FORMULATION, SYSTEMATIC OPTIMIZATION, IN VITRO, EX VIVO, AND STABILITY ASSESSMENT OF TRANSETHOSOME BASED GEL OF CURCUMIN

Objectives: The current work presents a formulation of curcumin-loaded transethosome (CRM-TE) in the form of a gel and its characterization.Methods: Thirteen formulations were prepared by varying the concentration of Phospholipon 90G as lipid, ethanol, and ratio of lipid: Span using Box- Behnken Design. The optimized formulation was characterized by vesicle size, entrapment efficiency, drug retention, drug permeation through skin, and morphology. Parameters of CRM-TE were compared to other vesicular systems that include liposomes, ethosomes, and transfersomes. Optimized CRM-TE was incorporated into gels, and comparative evaluation was performed. CRM-TE gel was kept at 5±3°C, 25±3°C, and 40±3°C for 180 days, further evaluated for entrapment efficacy and vesicle size.Results: CRM-TE showed 286.4 nm vesicle size, 61.2% entrapment efficiency, 19.8% drug retention, and 71.3% drug permeation at 24 h in the skin. It was found superior in terms of all the parameters as compared to other vesicular formulations. CRM-TE gel also exhibited best characteristics in terms of entrapment efficiency, drug retention, and drug permeation. CRM-TE gel exhibited better stability at 5±3°C in terms of vesicle size and entrapment efficiency as compared to other storage conditions.Conclusion: CRM-TE gel could offer efficient delivery of curcumin through topical route.

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Development and Optimization of Proniosomal Gel Containing Etodolac: In-vitro, Ex-vivo and In-vivo Evaluation

Ars Pharmaceutica (Internet) ◽

10.30827/ars.v62i3.17944 ◽

2021 ◽

Vol 62 (3) ◽

pp. 290-304

Author(s):

Moreshwar Patil ◽

Prashant Pandit ◽

Pavan Udavant ◽

Sandeep Sonawane ◽

Deepak Bhambere

Keyword(s):

Drug Release ◽

Zeta Potential ◽

Ex Vivo ◽

Entrapment Efficiency ◽

In Vivo Evaluation ◽

Vesicle Size ◽

Skin Delivery ◽

The Stability

Introduction: Etodolac is used in the treatment of acute pain and inflammation. It has low solubility because of high hydrophobicity and it is reported that upon oral administration shows gastric disturbances. This encourages the development of topical vesicular formulation. Method: In this work we used coacervation-phase separation method for the development of etodolac loaded vesicular system by using non-ionic surfactants, cholesterol and soya lecithin. Central composite design (rotatble) was used to optimize the concentrations of soy lecithin, surfactant and cholesterol. The prepared formulations were characterized by number of vesicles formed, vesicle size, zeta potential, entrapment efficiency, in-vitro permeation, ex-vivo permeation and anti-inflammatory study. Results: Etodolac was successfully entrapped in all formulations having efficiency in the range of 74.36% to 90.85%, which was more at 4 °C than room temperature. When hydrated with water; niosome in the range of 54 to 141 (per cubic mm) were spontaneously produced. The results of in-vitro diffusion study revealed that etodolac was released in the range of 71.86 to 97.16% over a period of 24 hrs. The average vesicle size of optimized formulation was found 211.9 nm with PDI of 0.5. The observed responses i.e. % encapsulation efficiency and drug release were 74.12 and 95.08 respectively. The zeta potential was -19.4mV revealed the stability of formulation which was further confirmed by no changes in drug content and drug release after stability studies. The % inhibition in paw volume was 40.52% and 43.61% for test and marketed proniosomal gel. Conclusion: Proniosomal gel formulation was stable and could enhance skin delivery of etodolac because of excellent permeation capability of vesicular system.

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FORMULATION AND OPTIMIZATION OF ITRACONAZOLE PRONIOSOMES USING BOX BEHNKEN DESIGN

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i2.23382 ◽

2018 ◽

Vol 10 (2) ◽

pp. 41

Author(s):

Ahmed M. Samy ◽

Afaf A. Ramadan ◽

Amal S.m. Abu El-enin ◽

Yasmin I. M. Mortagi

Keyword(s):

Zeta Potential ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Slow Phase ◽

Optimum Level ◽

Box Behnken Design ◽

Vesicle Size ◽

Transmission Electron ◽

Span 60

Objective: The aim of the present study was to obtain an optimized formula of itraconazole (ITC) proniosomes using Box Behnken design.Methods: Itraconazole proniosomes were prepared using span 60 and/or brij 35 as surfactants, cholesterol and lecithin as a penetration enhancer by slurry method. Various trials have been carried out for investigation of proniosomes. Parameters such as entrapment efficiency (EE%), in vitro drug release, zeta potential, vesicle size and Transmission Electron Microscope were assessed for evaluation of proniosomes.Results: Entrapment efficiency (EE%) was found to be between 78.56% and 95.46%. The release profile of itraconazole proniosomes occurred in two distinct phases, an initial phase for about 8 h, followed by a slow phase for 16 h. The release pattern shown by these formulations was Higuchi diffusion controlled mechanism. The zeta potential values for all itraconazole proniosomes were in the range of-21.71 to-34.53 mV which confirms their stability. All itraconazoleproniosomes formula was found to be nano-sized and were appeared to be spherical in shape with sharp boundaries. One way analysis of variance (ANOVA) study showed that HLB (X1) had the main effects on most responses (Y).Conclusion: Box behnken design facilitates optimization of the formulation ingredients on entrapment efficiency, in vitro release of itraconazole proniosomes, zeta potential and vesicle size. Finally, an optimum level of factors was provided by the optimization process.

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Design and Evaluation of Long Acting Biodegradable PLGA Microspheres for Ocular Drug Delivery

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681210666191223144755 ◽

2019 ◽

Vol 10 ◽

Author(s):

Anjali Pandya ◽

Rajani Athawale ◽

Durga Puro ◽

Geeta Bhagwat

Keyword(s):

Particle Size ◽

Drug Release ◽

Degradation Products ◽

Ex Vivo ◽

Research Work ◽

Entrapment Efficiency ◽

Rational Approach ◽

Plga Microspheres ◽

Long Acting

Background: The research work involves development of PLGA biodegradable microspheres loaded with dexamethasome for intraocular delivery. Objective: To design and evaluate long acting PLGA microspheres for ocular delivery of dexamethasone. Method: Present formulation involves the development of long acting dexamethasone loaded microspheres composed of a biodegradable controlled release polymer, Poly(D, L- lactide-co-glycolide) (PLGA), for the treatment of posterior segment eye disorders intravitreally. PLGA with monomer ratio of 50:50 of lactic acid to glycolic acid was used to achieve a drug release up to 45 days. Quality by Design approach was utilized for designing the experiments. Single emulsion solvent evaporation technique along with high pressure homogenization was used to facilitate formation of microspheres. Results: Particle size evaluation, drug content and drug entrapment efficiency were determined for the microspheres. Particle size and morphology was observed using Field Emission Gun-Scanning Electron Microscopy (FEG-SEM) and microspheres were in the size range of 1-5 μm. Assessment of drug release was done using in vitro studies and transretinal permeation was observed by ex vivo studies using goat retinal tissues. Conclusion: Considering the dire need for prolonged therapeutic effect in diseases of the posterior eye, an intravitreal long acting formulation was designed. Use of biodegradable polymer with biocompatible degradation products was a rational approach to achieve this aim. Outcome from present research shows that developed microspheres would provide a long acting drug profile and reduce the frequency of administration thereby improving patient compliance.

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Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy

Polymers ◽

10.3390/polym13060923 ◽

2021 ◽

Vol 13 (6) ◽

pp. 923

Author(s):

Shadab Md ◽

Nabil A. Alhakamy ◽

Hibah M. Aldawsari ◽

Mohammad Husain ◽

Nazia Khan ◽

...

Keyword(s):

Skin Cancer ◽

Zeta Potential ◽

Skin Permeation ◽

Entrapment Efficiency ◽

Aqueous Solubility ◽

Skin Layer ◽

Vesicle Size ◽

Cytotoxicity Activities

Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efficacy against skin cancer. The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities. The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of −27 ± 5.12 mV and entrapment efficiency of 76.42 ± 9.98%. The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion fluxes of CL gel and GM-loaded gel were 23.31 ±6.0 and 79.43 ± 12.43 µg/ cm2/h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed significantly (p < 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension. Thus, findings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer.

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Effect of Chitosan Coating on PLGA Nanoparticles for Oral Delivery of Thymoquinone: In Vitro, Ex Vivo, and Cancer Cell Line Assessments

Coatings ◽

10.3390/coatings11010006 ◽

2020 ◽

Vol 11 (1) ◽

pp. 6

Author(s):

Sultan Alshehri ◽

Syed Sarim Imam ◽

Md Rizwanullah ◽

Khalid Umar Fakhri ◽

Mohd Moshahid Alam Rizvi ◽

...

Keyword(s):

Breast Cancer ◽

Particle Size ◽

Oral Delivery ◽

Ex Vivo ◽

Cancer Cell Line ◽

Entrapment Efficiency ◽

Plga Nanoparticles ◽

Cancer Management ◽

Mcf 7

In the present study, thymoquinone (TQ)-encapsulated chitosan- (CS)-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were formulated using the emulsion evaporation method. NPs were optimized by using 33-QbD approach for improved efficacy against breast cancer. The optimized thymoquinone loaded chitosan coated Poly (d,l-lactide-co-glycolide) nanoparticles (TQ-CS-PLGA-NPs) were successfully characterized by different in vitro and ex vivo experiments as well as evaluated for cytotoxicity in MDA-MB-231 and MCF-7 cell lines. The surface coating of PLGA-NPs was completed by CS coating and there were no significant changes in particle size and entrapment efficiency (EE) observed. The developed TQ-CS-PLGA-NPs showed particle size, polydispersibility index (PDI), and %EE in the range between 126.03–196.71 nm, 0.118–0.205, and 62.75%–92.17%. The high and prolonged TQ release rate was achieved from TQ-PLGA-NPs and TQ-CS-PLGA-NPs. The optimized TQ-CS-PLGA-NPs showed significantly higher mucoadhesion and intestinal permeation compared to uncoated TQ-PLGA-NPs and TQ suspension. Furthermore, TQ-CS-PLGA-NPs showed statistically enhanced antioxidant potential and cytotoxicity against MDA-MB-231 and MCF-7 cells compared to uncoated TQ-PLGA-NPs and pure TQ. On the basis of the above findings, it may be stated that chitosan-coated TQ-PLGA-NPs represent a great potential for breast cancer management.

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Mannosylated Solid Lipid Nanocarriers Of Chrysin To Target Gastric Cancer: Optimization and Cell line Study.

Current Drug Delivery ◽

10.2174/1567201818666210319142206 ◽

2021 ◽

Vol 18 ◽

Author(s):

Sonia S. Pandey ◽

Farhinbanu I. Shaikh ◽

Arti R. Gupta ◽

Rutvi J. Vaidya

Keyword(s):

Gastric Cancer ◽

Particle Size ◽

Ex Vivo ◽

Biological Effects ◽

Entrapment Efficiency ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Solid Lipid ◽

Lipid Nanocarriers

Background: Despite significant biological effects, the clinical use of chrysin has been restricted because of its poor oral bioavailability. Objective: The purpose of the present research was to investigate the targeting potential of Mannose decorated chrysin (5,7- dihydroxyflavone) loaded solid lipid nanocarrier (MC-SLNs) for gastric cancer. Methods: The Chrysin loaded SLNs (C-SLNs) were developed optimized, characterized and further mannosylated. The C-SLNs were developed with high shear homogenizer, optimized with 32 full factorial designs and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) and Scanning Electron Microscope (SEM) and evaluated for particle size/polydispersity index, zeta-potential, entrapment efficiency, % release and haemolytic toxicity. The ex-vivo cytotoxicity study was performed on gastric cancer (ACG) and normal cell lines. Results: DSC and XRD data predict the chrysin encapsulation in lipid core and FTIR results confirm the mannosylation of C-SLNs. The optimized C-SLNs exhibited a narrow size distribution with a particle size of 285.65 nm. The % Entrapment Efficiency (%EE) and % controlled release were found to be 74.43% and 64.83%. Once C-SLNs were coated with mannose, profound change was observed in dependent variable - increase in the particle size of MC-SLNs (307.1 nm) was observed with 62.87% release and 70.8% entrapment efficiency. Further, the in vitro studies depicted MC- SLNs to be least hemolytic than pure chrysin and C-SLNs. MC-SLNs were most cytotoxic and were preferably taken up ACG tumor cells as evaluated against C-SLNs. Conclusion: These data suggested that the MC-SLNs demonstrated better biocompatibility and targeting efficiency to treat the gastric cancer.

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FORMULATION, OPTIMIZATION AND IN VITRO EVALUATION OF 5-FLUOROURACIL LOADED LIQUORICE CRUDE PROTEIN NANOPARTICLES FOR SUSTAINED DRUG DELIVERY USING BOX-BEHNKEN DESIGN

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2021v13i1.39932 ◽

2021 ◽

pp. 216-226

Author(s):

GEETHA V. S. ◽

MALARKODI VELRAJ

Keyword(s):

Drug Delivery ◽

Particle Size ◽

Drug Release ◽

Crude Protein ◽

Drug Loading ◽

Entrapment Efficiency ◽

Box Behnken Design ◽

Sustained Drug Delivery ◽

Drug Loading Efficiency

Objective: To formulate, optimize and evaluate 5-fluorouracil loaded liquorice crude protein nanoparticles for sustained drug delivery using Box-Behnken design. Methods: 5-fluorouracil (5-FU) loaded liquorice crude protein (LCP) nanoparticles were prepared by desolvation method using ethanol-water (1:2 ratio), Tween-80 (2%v/v) as stabilizing agent and gluteraldehyde (8% v/v) as cross linking agent. The optimization of prepared nanoparticles was carried out using Box-Behnken design with 3 factors 2 levels and 3 responses. The independent variables were A)5-FU concentration B)LCP concentration and C) sonication time while the responses were R1) Drug entrapment efficiency R2) Drug loading efficiency and R3) Particle size. The correlation between factors and responses were studied through response surface plots and mathematical equations. The nanoparticles were evaluated for FTIR, physicochemical properties like particle size and zeta potential by Photon correlation spectroscopy (PCS) and surface morphology by TEM. The entrapment efficiency, drug loading efficiency and in vitro drug release studies in PBS pH 7.4 (24 h) were carried out. The observed values were found to be in close agreement with the predicted value obtained from the optimization process. Results: 5-fluorouracil loaded LCP nanoparticles were prepared by desolvation method, the optimization was carried out by Box-Behnken design and the final formulation was evaluated for particle size (301.1 nm), zeta-potential (-25.8mV), PDI(0.226), with entrapment efficiency (64.07%), drug loading efficiency (28.54%), in vitro drug release (65.2% in 24 h) respectively. The formulated nanoparticles show Higuchi model drug release kinetics with sustained drug delivery for 24 h in pH7.4 buffer. Conclusion: The results were proved to be the most valuable for the sustained delivery of 5-Fluorouracil using liquorice crude protein as carrier. 5-FU–LCP nanoparticles were prepared using Tween-80 as stabilizing agent and gluteraldehyde as cross-linking agent to possess ideal sustained drug release characteristics.

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Olive Oil Based Organogels for Effective Topical Delivery of Fluconazole: In-vitro Antifungal Study

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2020/v32i2530821 ◽

2020 ◽

pp. 29-36

Author(s):

Mohammad Muqtader Ahmed ◽

Farhat Fatima ◽

Abdul Bari Mohammed

Keyword(s):

Olive Oil ◽

Ex Vivo ◽

Similarity Index ◽

Ex Vivo Permeation ◽

Efficient Delivery ◽

In Vitro Diffusion ◽

Permeation Studies ◽

The Stability ◽

Hot Melt

The objective of the study was to formulate olive oil based organogels for the topical application of fluconazole (FLZ), to ensure the efficient delivery of the drug deeper in to the skin layers. Methods: Nine formulations developed by hot-melt method using olive oil, sorbitan monostearate (SMS) and FLZ. Prepared formulations characterized for macro evaluations, pH, spreadibility, viscosity, gel-sol transition, in-vitro diffusion study. Further optimized formulation evaluated for ex-vivo percutaneous permeation, in-vitro antifungal studies and stability studies by similarity index. Results: The results of evaluated parameters ensure the stability and effectiveness of the prepared olive oil based organogels. In-vitro diffusion studied reflects decrease in drug release with increase in surfactant concentration due to increase in viscosity. Moreover, ex-vivo permeation studies revealed that the permeation of FLZ was enhanced for optimized formulations (F6) as compared to the marketed gel formulation. Further, the optimized formulation exhibits the broad zone of inhibition against fungal strains in comparison to control and marketed product during in-vitro antifungal study. Conclusion: The olive oil based organogels formulation shown the enhanced permeation of FLZ from organogel network structure with good antifungal activity as compared to the marketed formulation. Henceforth, the FLZ organogel formulations could be used topically for the effective treatment of fungal infection.

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Bioassay-guided optimization of lipid-based erythromycin microparticles

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i7.2 ◽

2020 ◽

Vol 19 (7) ◽

pp. 1351-1358

Author(s):

Ifeanyi T. Nzekwe ◽

Anselm C. Okere ◽

Ifeanyi E. Okoye ◽

Kokonne E. Ekere ◽

Adaobi A. Ezenwa ◽

...

Keyword(s):

Ex Vivo ◽

Drug Loading ◽

Entrapment Efficiency ◽

Antimicrobial Activities ◽

Hydrodynamic Size ◽

Chemical Assay ◽

Acid Ratio ◽

Drug Entrapment Efficiency ◽

Lower Variation

Purpose: To optimize erythromycin microparticles by in vitro bioassay methods based on its antibacterial activity. Methods: The microparticles were produced by high shear homogenization. The effects of different lipid-to-surfactant ratios were studied. The hydrodynamic size of the different batches was evaluated using dynamic light scattering while bioactive drug load per batch was assessed in agar using bioassay methods. The antimicrobial activities of selected batches were tested ex vivo by determination of reduction in bacteraemia following administration of the microparticles to infected animals. Results: All batches had particles with hydrodynamic sizes < 8.5 microns. Batch 7 with a 2: 5: 2.5 (drug: surfactant: stearic acid) ratio, represents the optimized batch with a hydrodynamic size of 2281 nm, a bioactive drug loading capacity (BLC) of 4.67 ± 0.70 % and bioactive drug entrapment efficiency (BEE) of 10.51 %. The “microparticle MIC” against Staphylococcus aureus was 1.74 x 10-3 μg/ml. Despite containing lower amounts of erythromycin than the pure sample, the microparticles achieved comparable reduction in bacteraemia, with the optimized batch exhibiting lower variation in bacteraemia than the pure drug. Conclusion: Erythromycin microparticles have been successfully optimized with the aid of bioassay methods which has the advantage that only the bioactive drug concentration is factored in. This method eliminates problems posed by inadequate or non-discriminating chemical assay methods. Keywords: Microparticles, Erythromycin, Gastrointestinal, Bioavailability Antimicrobial, Bioactivity, Encapsulation

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Formulation, Development and Evaluation of Ibuprofen Loaded Nano-transferosomal Gel for the Treatment of Psoriasis

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2019/v31i630356 ◽

2019 ◽

pp. 1-8

Author(s):

Marwa H. Abdallah ◽

Amr S. Abu Lila ◽

Md. Khalid Anwer ◽

El-Sayed Khafagy ◽

Muqtader Mohammad ◽

...

Keyword(s):

Drug Release ◽

Zeta Potential ◽

Drug Loading ◽

Entrapment Efficiency ◽

Tween 80 ◽

Formulation Development ◽

In Vitro Drug Release ◽

Vesicle Size

The present work was aimed to develop a transferosomal gel of ibuprofen (IBU) for the amelioration of psoriasis like inflammation. Three formulation of IBU loaded transferosomes (TFs1-TFs3) were prepared using different proportions of lipid (phospholipon 90H) and surfactant (tween 80) and further evaluated for vesicle size, zeta potential (ZP), entrapment efficiency and in vitro drug release. The IBU loaded transferosomes (TFs2) was optimized with vesicle size (217±8.4 nm), PDI (0.102), ZP (-31.5±4.3 mV), entrapment efficiency (88.4±6.9%) and drug loading (44.2±2.9%). Further, the optimized IBU loaded transferosomes (TFs2) was incorporated into 1% carbopol 934 gel base and characterized for homogeneity, extrudability, viscosity and drug content. The in vivo pharmacodynamic study of gel exhibited reduction in psoriasis like inflammation in mice. The ibuprofen loaded transferosomal gel was successfully developed and has shown the potential to be a new therapy against psoriasis like inflammation.

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