Confined crystallization of drug in directionally freeze-dried water-soluble template

Abstract Introduction Human-hair derived keratin (KOS) protein has been selected in this investigation for its ability to bind antibiotic compounds and provide sustained release while withstanding harsh proteolytic environments such as inflamed, damaged tissue. The need to control local flora has been recognized as an imperative for wound healing, as recovery is significantly hampered by infection. This study investigates the synthesis of KOS-based particulate matter, developed using acid-precipitation, to load and release the water-soluble antibiotic ciprofloxacin (CIP). We hypothesize that ionically bound CIP release is tied to the degradation of KOS, therefore, bacterial metabolism, which produces proteolytic enzymes, will trigger CIP release thereby creating a novel self-extinguishing delivery system for contaminated skin wounds. Methods Ciprofloxacin hydrochloride was solubilized in deionized water (pH 5.3) under constant stirring. Freeze-dried KOS powder was added for an ultimately 5% w/v and 0.8% w/v solution of KOS and CIP, respectively. To improve the stability of KOS a water-soluble diglycidyl ether crosslinker was added to solutions and stirred for 24 hours. CIP-loaded protein was precipitated out by a hydrochloric acid induced pH reduction. Samples were collected and frozen at -20 °C prior to lyophilization, thus forming the stable product. Degradation of KOS and commensurate release of CIP were measured using a bicinchoninic acid (BCA) assay and fluorescent measurements of hydrated material supernatant. The reduction of bacterial colonies was validated by a broth inhibition assay whereby CIP-loaded KOS or unloaded KOS controls where hydrated in bacterial-laden broth cultures of Pseudomonas aeruginosa or Methicillin-resistant Staphylococcus aureus. Cultures were sampled at 24, 48, or 72 hours and plated to quantify colony-forming units. Results The presence of CIP in the KOS protein was confirmed and release rates follow similar patterns to that of KOS degradation. CIP-loaded proteins significantly reduce bacterial colony presence in concentrated inoculant solutions up to 72 hours. Conclusions CIP release does appear to coincide with KOS degradation, which is bolstered in the presence of infectious levels of bacteria. Ongoing studies aim to observe more robust models of infection and more controlled antibiotic release.

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Changes in Leaf-Sugar Content and Enzyme Activity of Immature Sugarcane Following Foliar Application of Indole-3-Acetic Acid, 2,4-Dichlorophenoxyacetic Acid, and Maleic Hydrazide

The Journal of Agriculture of the University of Puerto Rico ◽

10.46429/jaupr.v49i1.13007 ◽

1969 ◽

Vol 49 (1) ◽

pp. 1-34

Author(s):

Alex G. Alexander

Keyword(s):

Acetic Acid ◽

Maleic Hydrazide ◽

Foliar Application ◽

Sugar Content ◽

Water Soluble ◽

Dichlorophenoxyacetic Acid ◽

Enzyme Preparations ◽

Freeze Dried ◽

2,4 Dichlorophenoxyacetic Acid ◽

Indole 3 Acetic Acid

Indole-3-acetic acid, 2,4-dichlorophenoxyacetic acid, and maleic hydrazide were applied as foliar sprays to 10-week-old sugarcane plants during initial studies of the interrelationships of growth-regulating materials with the sugar-metabolizing enzymes of sugarcane. Leaf samples were harvested at 1, 3, 9, and 27 days following treatment for sugar and enzyme assays. Sugar analyses were run for total ketoses, sucrose, fructose, and total reducing sugars, with glucose being determined by calculation. A series of acid phosphatase assays were conducted using as substrates the following compounds: ß-glycerophosphate, adenosinetriphosphate, uridine diphosphate glucose, glucose-1-phosphate, glucose-6-phosphate, fructose-6- phosphate, fructose-1,6-diphosphate, and 3-phosphoglyceric acid. Additional enzymes included invertase, amylase, hexokinase, phosphohexose isomerase, aldolase, triosephosphate dehydrogenase, phosphoglyceryl kinase, condensing enzyme, isocitric acid dehydrogenase, transaminase, peroxidase, and glucose oxidase. All enzyme preparations consisted of dialyzed water-soluble protein extracted from freeze-dried leaf tissue and precipitated with ammonium sulfate between 35 and 95 percent of saturation.

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Enhancement of Solubility and Improvement of Dissolution Rate of Atorvastatin Calcium Prepared as Nanosuspension

Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) ◽

10.31351/vol28iss2pp46-57 ◽

2019 ◽

Vol 28 (2) ◽

pp. 46-57

Author(s):

Ahmed H. Ali ◽

Shaimaa N. Abd-Alhammid

Keyword(s):

Particle Size ◽

Water Soluble ◽

In Vitro Dissolution ◽

Precipitation Method ◽

Size Analysis ◽

Dissolution Profile ◽

Disintegration Time ◽

Atorvastatin Calcium ◽

Freeze Dried

Atorvastatin have problem of very slightly aqueous solubility (0.1-1 mg/ml). Nano-suspension is used to enhance it’s of solubility and dissolution profile. The aim of this study is to formulate Atorvastatin as a nano-suspension to enhance its solubility due to increased surface area of exposed for dissolution medium, according to Noyes-Whitney equation. Thirty one formulae were prepared to evaluate the effect of ; Type of polymer, polymer: drug ratio, speed of homogenization, temperature of preparation and inclusion of co-stabilizer in addition to the primary one; using solvent-anti-solvent precipitation method under high power of ultra-sonication. In this study five types of stabilizers (TPGS, PVP K30, HPMC E5, HPMC E15, and Tween80) were used in three different concentrations 1:1, 1:0.75 and 1:0.5 for preparing of formulations. At the same time, tween80 and sodium lauryl sulphate have been added as a co-stabilizer. Atorvastatin nano-suspensions were evaluated for particle size, PDI, zeta potential, crystal form and surface morphology. Finally, results of particle size analysis revealed reduced nano-particulate size to 81nm for optimized formula F18 with the enhancement of in-vitro dissolution profile up to 90% compared to 44% percentage cumulative release for the reference Atorvastatin calcium powder in 6.8 phosphate buffer media. Furthermore, saturation solubility of freeze dried Nano suspension showed 3.3, 3.8, and 3.7 folds increments in distilled water, 0.1N Hcl and 6.8 phosphate buffers, respectively. Later, freeze dried powder formulated as hard gelatin capsules and evaluated according to the USP specifications of the drug content and the disintegration time. As a conclusion; formulation of poorly water soluble Atorvastatin calcium as nano suspension significantly improved the dissolution of the drug and enhances its solubility.

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Fine particulate matter PM2.5 generated by building demolition increases the malignancy of breast cancer MDA-MB-231 cells

10.21203/rs.2.23043/v1 ◽

2020 ◽

Author(s):

Chun-Wen Cheng ◽

Gwo-Tarng Sheu ◽

Jing-Shiuan Chou ◽

Pei-Han Wang ◽

Yu-Chun Cheng ◽

...

Keyword(s):

Breast Cancer ◽

Wound Healing ◽

Cancer Cells ◽

Fine Particulate Matter ◽

Water Soluble ◽

Migration And Invasion ◽

Control Group ◽

Increased Risk ◽

Freeze Dried ◽

Building Demolition

Abstract Background PM2.5 is associated with increased risk of mortality for a variety of cancers and all subjects, including breast cancer in females, and lung cancer in males. This study investigates the effects of water-extracted PM2.5 on a triple-negative breast cancer (TNBC) cell line, MDA-MB-231, by sampling suspended particulates around a building demolition site.Methods PM2.5 particles were obtained using a high-flow TISCH sampler. Being water-soluble, they were extracted from sampled filters using an ultrasonic oscillator and then freeze-dried. The heavy metal components of soluble PM2.5 particle was analyzed by ICP-MS. Cell viability was evaluated by MTT assay for cells that were exposed to PM2.5. Wound healing and transwell cell migration and invasion assays were used to measure cell motility and the invasiveness of cancer cells that had been exposed to PM2.5 into a chemo-attractant substance. Possible mechanisms of cancer malignancy were analyzed by Western blot analysis.Results The results revealed that nearby PM2.5 concentrations increased significantly during the deconstruction of buildings, and the Cd, Cu, Pb, Zn and Cr contents of soluble PM2.5 also significantly increased. Following exposure to PM2.5, the survival rate of breast cancer cells was significantly higher than that of the control group. Soluble PM2.5-treated cells also had a higher migration capacity, as determined by wound healing and transwell migration assays. The signaling pathway of FAK/PI3K/AKT proteins was more activated in PM2.5-treated cells than the control group. The data show that increased levels of Aurora B and Bcl-2 were associated with cell proliferation. Elevated levels of cathepsins D, β-catenin, N-cadherin, vimentin and MMP-9 were associated with breast cancer cell metastasisConclusion Soluble PM2.5 that is generated in building demolition may have a role in the promotion/progression of surviving in TNBC cells, increasing the malignancy of breast cancer. The prevention of environmental PM2.5 from deconstruction is strongly recommended.

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Preparation of Co-Amorphous Systems by Freeze-Drying

Pharmaceutics ◽

10.3390/pharmaceutics12100941 ◽

2020 ◽

Vol 12 (10) ◽

pp. 941

Author(s):

Melvin Wostry ◽

Hanna Plappert ◽

Holger Grohganz

Keyword(s):

Amino Acid ◽

Freeze Drying ◽

Sodium Dodecyl ◽

Solid Content ◽

Water Soluble ◽

Tween 20 ◽

Scanning Calorimetry ◽

Total Solid Content ◽

Amorphous Systems ◽

Freeze Dried

Freeze-drying was evaluated as a production technique for co-amorphous systems of a poorly water-soluble drug. Naproxen was freeze-dried together with arginine and lysine as co-former. To increase the solubility of naproxen in the starting solution, the applicability of five surfactants was investigated, namely sodium dodecyl sulfate, pluronic F-127, polyoxyethylene (40) stearate, tween 20 and TPGS 1000. The influence of the surfactant type, surfactant concentration and total solid content to be freeze-dried on the solid state of the sample was investigated. X-ray powder diffraction and differential scanning calorimetry showed that the majority of systems formed co-amorphous one-phase systems. However, at higher surfactant concentrations, and depending on the surfactant type, surfactant reflections were observed in the XRPD analysis upon production. Crystallization of both naproxen and amino acid occurred from some combinations under storage. In conclusion, freeze-drying was shown to be a feasible technique for the production of a selection of co-amorphous drug–amino acid formulations.

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ASSESMENT OF ANTI-INFLAMMATORY ACTIVITY AND CYTOTOXICITY OF FREEZE DRIED HYDROALCOHOLIC EXTRACT OF Bidens andicola ON ISOLATED NEUTROPHILS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i6.17574 ◽

2017 ◽

Vol 10 (6) ◽

pp. 160

Author(s):

Vinueza D ◽

LÓpez E ◽

Acosta K ◽

Abdo S

Keyword(s):

Freeze Drying ◽

Water Soluble ◽

Inflammatory Activity ◽

Hydroalcoholic Extract ◽

Cytotoxicity Assays ◽

Aerial Parts ◽

Controlled Conditions ◽

Freeze Dried ◽

Anti Inflammatory

Objective: The aim of this study was to evaluate anti-inflammatory activity and cytotoxicity in vitro of hydroalcoholic extract of Bidens andicola.Methods: B. andicola hydroalcoholic extract was obtained from aerial parts of B. andicola, following a standardized methodology. Briefly, aerial parts of B. andicola were extracted with ethanol 70% v/v and defatted with n-hexane, hydroalcoholic fraction was concentrated under controlled conditions in a rotary evaporator, and finally the residue was freeze-drying to obtain the hydroalcoholic extract of B. andicola. Anti-inflammatory activity and cytotoxicity assays were carried out using in vitro isolated neutrophils model using stable water-soluble tetrazolium salts.Results and Conclusions: The in vitro anti-inflammatory assay on isolated neutrophils demonstrated that the hydroalcoholic extract showed antiinflammatoryactivity compared to aspirin, with inflammatory inhibition percent values of 80.138±0.729 to hydroalcoholic extract of B. andicola and 82.117±0.762 to aspirin, each tested in five replicates at the concentration of 200 ppm of hydroalcoholic extract or reference.

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Use of Phycobiliproteins from Atacama Cyanobacteria as Food Colorants in a Dairy Beverage Prototype

Foods ◽

10.3390/foods9020244 ◽

2020 ◽

Vol 9 (2) ◽

pp. 244 ◽

Cited By ~ 6

Author(s):

Alexandra Galetović ◽

Francisca Seura ◽

Valeska Gallardo ◽

Rocío Graves ◽

Juan Cortés ◽

...

Keyword(s):

Food Industry ◽

Skim Milk ◽

Antioxidant Property ◽

Exchange Chromatography ◽

Water Soluble ◽

Antioxidant Power ◽

Natural Pigments ◽

Freeze Dried ◽

The Stability ◽

Sensory Tests

The interest of the food industry in replacing artificial dyes with natural pigments has grown recently. Cyanobacterial phycobiliproteins (PBPs), phycoerythrin (PE) and phycocyanin (PC), are colored water-soluble proteins that are used as natural pigments. Additionally, red PE and blue PC have antioxidant capabilities. We have formulated a new food prototype based on PBP-fortified skim milk. PBPs from Andean cyanobacteria were purified by ammonium sulfate precipitation, ion-exchange chromatography, and freeze-drying. The stability of PE and PC was evaluated by changes in their absorption spectra at various pH (1–14) and temperature (0–80 °C) values. Purified PBPs showed chemical stability under pH values of 5 to 8 and at temperatures between 0 and 50 °C. The antioxidant property of PBP was confirmed by ABTS (2,2′-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical ion scavenging, and FRAP (Ferric Antioxidant Power) assays. The absence of PBP toxicity against Caenorhabditis elegans was confirmed up to 1 mg PBP/mL. Skim milk fortified with PE obtained a higher score after sensory tests. Thus, a functional food based on skim milk-containing cyanobacterial PBPs can be considered an innovative beverage for the food industry. PBPs were stable at an ultra-high temperature (138 °C and 4 s). PBP stability improvements by changes at its primary structure and the incorporation of freeze-dried PBPs into sachets should be considered as alternatives for their future commercialization.

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Wet-Milling of Flours from Red, White and Low-Polyphenol Oxidase White Wheats

Food Science and Technology International ◽

10.1177/1082013205056778 ◽

2005 ◽

Vol 11 (4) ◽

pp. 243-249 ◽

Cited By ~ 1

Author(s):

A. Sayaslan ◽

P. A. Seib ◽

O. K. Chung

Keyword(s):

Wheat Flour ◽

Polyphenol Oxidase ◽

Water Soluble ◽

High Yield ◽

Wet Milling ◽

White Wheat ◽

Freeze Dried ◽

Flour Yield ◽

Milling Properties ◽

Wheat Flours

Straight-grade and high-yield flours milled from red, white and low-polyphenol oxidase (PPO) activity white wheats were wet-milled to give gluten, starch, tailings and water-soluble fractions. Wet gluten fractions were either oven-dried or freeze-dried and ground to obtain dry gluten. White wheats yielded slightly more flour with higher lightness ( L*) than the red wheat. The wet-milling properties of all flours were comparable. The wet and oven-dried gluten fractions isolated from the low-PPO flours were the lightest, followed by the gluten fractions from the white and red wheat flours. The L* of the oven-dried gluten fractions from the low-PPO flours were ~ 1-3% higher than those from the white and red wheat flours. As the flour yield increased, the L* of the dry gluten fractions from all flours decreased likewise. However, the high-yield low-PPO white wheat flour gave the dry gluten with almost equal L* to the gluten isolated from the straight-grade red wheat flour, indicating the potential of the low-PPO white wheat flour in manufacturing brighter gluten.

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Antioxidant Enriched Fractions fromZingiber OfficinaleRoscoe

E-Journal of Chemistry ◽

10.1155/2011/960193 ◽

2011 ◽

Vol 8 (2) ◽

pp. 721-726 ◽

Cited By ~ 5

Author(s):

Ismail Rahath Kubra ◽

Kulathooran Ramalakshmi ◽

Lingamallu Jagan Mohan Rao

Keyword(s):

Antioxidant Capacity ◽

Radical Scavenging ◽

Reducing Power ◽

Zingiber Officinale ◽

Pharmaceutical Formulations ◽

Water Soluble ◽

Antioxidant Potential ◽

Methanol Fraction ◽

Freeze Dried ◽

Ginger Rhizome

Ginger rhizome (Zingiber officinaleRoscoe) has many diverse properties and medicinal values such as antioxidant potential combined with the properties of a spice. Dried ginger (DG) were extracted with aqueous ethanol and freeze-dried. The extract was evaluated for antioxidant potential, using 1,1'-diphenyl-2-picryl-hydrazyl radical scavenging, antioxidant capacity and reducing power assays. DG extract was further fractionated into methanol (Mfr) and water-soluble (Wfr) fractions. The Mfr exhibited higher antioxidant capacity when compared to DG extract. Higher antioxidant potential of the methanol fraction may be due to the presence higher polyphenols and [6]-gingerol content. This suggests that alcoholic soluble fraction possess enormous scope to enhance the antioxidant potential when used as a supplement in various food as well as pharmaceutical formulations / products.

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Design, Fabrication and Characterization of Esomeprazole Nanocrystals for Enhancing the Dissolution Rate and Stability

Recent Patents on Nanotechnology ◽

10.2174/1872210514666201016150915 ◽

2020 ◽

Vol 14 ◽

Author(s):

Vijay Agarwal ◽

Meenakshi Bajpai

Keyword(s):

Particle Size ◽

Dissolution Rate ◽

Crystalline State ◽

Physical Mixture ◽

Water Soluble ◽

Dissolution Behavior ◽

Physical Treatment ◽

Pxrd Pattern ◽

Freeze Dried ◽

Bulk Drug

Background: Poor solubility and low dissolution rate limit the work at poorly water-soluble drugs like Esomeprazole. To overcome this problem, different technologies had to be used but could not resolve the problem, significantly. The main aim of this study was to prepare the nanocrystals using evaporative precipitation ultrasonication method in order to improve the dissolution rate and stability of Esomeprazole (ESM). Methods: For getting the nanocrystals, different nanoformulations were prepared using the pluronic F-68 in different concentration, and then screened formulation was lyophilized in presence of two distinct cryoprotectants; mannitol and sucrose. The obtained nanocrystals were characterized for their re-dispersibility, crystalline state, dissolution behavior, particle size, polydispersibility index and morphology. Dissolution study of ESM nanocrystals was performed in buffer solution of pH-7.4, and compare to that of bulk ESM sample and ESM/pluronic F-68 physical mixture. Results: Cryoprotectant containing nanocrystals exhibit the re-dispersion in water after the manual shaking. 5% mannitol containing nanocrystals showed the least polydispersity index (0.42 ± 0.11) and narrowest particle size (186 ± 12.9 nm). The powder x-ray diffraction (PXRD) pattern and differential scanning calorimeter (DSC) thermograms revealed that crystalline state of drug was not changed after the different physical treatment. Freeze-dried nanocrystals showed a faster dissolution rate and almost 99.45% of drug was released within 60 min. However, the bulk drug and a physical mixture of bulk drug/pluronic F-68 showed only 22.65% and 21.3% of drug release, respectively, after 60 min. Conclusion: The different findings revealed that nanocrystals could be a potential alternate for solving the dissolution rate and stability issue of ESM like poorly soluble drugs.

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