Physical compatibility of ceftriaxone and cefepime in 0.45% sodium chloride, Ringer's lactate solution, and Plasma-Lyte A.

OBJECTIVES: The compatibility of intravenous fluids with medications is of paramount concern to pharmacists and is an imperative component of ensuring patient safety. Data regarding the physical compatibility of medications with intravenous fluids has not been examined, or published with conflicting results or the concentrations studied were not consistent with current practice. Our objective was to determine the physical compatibility of ceftriaxone and cefepime in 0.45% sodium chloride, Ringer's lactate solution, and Plasma-Lyte A. METHODS: An in vitro analysis of the physical compatibility of ceftriaxone and cefepime at 10 mg/mL, 20 mg/mL, and 40 mg/mL concentrations was conducted in 0.45% sodium chloride, Ringer's lactate solution, and Plasma-Lyte A. Admixtures were evaluated in triplicate at hours 0, 1, 5, 8, and 24. Physical compatibility was assessed by visual inspection, spectrophotometry, and pH analysis. RESULTS: Ceftriaxone 40 mg/mL was found to be physically incompatible in 0.45% sodium chloride and Ringer's lactate solution beyond 5 hours and in Plasma-Lyte A beyond 8 hours. Cefepime was found to be physically incompatible with all fluids and in all concentrations beyond 1 hour. CONCLUSIONS: This work contributes to the body of literature dedicated to the evaluation of intravenous drug and fluid physical compatibility by identifying demonstrable changes in admixtures containing 0.45% sodium chloride, Plasma-Lyte A, and Ringer's lactate solution. Ceftriaxone should not be administered with 0.45% sodium chloride, Ringer's lactated solution, or Plasma-Lyte A at selected concentrations and time points and cefepime is not considered to be physically compatible at 10 mg/mL, 20 mg/mL, or 40 mg/mL in any of the studied fluids beyond 1 hour.

MALDI-TOF imaging analysis of benzalkonium chloride penetration in ex vivo human skin.

Benzalkonium chloride (BZK), alkyldimethylbenzlamonium chloride, is a cationic surfactant that is used as an antiseptic. BZK is classified as a quaternary ammonium compound composed of molecules of several alkyl chains of differing lengths, that dictate its effectiveness towards different microbes. As a result, BZK has become one of the most used preservatives in antibacterial solutions. Despite its widespread use, it is not clear whether BZK penetrates human skin. To answer this question, BZK treated skin was analyzed using matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry imaging. Solutions containing BZK and differing excipients, including citric acid, caprylyl glycol, and vitamin E, were applied ex vivo to excised human skin using Franz diffusion cells. Treated skin was embedded in gelatin and sectioned prior to MALDI-TOF imaging. BZK penetrates through the epidermis and into the dermis, and the penetration depth was significantly altered by pH and additives in tested solutions.

Skin penetration of caffeine from commercial eye creams and eye creams designed and optimized based on Hansen solubility parameters.

Computer-aided formulation design can streamline and speed up product development. In this study, ingredient screening and optimizing software, Formulating for Efficacy® (FFE), was used to design and optimize creams for the topical delivery of caffeine. FFE was set up to optimize lipophilic active ingredients, therefore, this study challenged the program's capabilities. The effect of two chemical penetration enhancers, including dimethyl isosorbide (DMI) and ethoxydiglycol (EDG), were studied based on their favorable Hansen Solubility Parameter physicochemical input parameters for the skin delivery of caffeine in the FFE® software application. Four oil-in-water emulsions containing 2% caffeine were formulated, one without a chemical penetration enhancer, one with five percent of DMI, one with five percent of EDG, and one with 2.5% of DMI and EDG each (DMI + EDG). Additionally, three commercial products were used as reference products. The cumulative amount of caffeine released and permeated, and the flux across Strat-M® membranes were determined using Franz diffusion cells. The eye creams had skin-compatible pH, excellent spreadability for the application area, were opaque emulsions with 14-17 µm droplet size, and were stable at 25 °C for 6 months. All four eye creams formulated released over 85% of caffeine in 24 h, outperforming the commercial products. DMI + EDG cream provided the highest permeation in vitro in 24 h, which was significantly higher than the commercial products (p < 0.05). FFE proved to be a valuable and quick tool to aid in the topical delivery of caffeine.

Intravenous Physical Compatibility of Heparin Sodium and Furosemide.

Continuous infusions of heparin and furosemide are often required for hospitalized patients to treat cardiac-related disease states. Concomitant infusion of heparin and furosemide through the same intravenous line minimizes the need for multiple intravenous sites. For concomitant infusions to be administered, knowledge of the physical compatibility for intravenous medications is imperative for patient safety and administering medications to maximize their effectiveness. Currently, heparin and furosemide are listed as Y-site compatible, but precipitation was reported at a large academic medical center, which questions this compatibility. This study investigated the in vitro physical compatibility of heparin sodium premix 25,000 units/250 mL in dextrose 5% water from two different manufacturers with furosemide 40 mg/4 mL at concentrations of 4:1 for heparin sodium and furosemide. The admixtures were prepared in triplicate using aseptic technique, stored at 19°C to 24°C and examined for visual precipitation, turbidity, and pH change at baseline, 1, 5, 8, 24, and 48 hours. Heparin sodium, B. Braun Medical Inc. or Hospira, Inc. solutions, and furosemide admixtures revealed changes over 48 hours. Changes in visual appearance, absorbance, and pH were observed at hour 5 compared to baseline for the B. Braun Medical Inc. admixture. The Hospira, Inc. admixture revealed visual changes by hour 48, but demonstrative changes in absorbance and pH did not occur. Our observations found demonstrative changes in physical compatibility in the admixtures of heparin sodium and furosemide at a ratio of 4:1. The findings suggest that a combination of the solutions in this study be avoided until further research is completed.

Meadowfoam seed oil as a natural dispersing agent for colorants in lipstick.

OBJECTIVE: Green and sustainable trends are growing and with that the demand for naturally derived ingredients is rising. Dispersing agents are essential components of lipsticks due to their ability to wet pigment particles, reduce agglomerates and prevent re-agglomeration by stabilizing pigment particles. In this study, meadowfoam seed oil was evaluated as a pigment-dispersing agent for lipsticks and compared with castor oil and octyldodecanol. METHODS: Dispersions of Red 7 Lake were formulated with 20, 30 and 40% solid content using castor oil, octyldodecanol or meadowfoam seed oil. Particle size, viscosity, spreadability, wetting, oil absorption and colour were measured. Four of the nine dispersions were then formulated into lipsticks, including all the 30% pigment dispersions and the 40% dispersion with meadowfoam seed oil. Lipsticks were tested for hardness, pay-off, friction, rheology, colour and stability for 4 weeks. RESULTS: Average particle size was between 6 and 9 µm across the dispersions. The castor oil dispersions were more viscous, stickier and harder to spread than the other dispersions. The wetting contact angle was very low for all three dispersing agents, indicating that all of the oils wet the pigment well. The lipsticks varied in hardness, as expected, based on differences in the viscosity of the dispersing agents, and oil absorption of the powder. Red 7 Lake absorbed the highest amount of castor oil, which contributed to higher stick hardness. The castor oil lipstick and the meadowfoam seed oil lipstick containing 40% pigment were the hardest and most elastic. The octyldodecanol lipstick was the softest. Friction was the lowest for the meadowfoam seed oil lipstick containing 40% pigment, while pay-off was the highest for the octyldodecanol lipstick. The colour of the lipsticks as a stick and after being spread on paper was very similar. CONCLUSION: While the chemical composition and physicochemical properties of the dispersing agents were different, all three dispersing agents studied formed dispersions and lipsticks with appropriate characteristics. Meadowfoam seed oil's performance was qualitatively and quantitatively similar to castor oil and octyldodecanol. By modifying the amount of pigment and dispersing agent used, lipsticks that have similar characteristics to commercial products can be formulated.

OBJECTIF: Les tendances écologiques et durables sont en hausse, ainsi que la demande en ingrédients d'origine naturelle. Les agents de dispersion sont des composants essentiels des rouges à lèvres en raison de leur capacité à mouiller les particules pigmentaires, à réduire les agglomérats et à prévenir la réagglomération en stabilisant les particules pigmentaires. Dans cette étude, l'huile de graines de limnanthe a été évaluée en tant qu'agent de dispersion pigmentaire pour les rouges à lèvres et comparée à l'huile de ricin et à l'octyldodécanol. MÉTHODES: Les dispersions de Red 7 Lake ont été formulées avec une teneur solide de 20, 30 et 40 % à l'aide d'huile de ricin, d'octyldodécanol ou d'huile de graines de limnanthe. La taille des particules, la viscosité, la facilité d'étalement, le mouillage, l'absorption de l'huile et la couleur ont été mesurés. Quatre des neuf dispersions ont ensuite été formulées dans des rouges à lèvres, y compris toutes les dispersions pigmentaires à 30 % et la dispersion à 40 % avec l'huile de graines de limnanthe. Les rouges à lèvres ont été testés pour la dureté, le résultat, la friction, la rhéologie, la couleur et la stabilité pendant 4 semaines. RÉSULTATS: La taille moyenne des particules était comprise entre 6 et 9 µm dans les dispersions. Les dispersions d'huile de ricin étaient plus visqueuses, plus collantes et plus difficiles à étaler que les autres dispersions. L'angle de contact de mouillage était très faible pour les trois agents de dispersion, indiquant que toutes les huiles humidifient bien le pigment. La dureté des rouges à lèvres variait, comme attendu, en fonction des différences de viscosité des agents dispersants et de l'absorption de l'huile de la poudre. Red 7 Lake absorbe la plus grande quantité d'huile de ricin, ce qui contribue à une dureté du bâton plus élevée. Le rouge à lèvres à base d'huile de ricin et le rouge à lèvres à base d'huile de graines de limnanthe contenant 40 % de pigment étaient les plus durs et les plus élastiques. Le rouge à lèvres à base d'octyldodécanol était le plus mou. La friction était la plus basse pour le rouge à lèvres à base d'huile de graines de limnanthe contenant 40 % de pigment, tandis que le résultat était le plus élevé pour le rouge à lèvres à base d'octyldodécanol. La couleur des rouges à lèvres en bâton et après avoir été étalés sur du papier était très similaire. CONCULSION: Alors que la composition chimique et les propriétés physicochimiques des agents de dispersion étaient différentes, les trois agents de dispersion étudiés ont tous formé des dispersions et des rouges à lèvres ayant des caractéristiques appropriées. Les performances de l'huile de graines de limnanthe étaient qualitativement et quantitativement similaires à celles de l'huile de ricin et de l'octyldodécanol. En modifiant la quantité de pigment et d'agent dispersant utilisée, des rouges à lèvres ayant des caractéristiques similaires aux produits commerciaux peuvent être formulés.

Blue light protection, part II-Ingredients and performance testing methods.

BACKGROUND: There are numerous cosmetic ingredients that have been identified to have blue light protection benefits. The urge to learn more about blue light protection claims has led to several substantiation test methods that can be utilized by companies to prove product efficacy. AIMS: Part II of this article provides up-to-date information on cosmetic ingredients that can provide protection from blue light, and methods companies can use to substantiate blue light protection claims. METHODS: An Internet search was completed using the Google Scholar database and a cosmetic ingredient supplier database (UL Prospector) for ingredients and relevant literature. RESULTS: Multiple ingredient categories, for example, algae-derived ingredients, UV filters, botanical extracts, antioxidants, and vitamins, are available on the market to fight against blue light-induced skin damage. There is not a formal standardized method to test for blue light protection; however, spectrophotometers, imaging devices, measuring oxidative stress, and visual evaluations are some of the methods being used today. CONCLUSIONS: The number of ingredients launched for blue light protection and new methods developed to test products for blue light protection claims is expected to increase in the near future as we are learning more about the mechanism of damage that occurs in the skin upon blue light exposure.

Blue Light Protection, Part I-Effects of blue light on the skin.

BACKGROUND: Blue light is emitted visible light between the wavelengths of 400 to 500 nm. The main source of blue light is sunlight, but digital screens, light-emitting diodes (LEDs), and fluorescent lighting serve as additional sources. Concerns about the negative effects of blue light on the skin have rapidly increased over the past 15 years, and consequently, the urge to learn more about this topic is increasing as well. AIMS: Part I of this article provides up-to-date information on the definition of blue light and the negative and positive effects of blue light on the skin. METHODS: An Internet search was completed using the Google scholar database for relevant literature. RESULTS: Blue light can be both harmful and beneficial to the skin, depending on intensity and wavelength. Short-term safety information is more readily available from clinical studies; however, the biological effects of repeated and/or longer-term exposure are not fully understood yet. CONCLUSIONS: Low-energy and low exposure times to high-energy blue light can help prevent skin diseases, while studies have revealed that longer exposure to high-energy blue light can increase the amount of DNA damage, cell and tissue death, and injury, eye damage, skin barrier damage, and photoaging.

Effect of Solvents on the In Vitro Sun Protection Factor and Broad-Spectrum Protection of Three Organic UV Filters.

Solvents play an essential role in the performance of ultraviolet (UV) filters. The goal of this study was to understand how the in vitro sun protection factor (SPF) and broad-spectrum protection of three organic UV filters (homosalate, ethylhexyl salicylate, and butyl methoxydibenzoylmethane) and a combination of these are influenced by solvents. Twenty-four solvents were selected based on the ingredient active gap for testing. Mixtures of UV filters and solvents were formulated, and in vitro SPF, wavelength of maximum absorbance, broad-spectrum protection, and spreadability were evaluated. Results indicate that in vitro SPF of organic sunscreens can be significantly enhanced by solvents. Relying on solubility data only was not found to be a good approach in this study. The most efficient solvents shared multiple similar structural characteristics, including ester bonds, conjugated structure, aromatic rings, and -CN groups; however, the absence of some of these structural elements did not necessarily prevent a solvent from being a booster. The wavelength of maximum absorbance was significantly shifted in the UVA range by most solvents, whereas minimal or no shift was observed in the UVB range. Results of this study provide practical information that can guide sunscreen formulators in selecting solvents for UV filters and making more effective sunscreens.

Evaluation of alkenones, a renewably sourced, plant-derived wax as a structuring agent for lipsticks.

OBJECTIVE: Waxes are used as structuring agents in lipsticks. There are a variety of waxes combined in a single lipstick to provide good stability, pleasant texture and good pay-off. Due to a significant growth for natural, green and sustainable products, there is a constant search for alternatives to animal-derived and petroleum-derived ingredients. In this study, a green, non-animalderived wax, namely long-chain ketones (referred to as alkenones), sourced from marine microalgae was formulated into lipsticks and evaluated as a structuring agent. METHODS: Alkenones were used as a substitute for microcrystalline wax, ozokerite and candelilla wax, typical structuring agents. In total, 384 lipsticks were formulated: L1 (control, no alkenones), L2 (alkenones as a substitute for ozokerite), L3 (alkenones as a substitute for microcrystalline wax) and L4 (alkenones as a substitute for candelilla wax). Products were tested for hardness (bending force), stiffness, firmness (needle penetration), pay-off (using a texture analyser and a consumer panel), friction, melting point and stability for 12 weeks at 25 and 45°C. RESULTS: Alkenones influenced each characteristic evaluated. In general, lipsticks with alkenones (L2-L4) became softer and easier to bend compared to the control (L1). In terms of firmness, lipsticks were similar to the control, except for L4, which was significantly (P < 0.05) firmer. The effect on pay-off was not consistent. L2 and L3 had higher pay-off to skin and fabric than L1. In addition, L4 had the lowest amount transferred, but it still had the highest colour intensity on skin. Alkenones influenced friction (glide) positively; the average friction decreased for L2-L4. The lowest friction (i.e. best glide) was shown in L4. Melting point of the lipsticks was lower when alkenones were present. Overall, L4, containing 7% of 4 alkenones in combination with microcrystalline wax, ozokerite and carnauba wax, was found to have the most desirable attributes, including ease of bending, high level of firmness, low pay-off in terms of amount, high colour intensity on skin and low friction (i.e. better glide). Consumers preferred L4 the most overall. CONCLUSION: Results of this study indicate that alkenones offer a sustainable, non-animal and non-petroleum-derived choice as a structuring agent for lipsticks.

OBJECTIF: Les cires sont utilisées comme agents de structuration dans les rouges à lèvres. Un rouge à lèvres contient plusieurs cires, afin d'obtenir une bonne stabilité, une texture agréable et un bon transfert de matière. En raison d'une croissance significative de la demande en produits naturels, écologiques et durables, les chercheurs s'efforcent constamment de trouver des alternatives aux ingrédients d'origine animale et dérivés du pétrole. Dans cette étude, les cétones à longue chaîne (appelés alkénones), une cire verte qui n'est pas d'origine animale, mais provenant de microalgues marines, a été formulée pour les rouges à lèvres et évaluée comme agent de structuration. MÉTHODES: Les alkénones ont été utilisés comme substitut pour la cire microcristalline, l'ozokérite et la cire de candelilla, des agents de structuration courants. Au total, 384 rouges à lèvres ont été formulés : L1 (contrôle, sans alkénone), L2 (alkénones comme substitut de l'ozokérite), L3 (alkénones comme substitut de la cire microcristalline) et L4 (alkénones comme substitut de la cire de candelilla). Des tests ont été réalisés sur les produits pour évaluer la dureté (force de flexion), la rigidité, la fermeté (pénétration de l'aiguille), le transfert de matière (à l'aide d'un analyseur de texture et d'un panel de consommateurs), la friction, le point de fusion et la stabilité pendant 12 semaines à 25 et 45 °C. RÉSULTATS: Les alkénones ont eu une influence sur chacune des caractéristiques évaluées. En général, les rouges à lèvres contenant des alkénones (L2 à L4) sont devenus plus mous et ont présenté une flexion plus facile que dans le cas du contrôle (L1). En termes de fermeté, les rouges à lèvres étaient similaires au contrôle, à l'exception de L4, qui était significativement (P < 0,05) plus ferme. L'effet sur le transfert de matière a été variable. L2 et L3 ont présenté un transfert de matière sur la peau et le tissu supérieur à celui de L1. En outre, dans le cas de L4, la quantité transférée était la plus faible, mais l'intensité de la couleur sur la peau était toujours la plus élevée. Les alkénones ont eu un effet positif sur la friction (glissement) ; la friction moyenne a diminué pour L2 à L4. La friction la plus basse (c.-à-d. le meilleur glissement) a été observée dans le cas de L4. Le point de fusion des rouges à lèvres était plus bas lorsque des alkénones étaient présents. Dans l'ensemble, L4, contenant 7 % d'alkénones en combinaison avec de la cire microcristalline, de l'ozokérite et de la cire de carnauba, s'est révélée avoir les caractéristiques les plus souhaitables, notamment une facilité de flexion, une fermeté élevée, un faible transfert de matière en termes de quantité, une intensité de couleur élevée sur la peau et une faible friction (c.-à-d. un meilleur glissement). En général, les consommateurs ont préféré L4. CONCLUSION: Les résultats de cette étude indiquent que les alkénones offrent un choix durable, non issu de l'animal et non dérivé du pétrole comme agent de structuration pour les rouges à lèvres.

Computer-based formulation design and optimization using Hansen solubility parameters to enhance the delivery of ibuprofen through the skin.

Trial-and-error approach to formulation development is long and costly. With growing time and cost pressures in the pharmaceutical industry, the need for computer-based formulation design is greater than ever. In this project, emulgels were designed and optimized using Formulating for Efficacy™ (FFE) for the topical delivery of ibuprofen. FFE helped select penetration enhancers, design and optimize emulgels and simulate skin penetration studies. pH, viscosity, spreadability, droplet size and stability of emulgels were evaluated. Franz cell studies were performed to test in vitro drug release on regenerated cellulose membrane, drug permeation in vitro on Strat-M® membrane and ex vivo on porcine ear skin, a marketed ibuprofen gel served as control. Emulgels had skin compatible pH, viscosity and spreadability comparable to a marketed emulgel, were opaque and stable at 25 °C for 6 months. Oleyl alcohol (OA), combined with either dimethyl isosorbide (DMI) or diethylene glycol monoethyl ether (DGME) provided the highest permeation in 24 h in vitro, which was significantly higher than the marketed product (p < 0.01). OA + DGME significantly outperformed OA ex vivo (p < 0.05). The computer predictions, in vitro and ex vivo penetration results correlated well. FFE was a fast, valuable and reliable tool for aiding in topical product design for ibuprofen.

Nanostructured Lipid Carrier Gel for the Dermal Application of Lidocaine: Comparison of Skin Penetration Testing Methods.

The aim of this research was to investigate the stability of a lidocaine-loaded nanostructured lipid carrier dispersion at different temperatures, formulate a nanostructured lipid carrier gel, and test the penetration profile of lidocaine from the nanostructured lipid carrier gel using different skin penetration modeling methods. The formulations were characterized by laser diffraction, rheological measurements and microscopic examinations. Various in vitro methods were used to study drug release, diffusion and penetration. Two types of vertical Franz diffusion cells with three different membranes, including cellulose, Strat-M®, and heat separated human epidermis were used and compared to the Skin-parallel artificial membrane permeability assay (PAMPA) method. Results indicated that the nanostructured lipid carrier dispersion had to be gelified as soon as possible for proper stability. Both the Skin-PAMPA model and Strat-M® membranes correlated favorably with heat separated human epidermis in this research, with the Strat-M® membranes sharing the most similar drug permeability profile to an ex vivo human skin model. Our experimental findings suggest that even when the best available in vitro experiment is selected for modeling human skin penetration to study nanostructured lipid carrier gel systems, relevant in vitro/in vivo correlation should be made to calculate the drug release/permeation in vivo. Future investigations in this field are still needed to demonstrate the influence of membranes and equipment from other classes on other drug candidates.

Exploring the Impact of Technology Use with Cosmetic Science Guest-Speakers: A Qualitative Study.

Improvements in current classroom technology such as video conferencing have allowed geographically-distant guest-speakers to participate in teaching. However, is time and effort that faculty may spend coordinating guest-speakers helpful for their students' learning? Relevance is key to motivation and learning, and therefore, it would seem that professionals who can share industry applications and their experiences should help promote relevance. During the core application-based cosmetic science coursework in an undergraduate cosmetic science and formulation design degree at the University of Toledo, multiple industry experts come in as guest-speakers. The majority of them join remotely via a real-time video conferencing tool. The purpose of this study was to both explore the impact of guest-speakers on these students' learning, as well as to understand how guest-speakers might also value these experiences. Twenty-two students and sixteen guest-speakers participated. Using a qualitative approach, authors used an inductive thematic analysis of transcripts from focus-groups of students and interviews of guest-speakers. Twenty-one codes were identified, and five themes were constructed for both the student and guest-speaker groups. Themes from both groups were integrated and distilled into an essence related to teaching and learning. Our results indicated that students greatly appreciated the relevance from guest-speakers to augment their introductory/foundational instruction from faculty. From guest-speakers' perspectives, teaching students was formative towards developing informed future coworkers for the cosmetic industry. Technology enabled much of this. Overall, we believe that professional, experienced guest-speakers can make an impact on students. We hope that other higher education institutions might consider technology to foster use of guest-speakers within their programs.

Application of Check-All-That-Apply (CATA) Questions for Sensory Characterization of Cosmetic Emulsions by Untrained Consumers.

The sales potential of cosmetic products is greatly determined by skin feel and skin sensory performance. To please the target audience, it is important to gather information about consumers' perception of products' sensory characteristics. In this study, six different emulsions were formulated. Samples represented three different types of emulsions, including steric-stabilized oil-in-water (O/W), liquid crystal-stabilized O/W, and water-in-oil emulsions, providing different skin feel and aesthetics. Emulsions within the same group differed in the emollients, providing similar sensory attributes. The aim was to have 50 consumers evaluate the emulsions' sensory characteristics. Using a check-all-that-apply (CATA) survey, consumers provided information about their perception of appearance, rub-out, pick-up, and afterfeel. Consumers effectively discriminated between the emulsions. Statistical analysis showed significant differences for 15 sensory attributes in the before, during, and after phases. Our findings suggest that emulsifiers, and not emollients, have the dominant role in determining the aesthetics of a skin care emulsion, similar to previous findings. The fact that untrained consumers provided similar results as trained panelists suggests the validity of the CATA survey and its reliability as a screening tool in the product development process. CATA questions may serve as a viable complimentary to descriptive sensory analysis performed by trained panelists.

Formulation and Evaluation of Antibacterial Creams and Gels Containing Metal Ions for Topical Application.

Background. Skin infections occur commonly and often present therapeutic challenges to practitioners due to the growing concerns regarding multidrug-resistant bacterial, viral, and fungal strains. The antimicrobial properties of zinc sulfate and copper sulfate are well known and have been investigated for many years. However, the synergistic activity between these two metal ions as antimicrobial ingredients has not been evaluated in topical formulations. Objective. The aims of the present study were to (1) formulate topical creams and gels containing zinc and copper alone or in combination and (2) evaluate the in vitro antibacterial activity of these metal ions in the formulations. Method. Formulation of the gels and creams was followed by evaluating their organoleptic characteristics, physicochemical properties, and in vitro antibacterial activity against Escherichia coli and Staphylococcus aureus. Results. Zinc sulfate and copper sulfate had a strong synergistic antibacterial activity in the creams and gels. The minimum effective concentration was found to be 3 w/w% for both active ingredients against the two tested microorganisms. Conclusions. This study evaluated and confirmed the synergistic in vitro antibacterial effect of copper sulfate and zinc sulfate in a cream and two gels.

A new modified wetting test and an alternative disintegration test for orally disintegrating tablets.

Industrial manufacturing of solid oral dosage forms require quality tests, such as friability, hardness, and disintegration. The United States Pharmacopeia (USP) disintegration test uses 900mL of water. However, recent studies of orally disintegrating tablets (ODTs) have shown that this volume does not accurately portray the oral environment. In our study, various tests were conducted with a more moderate amount of water that accurately resembles the oral environment. A simulated wetting test was performed to calculate the water absorption ratio. Results showed that wetting was comparable to disintegration. Although the wetting test worked for most types of ODTs, it had limitations that produced inaccurate results. This led to the use of a modified shaking water bath test. This test was found to work for all types of ODT products and was not subject to the limitations of the wetting test. The shake test could provide disintegration times rather than water permeation times; however, it could not be used to calculate the water absorption ratio. A strong correlation was observed between the standardized shake test and the USP disintegration times for the tablets. This shake test could be used during the development stages and quality tests for ODTs with relative ease.

Dosage uniformity problems which occur due to technological errors in extemporaneously prepared suppositories in hospitals and pharmacies.

The availability of suppositories in Hungary, especially in clinical pharmacy practice, is usually provided by extemporaneous preparations. Due to the known advantages of rectal drug administration, its benefits are frequently utilized in pediatrics. However, errors during the extemporaneous manufacturing process can lead to non-homogenous drug distribution within the dosage units. To determine the root cause of these errors and provide corrective actions, we studied suppository samples prepared with exactly known errors using both cerimetric titration and HPLC technique. Our results show that the most frequent technological error occurs when the pharmacist fails to use the correct displacement factor in the calculations which could lead to a 4.6% increase/decrease in the assay in individual dosage units. The second most important source of error can occur when the molding excess is calculated solely for the suppository base. This can further dilute the final suppository drug concentration causing the assay to be as low as 80%. As a conclusion we emphasize that the application of predetermined displacement factors in calculations for the formulation of suppositories is highly important, which enables the pharmacist to produce a final product containing exactly the determined dose of an active substance despite the different densities of the components.

Comparing suppository mold variability which can lead to dosage errors for suppositories prepared with the same or different molds.

Suppository molds must be properly calibrated to ensure accurate dosing. There are often slight differences between molds and even in the cavities within a mold. A method is presented for the calibration of standard aluminum 6-, 12-, 50-, or 100-well suppository molds. Ten different molds were tested using water for volume calibration, and cocoa butter for standardization involving establishing the density factor. This method is shown to be straightforward and appropriate for calibrating suppository molds.

Evaluation of powder mixtures and hydrophilic gastroretentive drug delivery systems containing zinc acetate and sodium bicarbonate.

The aim of this study was to develop and study floating controlled drug delivery systems consisting of a model drug (zinc acetate dihydrate), different forms of a matrix-forming polymer (Metolose 90 SH) and sodium bicarbonate as an effervescent component. The proportions of Metolose and bicarbonate were varied, and the effects of the different ratios on the properties of the resulting powders and tablets were determined. The water uptakes of different powder mixtures were initially evaluated. These tests indicated the interaction of the active and effervescent agent, this phenomenon leading to an unpredicted increase in the amount of liquid taken up. This interaction was evaluated as concerns the degradation of the hydrophilic matrix system. The disintegration of tablets with different compositions revealed that this interaction increases the time required for the disintegration of these systems. The study demonstrated that the interaction of the components induced significant changes in the parameters of this new sensitive delivery system. In the last steps, the buoyancy and dissolution properties of tablets that appeared appropriate for the formulation of a controlled drug delivery system were investigated.

Role of surface free energy and spreading coefficient in the formulation of active agent-layered pellets.

Formulation of layered pellets can be a useful method for the preparation of multiparticulate systems. The aims of this work were to study the properties of hydrophilic active agent (pirenzepine dihydrochloride) layers formed on different pellet cores, the efficacy of layering and the connection between the core and the layers. The carrier pellets were prepared from mixtures of a hydrophilic (microcrystalline cellulose) and a hydrophobic (magnesium stearate) component in different ratios. These cores were coated in a fluid bed apparatus with an aqueous solution of active agent, with or without the addition of hydroxypropyl methyl cellulose (HPMC) as an adhesive component. The wettability of the pharmaceutical powders was assessed by means of Enslin number and contact angle measurements, and the surface energy was determined. Spreading coefficients of the components were also calculated and correlated with pellet properties such as the content of active agent, the friability and the morphological appearance of the layered product. An increased friability of the layer formed and the lower effectiveness of the process were experienced with a reduction in the wetting of the core. The efficiency of layering on a less polar core could be increased by the addition of HPMC, but the sensitivity of these pirenzepine layers to mechanical stress was higher. The type of the abrasion of these particles was dissimilar to that for samples prepared without HPMC. Peeling of the layers containing HPMC was observed for hydrophobic cores, but this phenomenon was not detected for the hydrophilic ones. These results can be explained by the spreading coefficients, which revealed an insufficient adhesion of layers for the samples that exhibited peeling.

Evaluation of the composition of the binder bridges in matrix granules prepared with a small-scale high-shear granulator.

The aim of this work was to evaluate the binder bridges which can form in hydrophilic matrix granules prepared with a small-scale high-shear granulator. Matrices contained hydroxypropyl methylcellulose (HPMC) as a matrix-forming agent, together with lactose monohydrate and microcrystalline cellulose as filler. Water was used as granulating liquid. A 2(4) full factorial design was used to evaluate the effects of the operational parameters (impeller speed, chopper speed, dosing speed and wet massing time) on the granulation process. The temperature of the sample increased relevantly during the preparation in the small-scale apparatus. The same setup induced different temperature increases for different amounts of powder. This alteration enhances the solubility of lactose and decreases that of HPMC, and thus the quantities of the dissolved components can vary. Accordingly, changes in composition of the binder bridge can occur. Since exact determination of the dissolution of these materials during granulation is difficult, the consequences of the changes in solubility were examined. Differential scanning calorimetry (DSC), thermomechanical analysis (TMA) and X-ray diffraction (XRD) measurements were made to evaluate the films prepared from liquids with different ratios of soluble materials. The DSC and XRD measurements confirmed that the lactose lost its crystalline state in the film. The TMA tests revealed that increase of the quantity of lactose in the film decreased the glass transition temperature of the film; this may be attributed to the interaction of the additives. At a lactose content of 37.5%, a second glass transition appeared. This phenomenon may be indicative of a separate amorphous lactose phase.