Dermal Delivery of Meloxicam Nanosuspensions based Gel: Optimization with Box Behnken Design Experiment Approach: Ex Vivo and In Vivo Study

2020 ◽  
Vol 10 (6) ◽  
pp. 766-777
Author(s):  
Inayat B. Pathan ◽  
Mahesh Sakhare ◽  
Wahid Ambekar ◽  
Chitral M. Setty
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Skin Irritation ◽  
Oral Route ◽  
Stability Study ◽  
In Vivo Study ◽  
Therapeutic Effects ◽  
Box Behnken Design

Background: Transdermal delivery of meloxicam is advantageous than the oral route in the treatment of pain management. Objective: The goal of the present study is to formulate and evaluate meloxicam (MX) loaded nanosuspensions based gel for transdermal application. Methods: The formulation parameters were optimized using Box Behnken design (BBD) taking three independent variables and three responses. Formulations were evaluated for particle size (nm), polydispersity index (PDI), zeta potential (mV), ex vivo permeation, in vivo study, morphology, FTIR, skin irritation and, stability study. Optimized formulation having Poloxamer 188 (0.4 mg), PVP K30 (0.5 mg) and sonication time (60 min.) demonstrated smaller particle size (159.2 ± 3.5 nm), low PDI (0.120 ± 0.01) and higher zeta potential value (-29 ± 4mV). Results: In the ex vivo study, MX-NG showed a significant increase (p<0.05) in the flux (24.40 ± 2.6 μg/cm2/h) of meloxicam through the human cadaver skin as compared to other formulations. In the in- vivo study, MX-NG showed a significant (p<0.05) increase in anti-inflammatory activity as compared to marketed gel. Conclusion: Thus, it is concluded that the developed meloxicam loaded nanosuspensions based gel showed maximum therapeutic effects in rats.

scholarly journals Formulation and Characterization of Carvedilol Leciplex for Glaucoma Treatment: In-Vitro, Ex-Vivo and In-Vivo Study

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 197 ◽  
Author(s):  
Doaa Hassan ◽  
Rehab Abdelmonem ◽  
Menna Abdellatif
Keyword(s):  
Particle Size ◽  
Intraocular Pressure ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Molar Ratio ◽  
Duration Of Action ◽  
Corneal Permeability ◽  
Glaucoma Treatment

This study evaluated the efficacy of cationic nanoparticle (leciplex) to deliver carvedilol to ocular surface for glaucoma treatment as recent studies pointed out the effect of topical carvedilol on intraocular pressure, therefore carvedilol loaded leciplex formulae were prepared using soy phosphatidyl choline (SPC) and cationic surfactant (CTAB/DDAB) and characterized for morphology, entrapment efficiency, particle size, zeta potential and ex-vivo corneal permeation. Then the selected formula was evaluated via in-vivo studies in comparison with carvedilol solution. Leciplex nanoparticles appeared spherical in shape with entrapment efficiency exceeded 95% in all formulae. Leciplex formula composed of SPC and DDAB in (1:1) molar ratio showed the smallest particle size (16.04 ± 1.2 nm), highest zeta potential value (53.9 ± 0.91 mv) and highest apparent corneal permeability coefficient (0.1157 cm/h). Carvedilol leciplex reduced intraocular pressure (IOP) to normal range in ocular hypertensive rabbits after 30 min and duration of action lasted for 24 h, while carvedilol solution reduced IOP to normal value after 60 min and duration of action lasted for 6 h. Furthermore, histological examination of eyeballs of rabbits treated with carvedilol leciplex showed improvement of retinal atrophy of glaucomatous eyes. This study concluded that leciplex improve transcorneal permeation and bioavailability of carvedilol.

scholarly journals Enhanced Oral Bioavailability of Celecoxib Nanocrystalline Solid Dispersion based on Wet Media Milling Technique: Formulation, Optimization and In Vitro/In Vivo Evaluation

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 328 ◽  
Author(s):  
Zhuang Ding ◽  
Lili Wang ◽  
Yangyang Xing ◽  
Yanna Zhao ◽  
Zhengping Wang ◽  
...  
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Stability Study ◽  
Sprague Dawley ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Celecoxib (CLX), a selective COX-2 inhibitor, is a biopharmaceutics classification system (BCS) class II drug with its bioavailability being limited by thepoor aqueoussolubility. The purpose of this study was to develop and optimize CLX nanocrystalline(CLX-NC) solid dispersion prepared by the wet medium millingtechnique combined with lyophilizationto enhance oral bioavailability. In formulation screening, the resulting CLX-NC usingpolyvinylpyrrolidone (PVP) VA64 and sodiumdodecyl sulfate (SDS) as combined stabilizers showed the minimum particle size and a satisfactory stability. The formulation and preparation processwere further optimized by central composite experimentaldesign with PVP VA64 concentration (X1), SDS concentration (X2) and milling times (X3) as independent factors and particle size (Y1), polydispersity index (PDI, Y2) and zeta potential (Y3) as response variables. The optimal condition was determined as a combination of 0.75% PVP VA64, 0.11% SDS with milling for 90 min.The particle size, PDI and zeta potential of optimized CLX-NC were found to be 152.4 ± 1.4 nm, 0.191 ± 0.012 and −34.4 ± 0.6 mV, respectively. The optimized formulation showed homogeneous rod-like morphology as observed by scanning electron microscopy and was in a crystalline state as determined by differential scanning calorimetry and powder X-ray diffraction. In a storage stability study, optimized CLX-NC exhibited an excellent physical stability during six months’ storage at both the refrigeration and room conditions. In vivo pharmacokinetic research in Sprague-Dawley ratsdisplayed that Cmax and AUC0–∞ of CLX-NC were increased by 2.9 and 3.1 fold, compared with physical mixture. In this study, the screening and optimizing strategy of CLX-NC formulation represents a commercially viable approach forenhancing the oral bioavailability of CLX.

scholarly journals Nobiletin-loaded composite penetration enhancer vesicles restore the normal miRNA expression and the chief defence antioxidant levels in skin cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mahitab Bayoumi ◽  
Mona G. Arafa ◽  
Maha Nasr ◽  
Omaima A. Sammour
Keyword(s):  
Particle Size ◽  
Skin Cancer ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Physical Stability ◽  
Entrapment Efficiency ◽  
Penetration Enhancer ◽  
Oxidative Stress Biomarkers ◽  
Skin Deposition

AbstractSkin cancer is one of the most dangerous diseases, leading to massive losses and high death rates worldwide. Topical delivery of nutraceuticals is considered a suitable approach for efficient and safe treatment of skin cancer. Nobiletin; a flavone occurring in citrus fruits has been reported to inhibit proliferation of carcinogenesis since 1990s, is a promising candidate in this regard. Nobiletin was loaded in various vesicular systems to improve its cytotoxicity against skin cancer. Vesicles were prepared using the thin film hydration method, and characterized for particle size, zeta potential, entrapment efficiency, TEM, ex-vivo skin deposition and physical stability. Nobiletin-loaded composite penetration enhancer vesicles (PEVs) and composite transfersomes exhibited particle size 126.70 ± 11.80 nm, 110.10 ± 0.90 nm, zeta potential + 6.10 ± 0.40 mV, + 9.80 ± 2.60 mV, entrapment efficiency 93.50% ± 3.60, 95.60% ± 1.50 and total skin deposition 95.30% ± 3.40, 100.00% ± 2.80, respectively. These formulations were selected for cytotoxicity study on epidermoid carcinoma cell line (A431). Nobiletin-loaded composite PEVs displayed the lowest IC50 value, thus was selected for the in vivo study, where it restored skin condition in DMBA induced skin carcinogenesis mice, as delineated by histological and immuno-histochemical analysis, biochemical assessment of skin oxidative stress biomarkers, in addition to miRNA21 and miRNA29A. The outcomes confirmed that nobiletin- loaded composite PEVs is an efficient delivery system combating skin cancer.

scholarly journals Design and Optimization of Cationic Nanocapsules for Topical Delivery of Tretinoin: Application of the Box-Behnken Design, In Vitro Evaluation, and Ex Vivo Skin Deposition Study

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Saeed Ebrahimi ◽  
Reza Mahjub ◽  
Rasool Haddadi ◽  
Seyed Yaser Vafaei
Keyword(s):  
Particle Size ◽  
Ex Vivo ◽  
Skin Permeation ◽  
Skin Irritation ◽  
In Vitro Release ◽  
Topical Delivery ◽  
Free Drug ◽  
Acrylic Polymer ◽  
Box Behnken Design

Cationic nanocapsules represent a promising approach for topical delivery purposes. We elaborated on a novel formulation based on the cationic nanocapsules to enhance the pharmacodynamic efficacy, user compliance, and photostability of tretinoin (TTN). To achieve this goal, TTN nanocapsules were prepared by the nanoprecipitation method. In order to statistically optimize formulation variables, a Box-Behnken design, using Design-Expert software, was employed. Three independent variables were evaluated: total weight of the cationic acrylic polymer ( X 1 ), oil volume ( X 2 ), and TTN amount ( X 3 ). The particle size and encapsulation efficiency percent (EE%) were selected as dependent variables. The optimal formulation demonstrated spherical morphology under scanning electron microscopy (SEM), optimum particle size of 116.3 nm, and high EE% of 83.2%. TTN-loaded nanocapsules improved photostability compared to its methanolic solution. The in vitro release study data showed that tretinoin was released in a sustained manner compared to the free drug. The ex vivo skin permeation study demonstrated that greater drug deposition into the epidermal region rather than the deep skin was observed with a gel containing TTN-loaded nanocapsules than that of drug solution, respectively. The skin irritation test revealed that the nanoencapsulation of the drug decreased its irritancy compared to the free drug. These results revealed the promising potential of cationic nanocapsules for topical delivery of tretinoin

Quercetin Loaded Nanostructured Lipid Carriers-based Gel for Rheumatoid Arthritis: Formulation, Characterization and in vivo Evaluation

2018 ◽  
Vol 11 (1) ◽  
pp. 3967-3977
Author(s):  
Jayanti P Gokhale ◽  
Sanjay S Surana
Keyword(s):  
Rheumatoid Arthritis ◽  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
Blood Cells ◽  
Ex Vivo ◽  
In Vitro Drug Release ◽  
Texture Profile

Present research work describes the development of potential topical treatment containing nanostructured lipid carriers (NLCs) for rheumatoid arthritis (RA). Quercetin (QCT) is a renowned flavonol useful as model drug for carriers. QCT loaded NLCs were prepared and evaluated for particle size distribution, polydispersity index, zeta potential analysis, in vitro drug release study. Ex vivo study was carried out to evaluate the effect of NLCs on cell proliferation (HIG-82 cell line) and inflammation (TNF-α induction in RAW264.7 cells). The QCT-NLCs showed mean particle size of 155.6 ± 1.8 nm and polydispersity index (PDI) was 0.236 ± 0.4, entrapment efficiency of 95.63 ± 0.14 % and zeta potential of -27 ± 1.2 mV. For the ease of application, NLCs were incorporated into the gel base and final formulation was evaluated for rheological study, texture profile, drug release and antiarthritic activity. QCT-NLC gel showed pseudo plastic flow behavior with excellent texture profile parameters. In vitro drug release studies showed that, QCT-NLC gel has more prominent permeation profile as compared with QCT-loaded gel. In vivo activity was carried out using Complete Freund's adjuvant (CFA) induced arthritic model. Evaluation of the severity of rheumatoid arthritis was done by measurements of hind paw volume, arthritis score and haematological parameters such as rheumatoid factor (RF), C-reactive protein (CRP), red blood cells (RBCs), white blood cells (WBCs), erythrocyte sedimentation rate (ESR) and hemoglobin (Hb). Edema and erythema were not observed after administration of QCT-NLC- gel on the rat skin. In conclusion, the results of in vitro and ex vivo studies, QCT-NLC gel appears a viable formulation system for topical delivery of QCT in the treatment of RA.         

scholarly journals Design, Formulation, In-Vitro and Ex-Vivo Evaluation of Atazanavir Loaded Cubosomal Gel

2020 ◽  
Vol 11 (4) ◽  
pp. 12037-12054
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Relative Bioavailability ◽  
Transdermal Application ◽  
Study Results ◽  
Nano Formulation

In this study, Atazanavir (ATZ) was designed into the Nano formulation called cubosomes to improve its bioavailability and curtail the adverse effects by the transdermal route delivery of ATZ -loaded cubosomes. Around twenty cubosomal formulations were formulated using a Central composite factorial design. The effect of glyceryl monooleate (GMO), surfactant (Pluronic F 127), and Cetyltrimethylammonium bromide (CTAB) were studied using processes of emulsification and homogenization. Different concentrations of independent variables on particle size distribution, zeta potential, and entrapment efficiency were determined. FTIR, DSC, X-ray, and SEM, TEM results established that the drug was encapsulated in the cubosomes. The results suggested that the optimal formula exhibited a particle size of 100±7.9 - 345±6.4 nm and entrapment efficiency ranging from 61±4.6 - 93±0.8, zeta potential values ranging from -24.51 to -32.45 mV, polydispersity index values ranged from 0.35±0.01-0.54±0.02 of ATZ. The in vitro studies showed a controlled release pattern of drug release up to 24h. The ATZ cubosomal gel application on the in vivo absorption studies of the drug was studied in rats and compared with oral ATZ solution. The in vivo study results showed that the transdermal application of ATZ cubosomal gel considerably improves the absorption of drug compared to that of oral ATZ solution and found that the relative bioavailability is 4.6 times greater of oral ATZ solution. Thus it can be concluded that the ATZ cubosomal gel application via transdermal delivery route has the potential in increasing the bioavailability of the drug.

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

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.

scholarly journals FORMULATION AND EVALUATION OF NANOSTRUCTURED LIPID CARRIERS BASED ANTI-INFLAMMATORY GEL FOR TOPICAL DRUG DELIVERY SYSTEM

2019 ◽  
pp. 286-291
Author(s):  
ROHINI S KHARWADE ◽  
NILESH M MAHAJAN
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
Skin Irritation ◽  
In Vitro Release ◽  
Stability Study ◽  
Nanostructured Lipid Carrier ◽  
Topical Gel ◽  
Rat Paw Edema

Objective: Nanostructured lipid carrier (NLC)-based topical gel of lornoxicam (LXM) was formulated with the aim of controlled release action and to reduce systemic side effect for the treatment of an arthritic condition. Methods: NLCs developed using high-pressure homogenization method and optimized using a 32 factorial design with response surface methodology using design expert software. NLCs were characterized for particle size, zeta potential analysis, drug entrapment efficiency, and in vitro drug release studies to select the optimized formulation. The NLCs were suitably gelled and evaluated with respect to homogeneity, pH, viscosity, gel strength, spreadability, rheological characteristics, drug content, in vitro diffusion, and stability study. Safety of the NLC-based gel was assessed using primary skin irritation studies, and efficacy was confirmed using carrageenan-induced rat paw edema model. Results: NLCs formulation comprising 2% of lipid (60:40) and surfactant (1.50%) was confirmed as an optimized batch having a particle size (138.2±3.60 nm) with polydispersibility index value 0.344±0.034. The zeta potential value indicates good physical stability. Based on the results from the in vitro release study it was shown that the formed gels had the ability to extend release of LXM for 24 h and showing percentage drug release of 90.92%±1.96% at the end of 24 h. Skin irritation studies revealed that the optimized gel formulation shows no erythema, edema, or ulceration. Conclusion: The overall results of the present study clearly indicated promising potentials of NLC-based gel for delivering LXM topically over the conventional gel.

Formulation and Evaluation of Nanosuspension of Simvastatin

2015 ◽  
Vol 8 (2) ◽  
pp. 2858-2873
Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Factorial Design ◽  
Dissolution Rate ◽  
In Vitro Dissolution ◽  
Total Drug ◽  
23 Factorial Design ◽  
Rate Of Dissolution

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.

scholarly journals Investigating the Feasibility of Mefenamic Acid Nanosuspension for Pediatric Delivery: Preparation, Characterization, and Role of Excipients

Processes ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 574
Author(s):  
Nikhat Perween ◽  
Sultan Alshehri ◽  
T. S. Easwari ◽  
Vivek Verma ◽  
Md. Faiyazuddin ◽  
...  
Keyword(s):  
Particle Size ◽  
Mefenamic Acid ◽  
Hydroxypropyl Methylcellulose ◽  
Sodium Dodecyl ◽  
Aqueous Solubility ◽  
Oral Route ◽  
Precipitation Method ◽  
Antisolvent Precipitation

Molecules with poor aqueous solubility are difficult to formulate using conventional approaches and are associated with many formulation delivery issues. To overcome these obstacles, nanosuspension technology can be one of the promising approaches. Hence, in this study, the feasibility of mefenamic acid (MA) oral nanosuspension was investigated for pediatric delivery by studying the role of excipients and optimizing the techniques. Nanosuspensions of MA were prepared by adopting an antisolvent precipitation method, followed by ultrasonication with varying concentrations of polymers, surfactants, and microfluidics. The prepared nanosuspensions were evaluated for particle size, morphology, and rheological measures. Hydroxypropyl methylcellulose (HPMC) with varying concentrations and different stabilizers including Tween® 80 and sodium dodecyl sulfate (SLS) were used to restrain the particle size growth of the developed nanosuspension. The optimized nanosuspension formula was stable for more than 3 weeks and showed a reduced particle size of 510 nm with a polydispersity index of 0.329. It was observed that the type and ratio of polymer stabilizers were responsive on the particle contour and dimension and stability. We have developed a biologically compatible oral nanoformulation for a first-in-class drug beautifully designed for pediatric delivery that will be progressed toward further in vivo enabling studies. Finally, the nanosuspension could be considered a promising carrier for pediatric delivery of MA through the oral route with enhanced biological impact.

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