A molecular mechanism investigation of the transdermal/topical absorption classification system on the basis of drug skin permeation and skin retention

Background: HQ is used for hyper-pigmentation treatment using conventional creams and gels. These formulations show various disadvantages like poor skin permeation, allergic reactions, and repeated use decreasing patient compliance. Objectives: The present work involved formulation, statistical optimization, and characterization of nanostructured lipid carriers (NLCs) for efficient topical delivery of hydroquinone (HQ) for hyperpigmentation treatment. Methods: The NLCs were optimized exploring Box–Behnken design (BBD) using three independent variables and two dependent variables. Formulation having the minimum size and maximum drug entrapment was considered as optimized formulation. Optimized formulation was evaluated for drug release followed by its freeze-drying. The freeze-dried formulation was subjected to differential scanning calorimetry (DSC) analysis, X-raydiffraction (XRD) analysis, and Fourier transform-infrared spectroscopy (FT-IR) analysis. Furthermore, NLCs based gel was prepared by using Carbopol 934 as a gelling agent. NLCs based gel was evaluated for skin permeation, skin retention, and skin distribution (through confocal microscopic analysis) using pig ear skin. Results: Optimized NLCs showed smaller particle size [(271.9 ± 9) nm], high drug entrapment [(66.4 ± 1.2) %], tolerable polydispersity index (PDI) (0.221 ± 0.012), and zeta potential [(-25.9± 1.2) mV]. The FT-IR analysis revealed excellent compatibility between HQ and other excipients. The Carbopol 934 gel containing NLCs showed high transdermal flux [(163 ± 16.2) μg/cm2/h], permeability coefficient (0.0326 ± 0.0016), and skin permeation enhancement ratio (3.7 ± 0.4) compared to marketed cream of HQ. The results of confocal microscopic (CLSM) analysis revealed the accumulation of optimized NLCs in the lower epidermal layers of skin. Conclusion: NLCs based gel was considered effective in the topical delivery of HQ to treat hyper-pigmentation due high skin permeation, skin retention, and prolonged release of HQ.

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Investigating the potential of Quercetin enthused nano lipoidal system for the management of dermatitis

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.01127 ◽

2021 ◽

pp. 6516-6526

Author(s):

Deepti Dwivedi ◽

Shubham Pandey ◽

Shafaque Asif ◽

Vineet Awasthi ◽

Gurjeet Kaur ◽

...

Keyword(s):

Zeta Potential ◽

Skin Permeation ◽

Research Work ◽

Entrapment Efficiency ◽

Laser Scanning Microscopy ◽

Polydispersity Index ◽

In Vivo Studies ◽

Confocal Laser ◽

Skin Retention

Objective: The present research work was undertaken to develop quercetin enthused nanolipoidal systems and its characterization. The objective was to investigate potential of prepared system in the management of DNCB induced dermatitis. Method: Nanolipoidal system was prepared in different combinations with quercetin, L-α phosphatidylcholine (SPC) and ethanol and characterized for particle size, polydispersity index (PDI), zeta potential, drug entrapment efficiency, percentage drug release, skin retention and skin permeation. Selected batches were further incorporated into Carbopol 934 base gel. The vesicles were in size range 324.19-359 nm while polydispersity index (PDI) ranges from 0.241-0.554 and for zeta potential, it was from -26.33 to -39.3 nm. Entrapment efficiency was from 23.77-94.68 %. Confocal laser scanning microscopy showed penetration depth of rhodamine enthused ethosome across rat skin up to 45.23 µm which was significantly higher than the rhodamine solution (10 µm). In dinitrochlorobenzene (DNCB) induced mice dermatitis model histopathology study showed a marked decrease in amount of inflammatory cell nucleus in mice treated with quercetin loaded ethosomal gel followed by 76.13% decrease in-ear swelling and ear mass respectively in morphology study. The conventional marketed formulation showed a nominal decrease in epidermal thickness. Further Primary irritation index was less than 0.4 indicating negligible irritation in all the groups. Results: The optimized formulation F6 with SPC and ethanol in the ratio of 20:80 displayed the highest drug content and entrapment efficiency of 94.68±1.14%. PDI was 0.241±0.11 and skin retention 7.7%. Batch F6 with vesicle size and zeta potential of 324.9±19 nm and -26.33 mV, respectively, was incorporated in Carbopol 934 base gel and the prepared gel was evaluated for morphology, spreadability, in vitro, ex vivo release study, and kinetics study and in vivo studies. Conclusion: The present study revealed that the developed ethosomal gel can be used for enhanced delivery of Quercetin via skin. The in vitro studies indicated that the gel serves as an efficient carrier for Quercetin. It showed its effectiveness in the management of dermatitis. Further, Quercetin loaded nanoethosomal gel formulation can be viewed as a promising drug delivery system for the management of dermatitis.

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An Investigation of the Influence of PEG 400 and PEG-6-Caprylic/Capric Glycerides on Dermal Delivery of Niacinamide

Polymers ◽

10.3390/polym12122907 ◽

2020 ◽

Vol 12 (12) ◽

pp. 2907

Author(s):

Yanling Zhang ◽

Majella E. Lane ◽

David J. Moore

Keyword(s):

Skin Permeation ◽

Ternary Systems ◽

Pharmaceutical Products ◽

Porcine Skin ◽

Peg 400 ◽

Skin Delivery ◽

Dermal Delivery ◽

Binary And Ternary Systems ◽

Skin Retention

Polyethylene glycols (PEGs) and PEG derivatives are used in a range of cosmetic and pharmaceutical products. However, few studies have investigated the influence of PEGs and their related derivatives on skin permeation, especially when combined with other solvents. Previously, we reported niacinamide (NIA) skin permeation from a range of neat solvents including propylene glycol (PG), Transcutol® P (TC), dimethyl isosorbide (DMI), PEG 400 and PEG 600. In the present work, binary and ternary systems composed of PEGs or PEG derivatives combined with other solvents were investigated for skin delivery of NIA. In vitro finite dose studies were conducted (5 μL/cm2) in porcine skin over 24 h. Higher skin permeation of NIA was observed for all vehicles compared to PEG 400. However, overall permeation for the binary and ternary systems was comparatively low compared with results for PG, TC and DMI. Interestingly, values for percentage skin retention of NIA for PEG 400:DMI and PEG 400:TC were significantly higher than values for DMI, TC and PG (p < 0.05). The findings suggest that PEG 400 may be a useful component of formulations for the delivery of actives to the skin rather than through the skin. Future studies will expand the range of vehicles investigated and also look at skin absorption and residence time of PEG 400 compared to other solvents.

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FORMULATION AND EVALUATION OF GEL CONTAINING ETHOSOMES ENTRAPPED WITH TRETINOIN

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v8i5-s.1982 ◽

2018 ◽

Vol 8 (5-s) ◽

pp. 315-321

Author(s):

Rakhi Mishra ◽

Shradha Shende ◽

Prabhat Kumar Jain ◽

Vivek Jain

Keyword(s):

Transdermal Delivery ◽

Skin Permeation ◽

Three Dimensional ◽

Entrapment Efficiency ◽

Brick Wall ◽

Topical Formulation ◽

Ir Studies ◽

Skin Retention ◽

Drug Solution

A skin disease, like acne, is very common and normally happens to everyone at least once in their lifetime. The structure of the stratum corneum is often compared with a brick wall, with corneocytes surrounded by the mortar of the intercellular lipid lamellae. One of the best options for successful drug delivery to the affected area of skin is the use of ethosomes which can be transported through the skin through channel-like structures. Tretinoin is a widely used retinoid for the topical treatment of acne, photo-aged skin, psoriasis and skin cancer which makes it a good candidate for topical formulation. Yet side effects, like redness, swelling, peeling, blistering and, erythema, in addition to its high lipophilicity make this challenging. Drug loaded ethosomes had been prepared using phospholipid and ethanol, were optimized and characterized for entrapment efficiency, vesicular size, shape, In-vitro skin permeation, skin retention, drug‐membrane component interaction and stability. The ethosomal formulation having 0.5 %w/v of phospholipid and 20 %v/v of ethanol (F2) showing the greatest entrapment efficiency (80.25±0.23) with small particle size (205.40±2.31nm) was selected for further skin permeation studies. The skin permeation and skin retention studies were performed on ethosomal formulation, liposomal formulation (0.5 %w/v of phospholipid without alcohol), hydroethanolic drug solution and phosphate buffer saline (pH7.4) drug solution. Among them, ethosomal formulation showed higher cumulative percentage of drug permeation (93.36±0.45%) and 8 hours than the other formulations. Scanning electron microscopy confirmed the three dimensional nature of ethosomes. Dynamic light scattering technique proved that the ethosomes has smaller vesicular size than the liposomes prepared without alcohol. FT‐IR studies revealed no interaction between the drug and membrane components. The ethosomal vesicles were incorporated in carbopol gel base and its anti‐acne was compared with the marketed gel. Our results suggest that the ethosomes are an efficient carrier for dermal and transdermal delivery of tretinoin. Keywords: Tretinoin, Ethosomes, Diffusion, Carbopol gels, Transdermal delivery.

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Development and Evaluation of Ketoconazole Loaded Nano-sponges for Topical Drug Delivery

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2018.11.4.2 ◽

2018 ◽

Vol 11 (4) ◽

pp. 4154-4162

Author(s):

Harshal A. Pardeshi ◽

Makarand S Gambhire ◽

Kishore N. Gujar ◽

Aniket A Vaidhya

Keyword(s):

Drug Delivery ◽

Antifungal Activity ◽

Drug Release ◽

Ex Vivo ◽

Skin Permeation ◽

Controlled Drug Release ◽

Topical Drug Delivery ◽

Molar Ratios ◽

Skin Targeting ◽

Skin Retention

Beta-cyclodextrin nanosponges (NS) based hydrogel had been studied as a topical delivery of ketoconazole (KTZ) for effective eradication of cutaneous fungal infection. The purpose of the present study was to develop KTZ loaded NS for topical drug delivery with skin targeting to minimizing the adverse side effects and providing a controlled release. The four types of NS were synthesized by varying the molar ratios of β-cyclodextrin (β-CD) to diphenylcarbonate (DPC) as a cross linker viz. 1:2, 1:4, 1:6, and 1:8. The KTZ loaded NS shows particle size 274.6-367 nm and high loading efficacy was obtained, FTIR, DSC, XRD studies confirmed the complexation of KTZ with NS. Hydrogel were evaluated comparatively with commercial product with respect to physicochemical properties, ex-vivo skin permeation and skin retention on human cadaver skin and antifungal activity. Ex-vivo study of KTZ-NS hydrogel exhibited controlled drug release up to 8 hrs whereas skin retention studies show avoidance of the systemic uptake and better accumulative uptake of the drug compared to marketed formulation. The zone of inhibition of KTZ-NS hydrogel was higher in comparison with commercial formulation against Candida albicans. These results indicate that the KTZ-NS is having controlled drug release, potential of skin targeting with enhanced antifungal activity.

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The Effect of Cream and Gel Vehicles on the Percutaneous Absorption and Skin Retention of a New Eugenol Derivative With Antioxidant Activity

Frontiers in Pharmacology ◽

10.3389/fphar.2021.658381 ◽

2021 ◽

Vol 12 ◽

Author(s):

Edyta Makuch ◽

Anna Nowak ◽

Andrzej Günther ◽

Robert Pełech ◽

Łukasz Kucharski ◽

...

Keyword(s):

Antioxidant Activity ◽

Steam Distillation ◽

Skin Permeation ◽

Biologically Active ◽

Skin Permeability ◽

Skin Accumulation ◽

Radical Reduction ◽

Skin Retention

The effect of cream and gel vehicles containing clove water on skin permeability was compared for a new eugenol derivative (eugenyl dichloroacetate—EDChA) with antioxidant activity. In vitro permeation experiments were conducted in a Franz cell with porcine skin. The cumulative mass and skin accumulation of EDChA were investigated and compared. The antioxidative capacity of the studied vehicles was determined by using the diphenylpicrylhydrazyl (DPPH) free radical reduction method. The antioxidant activity (evaluated with DPPH, ABTS, and the Folin–Ciocalteu methods) of the fluid that penetrated through the pig skin and of the fluid obtained after the skin extraction, were also determined. For comparison, eugenol was also tested. The results of this work could contribute to the development of vehicles with antioxidant potential estimated after 24 h of conducting the experiment, which indicates long-term protection against reactive oxygen species (ROS) in the deeper layers of the skin. The waste water from the clove buds steam distillation -contains several valuable biologically active compounds, and its use is environmentally friendly. We observed that gel vehicles were the best enhancer of skin permeation for both eugenol and its derivative. In most cases, -similar cumulative masses of eugenol and its ester were found in the acceptor fluid. The accumulation of EDChA was higher for cream vehicles in relation to the parent eugenol when applied onto the skin. The greatest amounts of eugenol were accumulated in the skin when these compounds were used in gel vehicles.

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The Influence of Formulation and Excipients on Propranolol Skin Permeation and Retention

BioMed Research International ◽

10.1155/2018/1281673 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Cristina Padula ◽

Sara Nicoli ◽

Silvia Pescina ◽

Patrizia Santi

Keyword(s):

Skin Permeation ◽

Skin Penetration ◽

Infantile Hemangioma ◽

Skin Surface ◽

Time Frame ◽

Systemic Absorption ◽

Therapeutic Drug ◽

Topical Formulations ◽

Skin Retention

The objective of this work was to study in vitro propranolol permeation and skin retention after topical application of different semisolid vehicles, with the final aim of developing new topical formulations intended for the treatment of infantile hemangioma, able to produce therapeutic drug levels in the skin, avoiding systemic absorption. Propranolol ointments, creams, and gels were prepared and tested on pig skin, an accepted model of human skin. From the results obtained in the present work it is clear that the permeation of propranolol across the skin is a poor predictor of its skin retention, at least in the time-frame considered. With an application time of 4 h, reasonably close to the permanence time of a semisolid formulation on the skin surface, the best performance (high retention and low skin penetration) was obtained with lipophilic formulations, in particular with a lipophilic cream containing olive oil. Hydrophilic formulations, such as gels, are characterized by a significant permeation across the skin, probably leading to systemic side effects, accompanied by a limited skin retention. Overall, the results obtained in the present work pose the basis for the development of new topical formulations, containing propranolol, with better performance and reduced systemic absorption.

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Dermal Delivery Enhancement of Natural Anti-Ageing Compounds from Ocimum sanctum Linn. Extract by Nanostructured Lipid Carriers

Pharmaceutics ◽

10.3390/pharmaceutics12040309 ◽

2020 ◽

Vol 12 (4) ◽

pp. 309

Author(s):

Wantida Chaiyana ◽

Songyot Anuchapreeda ◽

Suvimol Somwongin ◽

Pachabadee Marsup ◽

Kuan-Han Lee ◽

...

Keyword(s):

Zeta Potential ◽

Droplet Size ◽

Skin Permeation ◽

In Vitro Release ◽

Correlation Spectroscopy ◽

Nanostructured Lipid Carriers ◽

Ocimum Sanctum ◽

Dermal Delivery ◽

Skin Retention

This study aimed to develop nanodelivery systems for enhancing the Ocimum sanctum Linn. extract delivery into the skin. Rosmarinic acid (RA) was used as a marker for the quantitative determination of the extract by high-performance liquid chromatography. Nanostructured lipid carriers (NLC), nanoemulsion, liposome, and niosome, were developed and characterized for internal droplet size, polydispersity index (PDI), and zeta potential using photon correlation spectroscopy. Irritation properties of each formulations were investigated by hen’s egg test on the chorioallantoic membrane. In vitro release, skin permeation, and skin retention are determined. NLC was suggested as the most suitable system since it enhances the dermal delivery of RA with the significant skin retention amount of 27.1 ± 1.8% (p < 0.05). Its internal droplet size, PDI, and zeta potential were 261.0 ± 5.3 nm, 0.216 ± 0.042, and −45.4 ± 2.4 mV, respectively. RA released from NLC with a sustained release pattern with the release amount of 1.29 ± 0.15% after 24 h. NLC induced no irritation and did not permeate through the skin. Therefore, NLC containing O. sanctum extract was an attractive dermal delivery system that was safe and enhanced dermal delivery of RA. It was suggested for further used as topical anti-ageing products.

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Formulation Consideration and Skin Retention-Permeation Study of Insitu Nanogel Containing Dimethylfumarate for Treatment of Psoriasis

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i54a33744 ◽

2021 ◽

pp. 248-261

Author(s):

Deepa Patel ◽

Sneha Patel

Keyword(s):

Skin Permeation ◽

Crosslinking Agent ◽

Topical Delivery ◽

Surface Epithelium ◽

Permeation Study ◽

Skin Uptake ◽

Full Factorial ◽

Retention Study ◽

Skin Retention ◽

32 Full Factorial Design

Aims and Objective: to develop and evaluate an insitu nanogel formulation containing dimethylfumarate for targeted topical delivery therapy of psoriasis. Study Design: 32 full factorial design Place and Duration of Study: Department of Pharmaceutics, Parul Institute of Pharmacy and Research, Parul University, Vadodara, between 2016 to 2019. Methodology: Nanogel were formulated by chemical cross linked gel method using Polyvinyl alcohol and Hyaluronic acid (1:5) ratio using Glutaraldehyde (GA) (25 %w/v) and Hydrochloric acid (HCl) (6%v/v) as a crosslinking agent and catalyst. Dimethylfumarate loaded nanogel were clear and showed physicochemical parameters desired for topical delivery and stability. Results: The Permeation profile of dimethylfumarate through rat skin from selected nanogel formulation exhibited highest skin uptake. The Micoscopic observations indicated that the optimized nanogel had n significant effect on the microscopic structure of the sin and epithelial cells appered mostly unchanged. The surface epithelium lining and the granular cellular structure of the skin were totally intact. The developed Nanogel may be a potential drug delivery vehicle for targeted topical delivery of dimethylfumarate in the treatment of psoriasis. Conclusion: As per drug retention study the highest amount of drug retained on the skin and lowest amount of drug permeate to the skin. Hence it was observed that there was no signiﬁcant correlation between skin retention and skin permeation study.

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