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

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.

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

Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3376
Author(s):  
Kamran Hidayat Ullah ◽  
Faisal Raza ◽  
Syed Mohsin Munawar ◽  
Muhammad Sohail ◽  
Hajra Zafar ◽  
...  
Keyword(s):  
Thioglycolic Acid ◽  
Drug Loading ◽  
Nail Plate ◽  
Gel Strength ◽  
Penetration Enhancer ◽  
Poloxamer 407 ◽  
Enhancement Effect ◽  
Hydrophobic Drugs ◽  
Gelation Temperature ◽  
Transungual Delivery

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.

scholarly journals Polishing the Therapy of Onychomycosis Induced by Candida spp.: Amphotericin B–Loaded Nail Lacquer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 784
Author(s):  
Aleph M. S. Souza ◽  
Renato C. A. Ribeiro ◽  
Gleyse K. L. O. Pinheiro ◽  
Francisco I. Pinheiro ◽  
Wógenes N. Oliveira ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Ex Vivo ◽  
Drug Loading ◽  
Drug Bioavailability ◽  
Candida Spp ◽  
Drying Time ◽  
Analytical Method Validation ◽  
Nail Lacquer ◽  
In Vitro Adhesion

Onychomycosis induced by Candida spp. has several limitations regarding its treatment. Nail lacquers display the potential to overcome these drawbacks by providing therapeutic compliance and increasing local drug bioavailability. Thus, this work aimed to produce a nail lacquer loaded with Amphotericin B (AmB) and evaluate its performance. The AmB-loaded nail lacquer was produced and preliminarily characterized. An AmB quantification method was developed. Stability, drug release, permeability and anti-Candida activity assays were conducted. The analytical method validation met the acceptance criteria. The drug loading efficiency was 100% (0.02 mg/g of total product), whereas the AmB stability was limited to ≅ 7 days (≅ 90% remaining). The nail lacquer displayed a drying time of 187 s, non-volatile content of around 20%w/w, water-resistance of approximately 2%w/w of weight loss and satisfactory in vitro adhesion. Moreover, the in vitro antifungal activity against different Candida spp. strains was confirmed. The AmB release and the ex vivo permeability studies revealed that AmB leaves the lacquer and permeates the nail matrix in 47.76 ± 0.07% over 24 h. In conclusion, AmB-loaded nail lacquer shows itself as a promising extemporaneous dosage form with remarkable anti-Candida activity related to onychomycosis.

Nanostructured Lipid Carriers for Intranasal Administration of Olanzapine in the management of Schizophrenia

2021 ◽  
Vol 14 ◽  
Author(s):  
Sarbjot Kaur ◽  
Ujjwal Nautiyal ◽  
Pooja A. Chawla ◽  
Viney Chawla
Keyword(s):  
Drug Delivery ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Nanostructured Lipid Carriers ◽  
Polydispersity Index ◽  
Poloxamer 407 ◽  
Ex Vivo Permeation ◽  
Permeation Studies ◽  
Vitro Release

Background: Background: Olanzapine belongs to a new class of dual spectrum antipsychotic agents. It is known to show promise in managing both the positive and negative symptoms of schizophrenia. Drug delivery systems based on nanostructured lipid carriers (NLC) are expected to provide rapid nose-to-brain transport of this drug and improved distribution into and within the brain. Objective: The present study deals with the preparation and evaluation of olanzapine loaded NLC via the intranasal route for schizophrenia. Methods: Olanzapine-NLC were formulated through the solvent injection method using isopropyl alcohol as the solvent, stearic acid as solid lipid, and oleic acid as liquid lipid, chitosan as a coating agent, and Poloxamer 407 as a surfactant. NLC were characterized for particle size, polydispersity index, entrapment efficiency, pH, viscosity, X-ray diffraction studies, in-vitro mucoadhesion study, in- vitro release and ex-vivo permeation studies. The shape and surface morphology of the prepared NLC was determined through transmission electron microscopy. To detect the interaction of the drug with carriers, compatibility studies were also carried out. Results: Average size and polydispersity index of developed formulation S6 was 227.0±6.3 nm and 0.460 respectively. The encapsulation efficiency of formulation S6 was found to be 87.25 %. The pH, viscosity, in-vitro mucoadhesion study, and in- vitro release of optimized olanzapine loaded NLC were recorded as 5.7 ± 0.05, 78 centipoise, 15±2 min, and 91.96 % respectively. In ex-vivo permeation studies, the percent drug permeated after 210 min was found to be 84.03%. Conclusion: These results reveal potential application of novel olanzapine-NLC in intranasal drug delivery system for treatment of schizophrenia.

scholarly journals Polyurethanes as New Excipients in Nail Therapeutics

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 276 ◽  
Author(s):  
Barbara Valdes ◽  
Ana Serro ◽  
Joana Marto ◽  
Rui Galhano dos Santos ◽  
Elena Cutrín Gómez ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Polymer Concentration ◽  
In Vitro Release ◽  
Nail Plate ◽  
Oral Drugs ◽  
Terbinafine Hydrochloride ◽  
Nail Lacquer ◽  
Nail Infection ◽  
Vitro Release

Onychomycosis affects about 15% of the population. This disease causes physical and psychosocial discomfort to infected patients. Topical treatment (creams, solutions, gels, colloidal carriers, and nail lacquers) is usually the most commonly required due to the high toxicity of oral drugs. Currently, the most common topical formulations (creams and lotions) present a low drug delivery to the nail infection. Nail lacquers appear to increase drug delivery and simultaneously improve the effectiveness of treatment with increased patient compliance. These formulations leave a polymer film on the nail plate after solvent evaporation. The duration of the film residence in the nail constitutes an important property of nail lacquer formulation. In this study, a polyurethane polymer was used to delivery antifungals drugs, such as terbinafine hydrochloride (TH) and ciclopirox olamine (CPX) and the influence of its concentration on the properties of nail lacquer formulations was assessed. The nail lacquer containing the lowest polymer concentration (10%) was the most effective regarding the in vitro release, permeation, and antifungal activity. It has also been demonstrated that the application of PU-based nail lacquer improves the nail plate, making it smooth and uniform and reduces the porosity contributing to the greater effectiveness of these vehicles. To conclude, the use of polyurethane in nail formulations is promising for nail therapeutics.

scholarly journals Constant Voltage Iontophoresis Technique to Deliver Terbinafine via Transungual Delivery System: Formulation Optimization Using Box–Behnken Design and In Vitro Evaluation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1692
Author(s):  
Anroop B. Nair ◽  
Bandar E. Al-Dhubiab ◽  
Jigar Shah ◽  
Bapi Gorain ◽  
Shery Jacob ◽  
...  
Keyword(s):  
Low Voltage ◽  
Ex Vivo ◽  
Topical Therapy ◽  
Nail Plate ◽  
Drug Accumulation ◽  
Constant Voltage ◽  
Box Behnken Design ◽  
Ex Vivo Permeation ◽  
Transungual Delivery

Topical therapy of antifungals is primarily restricted due to the low innate transport of drugs through the thick multi-layered keratinized nail plate. The objective of this investigation was to develop a gel formulation, and to optimize and evaluate the transungual delivery of terbinafine using the constant voltage iontophoresis technique. Statistical analysis was performed using Box–Behnken design to optimize the transungual delivery of terbinafine by examining crucial variables namely concentration of polyethylene glycol, voltage, and duration of application (2–6 h). Optimization data in batches (F1–F17) demonstrated that chemical enhancer, applied voltage, and application time have influenced terbinafine nail delivery. Higher ex vivo permeation and drug accumulation into the nail tissue were noticed in the optimized batch (F8) when compared with other batches (F1–F17). A greater amount of terbinafine was released across the nails when the drug was accumulated by iontophoresis than the passive counterpart. A remarkably higher zone of inhibition was observed in nails with greater drug accumulation due to iontophoresis, as compared to the passive process. The results here demonstrate that the optimized formulation with low voltage iontophoresis could be a viable and alternative tool in the transungual delivery of terbinafine, which in turn could improve the success rate of topical nail therapy in onychomycosis.

scholarly journals Onychomycosis: Potential of Nail Lacquers in Transungual Delivery of Antifungals

Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Nida Akhtar ◽  
Hemlata Sharma ◽  
Kamla Pathak
Keyword(s):  
Clinical Trials ◽  
Fungal Infection ◽  
Topical Application ◽  
Antifungal Agents ◽  
Nail Plate ◽  
Safety And Efficacy ◽  
Nail Bed ◽  
Nail Lacquer ◽  
Transungual Delivery ◽  
Toe Nails

Onychomycosis constitutes the most common fungal infection of the nail (skin beneath the nail bed) that affects the finger as well as toe nails. It is an infection that is initiated by yeasts, dermatophytes, and nondermatophyte molds. Nail lacquers are topical solutions intended only for use on fingernails as well as toenails and have been found to be useful in the treatment of onychomycosis. Thus, in the present review an attempt has been made to focus on the treatment aspects of onychomycosis and the ungual delivery of antifungals via nail lacquer. Several patents issued on nail lacquer till date have also been discussed. Penetration efficiency was assessed by several researchers across the human nail plate to investigate the potentiality of nail lacquer based formulations. Various clinical trials have also been conducted in order to evaluate the safety and efficacy of nail lacquers in delivering antifungal agents. Thus, it can be concluded that nail lacquer based preparations are efficacious and stable formulations. These possess tremendous potential for clinical topical application to the nail bed in the treatment of onychomycosis.

scholarly journals Effect of Film-Forming Polymers on Release of Naftifine Hydrochloride from Nail Lacquers

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Indrė Šveikauskaitė ◽  
Vitalis Briedis
Keyword(s):  
Ethyl Cellulose ◽  
Topical Therapy ◽  
Active Pharmaceutical Ingredient ◽  
Drying Time ◽  
Nail Lacquer ◽  
Film Forming ◽  
Ft Ir ◽  
Transungual Delivery ◽  
Further Development

The successful topical therapy of onychomycosis depends on effective drug release and penetration into nail, which can be achieved by using an adequately developed delivery system. This study evaluated and compared effect of film-forming polymers Eudragit RL100, Eudragit RS100, and ethyl cellulose on naftifine hydrochloride release from experimental nail lacquer formulations. Quality of formulations was evaluated by determining drying time and water resistance. Interactions between active pharmaceutical ingredient and excipients were investigated using microcalorimetry and FT-IR. Optimization of nail lacquer formulations was performed by naftifine hydrochloride release testing. Release of naftifine hydrochloride increased with increasing concentration of Eudragit RL100. Plasticizer triacetin affected the release of naftifine hydrochloride, when Eudragit RS100 polymer was used. Ethyl cellulose polymer was determined to be not applicable for naftifine hydrochloride nail lacquer formulations. Two compositions of nail lacquers were optimized and could be used in further development of transungual delivery systems.

scholarly journals Effect on Nail Structure and Transungual Permeability of the Ethanol and Poloxamer Ratio from Cyclodextrin-Soluble Polypseudorotaxanes Based Nail Lacquer

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 156 ◽  
Author(s):  
Elena Cutrín-Gómez ◽  
Soledad Anguiano-Igea ◽  
M. Delgado-Charro ◽  
José Gómez-Amoza ◽  
Francisco Otero-Espinar
Keyword(s):  
Film Formation ◽  
Aqueous Dispersion ◽  
High Water ◽  
Clobetasol Propionate ◽  
Poloxamer 407 ◽  
High Water Content ◽  
Adhesive Properties ◽  
Drug Permeation ◽  
Nail Lacquer ◽  
Transungual Delivery

Aqueous-based nail lacquers have shown potential in promoting the diffusion of drugs into the nail. In our laboratory, we have recently developed a transungual delivery system based on an aqueous dispersion of cyclodextrin-poloxamer soluble polypseudorotaxanes, supramolecular host−guest assemblies that improves the drug permeation into the nail. However, the high-water content and the rheological and adhesive properties of this lacquer negatively affect properties that play a fundamental role in the patients’ acceptance such as stickiness, nail film formation or drying rate, properties. In this work, we have optimized the composition of these lacquers to improve these properties whilst maintaining good drug permeation profiles. Incorporating ethanol into the vehicle and reducing the proportion of Poloxamer 407 (PL), provided a good strategy. The use of hydro-ethanolic mixtures (>50% ethanol) and the reduction of the poloxamer concentration significantly improved the lacquer drying speed by reducing the stickiness and promoting film formation on the nail surface. Additionally, in a surprising way, the use of hydro-ethanolic vehicles further enhanced the permeation of ciclopirox olamine and clobetasol propionate, used for the treatment of onychomycosis and nail psoriasis respectively, into the nail and hooves.

scholarly journals A Needle-Free Jet Injection System for Controlled Release and Repeated Biopharmaceutical Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1770
Author(s):  
Mojiz Abbas Trimzi ◽  
Young-Bog Ham
Keyword(s):  
Drug Delivery ◽  
Ex Vivo ◽  
Compressed Air ◽  
High Rate ◽  
Disease Spread ◽  
Injection System ◽  
Liquid Jet ◽  
Hydraulic Circuit ◽  
Jet Injection ◽  
Free Jet

Swift vaccination is necessary as a response to disease outbreaks and pandemics; otherwise, the species under attack is at risk of a high fatality rate or even mass extinction. Statistics suggest that at least 16 billion injections are administered worldwide every year. Such a high rate of needle/syringe injection administration worldwide is alarming due to the risk of needle-stick injuries, disease spread due to cross-contamination and the reuse of needles, and the misuse of needles. In addition, there are production, handling, and disposal costs. Needle phobia is an additional issue faced by many recipients of injections with needles. In addition to a detailed literature review highlighting the need for needle-free injection systems, a compressed air-driven needle-free jet injection system with a hydro-pneumatic mechanism was designed and developed by employing an axiomatic design approach. The proposed injection system has higher flexibility, uninterrupted force generation, and provides the possibility of delivering repeated injections at different tissue depths from the dermis to the muscle (depending on the drug delivery requirements) by controlling the inlet compressed air pressure. The designed needle-free jet injector consists of two primary circuits: the pneumatic and the hydraulic circuit. The pneumatic circuit is responsible for driving, pressurizing, and repeatability. The hydraulic circuit precisely injects and contains the liquid jet, allowing us to control the volume of the liquid jet at elevated pressure by offering flexibility in the dose volume per injection. Finally, in this paper we report on the successful design and working model of an air-driven needle-free jet injector for 0.2–0.5 mL drug delivery by ex vivo experimental validation.

Functionally Tailored Electro-Sensitive Poly(Acrylamide)-g-Pectin Copolymer Hydrogel for Transdermal Drug Delivery Application: Synthesis, Characterization, In-vitro and Ex-vivo Evaluation

2020 ◽  
Vol 10 (3) ◽  
pp. 185-196
Author(s):  
Sudha B. Patil ◽  
Syed Z. Inamdar ◽  
Kakarla R. Reddy ◽  
Anjanapura V. Raghu ◽  
Krishnamachari G. Akamanchi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Transdermal Drug Delivery ◽  
Ex Vivo ◽  
Transmission Rate ◽  
Electric Signal ◽  
Poly Vinyl Alcohol ◽  
Electric Stimulus ◽  
Copolymer Hydrogel ◽  
Transdermal Drug Delivery Systems

Background and Objectives: To develop electro-sensitive transdermal drug delivery systems (ETDDS) using polyacrylamide-grafted-pectin (PAAm-g-PCT) copolymer hydrogel for rivastigmine delivery. Methods: Free radical polymerization and alkaline hydrolysis technique was employed to synthesize PAAm-g-PCT copolymer hydrogel. The PAAm-g-PCT copolymeric hydrogel was used as a reservoir and cross-linked blend films of PCT and poly(vinyl alcohol) as rate-controlling membranes (RCMs) to prepare ETDDS. Results: The pH of the hydrogel reservoir was found to be in the range of 6.81 to 6.93 and drug content was 89.05 to 96.29%. The thickness of RCMs was in the range of 51 to 99 μ and RCMs showed permeability behavior against water vapors. There was a reduction in the water vapor transmission rate as the glutaraldehyde (GA) concentration was increased. The drug permeation rate from the ETDDS was enhanced under the influence of electric stimulus against the absence of an electric stimulus. The increase in flux by 1.5 fold was recorded with applied electric stimulus. The reduction in drug permeability observed when the concentration of GA was increased. Whereas, the permeability of the drug was augmented as an electric current was changed from 2 to 8 mA. The pulsatile drug release under “on– off” cycle of electric stimulus witnessed a faster drug release under ‘on’ condition and it was slow under ‘off’ condition. The alteration in skin composition after electrical stimulation was confirmed through histopathology studies. Conclusion: The PAAm-g-PCT copolymer hydrogel is a useful carrier for transdermal drug delivery activated by an electric signal to provide on-demand release of rivastigmine.

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