Poloxamer 407 Based Gel Formulations for Transungual Delivery of Hydrophobic Drugs: Selection and Optimization of Potential Additives

The current study aimed to develop poloxamer 407 (P407) gel for transungual delivery of antifungal hydrophobic drugs with sufficient gel strength and drug loading. Gel strength and drug loading of P407 gel was improved by use of functional additives. Hydration enhancement effect was used to select optimum nail penetration enhancer. Face-centered central composite design (FCCCD) was used to observe the effect of the selected penetration enhancer (thioglycolic acid (TGA)) and cosolvent (ethanol) on gelation behavior to develop formulation with enough loading of hydrophobic drug, i.e., terbinafine HCl (TBN), and its permeation across the nail plate without compromising on gel strength. It was observed that increasing concentration of P407 and TGA significantly reduced gelation temperature and enhanced the gel strength of P407 gel and can be used to improve P407 gel strength. Under the scanning electron microscope, the significant effect of TGA as an ungual penetration enhancer was observed on the morphology of the nail plate. Optimized P407 gel prepared with modified cold method showed a gelation temperature of 8.7 ± 0.16 °C, gel strength of 122 ± 7.5 s and drug loading of 1.2% w/w, which was four times more than the drug loading in the gels prepared with conventional cold method. Rheological behavior was pseudoplastic with 47.75 ± 3.48% of gel erosion after 12 washings and 67.21 ± 2.16% of drug release after 12 h. A cumulative amount of TBN permeated from P407 gel with and without PE after 24 h was 27.30 ± 4.18 and 16.69 ± 2.31 µg/cm2, respectively. Thioglycolic acid can be used as a nail penetration enhancer without the chemical modification or addition of extra additives while retaining the gel strength. Water miscible cosolvents with moderate evaporability such as ethanol, can be incorporated to P407 gel by minor modification in method of preparation to load the required dose of hydrophobic drugs. Developed P407 gel formulation with sufficient gel strength and drug loading will be a promising carrier for transungual delivery of hydrophobic antifungal agents.

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Novel Polypseudorotaxanes Hydrogel based Nail Lacquer of Efinaconazole for Transungual Drug Delivery

Drug Delivery Letters ◽

10.2174/2210303110999200918163213 ◽

2020 ◽

Vol 10 ◽

Author(s):

Rohan Aggarwal ◽

Monika Targhotra ◽

Bhumika Kumar ◽

P. K. Sahoo ◽

Meenakshi K. Chauhan

Keyword(s):

Drug Delivery ◽

Ex Vivo ◽

Sol Gel ◽

Nail Plate ◽

Penetration Enhancer ◽

High Rate ◽

Poloxamer 407 ◽

Drying Time ◽

Nail Lacquer ◽

Transungual Delivery

Aim: Due to the various drawbacks associated with current treatment therapy of onychomycosis, the main aim was to develop thermosensitive hydrogels and thermosensitive polypseudorotaxanes hydrogels-based nail lacquer for transungual delivery of Efinaconazole for management of onychomycosis. The objective is to enhance the permeation and retention of the drug in the nails and improve patient compliance. Method: Poloxamer 407 and Hydroxy Propyl -β- cyclodextrin was used to prepare the nail lacquers. 2-mercaptoethanol was added as a penetration enhancer to improve the penetration of the drug across the nail plate. The formulations were optimized by varying the concentration of poloxamer and water:ethanol ratio and evaluated based on basis of drying time, sol-gel transition temperature, ex vivo drug release and viscosity. The optimized formulation was further evaluated for pH, water resistance, non-volatile content, drug content, blush test, spreadability, and stability studies. Results: The increase in ethanol concentration, reduction in poloxamer proportion lead to reduction in lacquer stickiness thus, improving the lacquer drying time and penetration. The polypseudorotaxanes improved the permeation profile of the drug in comparison to the marketed nail lacquer. The presence of 2-mercaptoethanol also contributed in transungual delivery of Efinaconazole. Conclusion:: The polypseudorotaxanes based nail lacquer with the incorporation of penetration enhancer was able to achieve a high rate of drug penetration and retention, thus supporting the potential use of aqueous based-nail lacquer in transungual drug delivery for the onychomycosis treatment.

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Release of a Wound-Healing Agent from PLGA Microspheres in a Thermosensitive Gel

BioMed Research International ◽

10.1155/2013/387863 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

H. A. Machado ◽

J. J. Abercrombie ◽

T. You ◽

P. P. DeLuca ◽

K. P. Leung

Keyword(s):

Antimicrobial Activity ◽

Drug Loading ◽

Control Release ◽

Cell System ◽

Pluronic F127 ◽

Poloxamer 407 ◽

Gelation Temperature ◽

Release Process ◽

Broth Microdilution Method

The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4–7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil-water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50 : 50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and manufacturing parameters constant. Formulations were characterized for surface morphology, porous nature, drug loading,in vitrodrug release, and antimicrobial activity. Microspheres containing 20% peptide with porous surfaces and internal structure were prepared in satisfactory yields and in sizes varying from 25 to 50 μm. Gels of 20% Pluronic F127, which were liquid at or below 24.6°C and formed transparent films at body temperature, were used as carriers for the microspheres. Rheological studies showed a gelation temperature of 24.6°C for the 20% Pluronic F127 gel alone. Gelation temperature and viscosity of formulations A, B, and C as a function of temperature were very close to those of the carrier. A Franz diffusion cell system was used to study the release of peptide from the microspheres suspended in both, phosphate-buffered saline (PBS) and a 20% Pluronic F127 gel.In vitrorelease of greater than 50% peptide was found in all formulations in both PBS and the gel, and in one formulation there was a release of 75% in both PBS and the gel. Fractions collected from the release process were also tested for bactericidal activity againstStaphylococcus epidermidisusing the broth microdilution method and found to provide effective antimicrobial activity to warrant consideration and testing in animal wound models for treating combat-related injuries.

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Polymeric Micelles for the Enhanced Deposition of Hydrophobic Drugs into Ocular Tissues, without Plasma Exposure

Pharmaceutics ◽

10.3390/pharmaceutics13050744 ◽

2021 ◽

Vol 13 (5) ◽

pp. 744

Author(s):

Ijeoma F. Uchegbu ◽

Jan Breznikar ◽

Alessandra Zaffalon ◽

Uche Odunze ◽

Andreas G. Schätzlein

Keyword(s):

Polymeric Micelles ◽

Rabbit Model ◽

Penetration Enhancer ◽

Hydrophobic Drugs ◽

Ocular Tissues ◽

Ocular Penetration ◽

Self Assembling ◽

Similar Dose ◽

Oil In Water ◽

The Stability

Commercial topical ocular formulations for hydrophobic actives rely on the use of suspensions or oil in water emulsions and neither of these formulation modalities adequately promote drug penetration into ocular tissues. Using the ocular relevant hydrophobic drug, cyclosporine A (CsA), a non-irritant ocular penetration enhancer is showcased, which may be used for the formulation of hydrophobic actives. The activity of this penetration enhancer is demonstrated in a healthy rabbit model. The Molecular Envelope Technology (MET) polymer (N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan), a self-assembling, micelle-forming polymer, was used to formulate CsA into sterile filtered nanoparticulate eye drop formulations and the stability of the formulation tested. Healthy rabbits were dosed with a single dose of a MET–CsA (NM133) 0.05% formulation and ocular tissues analyzed. Optically clear NM133 formulations were prepared containing between 0.01–0.1% w/v CsA and 0.375–0.75% w/v MET polymer. NM133 0.01%, NM133 0.02% and NM133 0.05% were stable for 28 days when stored at refrigeration temperature (5–6 °C) and room temperature (16–23 °C), but there was evidence of evaporation of the formulation at 40 °C. There was no change in drug content when NM133 0.05% was stored for 387 days at 4 °C. On topical dosing to rabbits, corneal, conjunctival and scleral AUC0–24 levels were 25,780 ng.h g−1, 12,046 ng.h g−1 and 5879 ng.h g−1, respectively, with NM133 0.05%. Meanwhile, a similar dose of Restasis 0.05% yielded lower values of 4726 ng.h/g, 4813 ng.h/g and 1729 ng.h/g for the drug corneal, conjunctival and scleral levels, respectively. NM133 thus delivered up to five times more CsA to the ocular surface tissues when compared to Restasis. The MET polymer was non-irritant up to a concentration of 4% w/v. The MET polymer is a non-irritant ocular penetration enhancer that may be used to deliver hydrophobic drugs in optically clear topical ocular formulations.

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Transdermal Delivery of Ondansetron HCl from Thermoreversible Gel Containing Nanocomposite

Current Nanomaterials ◽

10.2174/2405461504666190530123120 ◽

2019 ◽

Vol 4 (2) ◽

pp. 137-147 ◽

Cited By ~ 1

Author(s):

Rabinarayan Parhi ◽

Surya Santhosh Reddy ◽

Suryakanta Swain

Keyword(s):

Drug Release ◽

Mechanical Strength ◽

Ex Vivo ◽

Poloxamer 407 ◽

Gelation Temperature ◽

Permeation Study ◽

Ex Vivo Permeation ◽

Model Animal ◽

Ex Vivo Permeation Study ◽

Thermoreversible Gel

Background: Application of thermoreversible gel can be a solution to the low residence time of the topical dosage forms such as normal gel, ointment and cream on the skin surface. Addition of another polymer and a nanocomposite can improve the poor mechanical strength and fast drug release of poloxamer 407 (POL 407) gel. Therefore, it is essential to add xanthan gum (XG) and graphene oxide (GO, thickness 1-2 nm, lateral dimension 1-5 µm) to POL 407 gel to enhance the mechanical strength and to sustain the drug release from the gel. Methods: Thermal gel of ondansetron hydrochloride (OSH) containing nanocomposite was prepared by adopting cold method. Interaction between drug and polymers was studied using FTIR method, morphological investigation was carried out by optical and scanning electron microscopy method, and rheological study was performed employing rotational rheometer equipped with a cone/plate shear apparatus, gelation temperature by glass bottle method and ex vivo permeation study was performed with cylindrical glass diffusion cell. Skin irritation potential was measured using rat as a model animal. Results: The FTIR spectrum of the selected gel showed that there is shifting of O-H stretching vibration of a hydroxyl group from 3408.72 to 3360.49 cm-1 and appearance of a new band at 1083.01 cm-1. The spectrum of the selected gel also showed the absence of characteristic peaks of GO at 1625.49 cm- 1. This result indicated that there may be an interaction between OSH and GO and hydrogen bonding between XG and POL 407. The gelation temperature was found to be decreased with the increase in GO content from 14.1±1.21°C 13±0.97°C. SEM micrograph demonstrated the uniform dispersion and intercalation of GO sheets in the gel. All the gel formulations showed a pseudo-plastic flow. Ex vivo permeation study (for 24 hr) exhibited highest (6991.425 µg) and lowest (2133.262 µg) amount of drug release, for OG1 and OG5, respectively. This is attributed to an increase in viscosity which led to a decrease in drug permeation across the abdominal skin of rats. The OG1 formulation (without GO) showed the highest flux of 76.66 µg/cm2/h, permeability coefficient (Kp) of 5.111× 10-3 cm/h and enhancement ratio of 3.277 compared to OG5 containing highest amount (9% w/w) of GO. The selected gel was found to be physically stable and there was minimum irritation score. Conclusion: All the above results indicated that thermal gel containing nanocomposite sustained the drug release and can be considered as an alternative to the orally administered tablet of OSH.

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Preliminary Observations about the Ultrastructure of the Human Nail Plate Treated with Thioglycolic Acid

Archives of Dermatological Research ◽

10.1007/bf00517687 ◽

1968 ◽

Vol 231 (4) ◽

pp. 344-354 ◽

Cited By ~ 16

Author(s):

R. Caputo ◽

E. Dadati

Keyword(s):

Thioglycolic Acid ◽

Nail Plate ◽

Human Nail

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In vitro evaluation of the antifungal efficacy of poloxamer 407-based formulations in an infected nail plate model

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2016.01.082 ◽

2016 ◽

Vol 505 (1-2) ◽

pp. 20-23 ◽

Cited By ~ 3

Author(s):

Anja Täuber ◽

Christel C. Müller-Goymann

Keyword(s):

Nail Plate ◽

Poloxamer 407 ◽

Plate Model ◽

In Vitro Evaluation ◽

Antifungal Efficacy

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Potential of Naftifine Application for Transungual Delivery

Molecules ◽

10.3390/molecules25133043 ◽

2020 ◽

Vol 25 (13) ◽

pp. 3043

Author(s):

Indrė Šveikauskaitė ◽

Vitalis Briedis

Keyword(s):

Co2 Laser ◽

Structural Changes ◽

Thioglycolic Acid ◽

Drug Dose ◽

Control Group ◽

Skin Infections ◽

Fractional Co2 Laser ◽

Human Nail ◽

Transungual Delivery ◽

Physical And Chemical

Naftifine is used to treat fungal skin infections as it inhibits dermatophytes, which are the cause of onychomycosis. However, naftifine’s ability to permeate the human nail barrier has not been investigated, thus, the antimycotic potential is not clearly established. This work aims to evaluate the effect of penetration enhancing factors on the accumulation of naftifine hydrochloride through human nail clippings. Naftifine polymeric nail lacquers with Eudragit RL100 were developed as a suitable delivery system. Low penetration of naftifine into nail has been determined as less than 10% of applied drug dose accumulated in the nail layers. Incorporation of thioglycolic acid into formulations resulted in increased accumulation of antifungal agent in the nail layers by 100% compared with a control group. Salicylic acid did not effect naftifine accumulation in the human nail. The permeation of naftifine through the nail increased by threefold when the thioglycolic acid-containing formulation was applied and the nail was pretreated with a fractional CO2 laser. Structural changes of the nail barrier, induced by fractional CO2 laser, were visualized by microscopy. The results suggest, that naftifine nail penetration could be significantly increased when physical and chemical enhancing factors are applied.

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Rheological and Drug Delivery Characteristics of Poloxamer-Based Diclofenac Sodium Formulations for Chronic Wound Site Analgesia

Pharmaceutics ◽

10.3390/pharmaceutics12121214 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1214

Author(s):

Jackson Russo ◽

Jennifer Fiegel ◽

Nicole K. Brogden

Keyword(s):

Drug Delivery ◽

Chronic Wounds ◽

Chronic Wound ◽

Diclofenac Sodium ◽

Barrier Properties ◽

Poloxamer 407 ◽

Tape Stripping ◽

Gelation Temperature ◽

Wound Site ◽

Topical Dosage

Chronic wounds are a significant and growing health problem, and clinical treatment is often a painful experience. A topical dosage form would be optimal to treat this pain. Poloxamer 407, a thermosensitive polymer that is a liquid at low temperatures but gels at higher temperatures, is well suited to administer topical analgesics to chronic wound sites. The goal of this study was to evaluate the gelation and drug delivery properties of poloxamer 407 gels containing diclofenac sodium for potential use in chronic wound analgesic delivery. The gelation properties of poloxamer formulations were evaluated rheologically. Drug delivery properties of poloxamers loaded with diclofenac sodium were evaluated using snakeskin dialysis membranes, intact porcine ear skin, and porcine ear skin impaired via tape stripping. A commercial gel product and a solution of diclofenac sodium in water were used as control formulations. Poloxamer concentration and gelation temperature varied inversely, and the addition of higher concentrations of diclofenac sodium correlated to significant increases in poloxamer gelation temperature. Poloxamer solutions were effective in limiting the permeation of diclofenac sodium through membranes with impaired barrier properties, and delivery of diclofenac sodium from poloxamer 407 did not vary significantly from delivery observed from the commercial gel product. The amount of drug delivered in 24 h did not change significantly with changes in poloxamer 407 concentration. The results of this study indicate that poloxamer 407 may be a useful formulation component for administration of an analgesic product to a chronic wound site.

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Application of Thermosensitive Poloxamer-Based Hydrogel in the Development of Transdermal Therapy Containing Herbal Medicine

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.719.57 ◽

2016 ◽

Vol 719 ◽

pp. 57-61

Author(s):

Wen Yi Wang ◽

Patrick Chi Leung Hui ◽

Frency S.F. Ng ◽

Chi Wai Kan ◽

Clara B.S. Lau ◽

...

Keyword(s):

Skin Permeation ◽

Sol Gel ◽

Penetration Enhancers ◽

Poloxamer 407 ◽

Enhancement Effect ◽

Sol Gel Transition ◽

Model Drug ◽

Permeation Properties ◽

Selection Of ◽

Gel Transition

Poloxamer 407 exhibits remarkable reversible sol gel transition which makes it attractive and promising in the application of transdermal therapy. This study mainly reports the skin permeation properties of model drug from poloxamer 407 based transdermal hydrogel therapy with the presence of chemical penetration enhancers. Poloxamer 407 based hydrogel was shown porous structure which faciliates the diffusional release of model drug. Compared with borneol and 1,2-propanediol, azone was the most effective enhancer for gallic acid skin permeation, and 3% of azone presented the optimal enhancement effect. This study also demonstrated that the selection of enhancers is of great importance for the skin permeation of model drug.

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