scholarly journals Experimental Design Based Optimization and Ex Vivo Permeation of Desmopressin Acetate Loaded Elastic Liposomes Using Rat Skin

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1047
Author(s):  
Mohammad A. Altamimi ◽  
Afzal Hussain ◽  
Sultan Alshehri ◽  
Syed Sarim Imam
Keyword(s):  
Diabetes Insipidus ◽  
Transdermal Delivery ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Central Diabetes Insipidus ◽  
Permeation Flux ◽  
Rat Skin ◽  
Suitable Alternative ◽  
Vesicle Size

The study aimed to develop elastic-liposome-based transdermal delivery of desmopressin acetate for enhanced permeation to control enuresis, central diabetes insipidus, and traumatic injury. Elastic liposomes (ELs)-loaded desmopressin acetate was prepared, optimized, and evaluated for improved transdermal permeation profiles using rat skin. Full factorial design with independent factors (X1 for lipid and X2 for surfactant) at three levels was used against four responses (Y1, Y2, Y3, and Y4) (dependent variables). Formulations were characterized for vesicle size, polydispersity index (PDI), zeta potential, % entrapment efficiency (% EE), in vitro drug release, in vitro hemolysis potential, ex vivo drug permeation and drug deposition (DD), and ex vivo vesicle–skin interaction using scanning electron microscopy studies. The optimized formulation ODEL1 based on desirability function was found to have vesicle size, % EE, % DR, and permeation flux values of 118.7 nm, 78.9%, 75.1%, and 5.3 µg/h·cm2, respectively, which were close to predicted values. In vitro release profiles indicated slow and sustained delivery. Permeation flux values of ODEL1 and ODEL2 were 5.3 and 3.1 µg/h·cm2, respectively, which are 7.5- and 4.4-fold higher as compared to DS (0.71 µg/h·cm2). The obtained flux was relatively higher than the clinical target value of the drug for therapeutic efficacy. Moreover, the DD value of ODEL1 was significantly higher than ODEL2 and DS. Hemocompatibility study confirmed safety concerns. Finally, vesicle–skin interaction corroborated mechanistic views of permeation through rat skin. Conclusively, the transdermal delivery may be a suitable alternative to oral and nasal delivery to treat nocturnal enuresis, central diabetes insipidus, hemophilia A and von Willebrand’s disease, and any traumatic injuries.

Sodium alginate nanoparticles as a new transdermal vehicle of glucosamine sulfate for treatment of osteoarthritis

2017 ◽  
Vol 9 (3-4) ◽  
Author(s):  
Asmaa S. El-Houssiny ◽  
Azza A. Ward ◽  
Dina M. Mostafa ◽  
Salwa L. Abd-El-Messieh ◽  
Kamal N. Abdel-Nour ◽  
...  
Keyword(s):  
Side Effects ◽  
Surface Charge ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Glucosamine Sulfate ◽  
Suspension Stability ◽  
Rat Skin ◽  
Release Studies ◽  
Vitro Release

AbstractGlucosamine sulfate (GS) has been used orally for the treatment of osteoarthritis (OA). However, it may be susceptible to the liver first pass phenomenon, which greatly affects its bioavailability, in addition to its side effects on the gastrointestinal tract. Alginate nanoparticles (Alg NPs) were investigated as a new drug carrier for transdermal delivery of GS to improve its effectiveness and reduce side effects. GS-Alg NPs were characterized by encapsulation efficiency, NP yield, particle size and surface charge properties. The in vitro release studies of GS and the ex vivo permeability through rat skin were determined using a UV-Vis spectrophotometer. GS-Alg NPs are within the nanometer range of size. High negative surface charge values are obtained and indicate the high suspension stability of the prepared formulation. The in vitro release studies showed that GS is released from Alg NPs in a sustained and prolonged manner. The ex vivo permeability of GS through rat skin is enhanced significantly after encapsulation in the negatively charged Alg NPs. We successfully reported a highly stable nanoparticlulate system using Alg NPs that permits the encapsulation of GS for topical administration, overcoming the disadvantages of oral administration.

Elastic Bilayer Vesicles of Flurbiprofen for Transdermal Delivery: Development and In-Vitro Characterization

2020 ◽  
Vol 10 (1) ◽  
pp. 54-60
Author(s):  
Rashmi Sareen ◽  
Nitin Jain
Keyword(s):  
Transdermal Delivery ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Systemic Circulation ◽  
Molar Ratio ◽  
Vesicle Size ◽  
Cholesterol Ratio ◽  
Niosomal Gel ◽  
Span 60

Objective: The purpose of the present study was to develop a novel elastic bilayer vesicle entrapped with Flurbiprofen (FLB) for transdermal use to avoid adverse effect associated with oral administration of the drug. Encapsulation of drug in vesicle prolongs the existence of the drug in the systemic circulation and thus enhances penetration into the target site and reduces toxicity. Method: Niosomes were prepared using surfactants (span 40 and span 60) and cholesterol in the molar ratio of 1:1, 2:1, 3:1 and 3:2. Vesicles prepared by thin film hydration method were characterized for morphology, vesicle size and zeta potential, thermal analysis and Entrapment Efficiency (EE). Results: Results revealed that the EE and size of niosomes were influenced by surfactant type and cholesterol ratio. F8 (span 60: cholesterol in 3:2) exhibited the highest encapsulation of FLB (76.77 ± 0.55) with vesicle size of 154 ± 2.96 nm and Polydispersity Index (PDI) of 0.09. The optimized formulation F8 was selected for incorporation into the gel. Niosomal gel was evaluated for homogeneity, pH, spreadability and in-vitro drug release. Conclusion: All the parameters of niosomal gel were found to be satisfactory and in-vitro release study revealed prolonged and complete release of entrapped FLB (93.23±0.65%) in comparison to FLB hydrogel (42.65±0.29%). The results suggested that niosomes may serve as promising vehicles for the transdermal delivery of FLB.

Improved in vitro Release and ex vivo Permeation of Zotepine as Microemulsion Gel Formulation through Transdermal Application

2021 ◽  
Vol 14 (1) ◽  
pp. 5343-5352
Author(s):  
Akhila Keshoju ◽  
Dinesh Suram ◽  
Chandra Mouli Golla ◽  
Nagaraj B
Keyword(s):  
Ex Vivo ◽  
In Vitro Release ◽  
Gelling Agent ◽  
Prolonged Release ◽  
Rat Skin ◽  
Skin Delivery ◽  
Ex Vivo Permeation ◽  
Vitro Release ◽  
Microemulsion Gel

Zotepine is atypical antipsychotic drug with poor oral bioavailability due to first-pass metabolism and poor aqueous solubility. The objective of the current investigation was preparation and ex vivo characterization of Zotepine (ZT) loaded microemulsion (ZT-ME) and microemulsion gel (ZT-MEG) for enhanced transdermal delivery.  ZT-ME formulation was prepared with 7.5% oleic acid, 30% w/v of Tween80 and 30%w/v of absolute ethanol as oil, surfactant and cosurfactant, respectively. Optimized ZT-ME formulation was selected and converted to ZT-MEG using carbopol as gelling agent. ZT-ME and ZT-MEG subjected to in vitro release and ex vivo permeation studies through rat skin, comparison with ZT coarse suspension (ZT-CS). ZT-ME formulation showed desirable physicochemical properties and stable with dilution stress. Prepared ZT-MEG formulation has showed better rheological behaviour and good spreadability. ZT-ME and ZT-MEG showed prolonged release compared with ZT-CS formulation over 24 h. ZT-ME and ZT-MEG exhibited 5-folds and 3.5-folds in permeation through rat skin compared with ZT-CS formulation. Overall, ZT-MEG formulation could be considered as an alternative delivery approach for enhanced skin delivery. 

scholarly journals Influence of Oleic Acid on the Rheology and in Vitro Release of Lumiracoxib from Poloxamer Gels

2010 ◽  
Vol 13 (2) ◽  
pp. 286 ◽  
Author(s):  
Tailane Sant´Anna Moreira ◽  
Valéria Pereira De Sousa ◽  
Maria Bernadete Riemma Pierre
Keyword(s):  
Oleic Acid ◽  
Rheological Behavior ◽  
Transdermal Delivery ◽  
In Vitro Release ◽  
Delivery Systems ◽  
Penetration Enhancer ◽  
Release Studies ◽  
Vitro Release ◽  
Gel Transition

Abstract PURPOSE: Transdermal delivery of anti-inflammatory lumiracoxib (LM) could be an interesting strategy to avoid the side effects associated with systemic delivery, but it is ineffective due to the drug poor skin penetration. We have investigated the effects of oleic acid (OA), a lipid penetration enhancer, on the in vitro release of LM from poloxamer-based delivery systems (PBDS). The rheological behavior (shear rate dependent viscosity) and gelation temperature through measurements of optimal sol-gel transition temperatures (Tsol-gel) were also carried out in these systems. METHODS: In vitro release studies of LM from PBDS were performed using cellulose acetate as artificial membrane mounted in a diffusion system. The amount of LM released was divided by exposition area (µg/cm2) and these values were plotted as function of the time (h). The flux of the drug across the membrane (J) was calculated from the slope of the linear portion of the plot and expressed as µg/cm2. h -1. The determination of viscosity was carried out at different shear rates (γ) between 0.1- 1000 S-1 using a parallel plate rheometer. Oscillatory measurements using a cone-plate geometry rheometer surrounded by a double jacket with temperature varying 4-40°C, was used in order to determine Tsol-gel. RESULTS: Increase of both polymer and OA concentrations increases the viscosity of the gels and consequently reduces the in vitro LM release from the PBDS, mainly for gels containing OA at 10.0% compared to other concentrations of the penetration enhancer. Tsol-gel transition temperature was decreased by increasing viscosity; in some cases the formulation was already a gel at room temperature. Rheological studies showed a pseudoplastic behavior, which facilitates the flow and improves the spreading characteristics of the formulations. CONCLUSIONS: Taken together, the results showed that poloxamer gels are good potential delivery systems for LM, leading to a sustained release, and also have appropriate rheological characteristics. Novelty of the work: A transdermal delivery of non-steroidal antinflammatory drugs like lumiracoxib (LM) can be an interesting alternative to the oral route of this drug, since it was recently withdraw of the market due to the liver damage when systemically administered in tablets as dosage form. There are no transdermal formulations of LM and it could be an alternative to treat inflammation caused by arthritis or arthrosis. Then, an adequate delivery system to LM is necessary in order to release the drug properly from the PBDS as well as have good characteristics related to semi-solid preparations for transdermal application, which were evaluated through in vitro release studies and rheological behavior in this paper, respectively.

scholarly journals Models and methods to characterise levonorgestrel release from intradermally administered contraceptives

2021 ◽  
Author(s):  
Adnan Al Dalaty ◽  
Benedetta Gualeni ◽  
Sion A. Coulman ◽  
James C. Birchall
Keyword(s):  
Ex Vivo ◽  
Extraction Procedure ◽  
In Vitro Release ◽  
Reversed Phase ◽  
Experimental Models ◽  
Detection Methods ◽  
Hormonal Contraceptives ◽  
Limit Of Quantification ◽  
Long Acting

AbstractMicroneedle (MN)-based technologies have been proposed as a means to facilitate minimally invasive sustained delivery of long-acting hormonal contraceptives into the skin. Intradermal administration is a new route of delivery for these contraceptives and therefore no established laboratory methods or experimental models are available to predict dermal drug release and pharmacokinetics from candidate MN formulations. This study evaluates an in vitro release (IVR) medium and a medium supplemented with ex vivo human skin homogenate (SH) as potential laboratory models to investigate the dermal release characteristics of one such hormonal contraceptive that is being tested for MN delivery, levonorgestrel (LNG), and provides details of an accompanying novel two-step liquid–liquid drug extraction procedure and sensitive reversed-phase HPLC–UV assay. The extraction efficiency of LNG was 91.7 ± 3.06% from IVR medium and 84.6 ± 1.6% from the medium supplemented with SH. The HPLC–UV methodology had a limit of quantification of 0.005 µg/mL and linearity between 0.005 and 25 µg/mL. Extraction and detection methods for LNG were exemplified in both models using the well-characterised, commercially available sustained-release implant (Jadelle®). Sustained LNG release from the implant was detected in both media over 28 days. This study reports for the first time the use of biologically relevant release models and a rapid, reliable and sensitive methodology to determine release characteristics of LNG from intradermally administered long-acting drug delivery systems. Graphical abstract

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.

Nanostructured Lipid Carriers for Intranasal Administration of Olanzapine in the management of Schizophrenia

2021 ◽  
Vol 14 ◽  
Author(s):  
Sarbjot Kaur ◽  
Ujjwal Nautiyal ◽  
Pooja A. Chawla ◽  
Viney Chawla
Keyword(s):  
Drug Delivery ◽  
Ex Vivo ◽  
In Vitro Release ◽  
Nanostructured Lipid Carriers ◽  
Polydispersity Index ◽  
Poloxamer 407 ◽  
Ex Vivo Permeation ◽  
Permeation Studies ◽  
Vitro Release

Background: Background: Olanzapine belongs to a new class of dual spectrum antipsychotic agents. It is known to show promise in managing both the positive and negative symptoms of schizophrenia. Drug delivery systems based on nanostructured lipid carriers (NLC) are expected to provide rapid nose-to-brain transport of this drug and improved distribution into and within the brain. Objective: The present study deals with the preparation and evaluation of olanzapine loaded NLC via the intranasal route for schizophrenia. Methods: Olanzapine-NLC were formulated through the solvent injection method using isopropyl alcohol as the solvent, stearic acid as solid lipid, and oleic acid as liquid lipid, chitosan as a coating agent, and Poloxamer 407 as a surfactant. NLC were characterized for particle size, polydispersity index, entrapment efficiency, pH, viscosity, X-ray diffraction studies, in-vitro mucoadhesion study, in- vitro release and ex-vivo permeation studies. The shape and surface morphology of the prepared NLC was determined through transmission electron microscopy. To detect the interaction of the drug with carriers, compatibility studies were also carried out. Results: Average size and polydispersity index of developed formulation S6 was 227.0±6.3 nm and 0.460 respectively. The encapsulation efficiency of formulation S6 was found to be 87.25 %. The pH, viscosity, in-vitro mucoadhesion study, and in- vitro release of optimized olanzapine loaded NLC were recorded as 5.7 ± 0.05, 78 centipoise, 15±2 min, and 91.96 % respectively. In ex-vivo permeation studies, the percent drug permeated after 210 min was found to be 84.03%. Conclusion: These results reveal potential application of novel olanzapine-NLC in intranasal drug delivery system for treatment of schizophrenia.

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