Viscosity Of Formulations Research Articles

Dermatopharmacokinetics of betamethasone 17-valerate: Influence of formulation viscosity and skin surface cleaning procedure

The objective was to compare the in vivo distribution profiles of betamethasone 17-valerate (BMV) across the stratum corneum (SC) following (a) delivery from gelled and un-gelled formulations, and (b) two different skin cleaning procedures at the end of the application period. BMV was dissolved in gelled and un-gelled vehicles comprising either medium chain triglycerides (MCT) or a brand microemulsion (ME). The BMV concentration was adjusted to 80% of saturation and applied to the forearms of healthy volunteers. After 2 h, the treated skin site was cleaned either with a dry paper towel or with an isopropyl alcohol swab, and the SC was then progressively removed by repeated adhesive tape-stripping. BMV distribution profiles across the SC showed reasonable reproducibility, and that delivery from the ME was significantly superior to that from MCT. Gelled vehicles were less efficiently removed from the skin surface by dry wiping than un-gelled formulations. Removing excess formulation more aggressively with isopropyl alcohol resulted in a lower apparent uptake of drug into the SC. Excess gelled formulation may be trapped in the skin ‘furrows’, and requires an efficient skin cleaning procedure to ensure its complete removal.

Photopolymerized Injectable RGD‐Modified Fumarated Poly(ethylene glycol) Diglycidyl Ether Hydrogels for Cell Growth

In this study, photopolymerized hydrogels of fumarated poly(ethylene glycol) diglycidyl-co- poly(ethylene glycol) diacrylate have been synthesized and modified with cell adhesion peptide, Arg-Gly-Asp (RGD). The structural and mechanical properties of the hydrogels are found to be poly(ethylene glycol) diacrylate (PEGDA) dependent. The percentage of gelation is increased from 72 to 89 wt.-% when the amount of the crosslinker co-monomer (PEGDA) in the hydrogel formulation is increased from 20 to 40 wt.-%. In the present case, the equilibrium mass swelling is decreased from 216 to 93%. The viscosities of the uncured formulations have also been measured and likewise, the results were influenced by the increasing amount of PEGDA that reduced the value from 83 to 36 cP. The compressive modulus of the prepared hydrogels was improved with the addition of the PEGDA. Cell growth experiments have been performed by comparing the properties of the hydrogels with and without RGD units. The results show that RGD units enhance the adhesion of cells to the surface of the hydrogels. SEM-EDS studies reveal that nitrogen and calcium are produced on the osteoblast-seeded surface of the scaffold within the culture time period. [Figure: see text].

Viscosity of Soy Protein Plastics Determined by Screw-Driven Capillary Rheometry

Soy protein plastics are a renewable, biodegradable alternative to fossil fuel-based plastic resins. Processing of soy protein plastics using conventional methods (injection molding, extrusion) has met with some success. Viscosities of processable formulations that contain soy protein along with the necessary additives, such as glycerol and cornstarch, have not been reported, but are necessary for extrusion modeling and the design of extrusion dies. Resins consisting of soy protein isolate-cornstarch ratios of 4:1, 3:2, and 2:3 were plasticized with glycerol and soy oil, compounded in a twin screw extruder and adjusted to 10% moisture. The effects on viscosity of added sodium sulfite, a titanate coupling agent and recycling were evaluated using a screw-driven capillary rheometer at shear rates of 100–800/s. The viscosities fit a power-law model and were found to be shear thinning with power-law indices, n, of 0.18–0.46 and consistency indices, m, of 1.1 × 104–1.0 × 105. Power-law indices decreased and consistency indices increased with increasing soy protein-to-cornstarch ratio and in the absence of sodium sulfite. Addition of the titanate coupling agent resulted in increased power-law index and decreased consistency index. Viscosities at a shear rate of 400/s decreased with recycling, except for the 4:1 soy protein isolate to cornstarch formulation, which displayed evidence of wall slip. Power-law indices were unaffected by recycling. Viscosities in the tested shear rate range were comparable to polystyrene and low-density polyethylene indicating soy protein plastics are potential drop-in replacements for commodity resins on conventional plastics processing equipment.

Tolérance de la carboxyméthylcellulose par voie orale chez deux malades ayant développé une anaphylaxie à la carboxyméthylcellulose injectable

Carboxymethylcellulose is a high-molecular-weight polysaccharide molecule used as a binding agent, for coating molecules and to increase the viscosity of formulations. It is present in a large number of pharmaceutical products but is also found in food and cosmetics. We report two cases of patients who presented anaphylactic reactions immediately after localised corticosteroid injections; intra-articular for the first and intralesional for the second. Allergological testing for different corticosteroids and carboxymethylcellulose by means of prick-tests and intradermal testing indicated that the immediate hypersensitivity reaction was caused by the excipient, carboxymethylcellulose. The excellent safety of oral reintroduction of carboxymethylcellulose in a pharmaceutical preparation in these two patients confirmed that this large molecule is not absorbed through the digestive system. The avoidance list of products containing carboxymethylcellulose could be greatly reduced and limited to only injectable pharmaceutical preparations containing carboxymethylcellulose and to oral contrast media containing large quantities of carboxymethylcellulose.

Factors influencing hydrocortisone permeation into human hair follicles: Use of the skin sandwich system

The aim of the present study was to use the in vitro human skin sandwich system in order to quantify the influence of formulation variables on intrafollicular hydrocortisone permeation. The investigated variables were the pH and the viscosity of the topical formulation as well as the presence of chemical enhancers (carvone, menthone, oleic acid and sodium lauryl sulphate). Furthermore, skin sandwich hydration was also varied in order to determine if the method itself can be run using only partially hydrated skin tissues. It was determined that the follicular contribution to hydrocortisone flux decreased marginally with increasing alkalinity in the pH range 3–8.8. Intrafollicular penetration was markedly reduced when HPMC gels were used instead of an aqueous solution. Pretreating the skin with chemical enhancers also reduced the follicular contribution to flux, probably due to permeabilisation of the continuous stratum corneum. Furthermore, it was not possible to satisfactorily modify the skin sandwich method so that it could be deployed using less hydrated skin.

Properties of a Formulated Paediatric Phenobarbitone Oral Liquid

ABSTRACTAimTo formulate a stable and palatable paediatric phenobarbitone 10 mg/mL oral liquid and compare its physicochemical stability to the existing formulation compounded in some New Zealand hospitals.MethodFormulations were compounded from pharmaceutical standard ingredients according to good manufacturing practices and stored in glass bottles at different storage conditions. The physical stability of the formulations was determined by pH, appearance, viscosity and microbial studies; chemical stability was assessed using high performance liquid chromatography.ResultsThe new formulation and the existing hospital formulation remained physically stable for 28 days in terms of pH, appearance, viscosity and microbial stability. The phenobarbitone sodium concentration remained within an acceptable range (above 95% of the original concentration) after 28 days of storage at different conditions. The viscosity of the new formulation facilitated in masking phenobarbitone sodium's bitter taste, thus improving palatability. The palatability of the new formulation was superior to the hospital formulation.ConclusionA palatable paediatric phenobarbitone oral liquid formulation with improved rheological properties was developed.

Spreadability Measurements to Assess Structural Equivalence (Q3) of Topical Formulations—A Technical Note

Due to the disadvantages associated with comparative clinical trials (e.g., extensive time and cost involved), in vitro methods are of high interest for evaluating the bioequivalence of topical formulations (1,2). The analysis of spreadability is one such method that can help assess bioequivalence of formulations that are qualitatively (Q1) and quantitatively (Q2) equivalent. The FDA will usually not request additional bioequivalence testing for solution formulations that are Q1 and Q2 equivalent. However, semi-solid formulations that are Q1 and Q2 equivalent may have differences in the physical attributes and state of the product (arrangement of matter, aggregation) that reflect changes in the manufacturing method or the physical state of starting materials. Thus, structural similarity (Q3) can be defined as a third aspect of equivalence (3). The rheology of semi-solids is sensitive to changes in the microstructure and is potentially able to detect Q3 differences. In addition, the viscosity of a topical formulation will affect its application and delivery of the active agent to and across the skin, resulting in variance in its therapeutic performance. Subjective spreadability has been shown to be related to rheology through a material’s yield stress, the minimum shear stress required to initiate flow (σο). Specifically, the spreadability is inversely proportional to σο. (4,5) Extensive studies have been completed for the yield stress analysis of semi-solid foods that can be extended to semi-solid pharmaceutical formulations (4,6–8). In this study, the vane method has been employed to determine the yield stress of Q1/Q2 topical formulations in an attempt to determine if they were Q3 equivalent. The vane method (Fig. 1) involves the immersion of the blades of a vane into a sample followed by slow rotation at a constant RPM until the torque exerted on the vane reaches a maximum value and the sample begins to flow. Torque vs. time curves are used to determine yield stress where Mo is the maximum torque exerted on the vane by the fluid. Fig. 1 A vane, used in the vane method, with blade height of H and blade diameter of d with the height (h) of vane immersed in a fluid. This geometry is used along with the maximum torque value obtained with the vane method to obtain the yield stress of the ... MATERIALS AND METHODS The materials used in these studies were four topical formulations containing the active ingredient Econazole Nitrate 1%, and these were obtained from the Food and Drug Administration. All three of the generic formulations were previously determined to be equivalent to the innovator product in clinical bioequivalence studies. In these studies, the creams were referred to as formulations A, B, C and D, where formulation C is the innovator and formulations A, B, and D are generic brands. These rheological flow tests were carried out on a Brookfield RV DV III + Digital Rheometer using a Brookfield cone (CPE 52) and plate apparatus. The rheological vane method experiments were carried out on a Brookfield RV DV III + Digital Rheometer using a vane spindle attachment. Flow Curves Procedure Flow curves for these formulations were constructed by discharging 0.5 mL of each formulation onto the center of the plate. The gap was then set for the cone and plate apparatus so that the cone was at an appropriate and consistent distance from the plate for each trial. The rheometer was then programmed with increasing RPM (shear rate) over a range of 1 to 24 s−1 at constant temperature (25°C).

Preparation of Fucoidan-Chitosan Hydrogel and Its Application as Burn Healing Accelerator on Rabbits

Treatment of dermal wounds with macromolecular agents such as natural polymers is one of the research areas of the biomaterial science. Fucoidan is a sulphated polysaccharide which is commonly obtained from seaweeds. The great number of studies on the different pharmacological properties of fucoidan is present, but there is limited information about using of fucoidan in the treatment of dermal burns. The aim of this study was to prepare fucoidan-chitosan hydrogels and to investigate their treatment efficiency on dermal burns. Hydrogels were prepared by swelling the polymers in acidic solution and their swelling, mechanical (hardness, cohesiveness and adhesiveness) and bioadhesive properties were investigated. The viscosity and water absorption capacity of formulations increased with increase in the polymer concentration. In contrast to the cohesiveness results, the adhesiveness of hydrogels increased with the polymer concentration. The bioadhesion was changed between 0.012-0.142 mJ x cm(-2) and enhanced with addition of fucoidan into gel formulations. It was formed dermal burns on seven adult male New Zealand white rabbits and the optimum gel formulation applied on the wounds. Control and treatment group biopsy samples were taken on days 7, 14 and 21 and each burn wound site was evaluated histopathologically. No edema was seen in tested groups except control after 3 d treatment. After 7 d treatment, fibroplasia and scar were fixed on wounds treated with fucoidan-chitosan gel and fucoidan solution. The best regeneration on dermal papillary formation and the fastest closure of the wounds were observed in fucoidan-chitosan hydrogels after 14 d treatment.

Development of an oral microemulsion formulation of alendronate: Effects of oil and co-surfactant type on phase behaviour

This study aimed to prepare a water-in-oil microemulsion formulation of alendronate. Pseudo-ternary phase diagrams were constructed by using different oils and co-surfactants. The final formulation was decided to be prepared with Captex 200®, lecithin, propylene glycol and bidistilled water. Rheological behaviour, phase stability and type of the microemulsion formulation were investigated by Brookfield viscosimeter, centrifugation test and dye method, consequently. Phase behaviour of the formulation was found to be Newtonian. No precipitation was observed in the stressed conditions and formulation was W/O. The physical characterization of the formulation (physical appearance, viscosity, refractive index, conductivity, density and turbidity) was investigated at 4°C and 25°C during 6 months while droplet size was investigated for 3 months. Droplet size of the formulation was between 224–280 nm while viscosity was between 89.9–99.5 mPa.S. The release of alendronate from the microemulsion formulation was examined by dialysis method and found to be 97.2% at the end of 7 h. None of the parameters except refractive index changed significantly during the determined periods. This study succeeded in preparing a stable microemulsion formulation of alendronate.

High dielectric anisotropy compound doped transmission gratings of HPDLC

Effects of high dielectric anisotropy compound (MLC) and oligomer molecular weight on the grating formation and electro-optical properties of transmission holographic polymer dispersed liquid crystal (HPDLC) have been studied. Addition of MLC reduced the response time and switching voltage with the increased formulation viscosity which introduced a sequence of phenomenon, i.e. slow diffusion, polymerization, phase separation, grating formation, and droplet coalescence giving small droplet size and enhanced diffraction efficiency of the film. Apparently, increase in oligomer molecular weight gave effects similar to those of increasing MLC content since both variables control droplet coalescence through different mechanisms.

Development and Evaluation of Herbal Formulations for Hair Growth

Hair formulation of Emblica officinalis (Euphorbiaceae), Bacopa, monnieri (Scrophulariaceae), Trigonella foenumgraecum (Leguminosae), Murraya koenigii (Rutaceae) in various concentrations in the form of herbal oil were studied for their hair growth activity. Each drug was tested for their hair growth activity in a concentration range for 1‐10% separately. Based on these results mixture of crude drugs Murraya koeniigi, leaf (Rutaceae), Bacopa monnieri, leaf (Scrophulariaceae), Trigonella foenumgraecum (Leguminosae), Murraya koenigii (Rutaceae) were prepared in varying concentration in the form of herbal hair oil by three different oils preparation techniques and were tested for hair growth activity. The result revealed that the hair growth activity of each drug was found proportional to the concentration range tested. Similarly higher concentrations of drug in the formulation were found to have higher hair growth activities. But looking towards the formulation viscosity the maximum concentration of combined drug was found to be 30% at their maximum level. The formulation containing 7.5% of each drug used for the study and showed excellent hair growth activity with standard (2% minoxidil ethanolic solution) by an enlargement of follicular size and prolongation of the anagen phase. It holds the promise of potent herbal alternative for minoxidil. Excellent results of hair growth were seen in formulation prepared by cloth pouch decoction method of oils preparation technique.

Influence of Formulation Viscosity on Drug Absorption Following Nasal Application in Rats

The aim of this research is to clarify the influence of the viscosity of the nasal formulation on in vivo nasal drug absorption and its mechanism using an in vitro Caco-2 system. The drug solution was made viscous by the addition of dextran (Dex). The disappearance of FITC-labeled Dextran (FD, a marker of the dosing solution) applied with control solution followed monoexponential kinetics, while FD applied with Dex solution showed biexponential elimination. The mean residence time of FD in the nasal cavity was increased with the increase in Dex concentration. The nasal absorption of acyclovir was similar in the formulation with low viscosity, increased in the formulation with moderate viscosity and markedly decreased in the formulation with high viscosity. The result from the normal Caco-2 transport study could not explain the relation of in vivo drug absorption with viscosity, while the modified Caco-2 system provided data partly reflecting the change in in vivo absorption in rats. In conclusion, the residence of the applied solution in the nasal cavity was enhanced by the addition of Dex in a viscosity-dependent manner. Moderate viscosity of the dosing solution improved the in vivo nasal absorption of acyclovir, while higher viscosity decreased it.

Bacillus thuringiensis fermentation of hydrolyzed sludge – Rheology and formulation studies

Rheology of Bacillus thuringiensis fermentation of hydrolyzed sludge was investigated in bench scale fermenter. Stable liquid formulations were developed and optimized for two-year based studies comprising various physical/chemical (viscosity, particle size, corrosion and suspendibility) and biological (microbial contamination, viable spores and entomotoxicity) parameters at different pHs and temperatures. The hydrolyzed sludge depicted non-Newtonian and pseudoplastic behaviour during fermentation with 90% to 96% confidence of fits into Casson, Power and IPC paste models. Higher values of consistency and flow index during exponential growth and stationary phase, respectively, affected downstream processing. The power law was also followed by stable formulations. Sorbitol, sodium monophosphate and sodium metabisulfite (2.2:1:1) as suspending agents produced suspendibility ranging from 69% to 94%. The stable formulation (FH-4) comprising sorbitol, sodium monophosphate and sodium metabisulfite deteriorated at pHs 6, 6.5 and temperatures, 40 and 50 degrees C, with no signs of corrosion and microbial contamination. The viscosity of FH-4 formulations decreased with shear rate which could improve handling and consequent spraying.

Scale invariance of viscosity and cluster structure of epoxy formulations

The concentration dependences of the relative viscosity of epoxydiane resins (M n = 400–650) in solutions of monoglycidyl esters, Cardura and Laproxide, and of the dynamic viscosity of filled epoxy formulations in a shear flow were studied. The optimal concentrations of the formulation components and structural parameters of the fractal aggregates of oligomers and clusters of pigment (filler) particles were calculated in the approximation of the cluster lattice model.

Automated determination of pot life of two-component reactive coatings

The process of pot life screening of two-component coatings is significantly accelerated by using an automated coating formulation system with viscosity measurement capability. High-throughput methods are revolutionizing the processes used in polymer and coatings development. A high-throughput approach to characterize the effect of formulation variables on pot life of two-component solventborne coatings is presented. Using an automated formulation system with viscosity measurement capability, the viscosity of the coatings formulations is measured periodically to determine the viscosity–time profile. As examples, variables such as catalyst type, catalyst level, polyol composition, polyol to isocyanate ratio, and pot life extender were selected as formulation variables and their role in pot life were explored. Compared to traditional pot life determination methods using efflux viscosity cups, the high-throughput approach greatly improves the speed and efficiency of the process and allows many more compositions to be explored.

In Vitro Stability of Insulin Lispro in Continuous Subcutaneous Insulin Infusion

The stability of insulin lispro for use in continuous subcutaneous insulin infusion (CSII) therapy was evaluated using a stress test incorporating high temperature and mechanical agitation combined with simulated basal/bolus administration. Insulin lispro formulation contained in MiniMed 507c (Medtronic MiniMed, Sylmar, CA), H-TRONplus (Disetronic Medical Systems, St. Paul, MN), and D-TRON CSII (Disetronic Medtronic Systems) devices was subjected to a stress test involving exposure to elevated temperature (37 degrees C) and mechanical agitation (shaking at 100 strokes/min) for 7 days. CSII devices were programmed for continuous infusion at 0.8 U/h (19.2 U/day), and three 6-U bolus doses were also manually delivered each day (18 U/day). Formulation infused from the devices was collected every 24 h over the 7-day study. The material obtained from each 24-h period was analyzed to assess the physicochemical properties of insulin lispro and the overall formulation. Insulin lispro potency, purity, high-molecular-weight protein (HMWP), and m-cresol content were determined using high-performance liquid chromatographic methods. Solution pH, delivered volume, and formulation physical appearance were also evaluated. The pH of the infused formulation remained unchanged throughout the entire study. Insulin lispro potency for each device remained within 95-105% of label claim each day of the stress test, indicating that adsorption or surface-induced denaturation of insulin lispro did not occur. Levels of insulin lispro deamidated at position 21 in the A-chain were essentially constant during the 7-day stress test. A time-dependent increase in HMWP and other insulin lispro chemical transformation products was observed over the testing period for each device. However, the levels of these known degradation products remained well below published specifications for these analytical properties. The concentration of the antimicrobial agent, m-cresol, was decreased because of absorption, but the levels remained sufficient to provide protection against microbial contamination. Total delivered volume results were in good agreement with expected values and confirmed that formulation viscosity remained unchanged. Samples collected from the infusion sets were clear and free of precipitates. Occlusion alarms did not occur, and no other electronic or mechanical malfunctions of the CSII devices were encountered. Insulin lispro demonstrates appropriate physicochemical stability for use in MiniMed 507c, H-TRONplus, and D-TRON CSII devices.

Percutaneous absorption of organic sunscreens

The increased awareness of protection against skin cancer has led to a rise in the use of topically applied chemical sunscreen agents. There is a concern about the systemic absorption of organic filters in sunscreen formulations. The present study briefly reviews theoretical models for the prediction of the percutaneous penetration of the organic molecules and the accepted methods for the in vitro and in vivo evaluations of the penetration. The influence of the vehicle and the formulation viscosity on the penetration of sunscreens are examined. The development of novel methods for the minimization of sunscreen absorption is also discussed.

Polyhydroxy Alcohols and Peach Oil Addition Influence on Liquid Crystal Formation and Rheological Behavior of O/W Emulsions

The aim of this study was to develop O/W emulsions with a self‐emulsifying base (SEB) containing liquid crystals (LC) and evaluate the influence of polyhydroxy alcohols and peach oil addition in liquid crystal formation as well as to analyze the rheological behavior of these systems. Formulations containing SEB were supplemented or not with glycerin, sorbitol, propylene glycol, and/or peach oil. All formulations studied had lamellar crystalline phases. Peach oil addition increased the viscosity of SEB, while humectants had different behavior, glycerin enhanced the viscosity of the studied formulations supplemented or not with peach oil, and propylene glycol decreased the viscosity of all formulations studied. On the other hand, sorbitol enhanced the viscosity of formulations containing peach oil. All emulsions presented pseudoplastic behavior and thixotropy.

Assays of physical stability and antioxidant activity of a topical formulation added with different plant extracts

In the present investigation the changes on physical stability (pH, viscosity, flow index and tixotropy) of topical formulations were evaluated following inclusion of different plant extracts containing flavonoids. Also, the antioxidant effect of these plant extracts alone and after addition in the formulation was evaluated using chemiluminescence and the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH ) assays, as well as the inhibition of lipid peroxidation. Formulation added with dl-α-tocopherol was used to compare the physical stability and antioxidant activity. Formulations with plant extracts showed pseudoplastic behavior with decreasing on viscosity and tixotropy. The Glycyrrhiza glabra (GG) and Ginkgo biloba (GB) extracts alone and the formulations containing these extracts showed great antioxidant and free radical scavenging activities while the other extracts studied (mixture of Glycyrrhiza glabra, Symphytum officinale L and Arctium majus root, Nelumbium speciosum and soybean) showed lower activity. The results suggest that GG and GB extracts may be used in topical formulations in order to protect skin against damage caused by free radical and reactive oxygen species.

Isotropic Systems of Medium‐Chain Mono‐ and Diglycerides for Solubilization of Lipophilic and Hydrophilic Drugs

The aim of this study was to investigate isotropic mono‐ and diglyceride‐based (MCMDG) systems, which are potential vehicles for injectable products containing both hydrophilic and lipophilic drugs. For two‐component systems, MCMDG was mixed with various masses of water. For three‐component systems, the samples were prepared by mixing propylene glycol or glycerol formal or short‐chain alcohols with MCMDG prior to the addition of water. The isotropic region was examined by visual inspection and confirmed using polarized light microscopy. Viscosities of formulations were measured. Solubilities of levamisole phosphate (hydrophilic) and abamectin (lipophilic) were determined in the isotropic formulations using high‐performance liquid chromatography assay. The isotropic region in the two‐component systems had a water content of up to 18% at 25°C. Solvents such as propylene glycol (PG), glycerol formal (FG), and ethyl alcohol increased the isotropic region. The area of isotropic region in these three‐component systems increased with increasing temperature. The area of the isotropic region became larger with decreasing dielectric constant and solubility parameter of the series of short‐chain alcohols, except n‐butyl alcohol, at 25°C. The systems exhibited Newtonian behavior. The solubility of both hydrophilic and lipophilic drugs was high in formulations at 25°C. It was concluded that more water was solubilized in MCMDG/short‐chain alcohols/water systems, and the isotropic region in the short‐chain alcohol systems enlarged compared with MCMDG/PG/water or MCMDG/GF/water systems, except the n‐butyl alcohol system. Hydrophilic and lipophilic drugs solubilize in the systems. The isotropic formulations containing MCMDG may represent an alternative to more traditional formulations for injectable formulations containing both lipophilic and hydrophilic drugs.