmitriptan Loaded Nano-Structured Lipid Carriers for Effective Treatment in Migraine

Objective: Zolmitriptan is a BCS class II drug having low solubility and poor bioavailability by formulating Nanostructured lipid carriers that will sustain the release of the drug for a longer period which leads to reduced dose and frequency of dose.
 Method: Zolmiptriptan-loaded Nanostructured lipid carriers were fabricated by a solvent diffusion evaporation method. The formulation parameters like the selection of solid (Precirol ATO 5) and liquid lipid (Miglyol 812), solid to liquid lipid ratio (3:1), drug: solid lipid ratio (1:4), the ratio of the organic phase (Acetone: Ethanol, 1:1), the concentration of surfactant (1.5% Tween 80) and temperature (70 °C) of secondary phase were optimized. NLC dispersion was finally lyophilized and converted into a tablet. A stability study of freeze-dried NLCs tablet was performed according to ICH Q1A (R2) guidelines.
 Result: Optimized formulation contained Particle size 11.39 ± 0.85 nm, Zeta potential -38.30 and %EE 76.56 ± 0.12. Characterization was performed by TEM and FTIR analysis. The residual solvent test confirms the concentration of organic solvents was in the acceptable range as per ICH guidelines. In-vitro drug permeation study of NLCs shows 88.91±0.238 % drug release while pure drug suspension shows 58.9±0.578 % drug release after 12 hrs. 
 Conclusion: Zolmitriptan-loaded NLCs show better absorption as compared to pure drug suspension which indicates prolonged release of medicament which may reduce dose or dose frequency.

Integrated Application of Low-Intensity Pulsed Ultrasound in Diagnosis and Treatment of Atrophied Skeletal Muscle Induced in Tail-Suspended Rats.

Long-term exposure to microgravity leads to muscle atrophy, which is primarily characterized by a loss of muscle mass and strength and reduces one′s functional capability. A weightlessness-induced muscle atrophy model was established using the tail suspension test to evaluate the intervention or therapeutic effect of low-intensity pulsed ultrasound (LIPUS) on muscle atrophy. The rats were divided into five groups at random: the model group (B), the normal control group (NC), the sham-ultrasound control group (SUC), the LIPUS of 50 mW/cm2 radiation group (50 UR), and the LIPUS of 150 mW/cm2 radiation group (150 UR). Body weight, gastrocnemius weight, muscle force, and B-ultrasound images were used to evaluate muscle atrophy status. Results showed that the body weight, gastrocnemius weight, and image entropy of the tail suspension group were significantly lower than those of the control group (p < 0.01), confirming the presence of muscle atrophy. Although the results show that the muscle force and two weights of the rats stimulated by LIPUS are still much smaller than those of the NC group, they are significantly different from those of the pure tail suspension B group (p < 0.01). On day 14, the gastrocnemius forces of the rats exposed to 50 mW/cm2 and 150 mW/cm2 LIPUS were 150% and 165% of those in the B group. The gastrocnemius weights were both 135% of those in the B group. This suggests that ultrasound can, to a certain extent, prevent muscular atrophy.

FORMULATION AND EVALUATION OF SOLID-SUPERSATURABLE-SNEDDS OF IBRUTINIB

Objective: The aim of current research is to develop a solid supersaturable self-nanoemulsifying drug delivery system (S-SNEDDS) of ibrutinib for enhancing the solubility and Bioavailability. Methods: Crossential O 94–Croduret 40SS–carbitol are chosen based on the maximum solubility of ibrutinib and were used to construct ternary phase diagrams with Smix in 3:1 ratio and 70 mg drug loading was done and evaluated for particle size, zeta potential, polydispersity index, entrapment efficiency, drug content and in vitro drug release. Final optimised one is characterised for FTIR, DSC, stability studies and in-vivo studies in rats. To choose a precipitation inhibitor, in vitro precipitation studies were carried out, and supersaturable SNEDDS were made the prepared formulations were evaluated for micromertitic properties and the final optimised one is characterized for FTIR, DSC, SEM and stability studies. Results: Out of all formulations, F15 exhibited good results with the highest drug release of 98.25% in 60 min. LSS9 with 3% HPMC E4M as the best precipitation inhibitor (PPI) exhibited the smallest droplet size of 65.4 nm, a zeta potential of-17.7 mV, and a PDI of 0.453. SSS1 with magnesium trisilicate as an adsorbent showed best flow characteristics and the highest drug content of 99.72%. The DSC, FT-IR and stability studies confirmed the complexation of ibrutinib and amorphous state of the drug and formulation to be stable for 3 mo. Cmax of the solid supersaturable SNEDDS 139.42±2.16 mg/l was significant (p&lt;0.05) as compared to the pure drug suspension formulation 38.15±1.46 mg/l. Tmax of solid supersaturable SNEDDS formulation and pure drug suspension was 1.00±0.06 h and 1.50±0.02h, respectively. Statistically, AUC of the solid supersaturable SNEDDS formulation was significantly higher (p&lt;0.05) as compared to pure drug suspension formulation. Conclusion: Thus, this study indicated that the solid SNEDDS could be used as a potential drug carrier for ibrutinib with improved solubility and and bioavailability.

Tuning the rheological properties of kaolin suspensions using biopolymers

Kaolin based suspensions have wide range of applications such as slurry wall, drilling fluids, adhesives, cosmetics, refractories and pharmaceuticals, due to their abundance in nature, low cost and non-swelling nature. On the other hand, the unique properties (i.e., biodegradability) of biopolymers make them suitable candidate for variety of applications including modification of clay suspensions. In this study, the rheological properties of kaolin suspensions modified with different biopolymers (xanthan gum (XG), sodium carboxymethyl cellulose (CMC), potato starch (PS), chitosan (Ch) and apple fibre (AF)) have been investigated by varying the biopolymer type, content and clay content. The main objective of the present study is to propose a substitute for the natural mud sample. Frequency sweep tests, stress ramp-up tests and time-dependent tests were performed by using the Couette geometry (coaxial cylinders) for the prepared suspensions. The rheological results showed that both viscosity and moduli were significantly influenced by adding different biopolymers into the kaolin suspensions. For instance, an increase in viscosity of modified suspensions was observed: 3 – 4 orders of magnitude by adding xanthan gum (1 wt%) or sodium carboxymethyl cellulose (5 wt%) and 6 orders of magnitude by adding apple fibre (5 wt%). Likewise, the incorporation of different biopolymers significantly affected the complex modulus of modified clay suspensions. For example, similar or higher values of complex modulus than the pure kaolin suspension were observed at low xanthan gum or sodium carboxymethyl cellulose content (0.1 wt%). In case of chitosan, the complex modulus of the modified suspensions was higher than the complex modulus of pure kaolin suspension, even at very low polymer content (1 wt%). In the case of potato starch, a decrease in complex modulus by increasing polymer content till 10 wt% was observed followed by an increase in complex modulus with polymer content. The shear rate ramp-up and ramp-down experiments showed that the time-dependent behaviour of kaolin suspensions was not strongly influenced by adding different biopolymers. This knowledge will provide a base to choose a suitable substitute for the natural mud sample.

FORMULATION, IN VITRO AND IN VIVO EVALUATION OF PALBOCICLIB SOLID DISPERSIONS

Objective: The current research is aimed to enhance the dissolution and bioavailability of Palbociclib by formulating into solid dispersion Methods: The Palbociclib solid dispersions (SD) prepared by adopting different methods: Surface solid dispersion technique (SSD1-SSD15), Melt granulation (MG1-MG15) and Liquisolid compacts (LSC1-LSC9). All formulations were evaluated for physico-chemical parameters followed by in vitro dissolution studies. The optimised formulation was subjected to bioavailability studies in rats. Results: The results indicated that the prepared formulation satisfactory results for all the evaluated parameters. The SD formulations prepared by liquisolid compact and Melt Granulation technique (LSC1 and MG 3) displayed maximum dissolution of 99.64% and 99.58%. The FTIR of LSC1 displayed no interaction among drug and excipients while XRD, SEM displayed amorphous nature of drug in formulation. The stability study results indicated that LSC 1 was stable over 3 mo. The in vivo bioavailability studies conducted on rats indicate that at any time point, the drug plasma concentrations in animals administrated with the SD formulation was higher than pure drug. The Cmax of the palbociclib SD was 970.76±1.22 ng/ml and was significant (p&lt;0.05) when compared to pure drug suspension formulation (105.84±0.19 ng/ml). The Tmax of both SD formulation and pure drug were 2.0±0.04 and 4±0.01 h, respectively. The AUC0-∞ for SD was higher 7816.61±1.37 ng. h/ml) than the pure drug suspension 2501.4±1.46 ng. h/ml indicating better systemic drug absorption from SD formulation prepared using Melt granulation technique. Conclusion: A significant enhancement in vitro dissolution profile and bioavailability of the melt granules was observed compared to the pure Palbocicilib and marketed product.

Therapeutic Potential of Quercetin-Loaded Nanoemulsion against Experimental Visceral Leishmaniasis: In Vitro/Ex Vivo Studies and Mechanistic Insights.

Visceral leishmaniasis (VL) is one of the most fatal and neglected tropical diseases caused by Leishmania donovani (L. donovani). The applications of currently available chemotherapy (amphotericin B, miltefosine, and others) in VL treatment have been limited due to their poor bioavailability, unfavorable toxicity profile, and prolonged parenteral dosing. Quercetin (QT), a potent natural antioxidant, is a prominent target when conducting investigations on alternative therapies against L. donovani infections. However, the therapeutic applications of QT have been restricted due to its low solubility and bioavailability. In the present study, we developed and evaluated the antileishmanial activity (ALA) of quercetin-loaded nanoemulsion (QTNE) against L. donovani clinical strains. In vitro anti-promastigote assay results demonstrated that QTNE (IC50 6.6 μM, 48 h) significantly inhibited the growth of parasites more efficiently than the pure QT suspension in a dose- and time-dependent manner. Results of the anti-amastigote assay revealed that the infected macrophages (%) of QTNE were significantly more than those of the pure QT suspension at all concentrations (6.6, 26.4, and 52.8 μM; p < 0.05, p < 0.01 compared to the control). Moreover, the results of in vitro and ex vivo studies assisted in determining the mechanistic insights associated with the ALA of QTNE. The overall findings suggested that QTNE exhibited potential ALA by enhancing the intracellular ROS and nitric oxide levels, inducing distortion of membrane integrity and phosphatidylserine release (AV/PI), rupturing the parasite DNA (late apoptosis/necrosis process), and upregulating the immunomodulatory effects (IFN-γ and IL-10 levels). Additionally, QTNE showed superior biocompatibility against all of the treated healthy cells (PBMCs, PECs, and BMCs) as compared to the control. In conclusion, QTNE acts as a potential antileishmanial agent targeting both promastigote and intracellular amastigote forms of L. donovani, which thus opens a new avenue for the use of QTNE in VL therapy.

Self-Assembly of Amphiphilic Cubes in Suspension.

We study the self-assembly of amphiphilic cubic colloids using molecular dynamics as well as rejection-free kinetic Monte Carlo simulations. We vary both the number and location of the solvophobic faces (patches) on the cubes at several colloid volume fractions and determine the resulting size and shape distributions of the self-assembled aggregates. When the binding energy is comparable to the thermal energy of the system, aggregates typically consist of only few spontaneously associating/dissociating colloids. Increasing the binding energy (or lowering the temperature) leads to the emergence of highly stable aggregates, e.g., small dimers in pure suspensions of one-patch cubes or large (system-spanning) aggregates in suspensions of multipatch colloids. In mixtures of one- and multipatch cubes, the average aggregation number increases with increasing number of solvophobic faces on the multipatch cubes as well with increasing fraction of multipatch cubes. The resulting aggregate shapes range from elongated rods over fractal objects to compact spheres, depending on the number and arrangement of solvophobic patches on the cubic colloids. Our findings establish the complex self-assembly pathways for a class of building blocks that combine both interaction and shape anisotropy, with the potential of forming hierarchically ordered superstructures.

Design and evaluation of sustained release mucoadhesive film of sumatriptan succinate containing grafted co-polymer as the platform

PurposeThe primary goal of this research is to improve the bioavailability and efficacy of Sumatriptan succinate by incorporating it in the mucoadhesive film for the treatment of migraine. Mucoadhesive film offers an excellent substitute to deliver the drug in the systemic circulation and eliminate the chance of first-pass metabolism. MethodUsing central composite design (CCD), various formulations were created by incorporating polymer, plasticizer, and water, and an optimized preparation was created using statistical screening. The optimization has been performed by applying a 34 factorial method based on dependent variables such as Drug content (%), Swelling index (%), Folding endurance (Number of times), and Mucoadhesive strength (g). ResultsThe actual experimental values obtained were compared with those predicted by the mathematical models. Formulation S9 was selected as an optimized formulation because it showed the lowest standard deviation between predicted and actual values compared to other formulations. In the case of the S9 formulation, approximately 77.12% of the drug was released within 24 h, but initially, it showed burst release. In addition, the in-vitro release of pure drug suspension showed 99.32% drug release within 2 h. That signified that the developed formulation provides sustained release due to presence of grafted co-polymer. ConclusionFormulation holding drug-loaded grafted film showed decent sustained and controlled drug release characteristics compared to a pure drug suspension. S9 formulation showed better results than other formulations in drug content, swelling index, folding endurance, and mucoadhesive strength, which is further used to treat migraine.