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1.
Artículo en Inglés | MEDLINE | ID: mdl-39291730

RESUMEN

Medicinal plants have been utilized for centuries as a source of healing compounds, which consist of thousands of known bioactive molecules with therapeutic potentials. This article aims to explore and emphasize the significance of medicinal plants and bioactive compounds in the development of topical pharmaceutical formulations. The journey from the extraction of phytochemicals to the development of topical pharmaceutical formulations is described with the aid of scientific evidence selected from PubMed, Google Scholar, ScienceDirect, and Web of Science. Articles published in English during 2018-2023 period were considered and selected randomly. The review discusses the extraction process of medicinal plants, solvent selection, and green synthesis of metal nanoparticles. Subsequently, various biological activities of plant extracts are elaborated especially focusing on antimicrobial, antioxidant, anti-inflammatory, and sun protection activities, along with the corresponding in vitro assays commonly employed for the evaluation. The article presents the process of compound isolation through bioactivity-guided fractionation and also the toxicity evaluation of isolated fractions. Finally, the formulation of medicinal plant extracts into topical pharmaceuticals is addressed, emphasizing the stability evaluation procedures necessary for ensuring product quality and efficacy.

2.
J Appl Toxicol ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134399

RESUMEN

In silico techniques, such as physiologically based pharmacokinetic modeling (PBKP), are recently gaining importance. Computational methods in drug discovery and development and the generic drugs industry enhance research effectiveness by saving time and money and avoiding ethical issues. One key advantage is the ability to conduct toxicology studies without risking harm to living beings. This study aimed to repurpose the multi-phase multi-layer mechanistic dermal absorption (MPML MechDermA) PBPK model for simulation permeation through porcine ear skin under in vitro conditions. The work was divided into four steps: (1) the development of a pig ear skin model based on a previously collected dataset; (2) testing the model's ability to discriminate permeation between pig ear, human abdomen, and human back skin; (3) development of a caffeine permeation model; and (4) testing the caffeine model's performance against in vitro generated data sourced from the scientific literature. Data from 31 manuscripts were used for the development of the pig skin model. Based on these data, values specific to pig skin were found for 22 parameters of the MPML MechDermA model. The model was able to discriminate permeation between pig and human skin. A caffeine model was developed and used to simulate seven experiments identified in the literature. The model's performance was assessed by comparing simulated to observed results. Based on a visual check, all simulations were considered acceptable, whereas three out of seven experiments met the twofold difference criterion. The variability of the experimental data was considered the biggest challenge for reliable model assessment.

3.
Molecules ; 29(12)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38931002

RESUMEN

Chronic wound treatments pose a challenge for healthcare worldwide, particularly for the people in developed countries. Chronic wounds significantly impair quality of life, especially among the elderly. Current research is devoted to novel approaches to wound care by repositioning cardiovascular agents for topical wound treatment. The emerging field of medicinal products' repurposing, which involves redirecting existing pharmaceuticals to new therapeutic uses, is a promising strategy. Recent studies suggest that medicinal products such as sartans, beta-blockers, and statins have unexplored potential, exhibiting multifaceted pharmacological properties that extend beyond their primary indications. The purpose of this review is to analyze the current state of knowledge on the repositioning of cardiovascular agents' use and their molecular mechanisms in the context of wound healing.


Asunto(s)
Fármacos Cardiovasculares , Reposicionamiento de Medicamentos , Cicatrización de Heridas , Humanos , Cicatrización de Heridas/efectos de los fármacos , Fármacos Cardiovasculares/farmacología , Fármacos Cardiovasculares/uso terapéutico , Animales
4.
Viruses ; 16(6)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38932280

RESUMEN

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.


Asunto(s)
Antivirales , Modelos Animales de Enfermedad , Herpes Genital , Herpesvirus Humano 1 , Herpesvirus Humano 2 , Queratitis Herpética , Animales , Conejos , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 2/efectos de los fármacos , Antivirales/administración & dosificación , Antivirales/farmacología , Antivirales/uso terapéutico , Ratones , Herpes Genital/tratamiento farmacológico , Herpes Genital/virología , Queratitis Herpética/tratamiento farmacológico , Queratitis Herpética/virología , Chlorocebus aethiops , Femenino , Células Vero , Interferón alfa-2/administración & dosificación , Interferón alfa-2/uso terapéutico , Replicación Viral/efectos de los fármacos , Administración Tópica , Soluciones Oftálmicas , Interferón-alfa/administración & dosificación , Humanos
5.
Drug Deliv Transl Res ; 14(8): 2032-2040, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38837116

RESUMEN

Drug delivery technology has advanced significantly over >50 years, and has produced remarkable innovation, countless publications and conferences, and generations of talented and creative scientists. However, a critical review of the current state-of-the-art reveals that the translation of clever and sophisticated drug delivery technologies into products, which satisfy important, unmet medical needs and have been approved by the regulatory agencies, has - given the investment made in terms of time and money - been relatively limited. Here, this point of view is illustrated using a case study of technology for drug delivery into and through the skin and aims:  to examine the historical development of this field and the current state-of-the-art;  to understand why the translation of drug delivery technologies into products that improve clinical outcomes has been quite slow and inefficient; and  to suggest how the impact of technology may be increased and the process of concept to approved product accelerated.


Asunto(s)
Administración Cutánea , Sistemas de Liberación de Medicamentos , Piel , Humanos , Piel/metabolismo , Animales , Absorción Cutánea , Preparaciones Farmacéuticas/administración & dosificación , Preparaciones Farmacéuticas/química
6.
J Pharm Biomed Anal ; 242: 116021, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38354540

RESUMEN

Multicomponent drugs are medications that combine two or more active pharmaceutical ingredients in a single dosage form. These dosage forms improve the patient compliance, reduce the risk of drug interactions, and simplify dosing regimens. However, quality control of these multicomponent dosage forms can be challenging, especially if the final product contains four or more ingredients that are active (comprise stabilizers, preservatives, excipients, and other components). This problem can be more pronounced if the excipients can interfere with the analysis. In this work, a stability indicating assay method was developed and validated (according to the ICH International Guidelines) for the simultaneous determination of hydroquinone (HQ), tretinoin (TRT), hydrocortisone (HCA), butylated hydroxytoluene (BHT), methyl paraben (MP) and propyl paraben (PP) in commercially available pharmaceutical creams. The proposed method is based on gradient elution using X-Bridge C18 (150 × 4.6 mm, 5 µm) column with a flow rate of 1 mL/min. The linear ranges (µg/mL) were 240-560 for HQ, 24-56 for MP, 132-308 for HCA, 6-14 for PP, 12-28 for BHT, 6.6-15 for TRT. During the validation process, the intra- and interday precision and trueness (evaluated as recovery) were found to be below 2.0% and between 100-102%, respectively. System suitability tests (SST) allow validating the herein proposed procedure specifically for pharmaceutical and industrial applications. SST test shows that the reported procedure fulfill with the Guidelines, allowing excellent separation of the analytes with very sensitive, accurate (precise and true) and reproducible quantitation of each analytes. The method was successfully applied in forced degradation studies of the six analytes. Specifically, acid degradation slightly affected HCA and BHT (91% recovery), while alkaline degradation drastically reduced HCA recovery (5.5%) and moderately affected BHT (85%). Photodegradation primarily influenced TRT quantity, and oxidative degradation intensified the BHT peak (130%).


Asunto(s)
Parabenos , Tretinoina , Humanos , Parabenos/análisis , Tretinoina/análisis , Hidrocortisona/análisis , Hidroxitolueno Butilado , Excipientes , Cromatografía Líquida de Alta Presión/métodos , Hidroquinonas/análisis
7.
Antioxidants (Basel) ; 12(9)2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37759987

RESUMEN

This work addresses the potential of the red seaweed Gelidium corneum as a source of bioactive ingredients for skin health and wellness in response to the growing awareness regarding the significance of sustainable strategies in developing new nature-based dermocosmetic products. Hydroalcoholic extracts from the dried biomass were subjected to sequential liquid-liquid partitions, affording five different fractions (F1-F5). Their cosmetic potential was assessed through a set of in vitro assays concerning their antioxidant, photoprotective, and healing properties. Additionally, their cytotoxicity in HaCaT cells and their capacity to induce inflammation in RAW 264.7 cells were also evaluated. As a proof-of-concept, O/W emulsions were prepared, and emulsion stability was assessed by optical microscopy, droplet size analysis, centrifugation tests, and rheology analysis. Furthermore, in vivo tests were conducted with the final formulation to assess its antioxidant capacity. At subtoxic concentrations, the most lipophilic fraction has provided photoprotection against UV light-induced photooxidation in HaCaT cells. This was conducted together with the aqueous fraction, which also displayed healing capacities. Regarding the physical and stability assays, the best performance was achieved with the formulation containing 1% aqueous extract, which exhibited water retention and antioxidant properties in the in vivo assay. In summary, Gelidium corneum displayed itself as a potential source of bioactive ingredients with multitarget properties for dermatological use.

8.
J Funct Biomater ; 14(9)2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37754896

RESUMEN

The novel amphiphilic polyacrylate grafted with cholesterol moieties, PAAbCH, previously synthesized, was deeply characterized and investigated in the lab and on a pre-industrial scale. Solid-state NMR analysis confirmed the polymer structure, and several water-based pharmaceutical and cosmetic products were developed. In particular, stable oil/water emulsions with vegetable oils, squalene, and ceramides were prepared, as well as hydrophilic medicated films loaded with diclofenac, providing a prolonged drug release. PAAbCH also formed polyelectrolyte hydrogel complexes with chitosan, both at the macro- and nano-scale. The results demonstrate that this polymer has promising potential as an innovative excipient, acting as a solubility enhancer, viscosity enhancer, and emulsifying agent with an easy scale-up transfer process.

9.
Braz J Microbiol ; 54(3): 1501-1511, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37338788

RESUMEN

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infect, respectively, 67% and 13% of the world population, most commonly causing mild symptoms, such as blisters/ulcers. However, severe conditions such as keratitis, encephalitis, and systemic infections may occur, generally associated with the patient's immunological condition. Although Acyclovir® (ACV) and its analogs are the reference drugs for herpetic infections, the number of ACV-resistant HSV infections is growing exponentially. Therefore, new natural products' bioactive compounds have been studied to develop novel effective anti-herpetics. Trichilia catigua is a plant widely used in traditional medicine, including the treatment of skin diseases and sexual infections. In our study, 16 extracts from the bark of T. catigua, obtained with different solvents and their combinations, were evaluated against HSV-1 AR and HSV-2, respectively, ACV resistance and genital strains in vitro. The extracts with the highest selectivity index were used to prepare new topical anti-herpetic formulations and confirmed in vivo. Two new topical formulations were suggested to treat cutaneous and genital herpetic recurrent lesions. The cytotoxicity and antiviral activity were tested using the MTT method. The cytotoxic (CC50) and inhibitory (IC50) concentrations of 50% and the selectivity index (SI: CC50/IC50) were determined. Tc12, Tc13, and Tc16 were added to the formulations. Infected BALB/c mice were treated for 8 days, and the severity of the herpetic lesions was analyzed daily. All CEs showed a CC50 value ranging from 143 to 400 µg/mL, except for Tc3 and Tc10. Tc12, Tc13, and Tc16 showed the best SI in the 0 h, virucidal, and adsorption inhibition assays. In the in vivo test against HSV-1 AR, the infected animals treated with creams were statistically different from the infected non-treated animals and similar to ACV-treated mice. In HSV-2-infected genitalia, similar effects were found for Tc13 and Tc16 gels. The present study demonstrated that extracts from the bark of T. catigua, traditionally used in folk medicine, are a valuable source of active compounds with anti-herpetic activity. The extracts showed a virucidal mechanism of action and prevented the initial stages of viral replication. The cutaneous and genital infections were strongly inhibited by the Tc12, Tc13, and Tc16 extracts. New topical therapeutic alternatives using Trichilia catigua extracts are suggested for patients infected with ACV-resistant strains of HSV.


Asunto(s)
Herpes Simple , Herpesvirus Humano 1 , Meliaceae , Ratones , Animales , Aciclovir/farmacología , Aciclovir/uso terapéutico , Reinfección , Antivirales/farmacología , Antivirales/uso terapéutico , Herpes Simple/tratamiento farmacológico , Herpesvirus Humano 2/fisiología , Genitales
10.
Pharmaceutics ; 15(5)2023 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-37242662

RESUMEN

The skin is a complex and selective system from the perspective of permeability to substances from the external environment. Microemulsion systems have demonstrated a high performance in encapsulating, protecting and transporting active substances through the skin. Due to the low viscosity of microemulsion systems and the importance of a texture that is easy to apply in the cosmetic and pharmaceutical fields, gel microemulsions are increasingly gaining more interest. The aim of this study was to develop new microemulsion systems for topical use; to identify a suitable water-soluble polymer in order to obtain gel microemulsions; and to study the efficacy of the developed microemulsion and gel microemulsion systems in the delivery of a model active ingredient, namely curcumin, into the skin. A pseudo-ternary phase diagram was developed using AKYPO® SOFT 100 BVC, PLANTACARE® 2000 UP Solution and ethanol as a surfactant mix; caprylic/capric triglycerides, obtained from coconut oil, as the oily phase; and distilled water. To obtain gel microemulsions, sodium hyaluronate salt was used. All these ingredients are safe for the skin and are biodegradable. The selected microemulsions and gel microemulsions were physicochemically characterized by means of dynamic light scattering, electrical conductivity, polarized microscopy and rheometric measurements. To evaluate the efficiency of the selected microemulsion and gel microemulsion to deliver the encapsulated curcumin, an in vitro permeation study was performed.

11.
Polymers (Basel) ; 15(10)2023 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-37242878

RESUMEN

Novel delivery systems for cosmetics, drugs, and food ingredients are of great scientific and industrial interest due to their ability to incorporate and protect active substances, thus improving their selectivity, bioavailability, and efficacy. Emulgels are emerging carrier systems that represent a mixture of emulsion and gel, which are particularly significant for the delivery of hydrophobic substances. However, the proper selection of main constituents determines the stability and efficacy of emulgels. Emulgels are dual-controlled release systems, where the oil phase is utilized as a carrier for hydrophobic substances and it determines the occlusive and sensory properties of the product. The emulsifiers are used to promote emulsification during production and to ensure emulsion stability. The choice of emulsifying agents is based on their capacity to emulsify, their toxicity, and their route of administration. Generally, gelling agents are used to increase the consistency of formulation and improve sensory properties by making these systems thixotropic. The gelling agents also impact the release of active substances from the formulation and stability of the system. Therefore, the aim of this review is to gain new insights into emulgel formulations, including the components selection, methods of preparation, and characterization, which are based on recent advances in research studies.

12.
Int J Pharm ; 641: 123085, 2023 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-37245739

RESUMEN

Peripheral neuropathy (PN) is a condition of peripheral nerve damage leading to severe pain. The first line therapies are associated with adverse psychotropic effects (PSE) and second line therapies are not efficient enough to relieve pain. There is an unmet drug need for relieving pain effectively without PSE in PN. Anandamide, an endocannabinoid activates cannabinoid receptors to relieve the pain due to peripheral neuropathy (PN). Anandamide has a very short biological half-life as they are extensively metabolized by fatty acid amide hydrolase enzyme (FAAH). Regional delivery of safe FAAH inhibitor (FI) with anandamide would be beneficial for PN without PSE. The objective of the study is to identify a safe FI and deliver the anandamide in combination with the FI topically for the management of PN. The FAAH inhibition potential of silymarin constituents was evaluated by molecular docking and in vitro studies. The topical gel formulation was developed to deliver anandamide and FI. The formulation was assessed in chemotherapeutic agent-induced PN rat models to relieve mechanical-allodynia and thermal-hyperalgesia. The molecular docking studies demonstrated that the Prime MM-GBSA free energy of silymarin constituents were in the order of silybin > isosilybin > silychristin > taxifolin > silydianin. In in vitro studies, silybin 20 µM inhibited > 61.8% of FAAH activity and increased the half-life of anandamide. The developed formulation increased permeation of anandamide and silybin across the porcine skin. Furthermore, on the application of anandamide and anandamide-silybin gel to rat paws, there was a significant increase in the pain threshold for allodynic and hyperalgesic stimulus up to 1 h and 4 h, respectively. The topical anandamide with silybin delivery approach could serve to alleviate PN efficiently and thus could minimize unwanted CNS side effects of synthetic or natural cannabinoids in patients.


Asunto(s)
Endocannabinoides , Neuralgia , Ratas , Animales , Silibina , Simulación del Acoplamiento Molecular , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , Hiperalgesia/inducido químicamente , Alcamidas Poliinsaturadas
13.
Pharmaceutics ; 15(4)2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37111561

RESUMEN

The evaluation of bioequivalence (BE) for topical dermatological drug products is challenging, and there has been significant interest from regulatory authorities in developing new BE methodologies in recent years. Currently, BE is demonstrated by comparative clinical endpoint studies; these are costly and time-consuming and often lack sensitivity and reproducibility. Previously, we reported excellent correlations between in vivo Confocal Raman Spectroscopy in human subjects and in vitro skin permeation testing (IVPT) with the human epidermis for skin delivery of ibuprofen and a number of excipients. The aim of the present proof-of-concept study was to evaluate CRS as a method to assess BE of topical products. Two commercially available formulations, Nurofen Max Strength 10% Gel and Ibuleve Speed Relief Max Strength 10% Gel, were selected for evaluation. Delivery of ibuprofen (IBU) to the skin was determined in vitro and in vivo by IVPT and CRS, respectively. The formulations examined were found to deliver comparable amounts of IBU across the skin over 24 h in vitro (p > 0.05). Additionally, the formulations resulted in similar skin uptake values measured with CRS in vivo, either at 1 h or 2 h after application (p > 0.05). This is the first study to report the capability of CRS for the demonstration of BE of dermal products. Future studies will focus on the standardisation of the CRS methodology for a robust and reproducible pharmacokinetic (PK)-based evaluation of topical BE.

14.
Saudi Pharm J ; 31(1): 154-169, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36685308

RESUMEN

Spray film-forming systems (SFFSs) provide great potential for the treatment of various types of wounds. Such systems afford to prolong the action of active substances, to prevent cross-contamination, and to ensure accelerated wound healing. Spray films are known since the mid-20th century, and nowadays they are widely used to treat minor skin injuries, but numerous clinical cases describe their successful use in the treatment of burns, wounds, bedsores, etc. The current level of polymer development and composite synthesis has greatly expanded the possibilities of creating compositions of spray film-forming systems. Scattered information and lack of standardization of such delivery systems creates difficulties for pharmaceutical development. This review highlights most of the existing requirements and suggestions from studies to standardize the characteristics of SFFSs and classify them based on scientific sources and regulatory documentation, as well as the position of such systems in the pharmaceutical market. The search and evaluation of known characterization methods and their modifications, as well as the approval of their list (separately for development and for standardization) can potentially increase the research interest in the problem of spray film-forming systems development and contribute to the registration of new drugs and medical devices in this promising dosage form, including with its own pharmacological effect.

15.
Gels ; 10(1)2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38247759

RESUMEN

Topical formulations of Acanthus mollis L. leaf and the optimization of the release of their active compounds and their topical bioavailability were investigated for the first time. In vitro, the release of active compounds from three formulations-an oil-in-water cream and two hydrogels (Carbopol 940 and Pluronic F-127)-was determined using Franz diffusion cells. Detection and quantification of the compounds was performed via high-performance liquid chromatography with a photodiode array (HPLC-PDA). DIBOA, a bioactive compound of this medicinal plant, exhibited release kinetics of the Weibull model for the Carbopol and Pluronic F-127 formulation, identifying it as a potential active agent to optimize the topical distribution of the formulations. The implications extend to applications in inflammation treatment and tyrosinase inhibition, suggesting that it can make a significant contribution to addressing skin conditions, including melanoma and various inflammatory diseases.

16.
Postepy Dermatol Alergol ; 40(6): 716-724, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38282869

RESUMEN

Azelaic acid (AZA) is a naturally occurring saturated dicarboxylic acid whose topical application has found multiple uses in dermatology. Its anti-inflammatory, antioxidant and antimicrobial properties against Propionibacterium acne are currently used in the treatment of various types of acne such as rosacea and acne vulgaris. AZA is an inhibitor of tyrosinase, mitochondrial respiratory chain enzymes and DNA synthesis, and is a scavenger of harmful free radicals and inhibits the production of reactive oxygen species by neutrophils. Interestingly, AZA also has anti-proliferative and cytotoxic effects on various cancer cells. To date, its inhibitory effect on melanocytes has been mainly used, making it widely used in the treatment of hyperpigmentation disorders such as melasma and post-inflammatory hyperpigmentation. Commercially available topical formulations with cosmetic and drug status contain 5% to 20% AZA in the form of gels and creams. The use of liposomal technology allows greater control over the pharmacokinetics and pharmacodynamics of the formulations. When applied topically, AZA is well tolerated, and side effects are limited to generally mild and transient local skin irritation. Importantly, liposomal technology has enabled the drug to penetrate all layers of the skin while maintaining a very high accumulation of the active ingredient. This solution could be revolutionary for the treatment of skin cancer, where until now the main obstacle was poor absorption through the skin, making the treatment require multiple applications to maintain long-term activity levels. In this review, we will present the mechanism of action and pharmacokinetics of AZA. We will summarize its use in the treatment of dermatoses and its potential in skin cancer therapy. We will provide an overview of the preparations available on the market, taking into consideration technologies used.

17.
Front Pharmacol ; 13: 1007496, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36532731

RESUMEN

Physiologically based pharmacokinetic (PBPK) models are widely accepted tools utilised to describe and predict drug pharmacokinetics (PK). This includes the use of dermal PBPK models at the regulatory level including virtual bioequivalence (VBE) studies. The current work considers the Topicort® Spray formulation, which contains 0.25% desoximetasone (DSM), as an example formulation. Quantitative formulation composition and in vitro permeation testing (IVPT) data were obtained from the public literature to develop a mechanistic model using the multi-phase, multi-layer (MPML) MechDermA IVPT module in the Simcyp Simulator. In vitro-in vivo extrapolation functionality was used to simulate in vivo PK for various scenarios and predict a 'safe space' for formulation bioequivalence using the VBE module. The potential effect of vasoconstriction, impaired barrier function, and various dosing scenarios on the formulation safe space was also assessed. The model predicted 'safe space' for formulation solubility suggesting that a 50% change in solubility may cause bio-in-equivalence, whereas viscosity could deviate by orders of magnitude and the formulation may still remain bioequivalent. Evaporation rate and fraction of volatile components showed some sensitivity, suggesting that large changes in the volume or composition of the volatile fraction could cause bio-in-equivalence. The tested dosing scenarios showed decreased sensitivity for all formulation parameters with a decreased dose. The relative formulation bioequivalence was insensitive to vasoconstriction, but the safe space became wider with decreased barrier function for all parameters, except viscosity that was unaffected.

18.
Clin Cosmet Investig Dermatol ; 15: 2445-2454, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36387960

RESUMEN

Purpose: Urea as an ingredient in topical skin applications can aid skin integrity and hydration and have keratolytic, anti-fungal, anti-bacterial, and anti-pruritic effects. Skin conditions that urea-containing formulations have been utilized to treat include hand eczema/dermatitis, seborrheic dermatitis and psoriasiform dermatoses of the scalp. Two monocentric, simple blind, observational studies were carried out in healthy participants to examine the efficacy and safety of two urea-containing products in these skin conditions. Patients and Methods: Study 1 tested the actions of a commercially available 30% urea topical cream on hand eczema. The product was applied ≥2/day for 28 ±2 days. Transepidermal water loss, skin redness, skin hydration, and participant ratings of efficacy and qualities were assessed prior to first product application and on days 14 and 29. Study 2 tested the actions of a commercially available foaming product containing 10% urea on seborrheic dermatitis and scalp psoriasiform dermatoses. The product was applied ≥2/day for 28 ±2 days. Desquamation index and surface occupied by squames, analysis of extracted squames, microscopic assessment of scalp photos and participant ratings of product efficacy and qualities was carried out prior to first product application and on days 14 and 29. Results: In Study 1 (n = 20 females), results showed a significant (p < 0.05) decrease in transepidermal water loss, with an increase in hydration level of the upper skin layers, and a decrease in skin redness. In Study 2 (n = 13 females, 7 males), product use led to significant (p < 0.05) decreases in desquamation measures and dryness. In both studies, the majority of participants "agreed" or "slightly agreed" that the product had good efficacy and was easy to apply. No adverse reactions were reported. Conclusion: These findings point to the utility of urea in topically applied vehicles for hand eczema, seborrheic dermatitis, and psoriasiform dermatoses.

19.
Pharmaceutics ; 14(10)2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36297542

RESUMEN

Previously, we reported the use of confocal Raman spectroscopy (CRS) as a novel non-invasive approach to determine drug disposition in the skin in vivo. Results obtained by CRS were found to correlate with data from the well-established in vitro permeation test (IVPT) model using human epidermis. However, these studies used simple vehicles comprising single solvents and binary or ternary solvent mixtures; to date, the utility of CRS for monitoring dermal absorption following application of complex marketed formulations has not been examined. In the present work, skin delivery of diclofenac sodium (DFNa) from two topical dermatological drug products, namely Diclac® Lipogel 10 mg/g and Primofenac® Emulsion gel 1%, was determined by IVPT and in vivo by both CRS and tape stripping (TS) methodologies under similar experimental conditions. The in vivo data were evaluated against the in vitro findings, and a direct comparison between CRS and TS was performed. Results from all methodologies showed that Diclac promoted significantly greater DFNa delivery to the skin (p < 0.05). The cumulative amounts of DFNa which permeated at 24 h in vitro for Diclac (86.5 ± 9.4 µg/cm2) were 3.6-fold greater than the corresponding amounts found for Primofenac (24.4 ± 2.7 µg/cm2). Additionally, total skin uptake of DFNa in vivo, estimated by the area under the depth profiles curves (AUC), or the signal intensity of the drug detected in the upper stratum corneum (SC) (4 µm) ranged from 3.5 to 3.6-fold greater for Diclac than for Primofenac. The shape of the distribution profiles and the depth of DFNa penetration to the SC estimated by CRS and TS were similar for the two methods. However, TS data indicated a 4.7-fold greater efficacy of Diclac relative to Primofenac, with corresponding total amounts of drug penetrated, 94.1 ± 22.6 µg and 20.2 ± 7.0 µg. The findings demonstrate that CRS is a methodology that is capable of distinguishing skin delivery of DFNa from different formulations. The results support the use of this approach for non-invasive evaluation of topical products in vivo. Future studies will examine additional formulations with more complex compositions and will use a wider range of drugs with different physicochemical properties. The non-invasive nature of CRS coupled with the ability to monitor drug permeation in real time offer significant advantages for testing and development of topical dermatological products.

20.
Ther Adv Ophthalmol ; 14: 25158414221112356, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35873277

RESUMEN

Conventional drug delivery formulations, such as eye drops and ointments, are mainly administered by topical instillation. The topical delivery of ophthalmic drugs is a challenging endeavor despite the eye is easily accessible. Unique and complex barriers, serving as protection against extrinsic harmful factors, hamper therapeutic intraocular drug concentrations. Bioavailability for deeper ocular tissues of the anterior segment of the eye is exceptionally low. As the bioavailability of the active substance is the major hurdle to overcome, dosing is increased, so the side effects do. Both provoke patient poor compliance, confining the desired therapeutic outcome. The incidence and severity of adverse reactions amplify evenly in the case of chronic treatments. Current research focuses on the development of innovative delivery strategies to address low ocular bioavailability and provide safe and convenient dosing schemes. The main objective of this review is to explore and present the latest developments in ocular drug delivery formulations for the treatment of the pathology of the anterior segment of the eye. Nanotechnology-based formulations, that is, organic nanoparticles (liposomes, niosomes/discosomes, dendrimers, nanoemulsions, nanosuspensions, nanoparticles/nanospheres) and inorganic nanoparticles, nanoparticle-laden therapeutic contact lenses, in situ gelling systems, and ocular inserts, are summarized and presented accordingly.

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