Fabrication of Tizanidine Loaded Patches Using Flaxseed Oil and Coriander Oil as a Penetration Enhancer for Transdermal Delivery

Transdermal drug delivery is important to maintain plasma drug concentrations for therapeutic efficacy. The current study reports the design, formulation, and evaluation of tizanidine transdermal patches formulated using chitosan and thiolated chitosan, ethyl cellulose (EC), polyvinylpyrrolidone (PVP), and Eudragit RL100 in different ratios. The tizanidine patches were formulated using flaxseed oil and coriander oil in the concentrations of 1% v/w, 2% v/w, 3% v/w, 4% v/w, 5% v/w, and 10% v/w. The patches were subjected to characterization of physicochemical property (thickness, weight uniformity, drug content, efficiency, percentage moisture uptake/loss), in vitro drug release and drug permeation, skin irritation, in vivo application, pharmacokinetics analysis, and stability studies. The results indicate that the interaction of thiolated chitosan with the negative charges of the skin opens the tight junctions of the skin, whereas flaxseed and coriander oils change the conformational domain of the skin. The novelty of this study is in the use of flaxseed and coriander oils as skin permeation enhancers for the formulation of tizanidine transdermal patches. The formulations follow non-Fickian drug release kinetics. The FTZNE23, FTZNE36 and FTZNE54, with 5% v/w flaxseed oil loaded formulations, exhibited higher flux through rabbit skin compared with FTZNE30, FTZNE35, FTZNE42, and FTZNE47, formulations loaded with 10% v/w coriander oil. The study concludes that flaxseed oil is a better choice for formulating tizanidine patches, offering optimal plasma concentration and therapeutic efficacy, and recommends the use of flaxseed and coriander oil based patches as a novel transdermal delivery system for tizanidine and related classes of drugs.

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Allopurinol Loaded Transferosomes for the Alleviation of Symptomatic After-effects of Gout: An Account of Pharmaceutical Implications

Current Drug Therapy ◽

10.2174/1574885515666200120124214 ◽

2020 ◽

Vol 15 (4) ◽

pp. 404-419

Author(s):

Ruchi Tiwari ◽

Gaurav Tiwari ◽

Rachna Singh

Keyword(s):

Drug Release ◽

Zeta Potential ◽

Ex Vivo ◽

Release Kinetics ◽

Skin Permeation ◽

Skin Irritation ◽

In Vivo Studies ◽

Transdermal Drug Delivery System

Background: The present study assessed the transdermal potential of transferosomes loaded with allopurinol for the treatment of gout. Methods: Transferosomes of allopurinol were composed of different ratios of tween-80, soya lecithin and solvent using a thin-film hydration method. Transferosomes were characterized for Scanning Electron Microscopy (SEM), zeta potential, % entrapment efficiency (%EE), Fourier Transform Infrared Spectroscopy (FTIR), in-vitro drug release and kinetics as well as stability. Then, optimized formulation was incorporated in gel and evaluated for viscosity, pH, extrudability, homogeneity, skin irritation study, spreadability, ex vivo skin permeation study, flux, and stability. Results: SEM studies suggested that vesicles were spherical and zeta potential were in the range of -11.4 mV to -29.6 mV and %EE was 52.4- 83.87%. FTIR study revealed that there was no interaction between allopurinol and excipients during the preparation of transferosomes. The cumulative percentage of drug release from various transferosomes was ranged from 51.87 to 81.87%. A transferosomal gel of F8 formulation was prepared using dispersion method reported pseudoplastic rheological behavior, optimum pH, spreadability and maximum drug permeation i.e. 79.84% with flux 13.06 g/cm2/hr, followed zero-order release kinetics. Irritation and in-vivo studies of optimized transferosomal gel G8 on rabbits revealed better results than the standard allopurinol. Conclusion: This research suggested that allopurinol loaded transferosomal gel can be potentially used as a transdermal drug delivery system for the treatment of gout.

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DESIGN, FORMULATION AND IN VITRO DRUG RELEASE FROM TRANSDERMAL PATCHES CONTAINING IMIPRAMINE HYDROCHLORIDE AS MODEL DRUG

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i6.16851 ◽

2017 ◽

Vol 9 (6) ◽

pp. 220 ◽

Cited By ~ 1

Author(s):

Swati Hardainiyan ◽

Krishan Kumar ◽

Bankim Chandra Nandy ◽

Richa Saxena

Keyword(s):

Drug Release ◽

Release Kinetics ◽

Skin Permeation ◽

Solvent Evaporation ◽

Hydrophilic Polymer ◽

In Vitro Drug Release ◽

Matrix Type ◽

Transdermal Patches ◽

Imipramine Hydrochloride

Objective: The aim of the present investigation was to form matrix type transdermal patches containing imipramine hydrochloride were prepared using two polymers by solvent evaporation technique to minimise the dose of the drug for lesser side effect and increase the bioavailability of a drug.Methods: In the present study, drug loaded matrix type transdermal films of imipramine hydrochloride were prepared by the solvent evaporation method with the help of polymers along with polyethene glycol (PEG) 400 was used as plasticizer and dimethyl sulfoxide (DMSO) was used as penetration enhancer. Drug-polymer interactions determine by FTIR and a standard calibration curve of imipramine hydrochloride was determined by using UV estimation.Results: The formulated transdermal patch by using PVP K-30, HPMC K100M showed good physical properties. All prepared formulations indicated good physical stability. The formulation F-1 gave the most suitable transdermal film with all desirable physicochemical properties. The thickness of the patches was varied from 0.263±0.67 mm to 0.301±0.61 mm, uniformity of patches showed that patches prepared by solvent evaporation while low standard deviation values ensued by thickness measurements of the film, and weights ranged between 50.5±0.75 mg and 52.15±2.15 mg, which indicates that different batches patch weights, were comparatively similar. Folding endurance was found to be>200 that is satisfactory for the patches, drug content was found to be 5.33±0.14 mg to 5.57±0.095 mg. In vitro, drug permeation studies of formulations were performed by using K-C diffusion cells using abdomen skin of the albino rat. The results were best in in-vitro skin permeation through rat skin as compared to all other formulations prepared with a hydrophilic polymer containing permeation enhancer. The formulation, F1 is considered as the best formulation, since it shows maximum in vitro drug release as 84.71±3.07 % at 24 h. The drug release kinetics studies showed that the majority of formulations were governed by Higuchi model and mechanism of release was non-Fickian mediated.Conclusion: In conclusion, controlled release transdermal drug delivery system (TDDS) patches of imipramine hydrochloride can be prepared using the polymer combinations, with plasticizer and enhancer. The release rate of drug through patched increased simultaneously as the concentration of hydrophilic polymer was increased. However, the mechanism of drug release of all formulations was non-Fickian. The properties of a film did not change during the period of study.

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COMPARATIVE EVALUATION OF SELECTED POLYMERS AND PLASTICIZER ON TRANSDERMAL DRUG DELIVERY SYSTEM

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i1.21960 ◽

2018 ◽

Vol 10 (1) ◽

pp. 67

Author(s):

Bhawana Sethi ◽

Rupa Mazumder

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Propylene Glycol ◽

Drug Delivery System ◽

Transdermal Drug Delivery ◽

Release Kinetics ◽

Content Uniformity ◽

Transdermal Drug Delivery System ◽

Transdermal Patches

Objective: The present work was aimed at preparation of transdermal patches by a solvent casting method using a varying concentration of polymers i.e. methocel (K15 and K100), ethocel (4 and 10), gelatin, chitosan, eudragit (RL and RS) grade using plasticizer (glycerin and propylene glycol).Methods: The ratio of drug to polymers and plasticizer was varied and the effect of formulation variables was studied. Prepared transdermal patches were evaluated for physicochemical properties, in-vitro permeation studies, content uniformity, primary skin irritation studies and FT-IR studies.Results: The formulated transdermal patch by using Methocel K 100 M showed good physical properties. The average weight of patches prepared using glycerin as a plasticizer were ranged from 42.33-67.00 mg and propylene glycol as a plasticizer were ranged from 40.67-67.67 mg. The percentage moisture absorption varies from 1.76 to 10.73 for patches formulated using glycerin and 2.28 to 7.97 for propylene glycol patches. The percentage moisture loss from patches prepared using glycerin was ranged from 2.75 to 11.54 and 2.87 to 12.02 from propylene glycol. The water vapour transmission rate from patches prepared using glycerin was ranged from 0.25 to 0.92 and 0.41 to 1.76. The formulated patch showed the acceptable quantity of medicament ranged from (100.20-101.05%). This result met the test content uniformity as per BP (85% to 115%). According to that, the drug was consistent throughout the patches. The formulation PGD is considered as the best formulation, since it shows a maximum in vitro drug release as 43.75 % at 24 h. The drug release kinetics studied showed that the majority of formulations was following zero order.Conclusion: In conclusion, controlled release transdermal drug delivery system patches of aliskiren can be prepared using polymer combinations, with a different plasticizer. The release rate of drug depends upon the polymer. However, release kinetics followed zero order.

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DESIGN AND CHARACTERISATION OF TRANSDERMAL PATCHES OF PHENFORMIN HYDROCHLORIDE

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2017v9i6.23437 ◽

2017 ◽

Vol 9 (6) ◽

pp. 90

Author(s):

Pratik Swarup Das ◽

Puja Saha

Keyword(s):

Drug Release ◽

Diffusion Mechanism ◽

Skin Irritation ◽

In Vitro Release ◽

Chemical Properties ◽

In Vitro Dissolution ◽

Release Mechanism ◽

Transdermal Patches ◽

The Matrix

Objective: In present work was designed to develop suitable transdermal matrix patches of Phenformin hydrochloride using various hydrophilic (HPMC) and hydrophobic (EUDRAGID) polymers as matrix formers.Methods: Transdermal patches containing Phenformin hydrochloride were prepared by the solvent casting evaporation technique.Results: Revealed that prepared patches showed good physical characteristics, no drug-polymer interaction and no skin irritation was observed. The in vitro release study revealed that F3 formulation showed maximum release in 24 h. Formulation F3 was subjected for accelerated stability studies. The F3 formulation was found to be stable as there was no drastic change in the Physico-chemical properties of the patches, which was also confirmed by FTIR.Conclusion: Thus conclusion can be made that stable transdermal patches of Phenformin hydrochloride has been developed. F1, F2, F3, F4 formulations showed highest cumulative percentage drug release of 98.13%, 95.50%, 98.65%, 97.21% were obtained during in vitro drug release studies after 24 h. The release of Phenformin hydrochloride appears to be dependent on lipophilicity of the matrix. Moderately lipophillic matrices showed best release. The predominant release mechanism of drug through the fabricated matrices was believed to be by diffusion mechanism. Based upon the in vitro dissolution data the F3 formulation was concluded as optimized formulation.

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Development and Evaluations of Transdermally Delivered Luteolin Loaded Cationic Nanoemulsion: In Vitro and Ex Vivo Evaluations

Pharmaceutics ◽

10.3390/pharmaceutics13081218 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1218

Author(s):

Mohammad A. Altamimi ◽

Afzal Hussain ◽

Sultan Alshehri ◽

Syed Sarim Imam ◽

Usamah Abdulrahman Alnemer

Keyword(s):

Drug Release ◽

Zeta Potential ◽

Transdermal Delivery ◽

Ex Vivo ◽

Skin Permeation ◽

Oral Drug ◽

In Vitro Drug Release ◽

Drug Deposition ◽

Drug Content

Introduction: Luteolin (LUT) is natural flavonoid with multiple therapeutic potentials and is explored for transdermal delivery using a nanocarrier system. LUT loaded cationic nanoemulsions (CNE1–CNE9) using bergamot oil (BO) were developed, optimized, and characterized in terms of in vitro and ex vivo parameters for improved permeation. Materials and methods: The solubility study of LUT was carried out in selected excipients, namely BO, cremophor EL (CEL as surfactant), labrasol (LAB), and oleylamine (OA as cationic charge inducer). Formulations were characterized with globular size, polydispersity index (PDI), zeta potential, pH, and thermodynamic stability studies. The optimized formulation (CNE4) was selected for comparative investigations (% transmittance as %T, morphology, chemical compatibility, drug content, in vitro % drug release, ex vivo skin permeation, and drug deposition, DD) against ANE4 (anionic nanoemulsion for comparison) and drug suspension (DS). Results: Formulations such as CNE1–CNE9 and ANE4 (except CNE6 and CNE8) were found to be stable. The optimized CNE4 based on the lowest value of globular size (112 nm), minimum PDI (0.15), and optimum zeta potential (+26 mV) was selected for comparative assessment against ANE4 and DS. The %T values of CNE1–CNE9 were found to be ˃95% and CEL content slightly improved the %T value. The spherical CNE4 was compatible with excipients and showed % total drug content in the range of 97.9–99.7%. In vitro drug release values from CNE4 and ANE4 were significantly higher than DS. Moreover, permeation flux (138.82 ± 8.4 µg/cm2·h), enhancement ratio (8.23), and DD (10.98%) were remarkably higher than DS. Thus, ex vivo parameters were relatively high as compared to DS which may be attributed to nanonization, surfactant-mediated reversible changes in skin lipid matrix, and electrostatic interaction of nanoglobules with the cellular surface. Conclusion: Transdermal delivery of LUT can be a suitable alternative to oral drug delivery for augmented skin permeation and drug deposition.

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Lipid Nanocapsules for Intracellular Drug Delivery of Anticancer Drugs

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2007.18114 ◽

2007 ◽

Vol 7 (12) ◽

pp. 4612-4617 ◽

Cited By ~ 33

Author(s):

Franck Lacoeuille ◽

Emmanuel Garcion ◽

Jean-Pierre Benoit ◽

Alf Lamprecht

Keyword(s):

Drug Delivery ◽

Cell Culture ◽

Drug Release ◽

Anticancer Drugs ◽

Cancer Cell ◽

Release Kinetics ◽

Laser Scanning Microscopy ◽

Lipid Nanocapsules ◽

Intracellular Drug Delivery ◽

Drug Concentrations

As non-phagocytic eukaryotic cells can internalize particles <1 μm in size, small size (25 to 110 nm) lipid nanocapsules (LNC) are proposed for the intracellular drug delivery of anticancer drugs to cancer cells. LNC ofdifferent diameters were loaded with etoposide or paclitaxel and subsequently tested for drug release kinetics and their efficiency to reduce cancer cell growth in cell culture. Relative high drug loads could be achieved and sustained drug release can be provided over a period ofseveral days (etoposide) up to a few weeks (paclitaxel). While particle size exhibited only minor influences on the release kinetics, higher initial drug load led to a distinctly lower burst release. In a cancer cell culture model, etoposide or paclitaxel LNC showed a 4-fold or 40-fold higher efficiency, respectively than the drug solution while blank LNC were found to be less toxic than the pure drug at equivalent concentrations. The uptake and intracellular accumulation ofLNC was confirmed by confocal laser scanning microscopy after fluorescence labeling of the nanocarriers. This nanoparticulate system is able to achieve efficient intracellular drug concentrations and seems to be therefore a promising therapeutic approach in cancer treatment.

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Drug-Loaded Hydrogels for Intraocular Lenses with Prophylactic Action against Pseudophakic Cystoid Macular Edema

Pharmaceutics ◽

10.3390/pharmaceutics13070976 ◽

2021 ◽

Vol 13 (7) ◽

pp. 976

Author(s):

Nadia Toffoletto ◽

Madalena Salema-Oom ◽

Soledad Anguiano Igea ◽

Carmen Alvarez-Lorenzo ◽

Benilde Saramago ◽

...

Keyword(s):

Drug Release ◽

Cataract Surgery ◽

Macular Edema ◽

Cystoid Macular Edema ◽

Release Kinetics ◽

Drug Loading ◽

In Vitro Release ◽

Intraocular Lenses ◽

Therapeutic Drug ◽

Drug Concentrations

Pseudophakic cystoid macular edema (PCME), caused by chronic inflammation, is the most common cause of visual impairment in the medium-term after cataract surgery. Therefore, the prophylactic topical administration of combined steroidal and non-steroidal anti-inflammatory drugs is commonly done. Drug-eluting intraocular lenses (IOLs) gained interest as an efficient way to overcome the compliance issues related to the use of ocular drops without the need for additional surgical steps. The incorporation of functional monomers and molecular imprinting were herein applied to design hydrogels suitable as IOLs and able to co-deliver steroidal (dexamethasone sodium phosphate) and non-steroidal (bromfenac sodium) drugs. The incorporation of N-(2-aminopropyl) methacrylamide (APMA) increased the drug uptake and improved the in vitro release kinetics. Imprinting with bromfenac resulted in a decreased drug release due to permanent drug bonding, while imprinting with dexamethasone increased the amount of dexamethasone released after dual-drug loading. The application of a mathematical model to predict the in vivo drug release behavior suggests the feasibility of achieving therapeutic drug concentrations of bromfenac and dexamethasone in the aqueous humor for about 2 and 8 weeks, respectively, which is compatible with the current topical prophylaxis after cataract surgery.

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Olive Oil Based Methotrexate Loaded Topical Nanoemulsion Gel for the Treatment of Imiquimod Induced Psoriasis-Like Skin Inflammation in an Animal Model

Biology ◽

10.3390/biology10111121 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1121

Author(s):

Sheikh Abdur Rashid ◽

Sajid Bashir ◽

Faiza Naseem ◽

Arshad Farid ◽

Irfan A. Rather ◽

...

Keyword(s):

Drug Release ◽

Olive Oil ◽

Release Kinetics ◽

Skin Permeation ◽

Physicochemical Characterization ◽

Entrapment Efficiency ◽

Tween 80 ◽

Penetration Enhancers ◽

Nanoemulsion Gel

Psoriasis, a chronic inflammatory illness, is on the rise and is linked to several other life-threatening diseases. The primary goal of this study was to create a nanoemulsion gel loaded with methotrexate and olive oil (MTX NEG). The formulation was evaluated for physicochemical characterization, entrapment efficiency, drug release kinetics, skin permeation studies and stability tests. In addition, the efficacy of MTX NEG against psoriasis was tested using imiquimod-induced psoriasis in a rat model. The final optimized MTX NEG was developed with a particle size of 202.6 ± 11.59 nm and a PDI of 0.233 ± 0.01, with a 76.57% ± 2.48% average entrapment efficiency. After 20 h, the release kinetics predicted a 72.47% drug release at pH 5.5. FTIR findings demonstrated that the optimized MTX NEG formulation effectively fluidized both the epidermis and dermis of the skin, potentially increasing drug permeability and retention. The application of Tween 80 and PEG 400, on the other hand, significantly enhanced these effects, as these are well known penetration enhancers. After 24 h, an average of 70.78 ± 5.8 μg/cm2 of methotrexate was permeated from the nanoemulsion gel with a flux value of 2.078 ± 0.42 μg/cm2/h, according to permeation measurements. Finally, in vivo experiments on rabbit skin revealed that the increased skin penetration of methotrexate-loaded nanoemulsion gel was not due to structural alterations in intercellular lipid layers in the stratum corneum. In vivo antipsoriatic studies on rats revealed that MTX NEG produced a PASI decrease that was extremely similar and even better than the 91% reduction seen in the MTX tablet group. According to the pharmacokinetic profile, Cmax was 8.5 μg/mL, Tmax was 12 h, and t1/2 was 15.5 ± 2.37 h. These findings reinforce that MTX-NEG based on olive oil could be a possible treatment for psoriasis and could decrease the remission of psoriasis-like symptoms.

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Design and Development of Propranolol Hydrochloride Transdermal Patches: In Vitro and Ex Vivo Characterization

Pharmaceutics and Pharmacology Research ◽

10.31579/2693-7247/007 ◽

2020 ◽

Vol 3 (1) ◽

pp. 01-08

Author(s):

Chinthakindi Shravya

Keyword(s):

Drug Release ◽

Moisture Absorption ◽

Ex Vivo ◽

Skin Permeation ◽

Diffusion Mechanism ◽

Propranolol Hydrochloride ◽

Matrix Type ◽

Transdermal Patches ◽

Percent Moisture

The main aim of this investigation is to design and develop matrix type transdermal patches of Propranolol Hydrochloride which is an anti-hypertensive drug. These matrix type transdermal patches were prepared by “Solvent Casting Technique” using drug, HPMC E15 and Eudragit L 100 in the ratio of 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5. All formulations carried 20%v/w of PEG-600 as plasticizer. The prepared patches were characterized for various physicochemical parameters like weight, thickness, folding endurance, drug content, percent moisture content, percent moisture absorption, in vitro drug release and ex vivo permeation. Among this 1:9 ratio was found to be an Optimized formulation and patches were prepared by using permeation enhancers (lemon grass oil, Eucalyptus oil, and clove oil). The cumulative amount of drug release in 12hrs for F7 formulation showed maximum and used for that formulation skin permeation on Goat abdominal skin. FTIR studies show no interaction between drug, polymer and other excipients. The drug permeation kinetics followed “First order” and “zero order” profile with diffusion mechanism.

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Formulation and Evaluation of DHA Oil based Nicotinamide Nanoemulsion Gel for Treating Atopic Dermatitis

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681210666200210115526 ◽

2020 ◽

Vol 10 (6) ◽

pp. 892-901

Author(s):

Gayathri P. Pradeep ◽

Vidya Viswanad

Keyword(s):

Drug Release ◽

Cell Line ◽

Skin Permeation ◽

Skin Irritation ◽

In Vitro Drug Release ◽

Release Studies ◽

Nanoemulsion Gel ◽

Permeation Studies ◽

Franz Diffusion Cells

Background: Atopic dermatitis (or eczema) can be defined as a chronic inflammatory condition accompanied by severe pruritus. Objective: The prepared gel was evaluated for in vitro drug release, in vitro occlusion studies, transepidermal water loss studies, skin permeation studies, in vitro skin irritation studies and antiinflammatory cell line studies. Methods: In vitro drug release studies were performed using Franz diffusion cells. The in vitro occlusion studies were carried out by the procedure reported by Wissing et al. TEWL determination was done by the method proposed by Reiger. The skin permeation studies were carried out using porcine skin using Franz diffusion cells. In vitro skin irritation study was carried out using HETCAM (Hen’s Egg Test on the Chorioallantoic Membrane) method. Anti-inflammatory cell line studies were carried out using RAW 264.7 cell lines. Results: In vitro drug release studies,drug release of nicotinamide from nanoemulsion gel was found to be more than marketed gel. Kinetic modelling showed a higuchi model with non-fickian diffusion. In vitro occlusion study showed the percentage of evaporated water from prepared nanoemulsion formulation after 72 h is very less compared with the other formulations. The TEWL measurement shows the reduction in TEWL has more in prepared nanoemulsion gel than other formulations. Anti-inflammatory cell line studies proved that the nanoemulsion gel has inhibition capacity on COX activity, LOX activity, Inducibe nitric oxide synthase and cellular nitrate levels. Conclusion: DHA oil based nicotinamidenanoemulsion gel were prepared successfully and the evaluation of prepared gel showed better drug release and skin permeation with better antiinflammatory activity.

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