HPLC-DAD-MS Fingerprint of Andrographis Paniculata (Burn. f.) Nees (Acanthaceae)

An HPLC-UV fingerprint analysis was developed for the quality evaluation of Andrographis paniculata aerial parts. HPLC-DAD-MS experiments allowed the identification of eleven diterpenes and five flavonoids. Plant material of Indian and Chinese origin was evaluated employing the developed method. The chemical fingerprints of the plant material of different origins do not show significant differences

Orodispersible Film (ODF) Platform Based on Maltodextrin for Therapeutical Applications

Orodispersible film (ODF) is a new dosage form that disperses rapidly in the mouth without water or swallowing. The main ingredient of an ODF is a polymer that can be both of natural or synthetic origin. Maltodextrin is a natural polymer, mainly used in pharmaceutical and nutraceutical fields. This review aims to examine the literature regarding ODFs based on maltodextrin as the platform for developing new products for therapeutical application. ODFs based on maltodextrin contain plasticizers that enhance their flexibility and reduce their brittleness. Surfactants; fillers, such as homopolymer and copolymer of vinylacetate; flavour and sweetener were introduced to improve ODF characteristics. Both water-soluble and insoluble APIs were introduced up to 100 mg per dosage unit. The solvent casting method and hot-melt extrusion are the most useful techniques for preparing ODFs. In particular, the solvent casting method allows manufacturing processes to be developed from a lab scale to an industrial scale. ODFs based on maltodextrin are characterized in terms of mechanical properties, dissolution rate, taste and stability. ODFs made of maltodextrin, developed by IBSA, were tested in vivo to evaluate their bioequivalence and efficacy and were demonstrated to be a valid alternative to the marketed oral dosage forms

Development and Characterization of an Orodispersible Film for Vitamin D3 Supplementation

Vitamin D plays a crucial and very well-known role in regulation of calcium homeostasis and bone metabolism and mineralization. However, a huge and more recent body of evidence supports the positive influence of vitamin D on the regulation of immune response, ranging from protection against respiratory tract infections to prevention and management of asthma. Nevertheless, vitamin D deficiency is a very common condition and there is an increasing need for suitable products for proper supplementation, allowing good compliance also in specific populations. Orally disintegrating tablets (ODT) were first developed to overcome the difficulty experienced by pediatric and geriatric patients of swallowing traditional oral dosage forms and, recently, orodispersible films (ODF) are gaining popularity as novel dosage form for assuming active pharmaceutical ingredients, vitamins, and ingredients for food supplements. This study describes a 2000 IU Vitamin D3 ODF for daily intake, consisting of hydrophilic polymers and suitable excipients, manufactured by film-casting process. Elongation-at-break (E%), Young’s modulus (Y), and tensile strength (TS) were investigated using a dynamometer. Chemical stability was evaluated assaying the vitamin D3 in the films stored at different environmental conditions. In addition, in vitro disintegration and dissolution studies were performed. Correlation existed between the mechanical properties of the film and the residual water, acting as plasticizer. The stability study showed that vitamin D3 assay was ≥90% also after 3 months at 40 °C. The film disintegrated in less than 1 min and the vitamin D3 released was ≥75% after 15 min. An ODF with suitable properties can be manufactured and used as innovative dosage form for vitamin D3 food supplements

DoE-Assisted Development of a Novel Glycosaminoglycan-Based Injectable Formulation for Viscosupplementation

The aim of the present work was the development of a novel glycosaminoglycan (GAG)-based injectable formulation intended for intra-articular administration that should best mimic the healthy synovial fluid. Hyaluronic acid (HA) was chosen among GAG polymers, since it is the most abundant component of the synovial fluid. A DoE (Design of Experiment) approach was used for the development of a formulation containing two HA (very high (VHMW) and low (LMW) molecular weight) grades. The rationale for this choice is that so far, no commercial product based on a single HA grade or even on binary HA mixture possesses optimal viscoelastic properties in comparison with healthy synovial fluid. A full factorial design was chosen to investigate the influence of concentration and relative fraction of the two polymer grades (retained as factors of the model) on formulation functional (viscosity and viscoelastic) properties, which are considered response variables. Thanks to the DoE approach, the composition of the optimized HA formulation was found. The addition to such formulation of an injectable grade fat-free soy phospholipid, which was rich in phosphatidylcholine (PC), resulted in improved lubrication properties. The final HA + PC formulation, packaged in pre-filled sterile syringes, was stable in long-term and accelerated ICH (International Council for Harmonisation) storage conditions. The overall results pointed out the formulation suitability for further steps of pharmaceutical developments, namely for the passage to pilot scale

Evaluation of the Efficacy of IALUSET VITAL® Cream in Helping the Improvement of the Atopic Dermatitis Symptoms in Adults: A Randomized, Double Blind, Vehicle-Controlled Clinical Trial

Atopic dermatitis (AD) is a chronic relapsing skin disease, associated with impaired skin barrier function and characterized by poorly defined pruritic, erythematous lesions. In this study, the efficacy of a new topical cream (IALUSET VITAL®), containing hyaluronic acid and the extract of Salvia haenkei, in reducing symptoms of moderate AD in adults was investigated. This study was a randomized, double blind, vehicle-controlled clinical study. Treatment efficacy was evaluated considering both objective parameters (Scoring Atopic Dermatitis, SCORAD) and subjective pa-rameters (Patient Oriented Eczema Measure, POEM, and an itching sensation) and through non-invasive bioengineering techniques to measure skin moisturization and Trans Epidermal Water Loss (TEWL). Under the experimental conditions of the study, IALUSET VITAL® significantly reduced AD severity, as shown by the SCORAD index, and was revealed to be effective in alleviating the most common signs and symptoms of moderate AD, suppressing itch and improving skin moisturization, and to have a good safety profile, being well-tolerated by patients. However, statistically significant differences between active and vehicle group were not found in the other parameters analyzed, likely because the basic formulation of IALUSET VITAL® guarantees good emollient properties and the addition of hyaluronic acid and extract of Salvia haenkei as active ingredients results in a great increase in effectiveness

Safety Assessment of High- and Low-Molecular-Weight Hyaluronans (Profhilo®) as Derived from Worldwide Postmarketing Data

Background. At present, dermal fillers based on hyaluronic acid (HA) represent the most popular intervention of dermoesthetic medicine for the treatment of skin aging. Recent studies have shown that the combination of HA chains of different lengths and molecular weights improves tissue repair and regeneration through a synergistic mechanism. Profhilo® is a product available that has been on the market since 2015 and is based on stable, hybrid, and cooperative complexes (HyCoCos) produced by means of NAHYCO® Hybrid Technology, which is an innovative thermal process that rules out the use of any chemical reagents. The result is a filler with high biocompatibility and low viscosity that favors optimal diffusion at the tissue level to obtain the target bioremodeling of the facial contour. The objective of this review is to provide data from the overall postmarketing experience after 3 years of use and more than 40,000 patients treated with the medical device. Methods. All spontaneous postmarketing adverse event (AE) reports received from physicians and healthcare professionals worldwide between February 9, 2015, and February 8, 2018, associated with the use of the studied medical device and sent to the IBSA global safety database were analyzed. Results. In total, 12 adverse event reports were logged in the global database, and none were considered serious. Early-onset injection site reactions, i.e., swelling, edema, redness, ecchymosis, and erythema, were the most frequently observed. Late-onset local reactions (e.g., swelling, nodules) followed. The genesis of these reactions was considered, both by the reporting physician and IBSA, as being local reactions of hypersensitivity and/or due to inappropriate injection techniques. In no case was the product held liable for direct damage. All events resolved without any complications according to the treatment guidelines. Two late-onset reactions were collected. Conclusions. Although underreporting of minor events cannot be ruled out, the overall number of reports is very low, thereby supporting the high tolerability and safety of the product. After 3 years of postmarketing experience, the safety profile of the studied medical device is favorable and consistent with the product information

In vitro assessment of nutraceutical compounds and novel nutraceutical formulations in a liver-steatosis-based model

Abstract Background Steatosis is a chronic liver disease that depends on the accumulation of intracellular fatty acids. Currently, no drug treatment has been licensed for steatosis; thus, only nutritional guidelines are indicated to reduce its progression. The aim of this study is to combine different nutraceutical compounds in order to evaluate their synergistic effects on a steatosis in vitro model compared to their separate use. In particular, three different formulations based on silymarin, curcumin, vitamin E, docosahexaenoic acid (DHA), choline, and phosphatidylcholine were assayed. Methods Human hepatocellular carcinoma cells (HepG2 cell line) were treated with a mixture of fatty acids in order to induce an in vitro model of steatosic cells, and then the amount of intracellular fat was evaluated by Oil Red O staining. The peroxisome proliferator-activated receptors α and γ (PPARα and γ) expression, closely correlated to lipid metabolism, was evaluated. The efficiency of these receptors was evaluated through the study of LPL mRNA expression, a marker involved in the lipolysis mechanism. Superoxide dismutase (SOD-2) and malondialdehydes (MDA) in lipid peroxidation were assayed as specific biomarkers of oxidative stress. In addition, experiments were performed using human liver cells stressed to obtain a steatosis model. In particular, the content of the intracellular fat was assayed using Oil Red O staining, the activation of PPARα and γ was evaluated through western blotting analyses, and the LPL mRNA expression level was analyzed through qRT-PCR. Results All formulations proved effective on lipid content reduction of about 35%. The oxidative stress damage was reduced by all the substances separately and even more efficiently by the same in formulation (i.e. Formulation 1 and Formulation 3, which reduced the SOD-2 expression and induced the PPARs activation). Lipid peroxidation, was reduced about 2 fold by foormulation2 and up to 5 fold by the others compared to the cells pretreated with H2O2.Formulation 1, was more effective on PPARγ expression (2.5 fold increase) respect to the other compounds on FA treated hepathocytes. Beside, LPL was activated also by Formulation 3 and resulted in a 5 to 9 fold-increase respect to FA treated control. Conclusions Our results proved that the formulations tested could be considered suitable support to face steatosis disease beside the mandatory dietetic regimen

Optimization of growth of Levilactobacillus brevis SP 48 and in vitro evaluation of the effect of viable cells and high molecular weight potential postbiotics on Helicobacter pylori

Several Levilactobacillus brevis strains have the potential to be used as probiotics since they provide health benefits due to the interaction of live cells, and of their secreted products, with the host (tissues). Therefore, the development of simple fermentation processes that improve cell viability to reduce industrial production costs, and at the same time the characterization and biological evaluation of cell-free postbiotics that can further promote application, are of great interest. In the present study, small scale batch fermentations on semi defined media, deprived of animal derived raw materials, were used to optimize growth of L. brevis SP48, reaching 1.2 ± 0.4 × 1010 CFU/ml of viable cells after 16 h of growth. Displacement, competition, and inhibition assays compared the effect, on Helicobacter pylori, of L. brevis cells to that of its partially purified potentially postbiotic fraction rich in exopolysaccharides and proteins. The expression of pro and anti-inflammatory biochemical markers indicated that both samples activated antimicrobial defenses and innate immunity in a gastric model. Moreover, these compounds also acted as modulators of the inflammatory response in a gut in vitro model. These data demonstrate that the high molecular weight compounds secreted by L. brevis SP48 can contrast H. pylori and reduce inflammation related to intestinal bowel disease, potentially overcoming issues related to the preservation of probiotic viability