scholarly journals Biopharmaceutical Development of a Bifonazole Multiple Emulsion for Enhanced Epidermal Delivery

Pharmaceutics ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 66 ◽  
Author(s):  
Joaquim Suñer-Carbó ◽  
Ana Calpena-Campmany ◽  
Lyda Halbaut-Bellowa ◽  
Beatriz Clares-Naveros ◽  
María Rodriguez-Lagunas ◽  
...  
Keyword(s):  
Water Solubility ◽  
Histological Analysis ◽  
Ex Vivo ◽  
Skin Permeation ◽  
In Vitro Release ◽  
Release Kinetic ◽  
Multiple Emulsion ◽  
Vertical Diffusion ◽  
Skin Integrity

Efficient topical delivery of imidazolic antifungals faces the challenge of overcoming its limited water solubility and its required long-lasting duration of treatments. In this paper, a hydrophilic multiple emulsion (ME) of Bifonazole (BFZ) is shown to maximize its skin retention, minimize its skin permeation, and maintain an acceptable level of being harmless in vivo. The formulations were pharmaceutically characterized and application properties were assessed based on viscosity measurements. Non-Newtonian pseudoplastic shear thinning with apparent thixotropy was observed, facilitating the formulation retention over the skin. The in vitro release profile with vertical diffusion cells showed a predominant square-root release kinetic suggesting an infinite dose depletion from the formulation. Ex vivo human skin permeation and penetration was additionally evaluated. Respective skin permeation was lower than values obtained with a commercial O/W formulation. The combination of amphoteric and non-ionic surfactants increased the bifonazole epidermal accumulation by a factor of twenty. This fact makes the possibility of increasing its current 24 h administration frequency more likely. Eventual alterations of skin integrity caused by the formulations were examined with epidermal histological analysis and in vivo preclinical measurements of skin elasticity and water retrograde permeation. Histological analysis demonstrated that the multiple emulsions were harmless. Additionally, modifications of in vivo skin integrity descriptors were considered as negligible.

scholarly journals Enhancement of Curcumin Anti-Inflammatory Effect via Formulation into Myrrh Oil-Based Nanoemulgel

Polymers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 577 ◽  
Author(s):  
Wafaa E. Soliman ◽  
Tamer M. Shehata ◽  
Maged E. Mohamed ◽  
Nancy S. Younis ◽  
Heba S. Elsewedy
Keyword(s):  
Ex Vivo ◽  
Skin Permeation ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Delivery Methods ◽  
Anti Cancer ◽  
Permeation Studies ◽  
Anti Inflammatory

Background: Curcumin (Cur) possesses a variety of beneficial pharmacological properties including antioxidant, antimicrobial, anti-cancer and anti-inflammatory activities. Nevertheless, the low aqueous solubility and subsequent poor bioavailability greatly limits its effectiveness. Besides, the role of myrrh oil as an essential oil in treating inflammatory disorders has been recently demonstrated. The objective of the current investigation is to enhance Cur efficacy via developing Cur nanoemulgel, which helps to improve its solubility and permeability, for transdermal delivery. Methods: The formulated preparations (Cur gel, emulgel and nanoemulgel) were evaluated for their physical appearance, spreadability, viscosity, particle size, in vitro release and ex vivo drug permeation studies. The in vivo anti-inflammatory activity was estimated using the carrageenan-induced rat hind paw edema method. Results: The formulated Cur-loaded preparations exhibited good physical characteristics that were in the acceptable range of transdermal preparations. The release of Cur from gel, emulgel and nanoemulgel after 12 h was 72.17 ± 3.76, 51.93 ± 3.81 and 62.0 ± 3.9%, respectively. Skin permeation of Cur was significantly (p < 0.05) improved when formulated into nanoemulgel since it showed the best steady state transdermal flux (SSTF) value (108.6 ± 3.8 µg/cm2·h) with the highest enhancement ratio (ER) (7.1 ± 0.2). In vivo anti-inflammatory studies proved that Cur-loaded nanoemulgel displayed the lowest percent of swelling (26.6% after 12 h). Conclusions: The obtained data confirmed the potential of the nanoemulgel dosage form and established the synergism of myrrh oil and Cur as an advanced anti-inflammatory drug.

scholarly journals Enhancement of the Anti-inflammatory Efficacy of Betamethasone Valerate via Niosomal Encapsulation

2021 ◽  
Vol 11 (6) ◽  
pp. 14640-14660
Keyword(s):  
Zeta Potential ◽  
Rheological Behavior ◽  
Ex Vivo ◽  
Histopathological Examination ◽  
Skin Permeation ◽  
In Vitro Release ◽  
Betamethasone Valerate ◽  
In Vivo Studies ◽  
Anti Inflammatory

Betamethasone valerate-loaded niosomes were formulated to improve drug anti-inflammatory efficacy and reduce its systemic side effects by providing prolonged and localized drug delivery into the skin. Niosomes were prepared by thin-film hydration using different molar ratios of surfactant, cholesterol, and charge inducers. Formulations were characterized for entrapment efficiency, morphology, size, and zeta potential. In-vitro release and stability studies were conducted on selected formulations. Two niosomal gels were evaluated for spreadability, pH, rheological behavior, ex-vivo skin permeation, and in-vivo anti-inflammatory efficacy. Formulations showed high encapsulation efficiency reaching 92.03±1.88%. Vesicles were spherical in shape, ranging from 123.1 to 782 nm, and had large negative values of zeta-potential. They showed a biphasic release pattern which was more sustained than free drug suspension. Niosomes demonstrated good physicochemical stability under refrigeration for up to 3 months. Niosomal gels exhibited good spreadability, suitable pH values, favorable rheological behavior, and higher skin permeation than the plain gel. In-vivo studies revealed that niosomal gels showed a better sustained anti-inflammatory effect than drug plain gel and the marketed product, which was confirmed by further histopathological examination of paw tissues. Niosomal gels are promising formulations for sustained local delivery of betamethasone valerate.

Chemical Permeation Enhancers for Transdermal Delivery of Thiocolchicoside: Assessment of Ex-vivo Skin Flux and In-vivo Pharmacokinetics

2017 ◽  
Vol 10 (5) ◽  
pp. 3827-3835
Author(s):  
Y Madhusudan Rao ◽  
Gayatri P ◽  
Ajitha M ◽  
P. Pavan Kumar ◽  
Kiran kumar
Keyword(s):  
Passive Control ◽  
Ex Vivo ◽  
Skin Permeation ◽  
In Vivo Studies ◽  
Permeation Enhancers ◽  
Casting Technique ◽  
Chemical Permeation Enhancers ◽  
Chemical Permeation ◽  
In Vivo Pharmacokinetics

Present investigation comprises the study of ex-vivo skin flux and in-vivo pharmacokinetics of Thiocolchicoside (THC) from transdermal films. The films were fabricated by solvent casting technique employing combination of hydrophilic and hydrophobic polymers. A flux of 18.08 µg/cm2h and 13.37µg/cm2h was achieved for optimized formulations containing 1, 8-cineole and oleic acid respectively as permeation enhancers. The observed flux values were higher when compared to passive control (8.66 µg/cm2h). Highest skin permeation was observed when 1,8-cineole was used as chemical permeation enhancer and it considerably (2-2.5 fold) improved the THC transport across the rat skin. In vivo studies were performed in rabbits and samples were analysed by LC-MS-MS. The mean area under the curve (AUC) values of transdermal film showed about 2.35 times statistically significant (p<0.05) improvement in bioavailability when compared with the oral administration of THC solution. The developed transdermal therapeutic systems using chemical permeation enhancers were suitable for drugs like THC in effective management of muscular pain.    

scholarly journals Enhanced Transdermal Delivery of Pranoprofen Using a Thermo-Reversible Hydrogel Loaded with Lipid Nanocarriers for the Treatment of Local Inflammation

2021 ◽  
Vol 15 (1) ◽  
pp. 22
Author(s):  
María Rincón ◽  
Marcelle Silva-Abreu ◽  
Lupe Carolina Espinoza ◽  
Lilian Sosa ◽  
Ana Cristina Calpena ◽  
...  
Keyword(s):  
Human Skin ◽  
Topical Application ◽  
Topical Treatment ◽  
Transdermal Delivery ◽  
Ex Vivo ◽  
Skin Permeation ◽  
In Vitro Release ◽  
Heterogeneous Structure ◽  
Clinical Environment ◽  
Local Skin

A biocompatible topical thermo-reversible hydrogel containing Pranoprofen (PF)-loaded nanostructured lipid carriers (NLCs) was studied as an innovative strategy for the topical treatment of skin inflammatory diseases. The PF-NLCs-F127 hydrogel was characterized physiochemically and short-time stability tests were carried out over 60 days. In vitro release and ex vivo human skin permeation studies were carried out in Franz diffusion cells. In addition, a cytotoxicity assay was studied using the HaCat cell line and in vivo tolerance study was performed in humans by evaluating the biomechanical properties. The anti-inflammatory effect of the PF-NLCs-F127 was evaluated in adult male Sprague Daw-ley® rats using a model of inflammation induced by the topical application of xylol for 1 h. The developed PF-NLCs-F127 exhibited a heterogeneous structure with spherical PF-NLCs in the hydrogel. Furthermore, a thermo-reversible behaviour was determined with a gelling temperature of 32.5 °C, being close to human cutaneous temperature and thus favouring the retention of PF. Furthermore, in the ex vivo study, the amount of PF retained and detected in human skin was high and no systemic effects were observed. The hydrogel was found to be non-cytotoxic, showing cell viability of around 95%. The PF-NLCs-F127 is shown to be well tolerated and no signs of irritancy or alterations of the skin’s biophysical properties were detected. The topical application of PF-NLCs-F127 hydrogel was shown to be efficient in an inflammatory animal model, preventing the loss of stratum corneum and reducing the presence of leukocyte infiltration. The results from this study confirm that the developed hydrogel is a suitable drug delivery carrier for the transdermal delivery of PF, improving its dermal retention, opening the possibility of using it as a promising candidate and safer alternative to topical treatment for local skin inflammation and indicating that it could be useful in the clinical environment.

scholarly journals Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2920
Author(s):  
Ameeduzzafar Zafar ◽  
Syed Sarim Imam ◽  
Nabil K. Alruwaili ◽  
Omar Awad Alsaidan ◽  
Mohammed H. Elkomy ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Oral Delivery ◽  
Ex Vivo ◽  
In Vitro Release ◽  
System Optimization ◽  
Globule Size

Hypertension is a cardiovascular disease that needs long-term medication. Oral delivery is the most common route for the administration of drugs. The present research is to develop piperine self-nanoemulsifying drug delivery system (PE-SNEDDS) using glyceryl monolinoleate (GML), poloxamer 188, and transcutol HP as oil, surfactant, and co-surfactant, respectively. The formulation was optimized by three-factor, three-level Box-Behnken design. PE-SNEDDs were characterized for globule size, emulsification time, stability, in-vitro release, and ex-vivo intestinal permeation study. The optimized PE-SNEDDS (OF3) showed the globule size of 70.34 ± 3.27 nm, percentage transmittance of 99.02 ± 2.02%, and emulsification time of 53 ± 2 s Finally, the formulation OF3 was transformed into solid PE-SNEDDS (S-PE-SNEDDS) using avicel PH-101 as adsorbent. The reconstituted SOF3 showed a globule size of 73.56 ± 3.54 nm, PDI of 0.35 ± 0.03, and zeta potential of −28.12 ± 2.54 mV. SEM image exhibited the PE-SNEDDS completely adsorbed on avicel. Thermal analysis showed the drug was solubilized in oil, surfactant, and co-surfactant. S-PE-SNEDDS formulation showed a more significant (p < 0.05) release (97.87 ± 4.89% in 1 h) than pure PE (27.87 ± 2.65% in 1 h). It also exhibited better antimicrobial activity against S. aureus and P. aeruginosa and antioxidant activity as compared to PE dispersion. The in vivo activity in rats exhibited better (p < 0.05) antihypertensive activity as well as 4.92-fold higher relative bioavailability than pure PE dispersion. Finally, from the results it can be concluded that S-PE-SNEDDS might be a better approach for the oral delivery to improve the absorption and therapeutic activity.

scholarly journals p-Coumaric Acid as An Active Ingredient in Cosmetics: A Review Focusing on its Antimelanogenic Effects

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 275 ◽  
Author(s):  
Yong Chool Boo
Keyword(s):  
Active Ingredient ◽  
Antioxidant Activities ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Skin Pigmentation ◽  
Experimental Models ◽  
Coumaric Acid ◽  
Inflammatory Reactions ◽  
Skin Lightening

Controlling unwanted hyperpigmentation is a major challenge in dermatology and cosmetology, and safe and efficacious antimelanogenic agents are deemed useful for this purpose. p-Coumaric acid is a natural metabolite contained in many edible plants, and its antioxidant activities in reducing oxidative stress and inflammatory reactions have been demonstrated in various experimental models. p-Coumaric acid has the optimal structure to be a competitive inhibitor of tyrosinase that catalyzes key reactions in the melanin biosynthetic pathway. Experimental evidence supports this notion as it was found to be a more potent inhibitor of tyrosinase, especially toward human enzymes, than other well-known tyrosinase inhibitors such as arbutin and kojic acid. p-Coumaric acid inhibited melanin synthesis in murine melanoma cells, human epidermal melanocytes, and reconstituted three-dimensional human skin models. Ex-vivo skin permeation experiments and in-vivo efficacy tests for p-coumaric acid confirmed its efficient transdermal delivery and functional efficacy in reducing erythema development and skin pigmentation due to ultraviolet radiation exposure. Human studies further supported its effectiveness in hypopigmentation and depigmentation. These findings suggest that p-coumaric acid has good potential to be used as a skin-lightening active ingredient in cosmetics. Future studies are needed to extensively examine its safety and efficacy and to develop an optimized cosmetic formulation for the best performance in skin lightening.

scholarly journals FABRICATION OF BIOADHESIVE OCUSERT WITH DIFFERENT POLYMERS: ONCE A DAY DOSE

2018 ◽  
Vol 10 (6) ◽  
pp. 309
Author(s):  
Aya M. Dawaba ◽  
Hamdy M. Dawaba ◽  
Amal S. M. Abu El-enin ◽  
Maha K. A. Khalifa
Keyword(s):  
In Vitro Release ◽  
Methyl Cellulose ◽  
Storage Period ◽  
Poly Vinyl Alcohol ◽  
Release Kinetic ◽  
Casting Technique ◽  
Process Characterization ◽  
Vitro Release

Objective: The objective of this current study is to fabricate ocuserts to control the drug release from chosen bioadhesive polymeric matrixes to enhance patient compliance. Ciprofloxacin HCl (CFX HCl) was selected as a model drug.Methods: Different bioadhesive polymers with different film forming capabilities namely Hydroxy Propyl Methyl Cellulose (HPMC K4M), Poly Vinyl Alcohol (PVA), Sodium Carboxy Methyl Cellulose (Na CMC), Hydroxy Propyl Cellulose (HPC), Sodium Alginate (Na Alg.), pullulan and Xanthan Gum (XG) in different ratios were used in fabricating ocuserts using solvent-casting technique. Propylene Glycol (PG) was used as a plasticizer to facilitate the fabrication process. Characterization tests of the developed ocuserts were performed as well as bioadhesive tests and in vitro release studies of the incorporated drug. The obtained results were analysed using different release kinetic models. Stability of the selected ocuserts was investigated at 40±0.5 °C and 75±5% Relative Humidity (RH) for three months’ storage period. In vivo ocular irritation test was performed to investigate the safety of the formula in rabbits’ eyes as well as to test the release profile and thus to estimate In vitro In vivo correlation.Results: All the prepared ocuserts showed the uniformity of film characterization and bioadhesion strength ranged from 240±66 and 158±52dyne/cm2. Selected formula from the in vitro release study tested for in vivo study showed the slow release of ciprofloxacin drug up to 24 h with no signs of eye irritancy. Results for In vitro In vivo correlation showed an excellent correlation with R2 value of 0.9982.Conclusion: PVA based ocuserts proven to be a promising once-daily, effective and safe ocular delivery system of the drug.

scholarly journals Monoolein Assisted Oil-Based Transdermal Delivery of Powder Vaccine

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 814
Author(s):  
Momoko Kitaoka ◽  
Atsushi Oka ◽  
Masahiro Goto
Keyword(s):  
Ex Vivo ◽  
Skin Permeation ◽  
Lipid Extraction ◽  
Skin Penetration ◽  
Isopropyl Myristate ◽  
Transdermal Administration ◽  
Common Skin ◽  
Model Protein ◽  
Specific Igg

An increasing number of protein vaccines have been researched for cancer, inflammation, and allergy therapies. Most of the protein therapeutics are administered through injection because orally-administered proteins are metabolized by the digestive system. Although transdermal administration has received increasing attention, the natural barrier formed by the skin is an obstacle. Monoolein is a common skin penetration enhancer that facilitates topical and transdermal drug delivery. Conventionally, it has been used in an aqueous vehicle, often with polyhydric alcohols. In the current study, monoolein was dissolved in an oil vehicle, isopropyl myristate, to facilitate the skin permeation of powder proteins. The skin permeabilities of the proteins were examined in-vivo and ex-vivo. Monoolein concentration-dependently enhanced the skin permeation of proteins. The protein permeability correlated with the zeta potential of the macromolecules. Dehydration of the stratum corneum (SC), lipid extraction from the SC, and disordering of ceramides caused by monoolein were demonstrated through Fourier transform infrared spectroscopic analysis and small-angle X-ray scattering analysis. An antigen model protein, ovalbumin from egg white, was delivered to immune cells in living mice, and induced antigen-specific IgG antibodies. The patch system showed the potential for transdermal vaccine delivery.

scholarly journals Nanocrystals of Fusidic Acid for Dual Enhancement of Dermal Delivery and Antibacterial Activity: In Vitro, Ex Vivo and In Vivo Evaluation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 199 ◽  
Author(s):  
Iman S. Ahmed ◽  
Osama S. Elnahas ◽  
Nouran H. Assar ◽  
Amany M. Gad ◽  
Rania El Hosary
Keyword(s):  
Fusidic Acid ◽  
Therapeutic Efficacy ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Fold Increase ◽  
Spherical Particles ◽  
Resistant Bacteria ◽  
Infection Model

With the alarming rise in incidence of antibiotic-resistant bacteria and the scarcity of newly developed antibiotics, it is imperative that we design more effective formulations for already marketed antimicrobial agents. Fusidic acid (FA), one of the most widely used antibiotics in the topical treatment of several skin and eye infections, suffers from poor water-solubility, sub-optimal therapeutic efficacy, and a significant rise in FA-resistant Staphylococcus aureus (FRSA). In this work, the physico-chemical characteristics of FA were modified by nanocrystallization and lyophilization to improve its therapeutic efficacy through the dermal route. FA-nanocrystals (NC) were prepared using a modified nanoprecipitation technique and the influence of several formulation/process variables on the prepared FA-NC characteristics were optimized using full factorial statistical design. The optimized FA-NC formulation was evaluated before and after lyophilization by several in-vitro, ex-vivo, and microbiological tests. Furthermore, the lyophilized FA-NC formulation was incorporated into a cream product and its topical antibacterial efficacy was assessed in vivo using a rat excision wound infection model. Surface morphology of optimized FA-NC showed spherical particles with a mean particle size of 115 nm, span value of 1.6 and zeta potential of −11.6 mV. Differential scanning calorimetry and powder X-ray diffractometry confirmed the crystallinity of FA following nanocrystallization and lyophilization. In-vitro results showed a 10-fold increase in the saturation solubility of FA-NC while ex-vivo skin permeation studies showed a 2-fold increase in FA dermal deposition from FA-NC compared to coarse FA. Microbiological studies revealed a 4-fofd decrease in the MIC against S. aureus and S. epidermidis from FA-NC cream compared to commercial Fucidin cream. In-vivo results showed that FA-NC cream improved FA distribution and enhanced bacterial exposure in the infected wound, resulting in increased therapeutic efficacy when compared to coarse FA marketed as Fucidin cream.

scholarly journals Ondansetron Hydrochloride in Treating Patients with Cancer and Chronic Nausea Vomiting

2017 ◽  
Vol 1 (2) ◽  
pp. 01-04
Author(s):  
Hye jin
Keyword(s):  
Ex Vivo ◽  
In Vitro Release ◽  
Extended Period ◽  
Release Mechanism ◽  
Content Uniformity ◽  
Ondansetron Hydrochloride ◽  
Backing Layer ◽  
Carbopol 934P

The objective of this study was to develop effective bioadhesive buccal bilayered tablets comprising of drug containing bioadhesive layer and drug free backing layer, expected to release the drug in unidirection for extended period of time. Tablets of ondansetron HCl were prepared by direct compression method using bioadhesive polymers like Carbopol 934P, Methocel K4M, Methocel K15M and Hydroxy propyl cellulose in different combinations and concentrations with backing layer of ethyl cellulose. Buccal tablets were evaluated by different parameters such as thickness, hardness, weight uniformity, content uniformity, swelling index, surface pH, ex vivo bioadhesive strength, ex vivo residence time, in vitro drug release, ex vivo drug permeation, stability studies in human saliva, in vivo mucoadhesive performance studies and FTIR studies. The modified in vitro assembly was used to measure the bioadhesive strength of tablets with fresh porcine buccal mucosa as model tissue. Bioadhesion strength was increased with increase in the concentration of carbopol. The tablets were evaluated for in vitro release in pH 6.6 phosphate buffer for 8 hr in standard dissolution apparatus. In order to improve the permeation of the drug, tauroglycholate (permeation enhancer) added in the optimized formulation at 10mM concentration. In order to determine the mode of release, the data was subjected to Korsmeyer and Peppas diffusion model. The optimized formula followed non-fickian release mechanism with zero order kinetics. Carbopol 934P and HPC in the ratio of 3:1 could be used to design effective and stable buccoadhesive tablets of ondansetron HCl. The present study concludes that buccal delivery of ondansetron HCl tablets can be good way to bypass the first pass metabolism.

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