International Journal of Pharmaceutics (v.429, #1-2)

Turbula bottle blenders are often used in lab-scale experiments during early-stage pharmaceutical product development. Unfortunately, applying knowledge gained with these blenders to larger-sized diffusion mixers is limited by the lack of blending models that include Turbula mixers. To address this need for lubrication blending scale-up, 2:1 blends of microcrystalline cellulose and spray-dried lactose or dibasic calcium phosphate were mixed with 1% magnesium stearate using Turbula bottle blenders, varying bottle volume, V (30–1250 mL); bottle headspace fraction, F headspace (30–70%); and the number of blending cycles, r (24 to ∼190,000 cycles). The impact of lubrication blending on tensile strength and bulk specific volume quality attributes, QA, was modeled by: QA QA 0 = ( 1 − β ) + β exp ( − γ × L × F headspace × r ) , where QA0 is initial QA value, β is sensitivity of QA to lubrication, γ is formulation-specific lubrication rate constant, and L is characteristic mixing length scale (i.e. 1.5V 1/3 for Turbula blenders, V 1/3 for simple diffusion mixers). The factor of 1.5 captures the bottle dimensions and the more complex mixing dynamics of the Turbula blender. This lubrication blending process model is valid for scale-up from 30-mL to 200-L blenders. Assessing bulk specific volume may provide a simpler, more material-sparing means for determining γ than tensile strength, since these QAs exhibited similar γ values.
Keywords: Scale-up; Lubrication; Tensile strength; Tablet; Specific volume; Bulk density; Magnesium stearate;

Preparation and characterization of controlled release matrices based on novel seaweed interpolyelectrolyte complexes by Héctor J. Prado; María C. Matulewicz; Pablo R. Bonelli; Ana L. Cukierman (12-21).
Novel interpolyelectrolyte complexes (IPECs) between naturally sulfated polysaccharides of the seaweed Polysiphonia nigrescens (PN) and cationized agaroses (CAG) and Eudragit E (EE) were prepared using an organic solvent free process, characterized, and explored for controlled drug release. Tablets containing model drug ibuprofen and IPECs were prepared by direct compression. Drug release in acid medium was low owing to the low solubility of ibuprofen in that condition and to the matrix action. Zero order drug release was determined in the buffer stage (pH = 6.8), with Fickian diffusion predominating over relaxation during the initial phases. Relaxation appears to increase along the release process and even overcomes diffusion for some systems. Drug release profiles could be controlled by varying the content of IPECs in the tablets. Also, the change in molecular weight and the degree of substitution of the components allowed altering the release profiles.
Keywords: Eudragit E; Polysiphonia nigrescens; Cationized agarose; Interpolyelectrolyte complexes (IPECs); Controlled drug release;

The assessment of in vivo drug absorption with in vitro permeability models demands the use of transport media with surface acting compounds. With the aim to establish their influence on in vitro permeability of 30 drugs through Caco-2 monolayers, cell vitality/integrity and micellar drug entrapment, taurocholate/lecithin (NaTC/Leci) and pig crude bile were applied. Drug permeabilities were correlated to fraction of drugs absorbed and appropriate NaTC/Leci and bile concentrations were proposed to simulate fasted/fed conditions in vitro (bile in the concentration range 1–5 v/v% or 0.2/0.05 mM NaTC/Leci for fasted; 10 v/v% bile or 3/0.75 mM NaTC/Leci for fed conditions) without detrimental effects on monolayer integrity/vitality (NaTC/Leci was more toxic than bile). Surfactants exerted different affinities for drugs; free drug concentration (c free ) of some was significantly lowered only by bile, while for the others NaTC/Leci and bile significantly diminished c free . For some substances NaTC/Leci and bile significantly increased their permeabilities (i.e. more than 3-times) in spite of profound c free decrease indicating the existence of an alternative absorption mechanism. Based on these data, the impact of bile on in vitro drug permeability and micellar drug entrapment cannot be adequately simulated by NaTC/Leci, because their effects on drug absorption differ.
Keywords: Bio-relevant conditions; Taurocholate; Lecithin; Bile; Permeability; Drug binding;

Matrix metalloproteinases (MMPs) overexpression plays a critical role in cancer invasion and metastasis. We utilized this key feature of tumor microenvironment to develop a disease-stimuli triggered drug delivery system. Poly(acrylic acid) hydrogels were synthesized by UV polymerization and pendant MMP-2 sensitive peptides (Gly-Pro-Leu-Gly-Val-Arg-Gly-Lys) conjugated throughout using EDC/sulfo-NHS chemistry. There were significantly more peptides released in the presence of MMP-2 compared with the control groups. The released peptide fragments were analyzed by HPLC and MALDI-MS and confirmed to be the expected fragments. In order to avoid nonspecific release of nonconjugated (i.e. unreacted) peptides, a novel method of electrophoretic washing was developed disrupting the strong electrostatic interactions between the peptides and the pendant groups of the hydrogel. After electrophoresis, the nonspecific peptide release in the absence of MMP-2 was minimized. This newly developed purification system significantly improved the control of release to be in response of the magnitude of the stimuli, i.e. MMP. Specifically, peptides were released proportionally to the concentration of MMP-2 present. Now that many of the design parameters have been examined, anticancer drugs will be conjugated to the MMP sensitive peptide linkers with the goal of implantation in a tumor void releasing anticancer reagent in response to elevated level of MMPs.
Keywords: Matrix metalloproteinase; Hydrogel; Peptide; Enzyme responsive drug delivery; Cancer;

Yellow coloration phenomena of incorporated indomethacin into folded sheet mesoporous materials by Shuichi Tanabe; Kenjirou Higashi; Makoto Umino; Waree Limwikrant; Keiji Yamamoto; Kunikazu Moribe (38-45).
Solid-state 13C nuclear magnetic resonance (NMR) spectroscopy that included relaxation time measurement was utilized to evaluate the yellow coloration of evaporated samples (EVPs) of indomethacin (IMC) with commercially available folded sheet mesoporous materials (TMPS). Colorimetric analysis by visible light reflection spectroscopy clarified the color differences in each sample: deep yellow-colored melt-quenched amorphous IMC, a slightly yellow-colored EVP of TMPS-1.5 (pore size: 1.8 nm), and a yellow-colored EVP of TMPS-7 (pore size: 7.3 nm). The color of EVPs changed from yellow to white after washing with ethanol, indicating the reversible coloration without a chemical reaction. Powder X-ray diffractometry and differential scanning calorimetry demonstrated that the EVPs of TMPS-7 entrapped greater amounts of amorphous IMC into the mesopore than TMPS-1.5. The amount of amorphous IMC in the mesopores could affect the strength of yellow coloration. Solid-state 13C NMR spectroscopy that included spin–lattice relaxation time (T1) measurement revealed that the mobility of the aromatic rings of amorphous IMC in TMPS mesopores was higher than that in melt-quenched amorphous IMC. The difference in color between amorphous IMC in TMPS mesopores and melt-quenched amorphous IMC can be explained by their distinct intramolecular π-conjugation systems.
Keywords: Coloration; Solid-state NMR; Differential scanning calorimetry; Powder X-ray diffractometry; Folded sheet mesoporous materials; Amorphous;

The particle engineering process, thin film freezing (TFF), was used to produce particulate voriconazole (VRC) formulations with enhanced properties. The effect of various processing parameters on the solid state properties and aerodynamic performance of the TFF-processed powders was investigated in order to evaluate the suitability of these formulations for dry powder inhalation and to optimize the aerodynamic properties. Thin film freezing of VRC solution without stabilizing excipients resulted in microstructured, crystalline low density aggregate particles with specific surface areas of approximately 10 m2/g. Thin film freezing of VRC–PVP solutions produced nanostructured, amorphous low density aggregate particles with specific surface areas ranging from 15 to 180 m2/g, depending on the solvent system composition, polymer grade, and drug to polymer ratio utilized. VRC formulations manufactured with 1,4-dioxane, with and without PVP K12, resulted in the lowest specific surface areas but displayed the best aerodynamic properties. Using a Handihaler® dry powder inhaler (DPI), microstructured crystalline TFF–VRC and nanostructured amorphous TFF–VRC–PVP K12 (1:2) displayed total emitted fractions of 80.6% and 96.5%, fine particle fractions of 43.1% and 42.4%, and mass median aerodynamic diameters of 3.5 and 4.5 μm, respectively.
Keywords: Poorly water-soluble drug; Crystalline; Amorphous; Dry powder inhalation; Ultra-rapid freezing, nanotechnology;

Hot-melt extrusion was applied to improve dissolution behavior of poorly soluble model drug fenofibrate. Blends of polymers were used as carrier: copovidone (COP), polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol copolymer (PVCL–PVAc–PEG) and hypromellose 2910/5 (HPMC). The ratio of fenofibrate to COP remained constantly 1 + 3 (weighted parts) with varying amounts of PVCL–PVAc–PEG and HPMC. Solid state of fenofibrate was characterized by X-ray diffractometry and differential scanning calorimetry. Dissolution performance was compared to marketed formulations Lipidil and Lipidil-Ter. Stability studies were conducted at 25 °C/60%rH.The dissolution rate from extrudates was significantly increased when compared to pure fenofibrate powder or physical mixture of the components. A supersaturation of 7.6–12.1 was reached with the pelletized extrudates. All extrudates were superior to marketed formulations. No recrystallization was observed after 26 weeks of storage for fenofibrate-COP extrudates 1 + 3 (weighted parts) with or without polymeric additives. Even so, both degree and duration of supersaturation decreased with increasing storage periods with the exception of fenofibrate-HPMC extrudates.Of particular interest is the finding that by adding polymers with differing release characteristics to the drug–carrier mixture, the dissolution performance of hot-melt extruded solid dosage forms can be readily adapted to meet specific requirements.
Keywords: Solid dispersion; Hot-melt extrusion; Fenofibrate; Dissolution; Oral drug delivery; Solubility; Polymeric drug carrier;

Polymorphic form of piroxicam influences the performance of amorphous material prepared by ball-milling by Kaisa Naelapää; Johan Peter Boetker; Peep Veski; Jukka Rantanen; Thomas Rades; Karin Kogermann (69-77).
The objective of this study was to investigate the influence of the starting solid state form of piroxicam (anhydrate form I: PRXAH I vs form II: PRXAH II) on the properties of the resulting amorphous material. The second objective was to obtain further insight into the impact of critical factors like thermal stress, dissolution medium and storage conditions on the thermal behavior, solid state transformations and physical stability of amorphous materials. For analysis differential scanning calorimetry (DSC), Raman spectroscopy and X-ray powder diffractometry (XRPD) were used. Pair-wise distribution function (PDF) analysis of the XRPD data was performed. PDF analysis indicated that the recrystallization behavior of amorphous samples was influenced by the amount of residual order in the samples. The recrystallization behavior of amorphous samples prepared from PRXAH I showed similarity to the starting material, whereas the recrystallization behavior of amorphous samples prepared from PRXAH II resembled to that of the PRX form III (PRXAH III). Multivariate data analysis (MVDA) helped to identify that the influence of storage time and temperature was more pronounced in the case of amorphous PRX prepared from PRXAH I. Furthermore, the wet slurry experiments with amorphous materials revealed the recrystallization of amorphous material as PRXMH in the biorelevant medium.
Keywords: Amorphous; Thermal behavior; Solid state transformations; Physical stability; Variable temperature X-ray powder diffractometry (VT-XRPD); Raman spectroscopy; Principal component analysis (PCA); Piroxicam polymorphs; Pair-wise distribution function (PDF);

New prospective in treatment of Parkinson's disease: Studies on permeation of ropinirole through buccal mucosa by V. De Caro; G. Giandalia; M.G. Siragusa; F.M. Sutera; L.I. Giannola (78-83).
The aptitude of ropinirole to permeate the buccal tissue was tested using porcine mucosa mounted on Franz-type diffusion cells as ex vivo model. Drug permeation was also evaluated in presence of various penetration enhancers and in iontophoretic conditions.Ropinirole, widely used in treatment of motor fluctuations of Parkinson's disease, passes the buccal mucosa. Flux and permeability coefficient values suggested that the membrane does not appear a limiting step to the drug absorption. Nevertheless, an initial lag time is observed but the input rate can be modulated by permeation enhancement using limonene or by application of electric fields. Absorption improvement was accompanied by the important reduction of the lag time; at once the time required to reach the steady state plasma concentration was drastically decreased.On the basis of these results we could assume that clinical application of ropinirole by buccal delivery is feasible.
Keywords: Buccal delivery; Ropinirole; Parkinson's disease; Absorption enhancement; Porcine buccal mucosa;

Estimates of the human oral absolute bioavailability were made by using a physiological-based pharmacokinetic model of absorption and the drug solubility at the gastrointestinal pH range 1.5–7.5, the apparent permeability (P app) in Caco-2 cells and the intrinsic clearance (Clint) in human hepatocytes suspensions as major drug related parameters. The predictive ability of this approach was tested in 164 drugs divided in four levels of input data: (i) in vitro data for both P app and Clint; (ii) in vitro data for Clint only; (iii) in vitro data for P app only and (iv) in silico data for both P app and Clint. In all scenarios, solubility was estimated in silico. Excellent predictive abilities were observed when in vitro data for both P app and Clint were used, with 84% of drugs with oral bioavailability predictions within a  ± 20% interval of the correct value. This predictive ability is reduced with the introduction of the in silico estimated parameters, particularly when Clint is used. Performance of the model using only in silico data provided 53% of drugs with bioavailability predictions within a  ± 20% acceptance interval. However, 74% of drugs in the same scenario resulted in bioavailability predictions within a  ± 35% interval, which indicates that a qualitative prediction of the absolute bioavailability is still possible. This approach is a valuable way to estimate a fundamental pharmacokinetic parameter, using data typically collected in the drug discovery and early development phases, providing also mechanistic information of the limiting bioavailability steps of the drug.
Keywords: Physiological-based pharmacokinetic model of absorption; In vitroin vivo correlation; In silicoin vivo correlation; Human absolute bioavailability;

Taste masked lipid pellets with enhanced release of hydrophobic active ingredient by Jonathan Vaassen; Kathrin Bartscher; Joerg Breitkreutz (99-103).
Solid lipid extrusion is a suitable technique to produce oral dosage forms with improved taste properties. The design of a lipid formulation for poorly water soluble drugs is a challenge because of the poor dissolution and potential bioavailability problems. In this study, solid lipid extrusion at room temperature was applied for the formulation development of the BCS Class II drug NXP 1210. Powdered hard fat (Witocan® 42/44 mikrofein), glycerol distearate (Precirol® ato 5) and glycerol trimyristate (Dynasan® 114) were investigated as lipid binders. Different amounts of polyvinylalcohol (PVA)–polyethyleneglycol (PEG)-graft copolymer (Kollicoat® IR) and crospovidone (Polyplasdone® Xl-10) were scrutinized as solubilizers. The dissolution profiles depicted a short lag time (about 2 min) and then fast and complete dissolution of NXP 1210 by increasing the amount of crospovidone. The initial release was more delayed with an increased amount of PVA–PEG-graft copolymer. Dissolution rate could also be influenced by changing the lipid binder from pure hard fat into a mixture of hard fat, glycerol distearate and glycerol trimyristate. The formulations are feasible for taste-masked granules or pellets containing poorly soluble drugs.
Keywords: Lipid extrusion; Taste-masking; Immediate release; Pellets;

Self nanoprecipitating preconcentrate of tamoxifen citrate for enhanced bioavailability by Sonali V. Kapse; Rajiv V. Gaikwad; Abdul Samad; Padma V. Devarajan (104-112).
Self nanoprecipitating preconcentrate of tamoxifen citrate presents an innovative approach for spontaneous preparation of drug loaded polymeric nanoparticles in situ by nanoprecipitation.We disclose a self nanoprecipitating preconcentrate (SNP) of tamoxifen citrate (TMX), which forms TMX loaded polymeric nanoparticles, on dilution with aqueous media. SNP comprised TMX, polymer (Kollidon SR) and surfactant/s dissolved in a pharmaceutically acceptable vehicle. Binary surfactant mixtures of Aerosol OT (AOT) with Tween 80 revealed synergistic reduction in surface tension to enable both high entrapment efficiency (EE) and low particle size (PS). Synergism of the surfactants was confirmed by molecular interaction parameter(β σ ). Combination of AOT and Tween 80 resulted in EE (∼85%) and PS (<250 nm). Formation of TMX-KSR nanoparticles in situ was reproducible under most experimental conditions and exhibited pH independent behavior. Dilution volume (>80 mL) influenced both PS and EE while dilution temperature influenced only PS. Marginal increase in size was evident at the end of 1 h nevertheless was not of concern as TMX SNP exhibited near complete release in 1 h. DSC and XRD studies revealed amorphous nature of TMX in nanoparticles. FTIR imaging confirmed uniform distribution of TMX in nanoparticles. ESEM and TEM revealed spherical nanoparticles. Biodistribution studies of 99mTc labeled TMX SNP in rats revealed no significant absorption however oral pharmacokinetics revealed enhanced oral bioavailability of TMX (165%) compared to TMX suspension. SNP presents a new in situ approach, for design of drug loaded polymeric nanoparticles.
Keywords: Self nanoprecipitating preconcentrate; Tamoxifen citrate; Polymeric nanoparticles; In situ nanoprecipitation; Bioavailability; Scintigraphy;

Magnetic micelles as a potential platform for dual targeted drug delivery in cancer therapy by Chi Huang; Zhaomin Tang; Yangbo Zhou; Xiaofeng Zhou; Yong Jin; Dan Li; Ying Yang; Shaobing Zhou (113-122).
The magnetic nanomicelles as a potential platform for dual targeted (folate-mediated and magnetic-guided) drug delivery were developed to enhance the efficiency and veracity of drug delivering to tumor site. The magnetic nanocarriers were synthesized based on superparamagnetic iron oxide nanoparticles (SPIONs), biocompatible Pluronic F127 and poly(dl-lactic acid) (F127-PLA) copolymer chemically conjugated with tumor-targeting ligand-folic acid (FA) via a facile chemical conjugation method. Doxorubicin hydrochloride (DOX·HCl) was selected as a model anticancer drug to investigate the in vitro drug release and antiproliferative effect of tumor cells in vitro and in vivo in the presence or absence of an external magnetic filed (MF) with strength of 0.1 T. The Alamar blue assay exhibited that these magnetic nanomicelles possessed remarkable cell-specific targeting in vitro. Additionally this smart system enabling folate receptor-mediated uptake into tumor cells, showed strong responsiveness to MF. The primary in vivo tumor model study, which was carried out in VX2 tumor-bearing male New Zealand white rabbits, demonstrated that the nanomicelles could be guided into tumor site more efficiently by application of MF, and further represented significant therapeutic efficiency to solid tumor.
Keywords: Micelles; Targeted drug delivery; Magnetic nanoparticles; Cancer therapy;

Synthesis and in vitro evaluation of novel lipophilic monophosphorylated gemcitabine derivatives and their nanoparticles by Dharmika S.P. Lansakara-P.; B. Leticia Rodriguez; Zhengrong Cui (123-134).
Novel lipophilic monophosphorylated gemcitabine derivatives in nanoparticles.Gemcitabine hydrochloride (HCl) is approved for the treatment of a wide spectrum of solid tumors. However, the rapid development of resistance often makes gemcitabine less efficacious. In the present study, we synthesized several novel lipophilic monophosphorylated gemcitabine derivatives, incorporated them into solid lipid nanoparticles, and then evaluated their ability to overcome major known gemcitabine resistance mechanisms by evaluating their in vitro cytotoxicities in cancer cells that are deficient in deoxycytidine kinase (dCK), deficient in human equilibrative nucleoside transporter (hENT1), over-expressing ribonucleotide reductase M1 subunit (RRM1), or over-expressing RRM2. In dCK deficient cells, the monophosphorylated gemcitabine derivatives and their nanoparticles were up to 86-fold more cytotoxic than gemcitabine HCl. The majority of the gemcitabine derivatives and their nanoparticles were more cytotoxic than gemcitabine HCl in cells that over-expressing RRM1 or RRM2, and the gemcitabine derivatives in nanoparticles were also resistant to deamination by deoxycytidine deaminase. The gemcitabine derivatives (in nanoparticles) hold a great potential in overcoming gemcitabine resistance.
Keywords: Gemcitabine resistance; Nanoparticles; In vitro cytotoxicity; Cancer cells;

Polyvinylalcohol (PVA) fiber web containing embedded bacteria was prepared by electrospinning technique. From the point of the complex functionality of such potential delivery systems, it will be of impact how bacteria can survive in such artificial biotopes. The present study suggests a possible fast method for the tracking of the viability of the embedded bacteria based on the changes of the supramolecular structure of the polymeric delivery system caused by the metabolic product of the bacteria. Positron annihilation lifetime spectroscopy (PALS) was applied to track the free volume changes of the system in the course of storage. The PALS method sensitively detected the free volume changes, thus the viability of the bacteria in the polymeric fiber web.
Keywords: Electrospinning; PVA fiber web; Bacteria; Viability; Positron annihilation lifetime spectroscopy;

Mesoporous silica nanoparticles for the improved anticancer efficacy of cis-platin by Chia-Hui Lin; Shih-Hsun Cheng; Wei-Neng Liao; Pei-Ru Wei; Ping-Jyun Sung; Ching-Feng Weng; Chia-Hung Lee (138-147).
We designed a novel cis-platin (CP) delivery system by modification of mesoporous silica nanoparticle (MSN) surfaces with a carboxylate group through a hydrazone bond. The further immobilization of CP can be achieved through the coordination of the carboxylate-modified MSN surfaces with the hydroxo-substituted CP. This new formulation can efficiently increase efficiency of both the cellular uptake and the drug release under endosomal or lysosomal pHs; therefore, the anti-proliferative effect of this new formulation on the colon cancer cell line (HT-29) was twenty times more than the free CP molecules. In addition, the encapsulation of CP complexes in the confined spaces of MSNs can decrease non-specific release from enzymatic hydrolysis because most hydrolytic enzymes have diameters considerably greater than the pore size of MSNs. The DNA fragmentation and caspase-3 activity assay showed that the apoptosis was induced by DNA damages and then an increase in caspase-3 activity. Thus, the TA-MSN-carboxylate-CP samples were induced cell apoptosis through the caspase-3 dependent pathway. Moreover, the hemolysis assay also indicated that the exposure of the carboxylate-modified MSNs in red blood cells (RBCs) did not observe the release of red hemoglobin from the cell lysis, and the further exposure of the TA-MSN-carboxylate-CP complexes to RBCs also did not observe notably the lysis of RBCs under the effectively therapeutic dosage. Therefore, our design of MSN with controllable release of CP has highly therapeutic effects and is highly biocompatible; however, a low cytotoxicity and site effect were observed.
Keywords: Drug delivery; Anticancer; Cis-platin; Controllable release;

Drug eluting sutures: A model for in vivo estimations by Tommaso Casalini; Maurizio Masi; Giuseppe Perale (148-157).
This work is focused on the development of a transient 1-dimension model to describe drug release from a bioresorbable suture thread in a living tissue and the pharmacologic behavior of the active substance being delivered from the device into the tissue. The model is based on fundamental conservation laws, represented by mass balances, being the thread degradation described through population balances and involving detailed hydrolysis kinetics. Monomer, water and drug diffusion are assumed as Fickian, and the increasing of diffusion coefficient is expressed with the “free volume” theory. Drug behavior in tissue is described with a “diffusion and reaction” approach. The model leads to a system of partial differential equations solved by applying the method of lines and then numerically integrated. Simulations allowed to estimate release dynamics and drug behavior in tissue and to obtain spatial and temporal profiles of drug in tissue. Moreover, phase diagrams, which show drug effect in time and space, are here introduced for the first time.
Keywords: Mathematical modeling; Drug delivery; Pharmaceuticals; Biopolymers; Suture threads;

The effect of Tween® 20 on silicone oil–fusion protein interactions by Nitin Dixit; Kevin M. Maloney; Devendra S. Kalonia (158-167).
There is evidence in the literature that silicone oil, a lubricant, can induce aggregation in protein formulations delivered through prefilled syringes. Surfactants are commonly used to minimize protein–silicone oil and protein–container interactions; however, these interactions are not well characterized and understood. The purpose of this manuscript was to understand the competitive interactions of a fusion protein with the silicone oil in the presence of Tween® 20. An adsorption isotherm for Tween® 20 at the silicone oil/water interface, using silicone oil coated quartz crystals, was generated at 25 °C to identify surface saturation concentrations. A concentration of Tween® 20 providing interfacial saturation was selected for protein adsorption studies at the silicone oil/water interface. The surfactant molecules adsorbed at the interface in a monolayer with a reduced viscoelastic character in comparison to the bound protein layer. A significant reduction in protein adsorption was observed when the surfactant was present at the interface. No desorption of the pre-adsorbed protein molecules was observed when Tween® 20 was introduced, suggesting that the protein has strong interactions with the interface. However, both, Tween® 20 and protein, adsorbed to the silicone oil/water interface when adsorption was carried out from a mixture of protein and Tween® 20.
Keywords: Silicone oil/water interface; Protein adsorption; Surfactant; Viscoelasticity;