Phenylboronic acid modified hydrogel materials and their potential for use in contact lens based drug delivery.

The use of hydrogel-based contact lens materials holds promise for ophthalmic drug delivery by increasing drug residence time, improving drug bioavailability, reducing administration frequency, and enhancing special site targeting. Issues such as ease of manufacturing, lens comfort and appropriate release kinetics must be considered. Furthermore, the high water content of hydrogel materials can result in rapid and poorly controlled release kinetics. Herein, we modified common hydrogels used in contact lens manufacturing with phenylboronic acid (PBA). PBA addresses these material design issues since boronate esters are easily formed when boron acid and diols interact, opening up a pathway for simple modification of the model lens materials with saccharide based wetting agents. The wetting agents have the potential to improve lens comfort. Furthermore, the hydrophobicity of PBA and the presence of diols can be useful to help control drug release kinetics. In this work, polymerizable 3-(acrylamido)phenylboronic acid (APBA) was synthesized and incorporated into various hydrogels used in contact lens applications, including poly(2-hydroxyethylmethacrylate) (PHEMA), polyvinylpyrrolidone (PVP) and poly(N,N-dimethyl acrylamide) (PDMA) using UV induced free radical polymerization. The APBA structure and its incorporation into the hydrogel materials were confirmed by NMR and FTIR. The materials were shown to interact with and bind wetting agents such as hyaluronan (HA) and hydroxypropyl guar (HPG) by simple soaking in an aqueous solution. The equilibrium water content of the modified materials was characterized, demonstrating that most materials are still in the appropriate range after the introduction of the hydrophobic PBA. The release of three model ophthalmic drugs with varying hydrophilicity, atropine, atropine sulfate and dexamethasone, was examined. The presence of PBA in the materials was found to promote sustained drug release due to its hydrophobic nature. The results suggest that the modification of the materials with PBA was able to not only provide a mucoadhesive property that enhanced wetting agent interactions with the materials, but had the potential to alter drug release. Thus, the modification of contact lens materials with mucoadhesive functionality may be useful in the design of hydrogel contact lenses for ophthalmic drug release and wetting agent binding.

Polymeric Microfiltration Membranes Modification by Supercritical Solvent Impregnation-Potential Application in Open Surgical Wound Ventilation.

This study investigated supercritical solvent impregnation of polyamide microfiltration membranes with carvacrol and the potential application of the modified membranes in ventilation of open surgical wounds. The impregnation process was conducted in batch mode at a temperature of 40 °C under pressures of 10, 15, and 20 MPa for contact times from 1 to 6 h. FTIR was applied to confirm the presence of carvacrol on the membrane surface. In the next step, the impact of the modification on the membrane structure was studied using scanning electron and ion beam microscopy and cross-filtration tests. Further, the release of carvacrol in carbon dioxide was determined, and finally, an open thoracic cavity model was applied to evaluate the efficiency of carvacrol-loaded membranes in contamination prevention. Carvacrol loadings of up to 43 wt.% were obtained under the selected operating conditions. The swelling effect was detectable. However, its impact on membrane functionality was minor. An average of 18.3 µg of carvacrol was released from membranes per liter of carbon dioxide for the flow of interest. Membranes with 30-34 wt.% carvacrol were efficient in the open thoracic cavity model applied, reducing the contamination levels by 27% compared to insufflation with standard membranes.

Why chitosan could be apt candidate for glaucoma drug delivery - An overview.

Most of the people in the world are affected by glaucoma, which leads to irreversible blindness. Several patient friendly treatments are available, nevertheless medications lack an easy and efficient way of sustained delivery. To make the delivery with enhanced bioavailability, biodegradable and non-biodegradable polymers-based drug carriers are explored. However, ocular drug delivery issues have not been resolved yet due to less adhesiveness, poor penetration ability, pH, and temperature dependent burst releases. Chitosan is found to be effective for ocular drug delivery due to excellent physio-chemical properties in terms of overcoming the existing issues. In this review, we aim to highlight why it has been chosen and the holy grail for ocular drug delivery. Besides, we have comprehensively reviewed recent patents on chitosan as a platform for ocular drug delivery and future perspectives on factors, lacunae and challenges that need to be addressed for better ocular delivery methods for glaucoma management.

Fibrous biomaterials: Effect of textile topography on foreign body reaction.

Foreign Body Reaction (FBR) is a critical issue to be addressed when polyethylene terephthalate (PET) textile implants are considered in the medical field to treat pathologies involving hernia repair, revascularization strategies in arterial disease, and aneurysm or heart valve replacement. The natural porosity of textile materials tends to induce exaggerated tissue ingrowth which may prevent the implants from remaining flexible. The purpose of this study is to assess the influence of the textile topography of various woven substrates on the wetting properties of these substrates and on their in vitro interaction with mesenchymal stem cells (MSC) at 24 and 72 hr. The tests were performed both at yarn and fabric level under forced wetting and ingrowth conditions in order to replicate the mechanisms going on in vivo under blood pressure. Results demonstrate that cell proliferation is influenced by the textile wetting properties, which can be tuned at yarn and fabric level. In particular, it is shown that a satin weave obtained from porous spun yarn limits cell proliferation due to the high porosity of the yarn and the limited saturation index of the weave. Yarn and fabric saturation seems to play a predominant role in cell proliferation on textile substrates.

Relationships between the material properties of silicone hydrogels: Desiccation, wettability and lubricity.

Silicone hydrogels (SiHy), represent composite matrices composed of hydrophobic gas permeable silicone (Si) rich core and a surface enriched with hydrophilic polymer moieties. Their utilization in contact lens design requires number of SiHy properties (hydration, wettability, lubricity) to be optimized for the challenging conditions at the ocular surface. Typical limitations in literature are that (i) these properties are studied in isolation, monitoring only one parameter but not the rest of them, and (ii) measurements are performed with hydrated samples immediately after removal from storage solutions. Here we study the simultaneous evolution of critical material properties (evaporative loss of water, water contact angle, coefficient of friction) of different SiHy subjected to continuous blink-like desiccation/rehydration cycling. SiHy with wetting agents incorporated in their core (narafilcon A, senofilcon A) were particularly susceptible to extended desiccation. Stenfilcon A, a material with only 3% bulk Si content maintained its performance for 4 h of cycling, and delefilcon A (80% surface water content) resisted extended 8 h of desiccation/rehydration runs. Strong correlation exists between the evolution of SiHy wettability and lubricity at ≥4 h of blink-like cycling. Understanding the interplay between SiHy properties bears insights for knowledge based design of novel ophthalmic materials.

Role of wetting agents and disintegrants in development of danazol nanocrystalline tablets.

Poor wetting and/or particle aggregation are the shortcomings of the dried nanocrystalline suspensions, which subsequently might hinder the superior dissolution performance of the nano-crystalline suspensions. The objective of this study was to evaluate the effect of wetting agents and disintegrants on the dissolution performance of dried nanocrystals of an active pharmaceutical ingredient (API) with poor wetting property. Danazol, a BCS Class II compound with high LogP and low polar surface area, was chosen as a model compound for this study. Danazol nanocrystalline suspension was prepared by wet-media milling and converted into powder via spray granulation either with mannitol or microcrystalline cellulose as carriers at a drug: carrier ratio of 1:9 w/w. Danazol nanocrystalline suspension showed a superior dissolution performance compared to an un-milled danazol suspension. Dried danazol nanocrystals suffered from poor wetting leading to hindered dissolution performance i.e. ~ 40% and ~ 15% drug dissolution within 15 min for the mannitol and microcrystalline cellulose-based granules, respectively. Addition of a lipophilic surfactant (i.e. docusate sodium) at a surfactant: drug ratio of 0.015: 1 w/w during granulation helped in retaining the superior drug dissolution rates i.e. more than 80% drug dissolution within 15 min for mannitol-based granules by enhancing the wettability of dried danazol nanocrystals when compared to a hydrophilic surfactant (i.e. poloxamer 188) or disintegrant (i.e. sodium starch glycolate or croscarmellose sodium). The fast-dissolving mannitol-based granules containing danazol nanocrystals and docusate sodium were compressed into a tablet dosage form. The tablets containing danazol nanocrystals with docusate sodium showed a superior dissolution performance compared to a tablet containing un-milled danazol with docusate sodium.

Combinational Biomimicking of Lotus Leaf, Mussel, and Sandcastle Worm for Robust Superhydrophobic Surfaces with Biomedical Multifunctionality: Antithrombotic, Antibiofouling, and Tissue Closure Capabilities.

Surface wetting occurring in daily life causes undesired contaminations, which are critical issues in various fields. To solve these problems, the nonwetting property of a superhydrophobic (SH) surface has proven its utility by preventing contaminant infiltration, serious infections, or malfunction. However, the application of SH surfaces in the biomedical field has been limited due to the weak durability and toxicity of the related components. To overcome these limitations, we developed a robust and biocompatible SH surface through combinational biomimicking of three natural organisms, lotus leaf, mussel, and sandcastle worm, for the first time. Using the water-immiscible and polycationic characteristics of mussel adhesive protein (iMglue), an SH iMglue-SiO2(TiO2/SiO2)2 coating was fabricated by solution-based electrical charge-controlled layer-by-layer growth of nanoparticles (NPs). The fabricated iMglue-SiO2(TiO2/SiO2)2 SH surface showed excellent durable nonwetting properties and was applied to an intracatheter tube coating to develop antithrombotic catheters under blood flow. Furthermore, we developed a iMglue-employed SH patch for a tissue closure bandage by spraying hydrophobic SiO2 NPs on the iMglue-covered cotton pads. The prepared iMglue-employing SH patch showed perfect bifunctionality with excellent antibiofouling and tissue closure capabilities. Our work presents a novel, useful strategy for fabricating a biomedically multifunctional, robust SH surface through combinational mimicking of natural organisms.

A catecholamine neurotransmitter: epinephrine as a CO2 wet scrubbing agent.

Bio-renewables are emerging as potential materials for CO2 sorption. Epinephrine is employed as a green scrubbing agent for CO2 capturing through the formation of a metal carbamate as proved by 1H, 13C and 1H-15N NMR and ex situ ATR-FTIR spectroscopy, as well as supported by quantum-chemical calculations.

Influence of Irrigation and Wetting Agent on Fungicide Residues in Creeping Bentgrass.

Fungicides (azoxystrobin, propiconazole, pyraclostrobin, and thiophanate-methyl) were applied to field plots of creeping bentgrass established on a sand-based root zone substrate and maintained at a cutting height of 0.34 cm. The wetting agent, a modified alkylated polyol, was applied 24 h prior to fungicide application. Irrigation (0.51 cm) was applied to plots immediately after the fungicide spray. Turf was sampled nine times over 42 days to examine fungicide residues in three components of the turf profile: verdure/thatch, roots, and soil. Residues were extracted from samples and then quantified using a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) procedure. The experiment was run twice. Wetting agent had little or no effect on fungicide distribution in any of the turf components. Postapplication irrigation had little effect on residues observed in the verdure/thatch component. Significant irrigation treatment effects were observed in root and soil components, but results varied among fungicides and sampling dates. Where significant effects were observed for the irrigation plus wetting agent treatment, results generally mirrored outcomes for irrigation treatment.

Surface modification of model hydrogel contact lenses with hyaluronic acid via thiol-ene "click" chemistry for enhancing surface characteristics.

Discontinuation of contact lens wear as a result of ocular dryness and discomfort is extremely common; as many as 26% of contact lens wearers discontinue use within the first year. While patients are generally satisfied with conventional hydrogel lenses, improving on-eye comfort continues to remain a goal. Surface modification with a biomimetic, ocular friendly hydrophilic layer of a wetting agent is hypothesized to improve the interfacial interactions of the contact lens with the ocular surface. In this work, the synthesis and characterization of poly(2-hydroxyethyl methacrylate) surfaces grafted with a hydrophilic layer of hyaluronic acid are described. The immobilization reaction involved the covalent attachment of thiolated hyaluronic acid (20 kDa) on acrylated poly(2-hydroxyethyl methacrylate) via nucleophile-initiated Michael addition thiol-ene "click" chemistry. The surface chemistry of the modified surfaces was analyzed by Fourier transform infrared spectroscopy-attenuated total reflectance and X-ray photoelectron spectroscopy. The appearance of N (1s) and S (2p) peaks on the low resolution X-ray photoelectron spectroscopy spectra confirmed successful immobilization of hyaluronic acid. Grafting hyaluronic acid to the poly(2-hydroxyethyl methacrylate) surfaces decreased the contact angle, the dehydration rate, and the amount of nonspecific sorption of lysozyme and albumin in comparison to pristine hydrogel materials, suggesting the development of more wettable surfaces with improved water-retentive and antifouling properties, while maintaining optical transparency (>92%). In vitro testing also showed excellent viability of human corneal epithelial cells with the hyaluronic acid-grafted poly(2-hydroxyethyl methacrylate) surfaces. Hence, surface modification with hyaluronic acid via thiol-ene "click" chemistry could be useful in improving contact lens surface properties, potentially alleviating symptoms of contact lens related dryness and discomfort during wear.

Effect of multipurpose solutions on in vivo surface wettability of a silicone hydrogel lens.

PURPOSE: To compare the in vivo surface wettability of silicone hydrogel (SiHy) contact lenses pre-soaked overnight in different multipurpose solutions (MPS) and normal saline. METHODS: In this double-blinded, randomized and self-controlled study, 36 subjects were fitted with three pairs of contact lenses (senofilcon A) pre-soaked overnight in five different MPS and saline in a randomized order. Each pair of lenses (pre-soaked in two different solutions the night before) were worn for 15min before assessment of pre-lens non-invasive tear break-up time (PL-NITBUT) using the Medmont corneal topographer (video recording). Corneal integrity was assessed using a slit lamp and a resting interval of 20min was allowed between each pair of lenses to ensure post-lens wear corneal integrity. RESULTS: Thirty subjects completed the study. The median PL-NITBUT ranged from 2.84s to 3.08s with lenses pre-soaked in different MPS, compared to 2.78s with lenses pre-soaked in saline. No significant differences in PL-NITBUT were found among lenses pre-soaked in different solutions (p=0.647). CONCLUSION: In vivo surface wettability, in terms of PL-NITBUT after 15min of lens wear, of senofilcon A contact lenses pre-soaked overnight in different MPS were not significantly different from those pre-soaked in saline.

Electrochemical decomposition of fluorinated wetting agents in plating industry waste water.

Electrochemical decomposition of fluorinated surfactants (PFAS, perfluorinated alkyl substances) used in the plating industry was analyzed and the decomposition process parameters optimized at the laboratory scale and production scale of a 500-liter reactor using lead electrodes. The method and system was successfully demonstrated under production conditions to treat PFAS) with up to 99% efficiency in the concentration range of 1,000-20,000 µg/l (1 ppm-20 ppm). The treatment also reduced hexavalent chromium (Cr(6+)) ions to trivalent chromium (Cr(3+)) ions in the wastewater. If the PFAS-containing wastewater is mixed with other wastewater streams, specifically from nickel plating drag out solution or when pH values >5, the treatment process is ineffective. For the short chain PFAS, (perfluorobutylsulfonate) the process was less efficient than C6-C8 PFAS. The process is automated and has safety procedures and controls to prevent hazards. The PFAS were decomposed to hydrogen fluoride (HF) under the strong acid electrochemical operating conditions. Analytical tests showed no evidence of organic waste products remaining from the process. Conventional alternative PFAS removal systems were tested on the waste streams and compared with each other and with the-E-destruct (electrochemical oxidation) process. For example, ion exchange resin (IX resin) treatment of wastewater to complex and remove PFAS was found to be seven times more efficient when compared to the conventional activated carbon absorption (C-treat) process. However, the E-destruct process is higher in capacity, exhibits longer service life and lower operating costs than either IX or C-treat methods for elimination of PFAS from these electroplating waste streams.

Application of yeast glycolipid biosurfactant, mannosylerythritol lipid, as agrospreaders.

The spreading property of mannosylerythritol lipids (MELs) was investigated in connection with our search for new application in agriculture. The wetting ability of MEL solutions for hydrophobic surfaces was evaluated based on contact angle measurements for several surfactant solutions on abiotic and biotic surfaces. The contact angle of MEL-A solution on a hydrophobic plastic surface at 100 s after placement decreased to 8.4°, and those of other MEL solutions decreased more significantly compared to those of commonly-used nonionic surfactants. In addition, the contact angle of MEL solutions also dropped down to around 10° on various plant leaf surfaces. MEL solutions, in particular, efficiently spread even on poorly wettable Gramineae plant surfaces on which general nonionic surfactant solutions could not. Moreover, the wetting ability of MEL solutions was found to be greatly affected by the structural difference in their carbohydrate configuration. Furthermore, surface pretreatment with MEL solution led to more efficient spreading and fixing of microbial cells onto plant leaf surface compared to several conventional surfactants used in this study. These results suggested that MELs have a potential to use as a natural bio-based spreading agent, particularly as agrochemical spreader for biopesticides.

Effect of a re-wetting agent on bond strength of an adhesive to primary and permanent teeth dentin after different etching techniques.

OBJECTIVE: This study investigated the effect of a re-wetting agent on the microtensile bond strengths (mTBS) of primary and permanent dentin after acid or laser etching. MATERIALS AND METHODS: Twelve permanent and 12 primary molar teeth were ground to expose an occlusal dentin surface. Each group teeth were randomly divided into groups; I-II: 37% phosphoric acid etching with/without re-wetting agent, III-IV: Erbium: Yttrium aluminium garnet laser etching with/without re-wetting agent. An etch-and-rinse adhesive was used, and vertical sticks were obtained for the microtensile test. RESULTS: mTBS of permanent teeth was higher than that of primary teeth (P < 0.05). Re-wetting agent groups were similar with control groups in both etching groups in the permanent teeth (P > 0.05). Re-wetting agent group was similar with the control group in acid etch group (P > 0.05) and lower than the control group in laser etch group in primary teeth (P < 0.05). CONCLUSION: Acid etching in permanent teeth; laser etching in primary teeth was found more successful. The use of re-wetting agent did not provide an advance on bond strength of the adhesive in both primary and permanent teeth after acid-etch or laser-etch.

Wetting-mediated collective tubulation and pearling in confined vesicular drops of DDAB solutions.

Whether driven by external mechanical stresses (shear flow) or induced by membrane-active peptides and/or proteins, the collective growth of tubules in membranous fluids has seldom been reported. The pearling destabilization of these membranous tubules which requires an activation of the shape distortion, often induced by optical tweezers, membrane-active biomolecules or an electrical field, has also rarely been observed under mild experimental conditions. Here we report such events of collective tubulation and pearling destabilization in sessile drops of a didodecyl-dimethylammonium bromide (DDAB) vesicular solution that are confined by a surrounding oil medium. Based on the wetting dynamics and the features of the tubulation process, we show that the growth of the tubules here relies on a mechanism of "pinning-induced pulling" from the retracting drop, rather than the classical hydrodynamic fingering instability. We show that the whole tubulation process is driven by a strong coupling between the bulk properties of the ternary (DAAB/water/oil) system and the dynamics of wetting. Finally, we discuss the pearling destabilization of these tubules under vanishing static interface tension and quite mild tensile force arising from their pulling. We show that under those mild conditions, shape disturbances readily grow, either as pearling waves moving toward the drop-reservoir or as Rayleigh-type peristaltic modulations. Besides revealing singular non-Rayleigh pearling modes, this work also brings new insights into the flow dynamics in membranous tubules anchored to an infinite reservoir.

Electrospun solid dispersions of Maraviroc for rapid intravaginal preexposure prophylaxis of HIV.

The development of topical anti-human immunodeficiency virus (HIV) microbicides may provide women with strategies to protect themselves against sexual HIV transmission. Pericoital drug delivery systems intended for use immediately before sex, such as microbicide gels, must deliver high drug doses for maximal effectiveness. The goal of achieving a high antiretroviral dose is complicated by the need to simultaneously retain the dose and quickly release drug compounds into the tissue. For drugs with limited solubility in vaginal gels, increasing the gel volume to increase the dose can result in leakage. While solid dosage forms like films and tablets increase retention, they often require more than 15 min to fully dissolve, potentially increasing the risk of inducing epithelial abrasions during sex. Here, we demonstrate that water-soluble electrospun fibers, with their high surface area-to-volume ratio and ability to disperse antiretrovirals, can serve as an alternative solid dosage form for microbicides requiring both high drug loading and rapid hydration. We formulated maraviroc at up to 28 wt% into electrospun solid dispersions made from either polyvinylpyrrolidone or poly(ethylene oxide) nanofibers or microfibers and investigated the role of drug loading, distribution, and crystallinity in determining drug release rates into aqueous media. We show here that water-soluble electrospun materials can rapidly release maraviroc upon contact with moisture and that drug delivery is faster (less than 6 min under sink conditions) when maraviroc is electrospun in polyvinylpyrrolidone fibers containing an excipient wetting agent. These materials offer an alternative dosage form to current pericoital microbicides.

Flotability and flotation separation of polymer materials modulated by wetting agents.

The surface free energy, surface tension and contact angles were performed to investigate the properties of wetting agents. Adsorption of wetting agents changes wetting behavior of polymer resins. Flotability of polymer materials modulated by wetting agents was studied, and wetting agents change significantly flotability of polymer materials. The flotability decreases with increasing the concentration of wetting agents, and the wetting ability is lignin sulfonate (LS)>tannic acid (TA)>methylcellulose (MC)>triton X-100 (TX-100) (from strong to weak). There is significant difference in the flotability between polymer resins and plastics due to the presence of additives in the plastics. Flotation separation of two-component and multicomponent plastics was conducted based on the flotability modulated by wetting agents. The two-component mixtures can be efficiently separated using proper wetting agent through simple flotation flowsheet. The multicomponent plastic mixtures can be separated efficiently through multi-stage flotation using TA and LS as wetting agents, and the purity of separated component was above 94%, and the recovery was more than 93%.

The roles of wetting liquid in the transfer process of single layer graphene onto arbitrary substrates.

Wet transfer is crucial for most device structures of the proposed applications employing single layer graphene in order to take advantage of the unique physical, chemical, bio-chemical and electrical properties of the graphene. However, transfer methodologies that can be used to obtain continuous film without voids, wrinkles and cracks are limited although film perfectness critically depends on the relative surface tension of wetting liquids on the substrate. We report the importance of wetting liquid in the transfer process with a systematic study on the parameters governing film integrity in single layer graphene grown via chemical vapor deposition. Two different suspension liquids (in terms of polar character) are tested for adequacy of transfer onto SiO2 and hexamethyldisiloxane (HMDS). We found that the relative surface tension of the wetting liquid on the surfaces of the substrate is related to transfer quality. In addition, dimethyl sulfoxide (DMSO) is introduced as a good suspension liquid to HMDS, a mechanically flexible substrate.

Sodium hypochlorite with reduced surface tension does not improve in situ pulp tissue dissolution.

INTRODUCTION: Sodium hypochlorite (NaOCl) solutions with added wetting agents are advertised to dissolve necrotic tissue in root canals faster than their counterparts without a lowered surface tension. This was tested in the current study, and the null hypothesis formulated was that there was no difference between a commercially available NaOCl solution with a lowered surface tension (Chlor-XTRA; Vista Dental Products, Racine, WI) and a counterpart containing the same amount of available chlorine without added wetting agents regarding the soft tissue that remains in oval-shaped canals after mechanical preparation and irrigation. METHODS: Formerly vital extracted teeth (N = 44, 22 pairs) with similar anatomy were radiographically paired and chemomechanically prepared. In 1 tooth from each pair, a 5.25% NaOCl solution with reduced surface tension was used; in the other, a pure, technical-grade NaOCl solution of 5.25% was used. The percentage of remaining pulp tissue (PRPT) was histologically assessed in root cross-sections. The non-Gaussian raw data were subjected to Kruskal-Wallis and Mann-Whitney U tests to verify the respective effect of the cross-section level and solution on the PRPT. The relationship between the cross-section level and the PRPT was estimated by the Spearman correlation test. The alpha-type error was set at 5%. RESULTS: The cross-section level significantly influenced the PRPT (P < .05), whereas the PRPT was not influenced by the solution used (P > .05). A significant inverse correlation was found between the cross-section level and the PRPT (P < .05, r = -0.330). The lower the distance to the apex, the higher the PRPT regardless of the solution used. CONCLUSIONS: Contrary to the advertised statement, the dental solution with a reduced surface tension did not dissolve vital pulp tissue in oval root canals any better than a conventional NaOCl solution of similar strength. Closer to the apex, pulp tissue dissolution is less efficient irrespective of the solution.

Rational design of lyophilized high concentration protein formulations-mitigating the challenge of slow reconstitution with multidisciplinary strategies.

An increasing number of protein therapies require chronic administration at high doses (>200 mg) by subcutaneous (sc) injection. Due to the injection volume limitation (<1.5 mL) associated with sc administration, high protein concentration formulations at or exceeding 100 mg/mL are required to achieve the dose. Development of a high concentration protein formulation can be challenging due to increased aggregation at higher concentration and/or chemical instability, which necessitates the development of lyophilized formulation for high protein concentration drug products. Unique challenges, such as long reconstitution time for a lyophilized high protein concentration drug product, can limit practical usage and commercial marketability of the product. In this paper, a systematic approach is presented to develop a lyophilized high concentration protein formulation. The focus is on achieving reasonable reconstitution times with multidisciplinary strategies. Many strategies have been shown to provide nominal improvement in reconstitution times, such as adding wetting agents in the diluents, incorporating high annealing steps in the lyophilization cycle and reconstituting under vacuum. The reconstitution strategy of reduced diluent volume, however, has enabled significant decrease in reconstitution time (4-7-fold) of lyophilized high protein concentration formulations.