Skin Irritation Studies Research Articles

Transdermal delivery of doxorubicin and methotrexate from polyelectrolyte three layer nanoparticle of graphene oxide/polyethyleneimine/dextran sulphate for chemotherapy: In vitro and in vivo studies

In the present work, novel dual drug loaded - anionic graphene oxide/cationic polyethyleneimine/poly anionic dextran sulfate (GO/PEI/DS) was synthesized by a layer-by-layer self-assembly technique for transdermal anti-cancer drug delivery. Doxorubicin (DOX) was loaded onto folic acid conjugated graphene oxide (GO) and methotrexate (MTX) was loaded onto dextran sulfate (DS). The drug carrier was characterized by fourier transform infrared spectroscopy, x-ray diffraction spectroscopy, dynamic light scattering analysis, scanning electron microscopy, atomic force microscopy, transmission electron microscopy, zeta-potential analysis, drug loading and encapsulation efficiency, equilibrium swelling studies, in vitro drug release studies, hemocompatibility assays, in vitro cytotoxicity assay, skin irritation studies, ex vivo skin permeation studies and in vivo pharmacokinetic studies.The cytotoxicity of synthesized materials was evaluated against MCF-7 breast cancer cells using an MTT assay and apoptosis assay. The synergistic effect of DOX and MTX to inhibit the growth of cancer cells was also confirmed. The final dual drug-loaded carrier showed a cell viability of 36.38 % towards MCF-7 cancer cells while it showed a cell viability of >87.65 % towards normal L929 cell lines. The in vivo pharmacokinetic studies in Wistar rats through oral and transdermal routes of administration, the transdermal route of administration of dual drug-loaded material provided a sustained and prolonged drug existence in the blood circulation system. The mean residence time of drugs in the bloodstream via oral administration was 83.98 ± 3.71 h, while that of the transdermal route of administration was 149.62 ± 6.11 h. The results revealed that the synthesized dual drug-loaded material showed a good pH-dependent controlled and sustained release profile for both DOX and MTX via the transdermal route of administration in comparison with oral delivery.

Preliminary Wound Healing Activity of Polyherbal Formulation Containing Cinnamon zeylanicum, Centella asiatica and Moringa oleifera

In the present work, a polyherbal gel formulation for wound healing activity was developed using 70% methanolic extract of Centella asiatica leaves, methanolic extract of Cinnamomum zeylanicum Nees stem bark as well as oil of Moringa olifera seed. The developed formulation was evaluated for organoleptic parameters like colour, odour, texture and physicochemical parameters like a loss on drying (LOD), pH, viscosity, spreadability, skin irritation study, etc. In-vitro antibacterial activity of both the extracts and oil of M. oleifera was carried out against two pathogenic bacteria Escherichia coli and Staphylococcus aureus by disc diffusion assay using tetracycline as a standard. Apart from that, the wound healing activity of a polyherbal formulation was evaluated by an incision model in Wistar rats. The results showed that the polyherbal formulation exhibited dark brown colour with a smooth texture and cinnamon-like odour. The gel showed 9% LOD, pH was found to be 7.5±0.3, viscosity was 4609.5± 13.44 cps at 10 rpm with spindle number 63, and spreadability was found to be 19.44±0.26 (g.cm/s), and no irritation was found on the healthy volunteer's skin. In the wound healing activity, polyherbal did not affect the normal feed and water uptake. The wound did not show any pus formation throughout the treatment period. In the Planimetry assessment, wounds treated with polyherbal formulation showed a good score at the end of the treatment. Results showed that polyherbal formulation containing 70% methanolic extract of C. asiatica leaves, methanolic extract of C. zeylanicum stem bark as well as oil of M. olifera seed have good wound healing activity.

Design, Development, and Evaluation of Treprostinil Embedded Adhesive Transdermal Patch.

Clinical application of treprostinil in pulmonary arterial hypertension is hampered by adverse effects caused by its high dosing frequency. The objective of this investigation was to Formulate an adhesive-type transdermal patch of treprostinil and evaluate it both in vitro and in vivo. A 32-factorial design was utilized to optimize the selected independent variables (X1: drug amount, X2: enhancer concentration) on the response variables (Y1: drug release, Y2: transdermal flux). The optimized patch was evaluated for various pharmaceutical properties, skin irritation, and pharmacokinetics in rats. Optimization results signify considerable influence (p < 0.0001) of X1 on both Y1 and Y2, as compared to X2. The optimized patch possesses higher drug content (>95%), suitable surface morphology, and an absence of drug crystallization. FTIR analysis revealed compatibility of the drug with excipients, whereas DSC thermograms indicate that the drug exists as amorphous in the patch. The adhesive properties of the prepared patch confirm adequate adhesion and painless removal, while the skin irritation study confirms its safety. A steady drug release via Fickian diffusion and greater transdermal delivery (~23.26 µg/cm2/h) substantiate the potential of the optimized patch. Transdermal therapy resulted in higher treprostinil absorption (p < 0.0001) and relative bioavailability (237%) when compared to oral administration. Overall, the results indicate that the developed drug in the adhesive patch can effectively deliver treprostinil through the skin and could be a promising treatment option for pulmonary arterial hypertension.

DOE-Assisted Formulation, Optimization, and Characterization of Tioconazole-Loaded Transferosomal Hydrogel for the Effective Treatment of Atopic Dermatitis: In Vitro and In Vivo Evaluation.

Tioconazole transferosomes suspension (TTFs) was formulated and optimized using a 32 factorial design. After that, the optimized batch of TTFs loaded into Carbopol 934 and sodium CMC was prepared with hydrogel and noted as TTFsH. Subsequently, it was evaluated for pH, spread ability, drug content, in vitro drug release, viscosity, in vivo scratching and erythema score, skin irritation, and histopathology study. The optimized batch of TTFs (B4) showed the values of vesicle size, flux, and entrapment efficiency to be 171.40 ± 9.03 nm, 48.23 ± 0.42, and 93.89 ± 2.41, respectively. All batches of TTFsH showed sustained drug release for up to 24 h. The F2 optimized batch released Tz in an amount of 94.23 ± 0.98% with a flux of 47.23 ± 0.823 and followed the Higuchi kinetic model. The in vivo studies provided evidence that the F2 batch of TTFsH was able to treat atopic dermatitis (AD) by reducing the erythema and the scratching score compared to that of the marketed formulation (Candiderm cream, Glenmark). The histopathology study supported the result of the erythema and scratching score study with intact skin structure. It showed that a formulated low dose of TTFsH was safe and biocompatible to both the dermis and the epidermis layer of skin. Thus, a low dose of F2-TTFsH is a promising tool that effectively targeted the skin for the topical delivery of Tz to treat atopic dermatitis symptoms.

Apremilast loaded lyotropic liquid crystalline nanoparticles embedded hydrogel for improved permeation and skin retention: An effective approach for psoriasis treatment

The present work aimed to prepare and evaluate Apremilast loaded lyotropic liquid crystalline nanoparticles (LCNPs) formulation for skin delivery to enhance the efficacy with reduced adverse effects of the oral therapy in psoriasis treatment. The LCNPs were prepared using the emulsification using a high shear homogenizer for size reduction and optimized with Box Behnken design to achieve desired particle size and entrapment efficiency. The selected LCNPs formulation was evaluated for in-vitro release, in-vitro psoriasis efficacy, skin retention, dermatokinetic, in-vivo skin retention, and skin irritation study. The selected formulation exhibited 173.25 ± 2.192 nm (polydispersity 0.273 ± 0.008) particle size and 75.028 ± 0.235% entrapment efficiency. The in-vitro drug release showed the prolonged-release for 18 h. The ex-vivo studies revealed that LCNPs formulation exhibited drug retention up to 3.2 and 11.9-fold higher, in stratum corneum and viable epidermis compared to conventional gel preparation. In-vitro cell line studies performed on immortal keratinocyte cells (HaCaT cells) demonstrated non-toxicity of selected excipients used in designed LCNPs. The dermatokinetic study revealed the AUC0–24 of the LCNPs loaded gel was 8.4 fold higher in epidermis and 2.06 fold in dermis, respectively compared to plain gel. Further, in-vivo animal studies showed enhanced skin permeation and retention of Apremilast compared to conventional gel.

Formulation and Evaluation of Film Forming Solution of Tavaborole for Treatment of Skin Infections

Film forming solutions (FFS) as a novel approach attracted the interest of pharmaceutical scientist for skin drug delivery system development and characterization concerning with their mechanical properties and water vapor permeability. FFS were developed by varying concentration of the film forming polymers also nature and content of the plasticizer. The formulations were prepared using 32 full factorial design. They were tested for drying time, drug release, antifungal activity, skin irritation and stability studies. The FFS was characterised for pH, viscosity, drug content, effective dosage volume and mechanical properties of the film formed after application; bioadhesion and water vapour permeability were also tested. All the formulations showed results within acceptable range for various tests. The optimized formulation showed drug release of 97.2% and antifungal activity in terms of efficacy as 99.2%. Such a formulation can be claimed to decrease duration of therapy, will be more accepted by the patients and be a breakthrough in treating skin infections.

Baicalin loaded transethosomes for rheumatoid arthritis: Development, characterization, pharmacokinetic and pharmacodynamic evaluation

The present research study limns the preparation of Baicalin-loaded transethosomes (BCL-TE) to improve BCL solubility, bioavailability and permeation through skin layers for transdermal delivery. BCL-TE was formulated using thin-film hydration method and optimization was done using Box-Behnken design (BBD). BCL-TEopt was characterized for Polydispersity index (PDI), vesicle size, entrapment efficiency, zeta potential and in vitro BCL release. For further evaluation, Pharmacokinetic study, Transmission electron microscopy (TEM), Skin permeation study and Confocal scanning laser microscopy (CLSM) were performed withal. The BCL-TEopt presented spherical and sealed shape vesicles with small vesicle size of 141.2 nm, entrapment efficiency of 76.39%, PDI of 0.1135 and in vitro release of 65.32%. The CLSM study unveiled that the developed formulation has greater permeation of BCL across the skin layers in comparison with the BCL suspension gel. The pharmacokinetic study demonstrated Cmax and AUC0–24 h of 7.94 ± 0.51 μg/ml and 42.92 ± 7.90 μg. h/ml via transdermal route in comparison to Cmax and AUC0–24 h of 3.94 ± 1.91 μg/ml and 24.96 ± 9.76 μg. h/ml presented by BCL-TE oral administration. The in vivo study revealed that the BCL-TE gel has good anti-arthritic potential in comparison with the standard diclofenac gel which was evinced by radiographic analysis and histopathological studies. Further, skin irritation study on Wistar albino rats confirm that the developed BCL-TE formulation is safer for skin application. The current investigation corroborated that the prepared TE vesicle formulation is a treasured carrier for the BCL transdermal delivery for the management of rheumatoid arthritis.

Nanotransethosomes for enhanced transdermal delivery of mangiferin against rheumatoid arthritis: formulation, characterization, invivo pharmacokinetic and pharmacodynamic evaluation

The present research study limns the preparation of MNF loaded transethosomes (MNF-TE) to improve MNF solubility, bioavailability and permeation through skin layers for transdermal delivery. MNF-TE was formulated using thin-film hydration method and optimization was done using Box-Behnken design (BBD). MNF-TEopt was characterized for Polydispersity index (PDI), vesicle size, entrapment efficiency, zeta potential and in vitro MNF release. For further evaluation, Pharmacokinetic study, Transmission electron microscopy (TEM), Skin permeation study and Confocal scanning laser microscopy (CLSM) were performed withal. The MNF-TEopt presented spherical and sealed shape vesicles with small vesicle size of 148.6 nm, entrapment efficiency of 74.23%, PDI of 0.1139 and in vitro release of 65.32%. The CLSM study unveiled that the developed formulation has greater permeation of MNF across the skin layers in comparison with the MNF suspension gel. The pharmacokinetic study demonstrated Cmax and AUC0-24 h of 6.94 ± 0.51 μg/ml and 43.92 ± 7.90 μg.h/ml via transdermal route in comparison to Cmax and AUC0-24 h of 3.74 ± 1.91 μg/ml and 22.96 ± 9.76 μg.h/ml presented by MNF-TE oral administration. The in vivo study revealed that the MNF-TE gel has good anti-arthritic potential in comparison with the standard diclofenac gel which was evinced by radiographic analysis and histopathological studies. Further, skin irritation study on Wistar albino rats confirm that the developed MNF-TE formulation is safer for skin application. The current investigation corroborated that the prepared TE vesicle formulation is a treasured carrier for the MNF transdermal delivery for the management of rheumatoid arthritis.

Preparation, optimization and evaluation of Osthole transdermal therapeutic system.

In the current study, the solubility and permeability of Osthole-loaded microemulsion were enhanced, which increased bioavailability. In addition, Carbomer 940 was added for prolonged drug delivery. The microemulsion was prepared after the screening of Kukui oil, Labrasol (surfactant), and transcutol-P (co-surfactant). Pseudoternary phase diagrams were employed to find the microemulsion region. Box Behnken Design (BBD) was employed for optimizing microemulsions. Variables were related and compared using mathematical equations and response surface plots (RSP). MEBG was then compared with control gel on the basis of stability studies, drug permeation, skin irritation studies, and anti-inflammatory studies. Microemulsion preparations depicted a pH of 5.27 - 5.80, a conductivity of 139 - 185 μS/cm, a poly-dispersity index of 0.116 - 0.388, a refractive index of 1.330 - 1.427, an average droplet size of 64 - 89 nm, homogeneity, spherical shape, viscosity 52 - 185 cP. Predicted values of Optimized microemulsions showed more reasonable agreement than experimental values. The microemulsion was stable and non-irritating on Rabbit skin. MEBG showed a significant difference from control gel for percent edema inhibition from the standard. The permeation enhancing capability of MEBG using a suitable viscosity fabricates it promising carrier for transdermal delivery of Osthole.

RETRACTED ARTICLE: Transdermal delivery of allopurinol-loaded nanostructured lipid carrier in the treatment of gout

BackgroundAllopurinol (ALP), a xanthine oxidase inhibitor, is a first line drug for the treatment of gout and hyperuricemia. Being the member of BCS class II drugs, ALP has solubility problem, which affects its bioavailability. Also, ALP has shorter half-life and showed GI related problems. In present study, ALP was encapsulated in nanostructured lipid carriers (NLCs) to ensure enhanced bioavailability, improved efficacy and safety in vivo.MethodologyALP-loaded NLCs were fabricated by micro-emulsion technique. The prepared NLCs were optimized via design expert in term of particle size, zeta potential and entrapment efficiency. FTIR, PXRD and TEM analysis were carried out to check chemical interaction, polymorphic form and surface morphology of the optimized formulation. ALP-loaded NLCs were then loaded into HPMC based poloxamer-407 gel and were characterized. In vitro and ex vivo analysis were carried out via dialysis membrane method and franz diffusion cell, respectively. Uric acid was used for induction of gout and the anti-gout activity of ALP-loaded NLCs gel was performed and compared with ALP suspension.ResultsThe optimized formulation had particles in nano-range (238.13 nm) with suitable zeta potential (-31.5 mV), poly-dispersity index (0.115) and entrapment of 87.24%. FTIR results confirmed absence of chemical interaction among formulation ingredients. XRD indicated amorphous nature of ALP-loaded NLCs, whereas TEM analysis confirmed spherical morphology of nanoparticles. The optimized formulation was successfully loaded in to gel and characterized accordingly. The in vitro release and drug release kinetics models showed sustained release of the drug from ALP-loaded NLCs gel. Furthermore, about 28 fold enhanced permeation was observed from ALP-loaded NLCs gel as compared to conventional gel. Skin irritation study disclosed safety of ALP-loaded NLCs gel for transdermal application. Furthermore, ALP-loaded NLCs gel showed significantly enhanced anti-gout activity in Sprague–Dawley rats after transdermal administration as compared to oral ALP suspension.ConclusionALP-loaded NLCs gel after transdermal administration sustained the drug release, avoid gastrointestinal side effects and enhance the anti-gout performance of ALP. It can be concluded, that NLCs have the potential to deliver drugs via transdermal route as indicated in case of allopurinol.

Statistical optimization of co-loaded rifampicin and pentamidine polymeric nanoparticles for the treatment of cutaneous leishmaniasis

Topical drug delivery against cutaneous leishmaniasis (CL) serves as an effective alternate approach to improve efficacy and reduce systemic adverse effects. The purpose of this study was to develop and investigate the potential of rifampicin and pentamidine co-loaded polymeric nanoparticles (RIF-PTM-PNP) for targeting the Leishmania infected macrophages and its effective antileishmanial therapy. RIF-PTM-PNP were prepared by modified ionic gelation method, trailed by their incorporation into 1% Carbopol gel to prepare RIF-PTM-PNP-Gel. The gel was formulated to ensure the retention of PNP on skin for extended period of time. Formulations were statistically optimized via Box-Behnken design (BBD) based on their particle size (P.S), zeta potential (Z.P) and percent entrapment efficiency (%EE). The optimized RIF-PTM-PNP formulation was further assessed for surface morphology and components compatibility via transmission electron microscopy (TEM) and Fourier-transform infrared spectroscopy (FTIR), respectively. Similarly, RIF-PTM-PNP-Gel was evaluated for physiochemical and rheological attributes. In-vitro drug release profile of RIF-PTM-PNP was determined and compared with RIF-Solution, PTM-Solution and RIF-PTM-PNP-Gel. Moreover, ex-vivo permeation analysis of all the test groups were performed to check their permeation profiles. The in-vitro antileishmanial assay, ex-vivo cell uptake, cell viability and cell toxicity studies of the developed formulations were also accomplished. The optimized formulation indicated suitable particle properties including, 163.1 nm P.S, 0.296 PDI, +29.7 mV Z.P and drug entrapment of RIF (89.10%) and PTM (79.31%), respectively. FTIR analysis showed no interactions between components of RIF-PTM-PNP. Moreover, RIF-PTM-PNP-Gel was homogeneous, has optimal pH with desirable viscosity. The in-vitro release of RIF and PTM from RIF-PTM-PNP and RIF-PTM-PNP-Gel showed more sustained release behavior as compared to RIF and PTM solutions. Similarly, significantly higher skin penetration was observed in case of RIF-PTM-PNP and RIF-PTM-PNP-Gel, when compared with conventional gel. Additionally, RIF-PTM-PNP showed superior percent inhibition, higher macrophage uptake and lower IC50 value against promastigotes in association with drugs solutions. Furthermore, in-vivo skin irritation and histopathology study indicated a safe and non-irritant behavior of the RIF-PTM-PNP-Gel, when compared with 0.8% formalin. Also, the optimized formulation (RIF-PTM-PNP) was found stable for at least 6 months. These findings suggested the successful preparation of co-loaded RIF-PTM-PNP and their incorporation into Carbopol-based RIF-PTM-PNP-Gel for topical administration with sustained drug release, enhanced skin permeation, macrophage uptake and improved antileishmanial effect.

Design-of-Experiments (DoE)-Assisted Fabrication of Quercetin-Loaded Nanoemulgel and Its Evaluation against Human Skin Cancer Cell Lines.

Background: Quercetin (QCT) is a natural polyphenolic flavonoid showing great potential in the treatment of skin cancer. However, its use is limited owing to its poor water solubility, poor absorption, quick metabolism and excretion, as well as low stability. Preparation of nanoemulgel has been proven to be an effective approach to deliver the drugs topically due to various advantages associated with it. Objectives: This study aimed to prepare stable nanoemulgel of QCT using a Design-of-Experiments (DoE) tool for optimization, to characterize and to assess its in vivo toxicity and efficacy against human cancer cell lines in vitro. Methods: An ultrasonication emulsification method was used for the preparation of QCT-loaded nanoemulsion (QCT@NE). Box-Behnken design was used for the optimization of developed nanoemulgel. Then, in vitro characterization of prepared nanoemulsion was performed using Fourier Transform-Infra Red (FT-IR) spectroscopy, Scanning Electron Microscopy (SEM), particle size analysis, determination of zeta potential and entrapment efficiency (%EE). Further, the developed QCT-loaded nanoemulgel (QCT@NG) was characterized in vitro using texture profile analysis, viscosity and pH determination. Eventually, the cell cytotoxicity studies of the prepared nanoemulgel were performed on the skin cancer cell lines A431 followed by an acute toxicity and skin irritation study on male wistar rats in vivo. Results: The developed QCT@NE was found to be nanometric in size (173.1 ± 1.2 nm) with low polydispersity index (0.353 ± 0.13), zeta potential (-36.1 ± 5.9 mV), and showed good %EE (90.26%). The QCT@NG was found to be substantially more effective against the human skin carcinoma (A431) cell lines as compared to plain QCT with IC50 values of 108.5 and 579.0 µM, respectively. Skin irritation study showed no sign of toxicity and ensured safety for topical application. Hematological analysis revealed no significant differences between the treatment and control group in any biochemical parameter. In the nanoemulgel treatment group, there were no discernible differences in the liver enzymes, bilirubin, hemoglobin, total leukocyte and platelet counts as compared to the control group. Conclusions: The optimized QCT@NG was found to be an ideal and promising formulation for the treatment of skin cancer without showing skin irritation and organ toxicity.

A comparison of dissolving microneedles and transdermal film with solid microneedles for iloperidone in vivo: a proof of concept.

Iloperidone (ILO) is a poorly soluble and bioavailable WHO-approved schizophrenia drug. Microneedles are a revolutionary delivery technology that overcomes many of the issues associated with traditional drug administration. The current research aimed to compare the antipsychotic activity and pharmacokinetics of ILO-loaded dissolving microneedles (DMNs) and transdermal film with a solid microneedle (STF). The DMNs were fabricated using the micromolding process, while the transdermal film was created using the solvent casting approach. Furthermore, an in vivo pharmacokinetic, pharmacodynamic, and skin irritation study was performed on Wistar rats. Studies were compared with transdermal film (TF) on untreated skin as a passive control. STF and DMNs had considerably greater AUC and Cmax (p ≤ 0.001) than transdermal film. In pharmacodynamic tests, STF and DMNs demonstrated significant (p ≤ 0.001) forelimb retraction time (FRT) and hindlimb retraction time (HRT) delay responses as compared to control and TF. In the skin irritation test, no adverse effects such as erythema or edema were observed at the end of the 48h. Thus, antipsychotic activity (paw test) and pharmacokinetics studies revealed sustained action of DMN and STF. This research revealed that improved efficacy of DMN and STF for antipsychotic drug delivery may be an alternative to the existing dosage form.

Natural Gums and Mucilage as Gelling agents in Topical Gel Formulation

The study was conducted to study the gelling efficiency of natural gums (tamarind seed gum) and mucilage (moringa mucilage) using ibuprofen as model drug. Topical drug delivery (TDS) eliminates first pass metabolism and improves bioavailability. Hydrogels are dispersions of network of polymer chains in water as colloidal gels. Ibuprofen an anti-inflammatory, was chosen as a model drug in the preparation of hydrogel for site targeted action and to avoid side effects. Physical properties like swelling index, solubility, loss on drying, flow properties were evaluated. Chemical characterization of isolated gum and mucilage revealed presence of polysaccharides. Ibuprofen topical gels with natural gum (tamarind seed gum (1-7%), moringa mucilage (2-8%) were compared with official xanthan gum (1-4%), guar gum (1-3%) as natural gelling agents and HPMC K4M (1-6%), HPMC K100M (1-6%) and sodium alginate (2-6%) as semi synthetic gelling agents. Drug and excipients are compatible with each other by FTIR studies. The prepared gel formulations were evaluated for clarity, homogeneity, spreadability, drug content, in-vitro diffusion, ex-vivo permeation, skin irritation and stability studies. All formulations have shown better physicochemical properties. Based on the maximum percentage of drug release, formulations containing natural polymers tamarind seed gum (5%), moringa mucilage (8%), xanthan gum (4%), guar gum (3%) were optimized. And semi synthetic polymers HPMC K4M (4%), HPMC K100M (3%), sodium alginate (6%) were optimized. NF10 formulation with guar gum (3%) is optimized based on the percentage of drug release (27.0±0.14%) for 8 hrs, flux of (427.2±0.09µg/cm2/hr), cumulative amount of drug permeated Q8 (329±1.53µg/cm²) and permeability coefficient of (17.08±1.04 ×10-3cm/hr) when compared with tamarind gum (5%), NF1 (23.8±0.13%), (290±1.04µg/cm²), (376.6±0.04µg/cm2/hr), (15.04±0.03×10-3cm/hr) and moringa mucilage (8%), NF3 (14.3±0.19%), (175±0.90µg/cm²), (227.1±0.03µg/cm2/hr), (9.08±0.02×10-3cm/hr). The drug release pattern was found to follow first order kinetics and korsemeyer peppas release mechanism with fickian diffusion release. Formulations were found to be non-irritant and stable. Tamarind gum and moringa mucilage were efficient as gelling agent in preparation of ibuprofen topical gel but showed retarding effect when compared with official guar gum.

Simvastatin Loaded Dissolvable Microneedle Patches with Improved Pharmacokinetic Performance.

Microneedle patches (MNPs) are one of the emerging approaches for drug delivery involving minimal invasion and improved skin penetration of macro- and micro-entities. Herein, we report dissolvable microneedle patches (dMNPs) as a novel tool for better systemic delivery of Simvastatin in the management of hypocholesteremia. Thiolated chitosan (TC), polyvinyl pyrolidone (PVP) and polyvinyl alcohol (PVA) were employed in the development of dMNPs. Developed patches were characterized through SEM, FTIR, DSC, TGA, PXRD, dissolution testing, tensile strength, elongation (%), skin irritation studies, moisture content and pharmacokinetic evaluation. dMNP F26 exhibited excellent tensile strength (9.85 MPa), penetration potential (~700 µm), moisture content (5.95%), elongation (35.54%) and Simvastatin release of 77.92%. Pharmacokinetic properties were also improved, i.e., Cmax 1.97 µg/mL, tmax 9 h, MRT 19.9 h and AUC 46.24 µg·h/mL as compared to Simvastatin solution displaying Cmax 2.55 µg/mL, tmax 3 h, MRT 5.91 h and AUC 14.20 µg·h/mL thus confirming higher and improved bioavailability. Kinetic modelling revealed zero order as the best fit model based on regression coefficient. Histopathological findings proved the biocompatibility of the developed dMNPs.

Optimization of Oxiconazole Topical Emulgel Formulation for the Treatment of Skin Infections

Emulgel is one of the promising topical drug delivery system for the delivery of hydrophobic drugs which overcome a variety of disadvantages of ointments and creams like greasiness as well as phase inversion. The aim of present work was to develop and evaluate Oxiconazole emulgel. Oxiconazole emulgel was prepared by using polymers like Carbopol 934 and HPMC K4M at different concentrations. Oxiconazole is a broad spectrum anti - fungal agent used in treat of various skin infections such as athlete’s foot, jock itch and ring worm. The prepared emulgels were evaluated in terms of physical appearance, measurement of pH, viscosity, spreadability, drug content and in vitro diffusion studies and skin irritation study. Formulation F1 containing carbapol 934 is considered as optimized formulation because it showed highest drug release i.e., 58.57% in 8 hrs.

STUDIES ON POLY HERBAL POWDER SHAMPOO FOR THE TREATMENT OF PEDICULOSIS CAPITIS AND PITYRIASIS CAPITIS INFESTATIONS

Objective: The main objective of this study was to the formulation containing polyherbal medicinal plants, which gives safety, and efficacy; rectify skin disease, scalp disorders and reducing the harmful effect from herbal anti-lice and dandruff shampoos for the treatment of Pediculosis capitis and Pityriasis capitis and to prevent hair fall. Methods: The formulation of herbal shampoo with various herbal ingredients were dried, milled, sieved (120#) and mixed in geometrical order and evaluated their physicochemical characteristics. Furthermore, particle characters, organoleptic properties, foaming index, skin irritation study, and Anti-lice activity were performed. Results: The prepared poly herbal powdered shampoo (PHPS) exhibits that was freely soluble, particle 20-25 μm size range and free-flowing powder. Lest moisture content (2.5%), ash value, acid value and reduced surface tension of liquid are referred as an ideal candidate for foaming, anti-lice potential with no skin irritations. Conclusion: Based on the evaluation parameters, the prepared powdered shampoo helps to remove hair grease, no hair fall and strengthen hair follicles. Preparation of PHPS formulation at laboratory scale and the compounding of several ingredients of herbal source have produced it possible to ensure safety, efficacy and secure highly effective PHPS.

Therapeutic Potential of Standardized Extract of Melilotus indicus (L.) All. and Its Phytochemicals against Skin Cancer in Animal Model: In Vitro, In Vivo, and In Silico Studies.

Melilotus indicus (L.) All. is known to have anti-inflammatory and anticancer properties. The present study explored the in vivo skin carcinogenesis attenuating potential of ethanolic extract of M. indicus (L.) All. (Miet) in a 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer model. The ethanolic extract of the plant was prepared by a maceration method. HPLC analysis indicated the presence of quercetin in abundance and also various other phytoconstituents. DPPH radical scavenging assay results showed moderate antioxidant potential (IC50 = 93.55 ± 5.59 μg/mL). A topical acute skin irritation study showed the nonirritant nature of Miet. Data for the skin carcinogenic model showed marked improvement in skin architecture in Miet and its primary phytochemicals (quercetin and coumarin) treated groups. Miet 50% showed comparable effects with 5-fluorouracil. Significant (p < 0.05) anticancerous effects were seen in coumarin–quercetin combination-treated animals than in single agent (coumarin and quercetin alone)-treated animals. Chorioallantoic membrane (CAM) assay results showed the antiangiogenic potential of Miet. Treatment with Miet significantly down-regulated the serum levels of CEA (carcinoembryonic antigen) and TNF-α (Tumor necrosis factor-α). Data for the docking study indicated the binding potential of quercetin and coumarin with TNF-α, EGFR, VEGF, and BCL2 proteins. Thus, it is concluded that Miet has skin cancer attenuating potential that is proposed to be due to the synergistic actions of its bioactive molecules. Further studies to explore the effects of Miet and its bioactive molecules as an adjuvant therapy with low dose anticancer drugs are warranted, which may lead to a new area of research.

Assessment of nano lipid carrier loaded transdermal patch of rizatriptan benzoate.

Migraine is a neurological disorder and is accompanied by different painful episodes. Hence the maintenance of a steady-state concentration of drug can be beneficial for the patients suffering with migraine. The present investigation focuses on the development of nano lipid carriers (NLCs) loaded transdermal patch of rizatriptan benzoate to sustain the effect of the drug for the enhancement of therapeutic effects. Stearic acid and peanut oil were used to make the NLCs. A central composite design was employed to observe the effect of formulation factors like solid lipid ratio, phase volume ratio, and concentration of surfactants on the formation of nanoparticles. The effects were evaluated for the responses like particle size and entrapment of the drug in the nanocarriers. The optimized formulation was subjected to compatibility, thermal, surface characteristics, and surface morphology studies. The optimized formulation was dispersed in HPMC 15CPS and PVP K30 polymer matrix and the transdermal patch was evaluated for its mechanical properties, drug release study, and skin irritation study. The experimental design was suitable to produce nanosized stable lipid carriers of the drug with high drug entrapment. The drug and excipients were found to be compatible. The thermal and surface characteristics study proved the high loading of drug in the nanoparticles. The surface morphology study showed the formation of irregular-shaped NLCs. The transdermal patch had good mechanical properties. The ex vivo study of the formulated patch showed a sustained release of the drug over 24h. No skin irritation was reported from the transdermal patch. Therefore, it can be concluded that the nanoparticles loaded transdermal patch of rizatriptan benzoate can be promising in controlling the divergent phases of migraine.

Formulation Development and Ex-Vivo Permeability of Curcumin Hydrogels under the Influence of Natural Chemical Enhancers.

Background: The aim of the present research was to formulate and evaluate curcumin hydrogel and to investigate the potential of natural essential oils as permeation enhancers. Methods: Curcumin 2% w/w hydrogel containing various concentrations of eucalyptus oil, aloe vera oil and clove oil was developed using carboxy methyl cellulose (CMC) as a gelling agent. Differential scanning calorimetry and Fourier Transform infrared spectroscopy were used to evaluate the compatibility between the drug and the excipients. In order to assess the efficacy of the formulation; rheological properties, skin irritation studies, in vitro release, ex vivo permeation and retention studies were conducted. Results: DSC and FTIR suggest no in-compatibility between curcumin and excipients. Studies proved that addition of suitable natural permeation enhancers to the hydrogels improved the in vitro release and ex vivo permeation and retention of curcumin. From the various natural essential oils, the aloe vera oil at a concentration of 3% w/w had the greatest effect on the permeability rate and skin retention of the Curcumin and produces the highest enhancement ratio amongst all the concentrations of essential oils examined. Conclusion: Aloe vera oil enhances the permeation of curcumin across the skin by altering the complex structure of the stratum corneum without itself undergoing any change. The developed curcumin hydrogels along with natural essential oils may present an effective choice regarding skin infection/wound healing.