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The incidence of "acid attacks" (vitreolage) is a global concern, with those affected often receiving lifelong medical care due to physical and psychological damage. The purpose of this study was to evaluate the effectiveness of several emergency skin decontamination approaches against concentrated (>99 %) sulphuric acid and to identify the effective window of opportunity for decontamination. The effects of four decontamination methods (dry, wet, combined dry & wet and cotton cloth) were assessed using an in vitro diffusion cell system containing dermatomed porcine skin. Sulphuric acid (H 2 SO 4 ) was applied to the skin with decontamination protocols performed at 10 s, 30 s, 8 min, and 30 min post exposure. Skin damage was quantified by tritiated water ( 3 H 2 O) penetration, receptor fluid pH and photometric stereo imaging (PSI), with quantification of residual sulphur (by SEM-EDS) to determine overall decontamination efficiency. Skin translucency (quantified by PSI) demonstrated a time-dependent loss of dermal tissue integrity from 10 s. Quantification of dermal sulphur content confirmed the rapid (exponential) decrease in decontamination efficiency with time. The pH of the water effluent indicated complete neutralisation of acid from the skin surface after 90 s of irrigation. Wet decontamination (either alone or immediately following dry decontamination) was the most effective intervention evaluated, although no decontamination technique was statistically effective after 30 s exposure to the acid. These data demonstrate the time-critical consequences of dermal exposure to concentrated sulphuric acid: we find no practical window of opportunity for acid decontamination, as physical damage is virtually instantaneous., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Breast cancer is one of the most frequently diagnosed cancers in women and the major cause of worldwide cancer-related deaths among women. Various treatment strategies including conventional chemotherapy, immunotherapy, gene therapy, gene silencing and deliberately engineered nanomaterials for receptor mediated targeted delivery of anticancer drugs, antibodies, and small-molecule inhibitors, etc are being investigated by scientists to combat breast cancer. Smartly designed/fabricated nanomaterials are being explored to target breast cancer through enhanced permeation and retention effect; and also, being conjugated with suitable ligand for receptor-mediated endocytosis to target breast cancer for diagnostic, and theranostic applications. These receptor-targeted nanomedicines have shown efficacy to target specific tumor tissue/cells abstaining the healthy tissues/cells from cytotoxic effect of anticancer drug molecules. In the last few decades, theranostic nanomedicines have gained much attention among other nanoparticle systems due to their unique ability to deliver chemotherapeutic as well as diagnostic agents, simultaneously. Theranostic nanomaterials are emerging as novel paradigm with ability for concurrent delivery of imaging (with contrasting agents), targeting (with biomarkers), and anticancer therapeutics with one delivery system (as cancer theranostics) and can transpire as promising strategy to overcome various hurdles for effective management of breast cancer including its most aggressive form, triple-negative breast cancer.

Cancer is one of the major leading causes of mortality in the world. The implication of nanotherapeutics in cancer has garnered splendid attention owing to their capability to efficiently address various difficulties associated with conventional drug delivery systems such as non-specific biodistribution, poor efficacy, and the possibility of occurrence of multi-drug resistance. Amongst a plethora of nanocarriers for drugs, this review emphasized lipidic nanocarrier systems for delivering anticancer therapeutics because of their biocompatibility, safety, high drug loading and capability to simultaneously carrying imaging agent and ligands as well. Furthermore, to date, the lack of interaction between diagnosis and treatment has hampered the efforts of the nanotherapeutic approach alone to deal with cancer effectively. Therefore, a novel paradigm with concomitant imaging (with contrasting agents), targeting (with biomarkers), and anticancer agent being delivered in one lipidic nanocarrier system (as cancer theranostics) seems to be very promising in overcoming various hurdles in effective cancer treatment. The major obstacles that are supposed to be addressed by employing lipidic theranostic nanomedicine include nanomedicine reach to tumor cells, drug internalization in cancer cells for therapeutic intervention, off-site drug distribution, and uptake via the host immune system. A comprehensive account of recent research updates in the field of lipidic nanocarrier loaded with therapeutic and diagnostic agents is covered in the present article. Nevertheless, there are notable hurdles in the clinical translation of the lipidic theranostic nanomedicines, which are also highlighted in the present review along with plausible countermeasures.

The buccal mucosa appears as a promissory route for biologic drug administration, and pharmaceutical films are flexible dosage forms that can be used in the buccal mucosa as drug delivery systems for either a local or systemic effect. Recently, thin films have been used as printing substrates to manufacture these dosage forms by inkjet printing. As such, it is necessary to investigate the effects of printing biologics on films as substrates in terms of their physical and mucoadhesive properties. Here, we explored solvent casting as a conventional method with two biocompatible polymers, hydroxypropyl methylcellulose, and chitosan, and we used electrospinning process as an electrospun film fabrication of polycaprolactone fibers due to its potential to elicit mucoadhesion. Lysozyme was used as biologic drug model and was formulated as a solution for printing by thermal inkjet printing. Films were characterized before and after printing by mechanical and mucoadhesive properties, surface, and ultrastructure morphology through scanning electron microscopy and solid state properties by thermal analysis. Although minor differences were detected in micrographs and thermograms in all polymeric films tested, neither mechanical nor mucoadhesive properties were affected by these differences. Thus, biologic drug printing on films was successful without affecting their mechanical or mucoadhesive properties. These results open way to explore biologics loading on buccal films by inkjet printing, and future efforts will include further in vitro and in vivo evaluations.

Hypothyroidism is a chronic and debilitating disease that is estimated to affect 3% of the general population. Clinical experience has highlighted the synergistic value of combining triiodothyronine (T 3 ) and thyroxine (T 4 ) for persistent or recurrent symptoms. However, thus far a platform that enables the simultaneous and independent dosing of more than one drug for oral administration has not been developed. Thermal inkjet (TIJ) 2D printing is a potential solution to enable the dual deposition of T 3 and T 4 onto orodispersible films (ODFs) for therapy personalisation. In this study, a two-cartridge TIJ printer was modified such that it could print separate solutions of T 3 and T 4 . Dose adjustments were achieved by printing solutions adjacent to each other, enabling therapeutic T 3 (15-50 μg) and T 4 dosages (60-180 μg) to be successfully printed. Excellent linearity was observed between the theoretical and measured dose for both T 3 and T 4 (R 2  = 0.982 and 0.985, respectively) by changing the length of the print objective (Y-value). Rapid disintegration of the ODFs was achieved (<45 s). As such, this study for the first time demonstrates the ability to produce personalised dose combinations by TIJ printing T 3 and T 4 onto the same substrate for oral administration., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Warfarin is a widely used anticoagulant that is critical in reducing patient morbidity and mortality associated with thromboembolic disorders. However, its narrow therapeutic index and large inter-individual variability can lead to complex dosage regimes. Formulating warfarin as an orodispersible film (ODF) using thermal ink-jet (TIJ) printing could enable personalisation of therapy to simplify administration. Commercial TIJ printers are currently unsuitable for printing the milligram dosages, typically required for warfarin therapy. As such, this study aimed to modify a commercial TIJ printing system to formulate personalised warfarin ODFs containing therapeutic dosages. A TIJ printer was modified successfully with the printer functionality intact; the substrate (paper) rolling mechanism of the printer was replaced by printing onto a stationary stage. Free film substrates were composed of hydroxypropyl methylcellulose (20%w/w) and glycerol (3%w/w). The resulting ODFs were characterised for morphology, disintegration, solid-state properties and drug content. Printed film stability was assessed at 40 °C/75% relative humidity for 30 days. Therapeutic warfarin doses (1.25 and 2.5 mg) were successfully printed onto the film substrates. Excellent linearity was observed between the theoretical and measured dose by changing the warfarin feed concentration (R 2  = 0.9999) and length of the print objective, i.e. the Y-value, (R 2  = 0.9998). Rapid disintegration of the ODFs was achieved. As such, this study successfully formulated personalised warfarin ODFs using a modified TIJ printer, widening the range of applications for TIJ printing to formulate narrow therapeutic index drugs., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The process of drying thin polymer films is an important operation that influences the film structure and solid state, and the stability of the product. The purpose of this work was to study and model the drying kinetics of multicomponent films based on two polymers: hydroxypropyl methylcellulose (HPMC, amorphous) and polyvinyl alcohol (PVA, semicrystalline). The isothermal drying kinetics of the films at different temperatures (40, 60, and 80°C) were studied using thermo-gravimetric analysis (TGA) and convection oven methods. Solid-state characterization tools used in the study included polarization and hot-stage microscopy, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). The drying kinetics of HPMC and PVA films in the TGA apparatus and convection oven were comparable. The three-parameter (W max , τ, n) Hill equation successfully modeled the experimental drying kinetics. The time factor τ in the Hill equation nicely explained two drying phases in the films. Solid-state phase changes occurring in the films during dehydration had a bearing on the drying kinetics and mechanisms. TGA can be used as a simple tool to determine the end points in drying processes using ovens or tunnels. The three-parameter Hill equation explained the drying kinetics and diffusion mechanisms of the solvent through the polymer films for the first time. This study advances our understanding of film drying, in particular for pharmaceutically relevant thin films.

The aim of the present work was to prepare tadalafil (TDF) nanocrystals-loaded oral polymeric films (OFs) and investigate the effect of hydrophilic surfactants and drug loads on the physico-mechanical and dissolution properties. The nanosuspensions of TDF were prepared by high shear homogenization. HPMC based placebo casting film gel was prepared and mixed with TDF nanosuspensions. Films were casted using an automated film applicator and dried at 60°C for 45min. Particle size (PS), polydispersity index (PDI), and zeta potential (ZP) of TDF nanosuspensions were measured in a Zetasizer. The films were characterized using SEM, AFM, DSC, TGA and PXRD. The mechanical properties and in vitro drug release were determined using standard methods. TDF existed in crystalline form and the particles remained in the nano-range in redispersed films. TDF nanocrystals were embedded in the polymeric matrix and the drug loaded films were rough on the surface. Mechanical properties of the films varied with changes in drug load and surfactant. Significant changes in the disintegration times were noticed in films containing surfactants compared to surfactant-free films. About 80% of the drug release was observed between 3 and 30min. TPGS showed better TDF release from the films at different drug loads., Chemical Compounds: Hydroxy propyl methyl cellulose (PubChem CID: 57503849); Glycerol (PubChem CID: 753); Pluronic F-68 (PubChem CID: 24751); Vitamin E TPGS (PubChem CID: 71406)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The effect of different plasticizers (glycerol, vitamin E TPGS and triacetin) and their concentrations on the physico-mechanical properties of pullulan based oral films was studied. A full factorial (3 2 ) design of experiments was used. Elastic modulus, tensile strength, elongation at break and disintegration time were selected as response variables. Modulated differential scanning calorimeter (MDSC) was used for determining glass transition temperature (T g ) of pullulan films. The surface morphology of films was evaluated by SEM, while ATR-FTIR was used to obtain a molecular level understanding of polymer-plasticizer interactions. The DoE analysis allowed for the modelling of tensile strength and elongation at break. The highest elongations were observed in glycerol at 20% w/w. Majority of the films disintegrated within one minute without significant differences. ATR-FTIR spectra of pullulan alone and different plasticizer blend films show characteristic molecular interactions. The present study concluded that glycerol is suitable plasticizer compared to others for manufacturing pullulan based oral films., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The intention of this study is to achieve higher entrapment efficiency (EE) of berberine chloride (selected hydrophilic drug) using nanoprecipitation technique. The solubility of drug was studied in various pH buffers (1.2-7.2) for selection of aqueous phase and stabilizer. Quality by design (QbD)-based 3(2) factorial design were employed for optimization of formulation variables; drug to polymer ratio (X1) and surfactant concentration (X2) on entrapment efficiency (EE), particle size (PS) and polydispersity index (PDI) of the nanoparticles. The nanoparticles were subjected to solid state analysis, in vitro drug release and stability study. The aqueous phase and stabilizer selected for the formulations were pH 4.5 phthalate buffer and surfactant F-68, respectively. The formulation (F-6) containing drug to polymer ratio (1:3) and stabilizer (F-68) concentration of 50 mM exhibited best EE (82.12%), PS (196.71 nm), PDI (0.153). The various solid state characterizations assured that entrapped drug is amorphous and nanoparticles are fairly spherical in shape. In vitro drug release of the F-6 exhibited sustained release with non-Fickian diffusion and stable at storage condition. This work illustrates that the proper selection of aqueous phase and optimization of formulation variables could be helpful in improving the EE of hydrophilic drugs by nanoprecipitation technique.

The present research work is focused on the development of solid lipid nanoparticles of cefuroxime axetil (CA-SLN) for its enhanced inhibitory activity against Staphylococcus aureus produced biofilm. CA-SLN was prepared by solvent emulsification/evaporation method using single lipid (stearic acid (SA)) and binary lipids (SA and tristearin (TS)). Process variables such as volume of dispersion medium, concentration of surfactant, homogenization speed and time were optimized. The prepared SLN were characterized for encapsulation efficiency, drug polymer interaction studies (DSC and FT-IR), shape and surface morphology (SEM and AFM), in vitro drug release, stability studies and in vitro anti biofilm activity against S. aureus biofilm. Among the process variables, increased volume of dispersion medium, homogenization speed and time led to increase in particle size whereas increase in surfactant concentration decreased the particle size. SLN prepared using binary lipids exhibited higher entrapment efficiency than the single lipid. DSC and FT-IR studies showed no incompatible interaction between drug and excipients. CA-SLN showed two folds higher anti-biofilm activity in vitro than pristine CA against S. aureus biofilm., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Targeted delivery of antiosteoarthritic drug diacerein to articular tissue could be a major achievement and soluble polysaccharide chondroitin sulfate (ChS) may be a suitable agent for this. Therefore, diacerein loaded solid lipid nanoparticles modified with ChS (ChS-DC-SLN) were prepared for synergistic effect of these agents to combat multidimensional pathology of osteoarthritis (OA). Prepared formulation were of size range 396±2.7nm, showed extended release up to 16h and increased bioavailability of diacerein by 2.8 times. ChS-DC-SLN were evaluated for their effect on histopathology of femoro-tibial joint of rat knee and amount of ChS and rhein (an active metabolite of diacerein) at targeted site. Concentration of rhein was significantly higher in case of ChS-DC-SLN (7.8±1.23μg/ml) than that of drug dispersion (2.9±0.45μg/ml). It can be stated that ChS served as homing to articular cartilage for targeting of drug. Thus, ChS-DC-SLN have great potential to enhance the overall efficacy of treatment for OA., From the Clinical Editor: This study demonstrates the feasibility of targeted delivery of diacerein to articular tissue using soluble polysaccharide chondroitin sulfate as the targeting vector. This approach has the potential to significantly increase anti-arthritic drug concentration in joints without leading to systemic toxicity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The objective of the present study is to investigate the influence of surface modification on systemic stability of NPs. Vitamin E TPGS (1% w/v) was used for surface modification of berberine chloride nanoparticles. Naked and surface modified NPs were incubated in different SBFs (pH 6.8 and 7.4) with or without bile salts and human plasma. NPs were observed for particle agglomeration and morphology by particle size analyzer and TEM, respectively. The haemocompatibility studies were conducted on developed NPs to evaluate their safety profile. The surface modified NPs were stable compared to naked NPs in different SBFs due to the steric stabilization property of vitamin E TPGS. Particle agglomeration was not seen when NPs were incubated in SBF (pH 6.8) with bile salts. No agglomeration was observed in NPs after their incubation in plasma but particle size of the naked NPs increased due to adhesion of plasma proteins. The TEM images confirmed the particle size results. DSC and FT-IR studies confirmed the coexistence of TPGS in surface modified NPs. The permissible haemolysis, LDH release, and platelet aggregation revealed that NPs were compatible for systemic administration. Thus, the study illustrated that the surface modification is helpful in the maintenance of stability of NPs in systemic conditions.

The objective of the present study was to develop self micro emulsifying formulation (SMEF) of valsartan to improve its oral bioavailability. The formulations were screened on the basis of solubility, stability, emulsification efficiency, particle size and zeta potential. The optimized liquid SMEF contains valsartan (20% w/w), Capmul MCM C8 (16% w/w), Tween 80 (42.66% w/w) and PEG 400 (21.33% w/w) as drug, oil, surfactant and co-surfactant, respectively. Further, Liquid SMEF was adsorbed on Aerosol 200 by spray and freeze drying methods in the ratio of 2 : 1 and transformed into free flowing powder. Both the optimized liquid and solid SMEF had the particle size <200 nm with rapid reconstitution properties. Both drying methods are equally capable for producing stable solid SMEF and immediate release of drug in in vitro and in vivo conditions. However, the solid SMEF produced by spray drying method showed high flowability and compressibility. The solid state characterization employing the FTIR, DSC and XRD studies indicated insignificant interaction of drug with lipid and adsorbed excipient. The relative bioavailability of solid SMEF was approximately 1.5 to 3.0 folds higher than marketed formulation and pure drug. Thus, the developed solid SMEF illustrates an alternative delivery of valsartan as compared to existing formulations with improved bioavailability.

Raloxifene hydrochloride (RL-HCL) is an orally selective estrogen receptor modulator (SERM) with poor bioavailability of nearly 2% due to its poor aqueous solubility and extensive first pass metabolism. In order to improve the oral bioavailability of raloxifene, raloxifene loaded solid lipid nanoparticles (SLN) have been developed using Compritol 888 ATO as lipid carrier and Pluronic F68 as surfactant. Raloxifene loaded SLN were prepared by solvent emulsification/evaporation method, and different concentrations of surfactant, and homogenization speed were taken as process variables for optimization. SLN were characterized for particle size, zeta potential, entrapment efficiency, surface morphology, and crystallinity of lipid and drug. In vitro drug release studies were performed in phosphate buffer of pH 6.8 using dialysis bag diffusion technique. Particle sizes of all the formulations were in the range of 250 to 1406 nm, and the entrapment efficiency ranges from 55 to 66%. FTIR and DSC studies indicated no interaction between drug and lipid, and the XRD spectrum showed that RL-HCL is in amorphous form in the formulation. In vitro release profiles were biphasic in nature and followed Higuchi model of release kinetics. Pharmacokinetics of raloxifene loaded solid lipid nanoparticles after oral administration to Wistar rats was studied. Bioavailability of RL-HCL loaded SLN was nearly five times than that of pure RL-HCL.

Objectives: Lipid nanoparticles as carrier for oral drug administration improve gastrointestinal solubility of poorly soluble drugs and thus enhance bioavailability. However, basic drugs may undergo rapid dissolution from such solid dispersions in the stomach and precipitate in the intestine due to their higher solubility in acidic medium. Therefore, the objective of this work was to study the enhancement in bioavailability of carvedilol phosphate (basic drug) by providing an alkaline gastric environment to drug-loaded solid lipid nanoparticles., Methods: An alkaline gastric environment in rats was created and maintained with oral administration of an antacid suspension 5 min before and 30 min post dosing., Key Findings: The formulation administered orally exhibited enhanced bioavailability (∼27%) when compared with drug suspension and sustained release behaviour when compared with formulation under ideal gastric conditions. The enhanced bioavailability is due to the presence of lipid nanoparticles as drug carrier while the sustained-release characteristic may be attributed to the presence of antacid, which resulted in elevation of gastric pH and reduced the drug's solubility., Conclusions: It may be concluded that although lipid nanoparticles can be instrumental in improving bioavailability, additional sustained release may be achieved by targeting intestinal release of basic drugs from lipid vehicles, which is possible by incorporating them into suitable enteric-coated formulations., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

The objective of the present study was to employ suitable adsorbent with free flowing characteristics for improving the stability and physical properties of solid lipid nanoparticles (SLN) for oral administration. Stearic acid based nanoparticles of carvedilol phosphate were fabricated by solvent emulsification evaporation technique in sodium taurocholate solution prepared in pH 7.2 buffers (I-KH2PO4/NaOH or II-NaH2PO4/Na2HPO4) with 1% polyvinyl alcohol. Nanoparticles were then adsorbed by passing the nanodispersion through a Neusilin US2 (adsorbent) column. Interestingly, scanning electron microscopy revealed round deformed and even collapsed nanoparticles in Buffer-I and discrete spherical to ellipsoidal nanoparticles in Buffer-II which indicates the inability of nanoemulsion to crystallize and form SLN in Buffer-I. The successful formation of SLN in Buffer-II was confirmed by differential scanning calorimetry and X-ray diffraction. The retention of SLN from the nanodispersion by adsorption on the adsorbent imparted good flow property and resulted in a marked stability improvement of the formulation in terms of drug retention efficiency and release profile as compared to the simple nanosuspension. In conclusion, the adsorbent technology would be instrumental in imparting additional features to the existing conventional colloidal system for pharmaceutical application which would ease the process of capsule filling at industrial scale, simplify the handling of formulations by patients and can significantly improve the shelf life of the product for a longer period of time as compared to liquid formulations., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Importance of the Field: The use of traditional medicines of natural origin is being encouraged for the treatment of chronic disorders, as synthetic drugs in such cases may cause unpredictable adverse effects. Berberine, a traditional plant alkaloid, is used in Ayurvedic and Chinese medicine for its antimicrobial and antiprotozoal properties. Interestingly, current clinical research on berberine has revealed its various pharmacological properties and multi-spectrum therapeutic applications., Areas Covered in This Review: An extensive search in three electronic databases (Unbound Medline, PubMed and ScienceDirect) and internet search engines (Scirus and Google Scholar) were used to identify the clinical studies on berberine, without any time constraints. This review elaborates the recent studies which reveal that with time, the drug has evolved with superior therapeutic activities. In addition, this review will also attract the attention of formulation scientists towards the issues and challenges associated in its drug delivery and the probable approaches that may be explored to help patients reap the maximum benefit of this potentially useful drug., What the Reader Will Gain: A relatively large number of studies discussed here have revealed the possible areas where this phytochemical constituent can exhibit its therapeutic activities in the treatment of chronic ailments or diseases including diabetes, cancer, depression, hypertension and hypercholesterolemia., Take Home Message: The potential of the drug remains to be harvested by designing a suitable formulation that could overcome its inherent low bioavailability.