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Iron oxide (magnetite) is the core of magnetic nanoparticles, which can be directed to the desired location using an external magnet. In this study, the magnetic nanoparticles were prepared by an emulsion solvent evaporation method and optimized using Box Behnken design. The mean particle size, polydispersity index, and zeta potential of optimized nanoparticles (formulation PMP-11) were 71.81 ± 4.4 to 384.1 ± 10.5 nm, 0.203 ± 0.008 to 0.777 ± 0.010, and −34.4 ± 3.1 to −10.2 ± 0.6 mV, respectively. The entrapment efficiency was found to be 84.64 ± 0.78%. TEM image confirmed formation of spherical nanoparticles. After 24 h, the formulations released 25.18%–56.63% and 54.38%–90.56% of loaded drug in phosphate buffer (6.8 pH) and 0.1 N HCl (pH 1.2), respectively. In HepG2 cell lines, the IC50value of optimized formulation was recorded to be 38.12 μg/mL. XRD analysis confirmed amorphous form of loaded drug. The mean average surface roughness for magnetite and optimized formulation was found to be 5.27025 nm and 8.29138 nm, respectively. The magnetization saturation for magnetite and optimized was 28.58 emu/g and 25.46 emu/g, respectively. Electron paramagnetic resonance spectroscopy of pure magnetite indicated g-Lande factor of 4.30 (typical for Fe3+ions). The g factor for optimized formulation was 4.24 suggesting superparamagnetic nature of the particles.

Lung cancer is a broad term that encompasses several subtypes of the leading cause of cancer-related mortality. Despite substantial gains in studying pulmonary tumor biology, advancements in earlier detection and multimodal management, and unraveling genetic routes of drug resistance, total curative results are still limited, particularly in metastatic illness. Tumor diagnosis and treatment are being impacted by nanotechnology, particularly nanoparticles (NPs). To manage lung tumors, nanoscale components have unique physical and chemical characteristics that enable a broader range of molecular instruments. As chitosan nanoparticles can adjust release rates and precisely transport chemotherapeutic drugs, they alleviate the limitations of conventional anti-cancer treatments while simultaneously making them more effective and cost-efficient than ever before. As a drug carrier, chitosan's mucoadhesive, permeation-enhancing, and site/cell-specific properties play a significant role in its performance. Microencapsulation and micro-nano mixing systems have been designed for nanocarriers to enable efficient pulmonary aerosolization and inhalation and a wide range of nanocarriers. As part of this review, we emphasize the advances and opportunities connected with using chitosan-coated nanomedicines for lung cancer treatment and the hurdles involved with clinical translation in this sector.

Background: Treatment by using magnetic nanoparticles is an emerging concept. Currently, magnetic nanoparticles (MNP) are being used for hyperthermia, targeting of drugs (active or passive), and for diagnostic purposes using nuclear magnetic resonance imaging. Objective: In the present study, imatinib-loaded chitosan magnetic nanoparticles were formulated by modified ionic gelation method. The purpose of the study was to explore the effect of the concentration of magnetite (X1) and the concentration of chitosan (X2) on the encapsulation of imatinib from magnetic nanoparticles using a central composite design. Methods: The formulated magnetic nanoparticles were characterized by laser light scattering, Fourier transform infrared spectroscopy, scanning electron microscope, and zeta potential measurement. Results: It was found that batch MNP-4 has the maximum encapsulation efficiency, loading capacity, and minimum particle size achieved for the optimized batch. Scanning Electron Microscopy (SEM) results confirmed a sphere-shaped or ellipsoidal morphology of the nanoparticles. A particle size analysis gives an average diameter of 188 nm. The encapsulation efficiency and drug loading were found to be (7.22 ± 0.13) and (5.16 ± 0.34) mg/100 mg, respectively, for the optimized batch. In-vitro drug release studies disclosed that 91.05% of the drug was released cumulatively. The magnetic characteristics were confirmed by a vibrating sample magnetometer. The saturation of magnetization was found to be 1.408 emu/g. VSM analysis confirmed that the as-prepared magnetic chitosan nanoparticles have a satisfactory magnetic receptivity for a prospective magnetic drug carrier for targeted delivery. The encapsulation efficiency was highest at the highest levels of chitosan and magnetite concentration. The encapsulation was lowest at the lowest level of the chitosan concentration. Conclusion: The magnetic and nano-effects due to the presence of magnetite and crosslinked chitosan are strong determining factors for the utilization of the prepared nanoparticles for various targeted applications. The model developed in the current study can be further utilized as response surface for the encapsulation efficiency of MNPs.

In the present study, spray-dried nanoparticles-in-microparticles system (NiMS) of Acetazolamide (ACZ) was formulated for preparing orally disintegrating tablets (ODT). The objective behind the study was to investigate the effect of - concentration of chitosan (X1), volume of sodium tripolyphosphate (NaTPP) (X2) and inlet temperature of spray dryer (X3) on entrapment efficiency of ACZ using Central Composite Design (CCD). The spray dried optimized NiMS were formulated into orally disintegrating tablets using direct compression method. It was found that batch NiMS-7 (formulated using 0.5 % w/v chitosan; 20 ml NaTPP at inlet temperature of 140°C) has a maximum entrapment efficiency 56.08% (w/w), loading capacity 68.39% (w/w), percentage yield 30.15%, (w/w) and particle size of 455 nm. Analysis of Variance (ANOVA) was applied on the entrapment efficiency of NiMS to study the fitting and the significance of the model. The estimated model may be further utilized as response surface for entrapment efficiency of NiMS. The batch NiMS-7 showed 90.70% drug release after three hours in phosphate buffer pH 7.4 and 61.52% in 0.1 N HCl. Infrared analysis of NiMS-7 showed no interaction between drug and polymer during the formulation process. The optimized batch was further formulated into ODT. The ODT was formulated using sodium starch glycolate (52.5 mg), microcrystalline cellulose (15 mg), lactose (34.5 mg), mannitol (15 mg), talc (1.50 mg) and magnesium stearate (1.50 mg). The formulated ODTs have a disintegration time of 38 seconds. The hardness, friability and weight variation of ODTs were found to be within pharmacopoeial limits. In vitro drug release studies revealed that cumulative percent of drug released was found to be 92.90% in 60 mins and the release data followed the first order kinetics. Therefore, this NiMS approach has been successfully applied to formulate ODT of ACZ and can be advantageous for the treatment of glaucoma in the case of paediatric patients.

AbstractObjective: To evaluate the efficacy of intrathecal hyperbaric bupivacaine premixed with dexmeditomidine compared with sequential administration in separate syringes on block characteristics, haemodynamic parameters, side effect profile and postoperative analgesic requirement.Trial design: This was a prospective, randomised clinical study
Method: Sixty orthopaedic patients scheduled for elective lower limb surgery under spinal anaesthesia were divided into two groups to receive either intrathecal hyperbaric bupivacaine 12.5 mg premixed (Group P) with dexmeditomidine 10 μg (diluted to 0.5 ml with normal saline) or by sequential administration in separate syringes (Group S).Outcome: Block characteristics, haemodynamic parameters, side effect profile and postoperative analgesic requirement were compared in both groups. 
Results: Time to achieve T10 spinal level was significantly less in group S (4.467 +  0.973 min) compared with group P (5.5 + 1.167 min). Similarly, patients in group S achieved Modified Bromage III earlier (6.1 + 1.296 min) than group P (7.5 + 1.333 min), p-value 0.0001. 
Conclusion: Dexmeditomidine given sequentially in a separate syringe as adjuvant to intrathecal hyperbaric bupivacaine can result in faster onset of both sensory and motor block and prolongs the duration of spinal anaesthesia, minimises clinically significant side effects and reduces the postoperative analgesic requirement.

There has been a tremendous development in the field of modeling and optimization methods starting from Taylor’s tool life model. Use of costly tools such as polycrystalline cubic boron nitride, polycrystalline diamond and ceramics in high-end computer numerical control machining forces the researcher to minimize the experimental runs to achieve the best cutting conditions with minimum tool wear and overall production cost. Machining process optimization to achieve said objectives comprises selecting optimum cutting parameters by applying low-cost mathematical models. This article attempts to evaluate the applicability of various modeling and optimization methods to specific response parameters in hard turning problems. Various empirical modeling techniques such as linear regression modeling, artificial neural networks, polynomial and fuzzy modeling along with process optimization through Taguchi, response surface methodology and genetic algorithm for hard turning applications have been discussed in length to provide the production engineers a ready database to compare relative merits and suitability of these techniques for a particular machining application. Also, article discusses integration of different modeling and optimization techniques to achieve desired goals when a single optimization technique is not able to provide the acceptable solution. The last part of the article highlights the current trends in hard turning applications and research priorities for future work.

In the present investigation an attempt has been made to explore the potential of MQL milling of Inconel-625 with coated carbide tool. The performance is compared in terms of surface roughness and tool flank wear in MQL milling with dry and wet milling operation of Inconel-625. The milling under MQL condition gives superior results over wet and dry milling operations. Factorial design of experiments ANOVA analysis was applied to investigate the statistically significant parameters. RSM-Desirability function optimization was applied to find out optimal setting of parameters to minimize tool wear and surface roughness in MQL machining of Inconel-625.

Cutting fluids cool and lubricate the cutting tool and machined area, wash away chips thereby increasing material removal rate, lengthen tool life and improve dimensional accuracy. However, strict environmental regulations prohibit liberal use of conventional coolants due to environment, health hazards and economic reasons. But, dry cutting although environmental friendly is not feasible under all machining applications. Some materials, when machined dry, tend to stick to tool face, spoiling tool and machined surface finish, can be efficiently machined under near dry machining (NDM) or under minimum quantity lubrication (MQL) conditions; in which cooling and lubrication in the cutting zone can be achieved by a tiny amount of cutting oil applied to tool tip with compressed air in mist form, thereby addressing the negative impact of flooded coolant machining. This paper, attempts to critically review research progress and current state of affairs in machining of difficult to machine alloys under NDM/MQL.

The various approaches have been utilized in the treatment of a variety of diseases by applying drug delivery system such as polymeric nanoparticles, self-emulsifying delivery systems, liposomes, microemulsions and micellar solutions. Recently, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and lipid-drug conjugates (LDCs) have been exploited as a carrier of lipophilic and hydrophilic/amphiphilic substances for invasive and non-invasive routes of delivery. SLNs are colloidal drug carrier system and are like nanoemulsion, however, the lipid content in SLNs is solid in nature. These novel type of lipid nanoparticles with solid matrix offers to develop new prototype therapeutics in drug delivery, which could be used for controlled release, drug targeting, gene therapy, physical and chemical stability and site-specific drug delivery and thereby attracted the research groups worldwide. This manuscript overviews the recent patents, advantages, formulation techniques, stability aspects and applications of SLNs.

Tuberculosis (TB) is reported as one of the most prevailing life-threatening health problems, affecting almost one third of the population globally. It is one of a major reason of death with an imposing amplified socio-economic impact. Tuberculosis patients have infrequent endocrine and metabolic derangements, but they are important when they occur. Multiple drug regimen, poor patient compliance, and stiff administration schedule are factors that are answerable for the development of and extensive drug resistance (XDR) and multi drug resistance (MDR) instances in TB along with poor drug targeting effects. The emerging resistance strains and high transmittance rate of the disease have prompted the need for studies in advanced drug delivery, particularly nanotechnology for the management of TB. Nanocarriers offer unique physicochemical properties that provide beneficial outcomes such as targeted effects and better patient compliance as drug delivery, thereby presenting as a promising solution to the constraints linked with conventional treatment strategy for TB. Both in vitroand in vivostudies have been reported to access release behavior of antitubercular agents with a view to being interpreted in clinical practice in the future. The present review highlights contemporary trends and advancements in drug delivery systems employed for the effective management of TB. This communication will be useful to the researchers working in the field of drug delivery systems for effective management of TB.

This article deals with developing an efficient and economical method to quantify the major products of ABE fermentation (sugars, volatile fatty acids, acetone, ethanol and butanol) using HPLC. Other techniques based on a similar principle have poor resolution between peaks of butyric acid, acetone and ethanol. The advantage of our method was that the overlapping peaks of butyric acid, acetone and ethanol were separated and thus quantified simultaneously during analysis. Also, flow programming was used to reduce the analysis time, thereby saving energy. The maximum separation of all components was achieved using a water–sulfuric acid mixture (5 mM H2SO4in water) as the mobile phase using flow programming with increasing flow rate from 0.6 ml to 0.9 ml within 21 min during analysis with a total run time of 26 min at a column temperature of 80 °C. A linear relationship over the analytical range of 10.0 to 0.01 g l−1was observed. The robustness of the developed method was evaluated using parameters such as the capacity factor, selectivity, plate number and resolution. The applicability of this approach was validated by quantifying the substrates and products of ABE fermentation using lignocellulosic waste hydrolysate as a carbon source. The results of analysis proved that the method is reproducible, accurate, precise, and sensitive.

Taste masking is an important factor in the development of oral dosage forms containing bitter active pharmaceutical ingredients. Currently numerous techniques are being applied to overcome this problem. Realizing this, several researchers and pharmaceutical companies are now engaged in developing novel techniques to address the problem of taste masking evident by numerous patents filed in this area in recent times. In this review the most recent patents for taste masking are discussed and how these patents overcome the limitations of conventional approaches of taste masking is also highlighted. Novel techniques based on some recent patents such as nanohybrid, melt extrusion, non-complex cyclodextrin compositions and off taste masking are providing new realms to taste masking of bitter drugs. The present article also provides an overview of various patented platform technologies based on different techniques/mechanisms employed for taste masking. The unique features and principles of taste-masking approaches used in various patented technologies are also discussed. A better understanding of these new patents and patented technologies will help researchers and pharmaceutical industries to select the appropriate platform, or to develop innovative products with improved taste masking properties.

Allelopathic potentiality of hexane, ethyl acetate and methanol extracts of the Himalyan lichen, Parmelia reticulateTaylor, at different concentrations (50, 25 and 12.5μg ml-1) was studied on germination and early seedling growth of highly devastating weed Phalaris minor. The experiments were carried out in portray maintained in natural environment. Current investigation has revealed concentration dependent allelopathic phenomenon of the lichen extracts on P. minor. Hexane and ethyl acetate extracts at 50μg ml-1exhibited maximum detrimental effect on seed germination (56% as compared to control i.e. 90%). Hexane extract at 50μg ml-1showed maximum inhibition of early seedling growths, determined in terms of shoot and root lengths of the test weed. It reduced shoot and root lengths to 2.5cm (control 10.7 cm) and 0.9 cm (control 3.4cm) respectively, indicating semipolar nature of constituents responsible for bioactivity.

The introduction of high speed tableting machines and the preference of direct compression as a method of tableting have increased the demands on the functionality of excipients mainly in terms of flowability and compressibility. Co-processed excipients, where in, excipients are combined by virtue of sub-particle level interaction have provided an attractive tool for developing high functionality excipients. The multifold advantages offered by co-processed excipients such as production of synergism in functionality of individual components, reduction of companys regulatory concern because of absence of chemical change during co-processing and improvement in physico-chemical properties have expanded their use in the pharmaceutical industry. In the recent years, there has been a spurt in the number of patents filed on co-processed excipients. Hence, the present review focuses on co-processed excipients and their application in pharmaceutical industry. The worldwide databases of European patent office (http://ep.espacenet.com) and United States patent office (www.uspto.gov) were employed to collect the patents and patent applications. The advantages, limitations, basis for the selection of excipients to be co-processed, methods of co-processing and regulatory perspective of co-processed excipients are also briefly discussed.

5-Fluorouracil (5-FU) is a hydrophilic drug with short plasma half-life. The objective of the current study was to prepare and optimize 5-FU loaded chitosan nanoparticles (CNPs) for controlled release. The nanoparticles were prepared by ionic gelation of chitosan with tripolyphosphate anions. A 23 central composite design (CCD) was employed to study the influence of formulation variables - concentration of Chitosan (X1), the concentration of sodium tripolyphosphate (NaTPP) (X2) and volume of NaTPP (X3) on the cumulative percentage of drug release. The relationship between the dependent and independent variables was further elucidated using multiple linear regression analysis (MLRA) and Pareto chart. The results show that cumulative percent of 5-FU release was highest and lowest at high levels of X1, X2, and low level of X3, and high level of X1, and low levels of X2 and X3, respectively. The optimized nanoparticles were studied morphologically by transmission electron microscopy (TEM) which showed separated and non-aggregated nanoparticles with spherical shapes and smooth surfaces. The mean particle size, entrapment efficiency and loading capacity of the optimal CNPs were found to be 109.6±2.28 nm, 83.84±1.46%, and 37.76±3.41%, respectively. Nanoparticles revealed a fast release during the first hour followed by a more gradual drug release during a 24-h period following a non-Fickian diffusion process. Analysis of variance (ANOVA) was applied on cumulative percent of drug release to study the fitting and significance of model. The estimated model may be further utilized as response surface for cumulative percent of drug release from nanoparticles. The 5-FU loaded CNPs optimized using CCD showed good entrapment efficiency and controlled release as well as can reduce dosing frequency, decrease side effects and improve patient compliance.

The present study was designed to investigate the effects ofdifferent variables on the release profile of ibuprofen microspheres formulated using modified emulsification method. Eight batches of microspheres (F1-F8) were prepared by applying 23factorial design. The amount of sodium alginate, amount of calcium Chloride, and amount of magnesium stearate were selected as formulation variables. All the batches were evaluated in terms of percentage yield, percentage encapsulation efficiency and in vitrorelease characteristics. The batch F7 was found to be Optimum batch and was further characterized via scanning electron microscopy (SEM) and particle size analysis. Multiple linear regression was applied to confirm significant effect of each variable on release characteristics. The model developed in the present study can be effectively utilized to achieve the formulation with desired release characteristics.

Nonalcoholic fatty liver disease (NAFLD) is a common indication for liver transplantation and can recur in the graft. To describe this recurrence, we performed a cohort study of individuals undergoing liver transplantation for NAFLD-related cirrhosis between 1993 and 2007. Predictors of NAFLD recurrence and outcomes in this cohort were also studied.