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Trichomoniasis is the most common nonviral sexually transmitted infection in the world, but its available therapies present low efficacy and high toxicity. Diphenyl diselenide (PhSe2) is a pharmacologically active organic selenium compound; however, its clinical use is hindered by its lipophilicity and toxicity. Nanocarriers are an interesting approach to overcome the limitations associated with this compound. This study designed and evaluated a vaginal hydrogel containing PhSe2-loaded Eudragit® RS100 and coconut oil nanocapsules for the treatment of trichomoniasis. Nanocapsules presented particle sizes in the nanometric range, positive zeta potential, a compound content close to the theoretical value, and high encapsulation efficiency. The nanoencapsulation maintained the anti-Trichomonas vaginalis action of the compound while improving the scavenger action in a DPPH assay. The hydrogels were prepared by thickening nanocapsule suspensions with locust bean gum (3%). The semisolids maintained the nanometric size of the particles and the PhSe2 content at around the initial concentration (1.0 mg/g). They also displayed non-Newtonian pseudo-plastic behavior and a highly mucoadhesive property. The chorioallantoic membrane method indicated the absence of hemorrhage, coagulation, or lysis. The compound, from both non-encapsulated and nano-based hydrogel delivery systems, remained on the surface of the bovine vaginal mucosa. Therefore, the formulations displayed the intended properties and could be a promising alternative for the treatment of trichomoniasis. [ABSTRACT FROM AUTHOR]

[Display omitted] Despite the continuous research on understanding how topical drugs and the skin interact, the development of a topical generic product remains a challenge. Due to their local action effect rather than systemic, establishing suitable frameworks for documenting bioequivalence between reference and test formulations is anything but straightforward. In previous years, clinical endpoint trials were considered the gold standard method to demonstrate bioequivalence between topical products. Nevertheless, significant financial and time resources were required to be allocated owing to the inherent complexity of these studies. To address this problem, regulatory authorities have begun to accept alternative approaches that could lead to a biowaiver, avoiding the need for clinical endpoint trials. These alternatives encompass various in vitro and/or in vivo techniques that have been analysed and the benefits and drawbacks of each method have been considered. Furthermore, other factors like the integration of a quality by design framework to ensure a comprehensive understanding of the product and process quality attributes have also been taken into account. This review delves into international regulatory recommendations for semisolid topical products, with a focus on those established by the European Medicines Agency, as well as the Food and Drug Administration. Both approaches were carefully examined, discussing aspects such as acceptance criteria, sample size, and microstructure evaluation. Additionally, novel and innovative therapeutic-driven approaches based on in vitro disease models for the rapid and effective development of topical generic products are presented. [ABSTRACT FROM AUTHOR]

The medical cannabis has been used for many of years for medicinal purpose, in different pharmaceutical formulation, mostly as a magistral preparation for the relief of pain in cancer patients or chronical painful diseases. Over than 540 substances were found from which more than 100 that have been found to be cannabinoids due to their similar chemical structure. The component with the most psychotropic action is Δ9 -tetrahydrocannabinol (Δ9 - THC), and the major non-psychoactive ingredient is cannabidiol (CBD). Δ9 -tetrahydrocannabinol firstly was isolated in 1969 by Robert Mechoulm and Yechiel Gaoni. In 2003 World Health Organization put Δ9 - tetrahydrocannabinol in Schedule IV of the convention. Several therapeutic indications relate to the Δ9 -THC and CBD as analgesia, inflammatory and neurodegenerative diseases, and many other cases. In some studies, there are reported safety concerns about the registered side effects of Δ9 - THC as a psychoactive. For that reason, the legal usage of cannabis for medicinal purposes and for recreational use is regulated differently. The most relevant explanation is related to the not enough sufficient results and data obtained from the pharmacokinetic studies and research in pharmacological behavior. Extracts of cannabis was used from many years ago. Nowadays in pharmaceutical industry as the development of technology there are many dosage forms in where extracts, cannabinoids, flower are used. Medicinal cannabis products can come in many different forms, including capsules, drops, chewable, creams, crystals, flower, lozenges, oil (most common), oro-mucosal sprays, tinctures and many more. Also, there are synthetic analogs to nature cannabinoids in pharmaceutical market. In this study will be discussed about production of semisolid pharmaceutical forms obtained from medical cannabis. They are produced in pharmaceutical grade equipment, high-pressure homogenizer mixer. In this study it will be discussed about the process of equipment qualification. Firstly, by the user requirement specification, design qualification protocol was approved. Then factory acceptance test was performed in production site of equipment and site acceptance test was performed in costumer’s site. Then installation qualification protocol was look through and then operational qualification protocol also. All the qualification protocols were approved by both sides. In different qualification protocols, different tests were performed, and they are explained separately. During the qualification process, there are considered some of the parameters which later during the production process can affect in the quality of finished products. These parameters are called critical process parameters and accent will be put on this process parameters that are with a critical effect on quality of the final products. This critical process parameters were considered and concluded from qualification protocols where all the parameters that can affect quality of the product were separately examine. [ABSTRACT FROM AUTHOR]

Trichomoniasis is the most common nonviral sexually transmitted infection in the world, but its available therapies present low efficacy and high toxicity. Diphenyl diselenide (PhSe2) is a pharmacologically active organic selenium compound; however, its clinical use is hindered by its lipophilicity and toxicity. Nanocarriers are an interesting approach to overcome the limitations associated with this compound. This study designed and evaluated a vaginal hydrogel containing PhSe2-loaded Eudragit® RS100 and coconut oil nanocapsules for the treatment of trichomoniasis. Nanocapsules presented particle sizes in the nanometric range, positive zeta potential, a compound content close to the theoretical value, and high encapsulation efficiency. The nanoencapsulation maintained the anti-Trichomonas vaginalis action of the compound while improving the scavenger action in a DPPH assay. The hydrogels were prepared by thickening nanocapsule suspensions with locust bean gum (3%). The semisolids maintained the nanometric size of the particles and the PhSe2 content at around the initial concentration (1.0 mg/g). They also displayed non-Newtonian pseudo-plastic behavior and a highly mucoadhesive property. The chorioallantoic membrane method indicated the absence of hemorrhage, coagulation, or lysis. The compound, from both non-encapsulated and nano-based hydrogel delivery systems, remained on the surface of the bovine vaginal mucosa. Therefore, the formulations displayed the intended properties and could be a promising alternative for the treatment of trichomoniasis.

Currently, a wide variety of complex non-oral dosage forms are entering the global healthcare market. Although many assays have been described in recent research, harmonized procedures and standards for testing their in vitro performance remain widely unexplored. Among others, dialysis-based techniques such as the Pharma Test Dispersion Releaser are developed for testing the release of drugs from nanoparticles, liposomes, or extracellular vesicle preparations. Here, we provide advanced strategies and practical advice for the development and validation of dialysis-based techniques, including documentation, analysis, and interpretation of the raw data. For this purpose, key parameters of the release assay, including the hydrodynamics in the device at different stirring rates, the selectivity for particles and molecules, as well as the effect of excipients on drug permeation were investigated. At the highest stirring rate, a more than twofold increase in the membrane permeation rate (from 0.99 × 10−3 to 2.17 × 10−3 cm2/h) was observed. Additionally, we designed a novel computer model to identify important quality parameters of the dialysis experiment and to calculate error-corrected release profiles. Two hydrophilic creams of diclofenac, Voltaren® Emulgel, and Olfen® gel, were tested and provide first-hand evidence of the robustness of the assay in the presence of semisolid dosage forms.

High-pressure die casting is the most common method used to produce magnesium castings, due to the excellent balance of cost and properties for high production volumes with limitations in terms of final mechanical properties. A newly developed process based on employing low injection speeds, in a range slightly over the standard semisolid speeds with a modified die, with thick gates and high die temperatures has been developed. Despite working with speeds that are not in the lamellar flow, the obtained parts present very low porosity, allowing the use thermal treatments to increase the ductility without producing blisters. The demonstration has been performed in a AM60B magnesium body joint produced by the squeeze casting process. Finally, the microstructure and the mechanical properties of as-cast and T4 heat-treated samples were studied. The results indicate the improvement of the mechanical properties in T4 heat-treated parts; specifically, a 40% improved deformation-to-failure, 40-60% improved penetration force and 90% of energy absorption were possible to obtain employing the newly developed SC + T4 process. [ABSTRACT FROM AUTHOR]

Rheological behaviour of pharmaceutical semisolid preparations significantly affects manufacturing process, administration, stability, homogeneity of incorporated drug, accuracy of dosing, adhesion in the place of application, drug release, and resulting therapeutic effect of the product. We performed test of consistency by penetrometry, rotational, oscillation and creep tests, and squeeze and tack tests of model samples to introduce methods suitable for characterization and comparison of semisolids in practice. Penetrometry is a simple method allowing sorting the semisolids to low and high stress-resistant materials but deficient for rheological characterization of semisolids. Value of yield stress, generally considered to be appropriate feature of semisolids, is significantly influenced by the method of testing and the way of evaluation. The hysteresis loops of model semisolids revealed incomplete thixotropy, therefore, three-step thixotropy test was employed. Semisolids showed nonlinear response in the creep phase of tests and partial recovery of structure by storing energy in the recovery phase. Squeeze and tack tests seem to be convenient ways for comparison of semisolids. Our study can contribute to a better understanding of different flow behaviour of semisolids given by different physicochemical properties of excipients and can bring useful approaches to evaluation and comparison of semisolids in practice. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effect of dispersion states of azone in gels on the transdermal permeation of levamisole hydrochloride (LH). LH hydroalcoholic gels containing azone of different dispersion states were prepared by varying the contents of azone and Tween 80, and the in vitro transdermal permeation of LH across excised rat skin was evaluated. Depending on the content of azone, mixed solvents, and solubilizer used, azone presented as dissolved molecules, solubilized in micelles, and fine or coarse emulsion droplets in gels. Dramatically increased transdermal permeation of LH within the azone contents between 0.25% and 0.75% indicated high transdermal enhancement efficiency of the molecular or micellar azone, and extra azone that existed as oil droplets did not fully exert transdermal penetration enhancement of LH. Although solubilizer (Tween 80) can greatly increase the solubility of azone, only small amount of Tween 80 (0.5%) in the gel significantly increased the steady-state flux of LH. Addition of extra amount of Tween 80 (>0.5%) reduced the amount of azone distributed in the skin, and thus decreased the transdermal drug permeation. The results partly elucidated the versatile effects of the dispersion states of azone on the transdermal permeation of hydrophilic drug from semisolid gels. [ABSTRACT FROM AUTHOR]

Unique properties of thermodynamic activity of solvents in topical semisolids and its effects on in vitro product performance have not been fully understood. Mechanistic investigation was undertaken to demonstrate the significance of thermodynamic potential of solvents [water activity (a w ) or solvent activity (a s )] on in vitro performance of model topical formulations. Drug transport across synthetic membranes was found to decrease with decreasing water activity of formulations. Similarly, in vitro permeation of model permeant (caffeine) across porcine epidermis was found to decrease with decreasing water activity of formulations. Notably, relatively low water activity formulations (a w , 0.78) induced dehydration in porcine skin associated with significant structural changes like detachment of individual stratum corneum layers. Inclusion of hydrating agents (propylene glycol) in low water activity (a w , 0.78) formulations restored hydration levels and structural integrity of porcine skin. Most importantly, incremental inclusion of propylene glycol in low water activity formulations (a w , 0.78) enhanced in vitro permeation of model permeant (fluorescein sodium). Further investigation revealed that variability in processing conditions (high shear mixing during emulsification step) could modulate water activity in semisolid formulations despite their compositional sameness. In retrospect, water activity was found to be a critical quality attribute of topical semisolid products which impacts overall product performance and drug delivery. [ABSTRACT FROM AUTHOR]

Vaginal semisolid products are frequently used to treat vaginal infections and atrophy-related symptoms of menopause. Formulations composition and the methods for their characterization, especially those developed concerning the target epithelia, are key tools to predict in vivo results at early stages of product development. However, recent studies on this subject have been almost exclusively focused on anti-HIV preparations. The aim of this work consists on improving traditional characterization methods by using physiological parameters in order to construct predictive tools to characterize a new ideal vaginal semisolid formulation whatever target it may have. Ten vaginal antimicrobial and hormonal products already available in the market were studied (Gino-Canesten®, Sertopic®, Dermofix®, Gyno-pevaryl®, Lomexin®, Gino Travogen®, Dalacin V®, Ovestin®, Blissel®, Colpotrophine®). Furthermore, Universal Placebo gel and Replens® were used for comparison. Products were characterized in terms of: pH and buffering capacity in a vaginal fluid simulant (VFS); osmolality - directly and upon dilution in VFS; textural parameters (firmness, adhesiveness and bioadhesion) using vaginal ex vivo porcine epithelium; and viscosity (including VFS dilution at 37 °C and after administration on an ex vivo model). Interestingly, the majority of the tested commercial vaginal formulations did not present technological characteristics close to the ideal ones when tested under target biological conditions. The inclusion of such methodologic adaptations is expected to optimize cost-efficiency of new formulations development by predicting efficacy and safety profiles at early stages of product development. [ABSTRACT FROM AUTHOR]

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Skin diseases are usually treated using topical formulations. Frequently, multiple applications per day are necessary, as up to 90% of the formulation (and thus of the active) are withdrawn from the skin by contact with the environment. During the development of topical formulationsex vivopermeation and penetration experiments are deployed to characterize the formulations. Still, these tests do not take into account the removal of formulations during the application period. To date, only few methods exist to probe the substantivity of dermal formulations. The aim of this investigation was to develop methods that simulate skin-to-skin or clothing-to-skin contact and enable the determination of the amount of formulation that is removed from the skin due to the contact. Three different types of formulations were used to validate the systems: a conventional semisolid cream, an oil-in-oil-emulsion, and a film forming formulation. The results showed that the substantivity decreased in the order: film forming formulation > semisolid cream > oil-in-oil-emulsion. A similar trend could be determined with both methods although the total amounts of withdrawn formulation differed. The developed methods can add to the knowledge about the formulation and can be used to develop formulations that exhibit higher substantivity. [ABSTRACT FROM AUTHOR]

For more than five decades, pharmaceutical manufacturers have been relying heavily on batch manufacturing that is a sequential, multistep, laborious, and time-consuming process. However, late advances in manufacturing technologies have prompted manufacturers to consider continuous manufacturing (CM) is a feasible manufacturing process that encompasses fewer steps and is less tedious and quick. Global regulatory agencies are taking a proactive role to facilitate pharmaceutical industries to adopt CM that assures product quality by employing robust manufacturing technologies encountering fewer interruptions, thereby substantially reducing product failures and recalls. However, adopting innovative CM is known to pose technical and regulatory challenges. Hot melt extrusion (HME) is one such state-of-the-art enabling technology that facilitates CM of diverse pharmaceutical dosage forms, including topical semisolids. Efforts have been made to continuously manufacture semisolids by HME integrating the principles of Quality by Design (QbD) and Quality Risk Management (QRM) and deploying Process Analytical Technologies (PAT) tools. Attempts have been made to systematically elucidate the effect of critical material attributes (CMA) and critical process parameters (CPP) on product critical quality attributes (CQA) and Quality Target Product Profiles (QTPP) deploying PAT tools. The article critically reviews the feasibility of one of the enabling technologies such as HME in CM of topical semisolids. The review highlights the benefits of the CM process and challenges ahead to implement the technology to topical semisolids. Once the CM of semisolids adopting melt extrusion integrated with PAT tools becomes a reality, the process can be extended to manufacture sterile semisolids that usually involve more critical processing steps.

Propoleos constitutes the base of a lot of pharmaceutical formulations. The present research proposes the preliminary characterization of propoleos jelly for the treatment of the gingivitis. An experimental study was carried out in the pharmaceutical technology laboratory of the Orient University in the months of March to May 2013, the elaboration of the jelly a propoleos jelly was formulated using the incorporating method, and the jelly quality parameters were evaluated. The results revealed a light brownish - gray color, with a typical propoleos smell, homogeneous, sparkly neither non-lumpy nor sandy formulation. The pH oscillated between 6,26 and 6,28, viscosity of 0,366 0 Pa.s, and an extendibility area of 89,80 cm², a thixotropic pseudoplastic flow was observed. No pathogenic microorganism growth was observed. The real concentration of poly-phenols was determined, using the Folin Ciocalteau method, obtaining concentration of 8,779 mg/mL. These results allow the preliminary characterization of the new formulation proposal of. [ABSTRACT FROM AUTHOR]

Objective: Development of a hydrogel containing rutin at 0.025% (w/w) and evaluation of its in vivo efficacy in cutaneous wound healing in rats. Methods: Hydrogels were prepared using Carbopol Ultrez® 10 NF and an aqueous dispersion of rutin in polysorbate 80. Hydrogels were characterized by means of pH measurement, rheological and spreadability analysis and rutin content determination by liquid chromatography. The in vivo healing effect was evaluated through the regression of skin lesions in rats and by analysis of oxidative stress. Results and discussion: Hydrogels showed adequate pH values (5.50-6.50) and pseudoplastic non-Newtonian behavior. After 5 days of treatment of wounds, hydrogels containing rutin presented a higher decrease in the wound area compared to the control hydrogels. Analysis of the oxidative stress showed a decrease in lipid peroxidation and protein carbonyl content as well as an increase in catalase activity after the treatment with the hydrogel containing rutin. Furthermore, this treatment increased total protein levels. Conclusion: This study shows for the first time the feasibility of using dermatological formulations containing rutin to improve skin wound healing. [ABSTRACT FROM AUTHOR]

Rapid compression tests are useful to characterize the semisolid behaviour in thixoforming conditions. The load-displacement curves typically display a peak load. The origin, the maximum value and the height of this peak are discussed comparing calculated results obtained using a micro-macro model and experimental data obtained in earlier work. As suggested by experiments, the calculated peak load originates from a 3D continuous solid skeleton, which breaks down under load. For the same initial semisolid structure, the model predicts that decreasing the ram speed decreases the maximum of the peak because of a strain rate effect. In addition, the peak load is found to be quite sensitive to initial internal structure, namely the volume fraction of entrapped liquid, which may change for various soaking times. Finally, the time for the solid skeleton breakdown is found to be in good agreement with experimental results. [ABSTRACT FROM AUTHOR]

In the oral cavity, the food is subjected to several mechanical and chemical processes. It is fractured by the teeth, diluted and broken down by saliva, heated or cooled by the ambient temperature of the mouth, formed into a bolus and finally swallowed. Numerous receptors in the oral cavity and nose respond to the initially ingested food and monitor the changes during processing. This leads to central perceptions of taste, odor, irritation and texture of the food. Most sensations associated with food texture occur only when the food is manipulated, deformed or moved across the oral receptors. In addition, people assessing the same stimulus differ in their ratings of that stimulus and their oral physiological parameters also exhibit inter-individual variations. This paper is based on the PhD thesis of one of the authors. It gives an overview of this study and includes related work of other authors. The aim of our research was to improve the understanding of oral texture perception, in particular to examine the role of oral physiological processes in oral texture perception of semisolids and to investigate whether individual differences in perception could be attributed to differences in oral physiology among subjects. The results of our study demonstrate that oral physiological parameters such as oral sensitivity, tongue movements, temperature and saliva composition are of importance for texture perception of semisolids. Many parameters of oral physiology correlate with various perceived texture attributes. This implies that intra-individual differences in texture perception could be attributed to variations in oral physiology. Oral physiology thus plays a role in texture perception of semisolids and should be taken into account in future texture research. PRACTICAL APPLICATIONS By understanding the processes in the mouth while eating, a better understanding of the sensations and the perceptions of the food can be gained. Taking for each food the relevant physiological parameter into consideration when performing and designing rheological/instrumental measurements grants more natural conditions and better predictions of sensory perception. This could save time and money on time-consuming and expensive sensory panels in the earlier steps of product development and renovation. Knowing how physiological processes highlight specific flavor/texture sensations may be useful for product development or quality control where one typically wants to focus on certain sensations and ignores others. In addition, a future application could be to tailor products for personalized nutrition, individual choices or clinical nutrition based on physiological groups. [ABSTRACT FROM AUTHOR]

We have developed an efficient screening method to identify liquid and semisolid formulations for low-solubility compounds. The method is most suitable for identifying dosing vehicles for compounds in lead optimization, where compound supply is limited and long-term stability is not a requirement. Dilute compound and excipient stock solutions are prepared in organic solvent and then dispensed and mixed in 96-well plates. The solvent is removed in a vacuum centrifuge evaporator, leaving neat formulation (e.g., 10–40 µg compound, 0.4 mg excipient) at the bottom of each well. After an aging step, an aqueous dilution medium is added and the plates are incubated (agitation by orbital shaking). The diluted formulations are then filtered and analyzed by ultraviolet (UV) absorbance or high-performance liquid chromatography (HPLC). To illustrate the method, two compounds (aqueous solubility ≤1 µg/mL) were combined with eight solubilizing excipients, at four drug-loading levels (25, 50, 75, and 100 mg/g) and three incubation times (0.5, 2, and 24 h). This allowed identification of the excipients and loading levels, which generated the highest and most stable kinetic solubility upon dilution. The peak kinetic solubility was strongly correlated with the equilibrium solubility. Application of the method to screening compound/surfactant/oil formulations is also presented. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:1548–1563, 2007 [ABSTRACT FROM AUTHOR]

Abstract: Clay minerals are included in several health care formulations. In particular, they are presented in many semisolid preparations with different functions, including stabilization of suspensions and emulsions, viscosizing and other special rheological tasks, protection against environmental agents, adhesion to the skin, adsorption of greases, control of heat release, etc. These functions are possible because of the special disposition of clay mineral particles when dispersed in polar solvents, due to their high surface areas and colloidal dimensions. When necessary, clays are processed or even modified to exalt or change some properties and new clay-like materials with special features are also synthesized. Finally, clays are frequently used concomitantly with other rheological modifiers to obtain synergic effects, influencing the stability and/or other technical properties of the health care products. This paper reviews the properties of clay mineral dispersions and the different functions derived from those properties, providing examples of applications in products intended to fulfil health care aims. [Copyright &y& Elsevier]

Abstract: The purpose of this article is to review USP and non-pharmacopeial dissolution testing methods for conventional and novel pharmaceutical dosage forms and give an insight to possible alternatives in drug dissolution study design and appropriate choices for dissolution media. For each dosage form first the USP method(s) for dissolution testing are reviewed followed by alternative methods used in research and development. [Copyright &y& Elsevier]

This work examined the influence of oral temperature on oral perception of temperature in liquids and semisolids. A panel of 20 adults assessed the temperature of water, custard dessert and mayonnaise. Oral temperatures were manipulated by 5-s mouth rinses of 10, 35 and 55°C performed prior to assessments, which resulted in oral temperatures of 27, 35 and 43°C, respectively. The products were evaluated at 10, 22 and 35°C. Results show that subjects were able to differentiate between the product temperatures. A large effect of type of product was seen on perceived temperature, where water was, overall, perceived as significantly colder than custard dessert and mayonnaise. The range of perceived thermal ratings was widest for custard dessert, followed by water and mayonnaise. This might be due to differences in composition and structure of the products. Even though oral temperature was varied considerably in the present study, this did not exert large effects on perceived temperature. [ABSTRACT FROM AUTHOR]

The purpose of this study was to scale up an oil/water (o/w) cream formulation containing 40% diethylene glycol monoethyl ether (DGME), developed via 300-g laboratory batches in a 25-2 fractional factorial design, to 7-kg batch sizes in a Brogli-10 homogenizer. The o/w cream was manufactured via a standard phase-inversion process in the Brogli-10 homogenizer. Partitioning studies of DGME were conducted in test tubes at ambient temperature and after 24 hr at 70°C in a convection oven. Phase height was measured by vernier calipers. Microscopy studies of excipients with and without treatment with water or a DGME/water mixture were conducted with a Nikon microscope after equilibration at 35°C for 24 hr. During creation of the 7-kg pilot-scale batches, congealed material was observed between the sweep agitation blade and the discharge port, where the Brogli-10 homogenizer is not temperature jacketed. Factors that increased the amount of congealed material were higher temperatures during primary emulsification and longer cooling times. Partitioning studies revealed that DGME resides in the aqueous external phase of this formulation. Microscopy studies revealed that DGME in the external phase of this cream has a profound impact on the solubility of certain solid, waxy excipients (e.g., cetyl alcohol and polyoxyethylene-2-stearyl ether) at 35°C. From this study, it appears that DGME resides in the external phase of the o/w cream. During manufacturing, it is hypothesized that the presence of DGME in the external phase alters the solubility of certain solid, waxy excipients in the formula such that they no longer primarily reside in the internal oil phase. On cooling, these materials precipitate or congeal in the external phase. The fractional factorial experimental design at the 300-g laboratory scale did not predict the issues encountered during scale-up. Differences between laboratory scale and pilot plant scale that explain why this phenomenon was not... [ABSTRACT FROM AUTHOR]

Currently, a wide variety of complex non-oral dosage forms are entering the global healthcare market. Although many assays have been described in recent research, harmonized procedures and standards for testing their in vitro performance remain widely unexplored. Among others, dialysis-based techniques such as the Pharma Test Dispersion Releaser are developed for testing the release of drugs from nanoparticles, liposomes, or extracellular vesicle preparations. Here, we provide advanced strategies and practical advice for the development and validation of dialysis-based techniques, including documentation, analysis, and interpretation of the raw data. For this purpose, key parameters of the release assay, including the hydrodynamics in the device at different stirring rates, the selectivity for particles and molecules, as well as the effect of excipients on drug permeation were investigated. At the highest stirring rate, a more than twofold increase in the membrane permeation rate (from 0.99 × 10 -3 to 2.17 × 10 -3 cm 2 /h) was observed. Additionally, we designed a novel computer model to identify important quality parameters of the dialysis experiment and to calculate error-corrected release profiles. Two hydrophilic creams of diclofenac, Voltaren ® Emulgel, and Olfen ® gel, were tested and provide first-hand evidence of the robustness of the assay in the presence of semisolid dosage forms.

• NC-I3C showed enhanced anti- Trichomonas vaginalis activity in vitro. • Hydrogel was obtained by thickening NC-I3C with gellan gum. • Gellan gum hydrogel containing NC-I3C was suitable for vaginal administration. • Gellan gum hydrogel containing NC-I3C is promising for trichomoniasis treatment. Trichomonas vaginalis infection is the STI most common worldwide. Indole-3-carbinol (I3C) is a phytochemical presenting promising biological activities. In this study, design, formulation, and evaluation of a vaginal hydrogel containing I3C-loaded nanocapsules for the treatment of trichomoniasis have been investigated. Nanocapsules of Eudragit® RS100 and rosehip oil containing I3C (NC-I3C) were prepared by interfacial deposition of preformed polymer method. In vitro evaluations showed that free I3C (IC50 = 3.36 µg/mL) was able to reduce the trophozoites viability at higher concentrations (3.13 and 6.25 µg/mL), while nanoencapsulation (IC50 = 2.09 µg/mL) reduced the viability at all concentrations evaluated. Comparing free and nanoencapsulated I3C, we observe that nanoencapsulation improved anti- T. vaginalis activity. In order to obtain a formulation for vaginal administration, hydrogels (HG-NC-I3C) were prepared by thickening the NC-I3C with gellan gum. HG-NC-I3C presented particle size below 195 nm, low polydispersity index (<0.2), I3C content = 0.50 ± 0.01 mg/g, pH = 7.05, non-Newtonian pseudoplastic flow behavior and exhibited mucoadhesion to cow's vaginal mucosa. Evaluation of irritation potential by chorioallantoic membrane method indicated that the formulations are considered non-irritating. Besides that, permeation through the cow's vaginal mucosa showed that nanoencapsulation promoted I3C controlled release. This way, the developed HG-NC-I3C can be considered a promising approach for trichomoniasis treatment through vaginal administration. Image, graphical abstract [ABSTRACT FROM AUTHOR]

The current study developed an innovative Pemulen® TR2 hydrogel containing silibinin-loaded pomegranate oil-based nanocapsules (HP-NC SB) intending cutaneous application. The formulation anti-inflammatory activity in an in vivo model and biometric studies on the skin of healthy volunteers were also performed. The nanocapsules were prepared using the interfacial deposition of preformed polymer technique and the hydrogels were obtained by thickening of nanocapsules suspension with Pemulen® TR2. Formulations with free compound, vehicle and blank nanocapsules were also produced. The hydrogels were evaluated concerning pH, silibinin content, particle size, spreadability profile, rheology, in vitro drug release, cutaneous permeation, bioadhesive potential and cutaneous biometry evaluation. Furthermore, a model of contact dermatitis croton oil-induced in mice was performed to evaluate the hydrogels anti-inflammatory potential. The formulations presented adequate characteristics for skin administration: particle within nanometric size, pH values in the acid range, silibinin content close theoretical values (1 mg/g) and non-Newtonian pseudoplastic behavior. Nano-based hydrogels showed high bioadhesive properties, increased silibinin in vitro release profile and its retention in the stratum corneum. The best anti-inflammatory effect was exhibited by HP-NC SB, which reduced both ear edema and inflammatory cells infiltration in comparison to the induced group. Furthermore, cutaneous biometric evaluation showed that formulations containing free or nanoencapsulated silibinin caused no modification in normal skin conditions (pH, tissue hydration, transepidermal water loss and erythema). In summary, the results demonstrated that the Pemulen® TR2 hydrogel containing NC SB was successfully developed, indicating its potential as an alternative treatment for irritant contact dermatitis. Unlabelled Image [ABSTRACT FROM AUTHOR]