Pemulen TR-2 Research Articles

Analyzing the storage stability of diesel emulsified fuels: a comparative standpoint

ABSTRACT The storage stability of a diesel emulsified fuel plays a crucial role in its commercial application and carries forward its environment-friendly advantage of lowering nitrogen oxides and particulate matter emissions. This article compares storage stability aspects of hydrous ethanol-diesel-Al2O3 nano (HEDA) and hydrous ethanol-diesel-Al2O3 nano-Pemulen TR-2 (HEDAP) emulsified fuels via various stability tests (visual inspection, heat storage test, centrifuge test, pH test, density, and viscosity measurements) under freeze-thaw storage condition. The production cost analysis was made to find their commercial suitability. Stability test results found higher storage stability of HEDA fuel, compared to that of HEDAP fuel. A heterogeneous mixing of Pemulen TR-2 and its weaker hydrogen bonding with other compounds could be major factors to lower the stability of HEDAP fuel. The stability of both fuels decreased with an increase in the water proportion. HEDA fuel production cost estimation was found to be lower than HEDAP fuel and slightly higher compared to diesel, which was a good sign of its commercial applicability. The powder X-ray diffraction analysis reported 41.28 nm average crystallites size of Al2O3 nanoparticles. HEDA emulsified fuel showed better storage stability along with a lower production cost in comparison with the HEDAP fuel.

Stability of Fluid Ultrathin Polymer Films in Contact with Solvent-Loaded Gels for Cultural Heritage.

The removal of ultrathin amorphous polymer films in contact with an aqueous gelled solution containing small amounts of good solvent is addressed by means of specular and off-specular neutron reflectometry. The distribution of heavy water and benzyl alcohol is revealed inside Laropal A81, often employed as a protective varnish layer for Culture Heritage in the restoration of easel paintings. The swelling kinetics, interface roughness, and film morphologies were recorded as a function of temperature and increasing benzyl alcohol concentration in the dispersion of Pemulen TR-2, a hydrophobically modified acrylic acid copolymer. The addition of small amounts of good solvent results in the appearance of water-filled cavities inside the varnish, which grow with time. It is shown that while increasing the solvent concentration greatly enhances the hole growth kinetics, an increase in temperature above the glass transition temperature does not have such a big effect on the kinetics.

Comparative analysis of carbomer polymers for pharmaceutical and cosmetic practice

The aim of the study. Given the wide range of carbomers, their manufacturing technologies, solvent systems for their synthesis, differences in name and regulation, there is a need to systematize this group of excipients for the pharmaceutical and cosmetic industries. When using carbomers in the pharmaceutical development of medicines, the results of additional studies on the compliance of quality with pharmacopoeial indicators should be provided in registration materials.Materials and methods. As materials used were data from the official websites of the Ministry of Health of Ukraine, the FDA and Lubrizol; Pharmacopoeias of the United States (USP/NF), Europe (Ph. Eur) and Japan (JPE); scientific publications. Methods of information retrieval, systematization of theoretical and practical material were used.Results. As a result of studying the official regulatory documents it has been found that the US Pharmacopoeia (USP/NF) contains monographs called “Carbomer Copolymer”, “Carbomer Interpolymer” and “Carbomer Homopolymer”, which are classified into types A, B, C for polymers synthesized without the use of benzene, and monographs “Carbomer934”, “Carbomer 934Р”, “Carbomer940”, “Carbomer941”, “Carbomer1342” – for polymers synthesized using benzene. The Pharmacopoeia of Europe (Ph. Eur) contains a monograph “Carbomers” of a general nature, the requirements of which are met only in “Carbomer Homopolymer” polymers synthesized without the use of benzene by USP/NF. The Japan Pharmacopoeia (JPE) contains the monograph “Carboxyvinyl Polymer”, which includes carbomers synthesized both with and without benzene.Conclusions. The USP/NF pharmacopoeial quality requirements are met in the trademarks of carbomers: Carbopol 71G NF, Carbopol 971P NF, Carbopol 974P NF, Carbopol 980 NF, Carbopol 981 NF, Carbopol 5984 EP, Carbopol 934 NF, Carbopol 934P NF, Carbopol 940 NF, Carbopol 941 NF, Carbopol 1342 NF, Carbopol Ultrez 10 NF, Carbopol ETD 2020 NF, Pemulen TR-1 NF, Pemulen TR-2 NF, Noveon AA-1 USP. Only 6 brands of carbomers meet the requirements of the European Pharmacopoeia: Carbopol 71G NF, Carbopol 971P NF, Carbopol 974P NF, Carbopol 980 NF, Carbopol 981 NF, Carbopol 5984 EP.

Inhibitory effect of emulsifiers in sedds on protease activity: Just an illusion?

AimEvaluation of inhibitory effect of emulsifiers on pancreatic trypsin and α-chymotrypsin. MethodsThe inhibitory effect of Cremophor EL, Cremophor RH 40, Brij O10, Tween 20, polyethylene glycol 8000, polyethylene glycol 400, Carbitol, Pemulen TR-1, Pemulen TR-2, Carbopol Ultrez 20 and Carbopol Ultrez 21 on pancreatic trypsin and α-chymotrypsin was tested. BAEE (Nα-Benzoyl-l-arginine ethyl ester), BTEE (N-Benzoyl-l-tyrosine ethyl ester), casein and insulin were used as substrates for trypsin and α-chymotrypsin. SEDDS containing Pemulen TR-2 were developed, loaded with insulin-DMPG (dimyristoylphosphatidylglycerol) complex, characterized and tested regarding the protective effect towards the proteolytic degradation of insulin. ResultsCremophor EL, Cremophor RH 40, Brij O10, Tween 20, polyethylene glycol 8000, polyethylene glycol 400, Carbitol did not show any inhibitory effect towards trypsin and α-chymotrypsin, whereas Pemulen TR-1, Pemulen TR-2, Carbopol Ultrez 20 and Carbopol Ultrez 21 inhibited the enzymes in a concentration dependent manner. Moreover, Pemulen and Carbopol Ultrez emulsifiers exhibited comparable inhibitory properties (p>0.05). The incorporation of 0.34% w/w of Pemulen TR-2 in SEDDS decreased the degradation rate of the loaded insulin-DMPG complex compared to the blank formulation (p<0.05). ConclusionThe present study revealed that commonly used emulsifiers in SEDDS do not have inhibitory properties on the proteolytic activity of trypsin and α-chymotrypsin. Moreover, it was demonstrated that the incorporation of emulsifiers with inhibitory properties towards trypsin and α-chymotrypsin in SEDDS play a minor role in the protection of embedded drugs from enzymatic degradation.

Combination of SEDDS and Preactivated Thiomer Technology: Incorporation of a Preactivated Thiolated Amphiphilic Polymer into Self-Emulsifying Delivery Systems.

The aim of the study was to create novel mucoadhesive drug delivery systems by incorporating amphiphilic hydrophobically modified, thiolated and preactivated polymers (preactivated thiomers) into self-emulsifying drug delivery systems (SEDDS). L-Cysteine methyl ester was covalently attached to the polymeric backbone of Pemulen TR-2 and preactivated using 2-mercaptonicotinic acid (2-MNA). These thiomers were incorporated in a concentration of 0.3% (w/v) into SEDDS. The size distribution and the zeta potential of the emulsions were evaluated by dynamic light scattering. Mucoadhesive properties of thiomers-SEDDS spiked with FDA (fluorescein diacetate) were examined utilizing rheological measurement, permeation studies and in vitro residence time study on porcine mucosa. Cell viability tests were additionally performed. 734±58μmol L-Cysteine methyl ester and 562±71μmol 2-MNA could be attached per gram polymer of Pemulen TR-2. Emulsions exhibited a droplet size range between 180 and 270nm. Blank SEDDS possessed a zeta potential value between -5.7 and -8.6mV, whereas thiomers-SEDDS between -14.6 and -17.2mV. Viscous modulus of thiomer and preactivated thiomer containing SEDDS-mucus mixture was 8-fold and 11-fold increased in comparison to reference. The amount of FDA permeated the mucus layer was 2-fold lower in case of thiomers-SEDDS compared to blank SEDDS. A prolonged residence time was observed for thiomers-SEDDS over 45min. During cell viability studies no severe toxic effects were detected. The novel developed SEDDS with incorporated thiomers might be a promising tool for mucoadhesive oral drug delivery.

Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid) in Simulated Intestinal Fluids.

A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium) or fed state (FeSSIF). The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated.

Physicochemical investigations on an engineered lipid–polymer hybrid nanoparticle containing a model hydrophilic active, zidovudine

The objective of this work was to develop an optimized lipid–polymer hybrid nanoparticle (LPN) for zidovudine (AZT), a model hydrophilic active, and further to investigate its crystallization behavior and possible molecular interactions with the carrier during the LPN processing. AZT-LPNs were prepared by melt emulsification-probe sonication technique using a 23 factorial design. Transmission electron microscopy (TEM) revealed spherical LPNs with two distinct boundaries representing the drug loaded lipid core surrounded by a polymer. The optimized batch (LPN-2) achieved a size of 175±2.5nm, drug encapsulation of 49.26±0.75%, and revealed a significant stability for six months. Molecular interactions among the component of LPN were studied by using proton nuclear magnetic resonance (1H NMR), and Fourier transform infrared spectra (FT-IR). The complete amorphization of drug was noted in the melt sample while LPN-2 showed a partial drug recystallization. This was confirmed by the thermal analysis and diffractometry studies. The presence of pemulen polymer was significant to restrict sonication assisted recrystallization of the active. The oscillatory measurement using stress sweep and frequency sweep demonstrated elastic nature of the LPN-2, and was subsequently confirmed through the phase angle (δ°). Fickian diffusion (n<0.5) was identified as drug release mechanism from LPN-2. The partial hydrophilic nature of lipid and the presence of amphiphilic surfactant (Acconon® CO-7) influenced AZT release from LPN. Finally, based on the understanding of molecular interactions, the LPNs made of polar lipid (Cutina® HR) and hydrophobically modified polymer (Pemulen TR-2®) hold the promise to entrap model hydrophilic active, zidovudine, and it is possible to optimize drug release to desired level.

Optimized formulation for topical administration of clotrimazole using Pemulen polymeric emulsifier

Background: Emulgel topical formulation is a vehicle of potential for topical delivery of antifungal drugs.Methods: The imidazole derivative antifungal drug, clotrimazole (CZ), was formulated into emulgels using two grades of hydrophobically modified co-polymers of acrylic acid, namely Pemulen TR1 and TR2. The prepared emulgels were evaluated for their rheological properties, short- and long-term stability, in vitro release at 37°C. Microbiological evaluation of the formula showed that optimum stability and release was carried out to measure its antifungal activity.Results: All formulae showed non-Newtonian shear thinning behavior with little thixotropy or antithixotropy. Five of the prepared formulae showed good physical stability under different treatment conditions. Isopropyl myristate (IPM) emulgels exhibited higher rate of CZ release than either jojoba oil (JB) or liquid paraffin-based emulgels. A selected formula containing JB together with a combination of Pemulen TR1 and TR2 showed excellent stability as well as high rate of CZ release. Microbiological evaluation of the selected formula containing similar amount of CZ revealed 1.2-folds increase in the antifungal activity compared to commercially available formulation.Conclusion: Emulgel dosage form based on Pemulen polymeric emulsifier and JB is a promising vehicle for topical delivery of CZ and further in vivo animal studies are recommended.

Mucoadhesive behaviour of emulsions containing polymeric emulsifier

Over the last two decades the attention has been focused on mucoadhesive dosage forms as a possibility to improve the residence time on a specified region of the body. In addition to bioadhesivity, controlled drug release from the dosage form is also desirable. Pemulen TR1 and Pemulen TR2 are cross-linked block copolymers of poly(acrylic acid) and hydrophobic long-chain methacrylates. They are able to stabilize o/w emulsions because their short lipophilic part integrates into the oil droplets whilst their long hydrophilic part forms a micro-gel around the droplet. In this study, correlations between the microstructure of these emulsions and the bioadhesive behaviour were found. Rheological and thermogravimetric methods were used to examine the microstructure of the emulsions. The mucoadhesive measurements were performed by tensile test and the bioadhesive bond between the polymer emulsifier and mucin was visualized by confocal laser scanning microscopy. It was established that (i) these emulsion form a special structure, which depends on the components, (ii) there were no remarkable changes in bioadhesive force and work when the oil content was increased in the emulsions, and (iii) the emulsions in which the polymeric emulsifier formed a special structure showed stronger adhesivity than the ones with simple polymer network.

An investigation into interactions between polyacrylic polymers and a non-ionic surfactant: an emulsion preformulation study

The aim of this study was to investigate possible interactions between a polymeric emulsifier and a non-ionic surfactant, with a view of achieving better understanding of emulsion stabilisation mechanisms. The polymeric emulsifier used was acrylates/C 10–30 alkyl acrylate crosspolymer (Pemulen TR-2®), while Polyoxyethylene 20 sorbitan mono-oleate (Polysorbate 80) has been chosen as a model surfactant. Both materials were used within the concentration range relevant for their practical application. A 0.2%w/w aqueous dispersion of polymeric emulsifier, containing various amounts of surfactant (from 0.01 to 1.0% w/w) was used throughout the study. Interfacial aspects of the proposed polymer/surfactant interactions were analysed by means of surface tension measurements. Changes in the network structure of the test dispersions were quantified by continuous shear rheometry, supported by the texture analysis. To analyse the influence of hydrophobic alkyl groups present on the Pemulen TR-2® chains, an unmodified, hydrophilic polyacrylic acid polymer, Carbopol 934P®, was assessed under the same conditions. The results obtained by both surface tension and rheological studies have revealed large differences in behaviour of the two polymers in the presence of the model surfactant. Pemulen TR-2® was shown to desorb the surfactant from the surface, within the whole concentration range studied. Furthermore, an increase in viscosity and texture profile parameters with increasing Polysorbate 80 concentration up to 0.3% w/w was evident in the case of Pemulen TR-2® dispersions. This was followed by a decrease in the gel network strength at higher surfactant concentrations. On the other hand, Carbopol 934P® has shown no signs of surfactant desorption and only small changes in the network structure with the increasing concentration of surfactant. It is shown in this study that an interaction between a polymeric emulsifier Pemulen TR-2® and a non-ionic surfactant Polysorbate 80 does occur in their aqueous dispersion, and that it is: (a) hydrophobic in nature; (b) concentration-dependent; and (c) has an impact on the rheological properties of dispersion.

The Influence of Processing Variables on Performance of O/W Emulsion Gels Based on Polymeric Emulsifier (Pemulen ®TR‐2NF)

Pemulens(R) (BF Goodrich) are hydrophobically-modified copolymers of acrylic acid (Acrylates/C10-C30 alkyl acrylates) that could act both as primary emulsifiers for o/w emulsions and viscosity enhancing agents. The aim of this study was to assess the influence of different processing conditions (mixing equipment, speed and time of agitation) on the aesthetic characteristics, viscosity and physical stability of o/w emulsion gels based on the polymeric emulsifier (Pemulen TR-2 NF). This objective was achieved by applying a two-factor three-level experimental design at two sets: using a laboratory mixer and a disperser. Independent variables were mixing speed and time and dependant variables i.e. responses, were millimetres of oil phase separated after centrifugation at 3500 rpm in a laboratory centrifuge, and viscosity at shear rate 180 l/s. The responses were fitted into a second order model by means of a multiple regression analysis. For the samples prepared on the laboratory mixer it was shown that mixing time and speed produce a statistically important influence on viscosity, but not on physical stability: with increasing mixing speed and time the viscosity linearly increases. If we assume that greater energy input obtained by increasing the mixing speed and time produces a decrease in drop size and polydispersity and better developed gel network, then the optimal processing conditions will be at the point where maximal viscosity is attained. This result was in accordance with the centrifugation test - the best stability appeared when maximal mixing speed and time were applied, although this effect appeared not to be statistically significant. For samples prepared using dispersers no statistically important influence of processing variables on viscosity and physical stability was found. Additionally, emulsion samples prepared using the laboratory mixer appeared homogenous, while in samples prepared using the disperser, undispersed polymer lumps appeared. Based on physical characteristics of the emulsions, it could be concluded that the disperser is an inappropriate tool for processing the emulsions based on Pemulen polymers.

A rheological assessment of the nature of interactions between mucoadhesive polymers and a homogenised mucus gel

The ability of mucoadhesive materials to produce a large increase in the resistance to deformation when incorporated into a mucus gel, relative to when the mucus gel and test materials are evaluated separately at the same concentration, has been reported in several previous studies. It has been proposed that this phenomenon, termed rheological synergism, can be used as a measure of the strength of the mucoadhesive interaction. This study investigated the interactions between four putative mucoadhesive polymers (Noveon, Pemulen TR-2, carageenan and sodium carboxymethylcellulose) and a homogenised mucus gel, using dynamic oscillatory rheology. It was shown that, with the exception of sodium carboxymethylcellulose, incorporating a mucoadhesive polymer into a mucus gel produces rheological behaviour indicative of a weakly cross-linked gel network, which suggested a structure containing physical chain entanglements and non-covalent (probably hydrogen) bonds. Optimum gel strengthening occurred in a weakly acidic environment, suggesting an optimum conformation and degree of ionisation of the polymer and mucus molecules. Subsequent work suggested that the macromolecular interactions between polymer and mucus are sensitive to temperature, with the dynamic moduli decreasing with increasing temperature, further indicating bonding of a non-covalent nature. This work provide further evidence that rheological methods can be used as a tool to evaluate the interactions between a mucoadhesive macromolecule and a mucus gel. It also adds to the perception that molecular interpenetration may be an important factor in mucoadhesion by strengthening the mucus in the mucoadhesive/mucosal interfacial layer.

Formulation of topical insect repellent N, N-diethyl- m-toluamide (DEET): vehicle effects on DEET in vitro skin permeation

The broad-spectrum topical insect repellent N, N-diethyl- m-toluamide (DEET) is highly skin permeable, and serious adverse effects associated with the use of commercial DEET products have occurred in users due to extensive DEET skin permeation. In an effort to develop topical DEET formulations with reduced DEET skin permeation and extended repellency, this study investigated the effects of vehicle on DEET in vitro skin permeation from topical DEET solution and gel emulsion formulations prepared with ethanol, polyethylene glycol 400 (PEG 400), stearic acid and polyacrylic acid polymers Carbopol 940NF and Pemulen TR-2. In vitro skin permeation of DEET was evaluated in Franz diffusion cells using freshly excised abdominal cotton rat skin at 32±1°C. The receiver phase samples were analyzed by HPLC with N, N-diethyl-2-phenylacetamide as reference standard. Relative to technical DEET, 40 and 50% (v/v) aqueous ethanol solutions increased DEET steady-state skin flux ( J ss) by 157 and 137%, respectively, while 75% (v/v) aqueous ethanol solution, neat ethanol and PEG 400 decreased the J ss by 67, 74 and 59%, respectively. The incorporation of skin humectants glycerol, dimethicone or mineral oil to DEET gel emulsions based on Carbopol 940NF and stearic acid at 15% (w/w) did not significantly reduce the J ss. Compared with a name-brand lotion of 7.125% (w/w) DEET, the use of 20% (w/w) PEG 400 and 1% (w/w) Tween 80, or 75% (v/v) aqueous ethanol in Carbopol 940NF and Pemulen TR-2 based formulations containing 7.5% (w/w) DEET resulted in 22.7, 18.2 and 9.1% reduction in the J ss, respectively. For safety concerns, the incorporation of ethanol in commercial DEET products needs to be reevaluated. The topical formulation vehicle based on PEG 400, Carbopol 940NF and Pemulen TR-2 was effective in reducing DEET skin permeation.

The significance of the zone melting theory for the electron beam multi-chamber furnace : H. Fiedler, G. Scharf and F. Esser, Vacuum19, No. 4, p. 205

Evaluation of inhibitory effect of emulsifiers on pancreatic trypsin and α-chymotrypsin.The inhibitory effect of Cremophor EL, Cremophor RH 40, Brij O10, Tween 20, polyethylene glycol 8000, polyethylene glycol 400, Carbitol, Pemulen TR-1, Pemulen TR-2, Carbopol Ultrez 20 and Carbopol Ultrez 21 on pancreatic trypsin and α-chymotrypsin was tested. BAEE (Nα-Benzoyl-l-arginine ethyl ester), BTEE (N-Benzoyl-l-tyrosine ethyl ester), casein and insulin were used as substrates for trypsin and α-chymotrypsin. SEDDS containing Pemulen TR-2 were developed, loaded with insulin-DMPG (dimyristoylphosphatidylglycerol) complex, characterized and tested regarding the protective effect towards the proteolytic degradation of insulin.Cremophor EL, Cremophor RH 40, Brij O10, Tween 20, polyethylene glycol 8000, polyethylene glycol 400, Carbitol did not show any inhibitory effect towards trypsin and α-chymotrypsin, whereas Pemulen TR-1, Pemulen TR-2, Carbopol Ultrez 20 and Carbopol Ultrez 21 inhibited the enzymes in a concentration dependent manner. Moreover, Pemulen and Carbopol Ultrez emulsifiers exhibited comparable inhibitory properties (p > 0.05). The incorporation of 0.34% w/w of Pemulen TR-2 in SEDDS decreased the degradation rate of the loaded insulin-DMPG complex compared to the blank formulation (p < 0.05).The present study revealed that commonly used emulsifiers in SEDDS do not have inhibitory properties on the proteolytic activity of trypsin and α-chymotrypsin. Moreover, it was demonstrated that the incorporation of emulsifiers with inhibitory properties towards trypsin and α-chymotrypsin in SEDDS play a minor role in the protection of embedded drugs from enzymatic degradation.