scholarly journals Linagliptin loaded Solid-SMEEDS for enhanced solubility and dissolution: Formulation development and optimization by D-optimal design

2019 ◽  
Vol 9 (2) ◽  
pp. 47-56
Author(s):  
Madhubhai M Patel ◽  
Rahulkumar J Patel
Keyword(s):  
Electron Microscopy ◽  
Drug Delivery ◽  
Transmission Electron Microscopy ◽  
Optimal Design ◽  
Zeta Potential ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Dissolution Profile ◽  
Transmission Electron

The aim of the present investigation was to formulate and evaluate solid self-micro emulsifying drug-delivery systems (S-SMEDDS) to improve solubility and dissolution profile of Linagliptin. Solubility of Linagliptin in different oils, surfactants and co-surfactants was assessed and optimizations of pseudo-ternary plots were also carried out for preparation of liquid SMEDDS. D-optimal design mixture was used in the optimization of Linagliptin loaded liquid SMEEDS. The optimized SMEEDS were characterized for globule size, zeta potential, dilution stability, transmittance, pH and in-vitro release profile. The morphology of the Linagliptin SMEEDS was observed by Transmission Electron Microscopy (TEM). Among the different silicates, Nusillin US2 was used as the solid carrier/absorbent to formulate S-SMEEDS of Linagliptin. Improved in-vitro dissolution profile of optimized formulation was observed, resulting in multifold improvement in the absorption profile of Linagliptin as compared with pure drug. In a nutshell, this optimized S-SMEDD formulation holds great promise for enhancement of its physiochemical and biological attributes. Keywords: Linagliptin, Solid Self-micro Emulsifying Drug Delivery Systems, D-optimal design, Zeta-potential, Transmission Electron Microscopy

scholarly journals Transmission Electron Microscopy: Novel Application of Established Technique in Characterization of Nanoparticles as Drug Delivery Systems

PRILOZI ◽  
2019 ◽  
Vol 40 (2) ◽  
pp. 67-72 ◽  
Author(s):  
Marija Petrushevska ◽  
Kristina Pavlovska ◽  
Jovanka Laskova ◽  
Pance Zdravkovski ◽  
Marija Glavas Dodov
Keyword(s):  
Electron Microscopy ◽  
Drug Delivery ◽  
Transmission Electron Microscopy ◽  
Drug Delivery Systems ◽  
Dominant Role ◽  
Chemical Properties ◽  
Delivery Systems ◽  
Potential Measurement ◽  
Nanoparticle Characterization ◽  
Transmission Electron

Abstract Nanotechnology presents a modern field of science that in the last twenty-five years plays a dominant role in the biomedicine. Different analytical methods are used for evaluation of the physico-chemical properties of nanoparticles including chromatography, electrophoresis, X-ray scattering, spectroscopy, mass spectrometry, zeta potential measurement and microscopy on which this article will focus. Herein, we present novel application of the long-established TEM technique that is focused on characterization and evaluation of various nanoparticles in development of drug delivery systems. Transmission electron microscopy images were taken of samples from native nanoparticles, nanoparticles labeled using stannous chloride labeling procedure, inorganic silica nanoparticles loaded with budesonide and native micelles and micelles carrier of anticancer drug camptothecin. In the case of radiolabeled nanoparticles, beside for nanoparticle characterization, TEM technique was used to confirm the stability of the nanoparticles after radiolabeling. Furthermore, the porous structure of hybrid silica particles loaded with budesonide was examined under TEM. Transmission electron microscopy technique offers exceptional benefits for nanoparticle characterization. Additionally, the necessity of ultrastructural analysis demonstrates the potential of TEM in the field of nanomedicine. Hence, the long-established and well-known TEM has been only partially exploited and offer researchers very detailed images of specimens at microscopic and nano scale.

scholarly journals Fluorescence and electron microscopy to visualize the intracellular fate of nanoparticles for drug delivery

2016 ◽  
Vol 60 (2) ◽  
Author(s):  
M. Costanzo ◽  
F. Carton ◽  
A. Marengo ◽  
G. Berlier ◽  
B. Stella ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Drug Delivery ◽  
Transmission Electron Microscopy ◽  
Cultured Cells ◽  
Cell System ◽  
Functional Relationships ◽  
Cell Internalization ◽  
Transmission Electron ◽  
Intracellular Fate

<p>In order to design valid protocols for drug release <em>via</em> nanocarriers, it is essential to know the mechanisms of cell internalization, the interactions with organelles, and the intracellular permanence and degradation of nanoparticles (NPs) as well as the possible cell alteration or damage induced. In the present study, the intracellular fate of liposomes, polymeric NPs and mesoporous silica NPs (MSN) has been investigated in an <em>in vitro</em> cell system by fluorescence and transmission electron microscopy. The tested nanocarriers proved to be characterized by specific interactions with the cell: liposomes enter the cells probably by fusion with the plasma membrane and undergo rapid cytoplasmic degradation; polymeric NPs are internalized by endocytosis, occur in the cytoplasm both enclosed in endosomes and free in the cytosol, and then undergo massive degradation by lysosome action; MSN are internalized by both endocytosis and phagocytosis, and persist in the cytoplasm enclosed in vacuoles. No one of the tested nanocarriers was found to enter the nucleus. The exposure to the different nanocarriers did not increase cell death; only liposomes induced a reduction of cell population after long incubation times, probably due to cell overloading. No subcellular damage was observed to be induced by polymeric NPs and MSN, whereas transmission electron microscopy revealed cytoplasm alterations in liposome-treated cells. This important information on the structural and functional relationships between nanocarriers designed for drug delivery and cultured cells further proves the crucial role of microscopy techniques in nanotechnology.</p>

Solid self-emulsifying drug delivery system (Solid SEDDS) for testosterone undecanoate: in vitro and in vivo evaluation

2020 ◽  
Vol 17 ◽  
Author(s):  
Xi Liang ◽  
Yabing Hua ◽  
Qian Liu ◽  
Zhiguo Li ◽  
Fanglin Yu ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Drug Delivery ◽  
Delivery System ◽  
High Fat Diet ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
High Fat ◽  
Testosterone Undecanoate

Objective: The current study aimed to investigate the potential of solid self-emulsifying drug delivery systems (solid SEDDS) loaded with testosterone undecanoate (TU) (solid TU-SEDDS). The solid TU-SEDDS was composed of TU, medium-chain triglycerides (MCT, oil), 2-Chloro-1-(chloromethyl) ethyl carbamate (EL-35, surfactant) and polyethylene glycol (PEG400, cosurfactant). It was expected to improve the dissolution and oral bioavailability of TU, as a result of investigating the feasibility of clinical application of SEDDS. Methods: First, a TU-SEDDS was developed by using rational blends of components with good solubilizing ability for TU. Next, a ternary phase diagram was constructed to determine the self-emulsifying region, and the formulation was optimized. Then, the solid TU-SEDDS formulation was established by screening suitable solid adsorptions. Finally, the prepared SEDDS, TU-SEDDS and solid TU-SEDDS formulations were evaluated in vitro and in vivo. Results: The size of the solid TU-SEDDS was 189.1 ± 0.23 nm. The transmission electron microscopy (TEM) results showed that the oil droplets were homogenous and spherical with good integrity. The differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) results indicated that the solid TU-SEDDS formulation almost preserves the amorphous state. Scanning electron microscopy (SEM) indicated that neusilin US2 successfully adsorbed the TU-SEDDS. Drug release indicated that the dissolution of the solid TU-SEDDS was faster than that of Andriol Testocaps®. Furthermore, in vivo pharmacokinetic (PK) studies in Sprague-Dawley (SD) rats showed that the area under the curve (AUC) of the solid TU-SEDDS (487.54±208.80 µg/L×h) was higher than that of Andriol Testocaps® (418.93±273.52 µg/L×h, P < 0.05). In beagles not fed a high-fat diet, the AUC of the solid TU-SEDDS (5.81±4.03 µg/L×h) was higher than that of Andriol Testocaps® (5.53±3.43 µg/L×h, P > 0.05). In beagles fed a high-fat diet, the AUC of the solid TU-SEDDS (38.18±21.90 µg/L×h) was higher than that of Andriol Testocaps® (37.17±13.79 µg/L×h, P > 0.05). Conclusion: According to the results of this research, oral solid TU-SEDDS is expected to be another alternative delivery system for the late-onset hypogonadism. This is beneficial to the transformation of existing drug delivery systems into preclinical and clinical studies.

Development and in vitro evaluation of zeta potential changing self-emulsifying drug delivery systems for enhanced mucus permeation

2016 ◽  
Vol 510 (1) ◽  
pp. 255-262 ◽  
Author(s):  
Wongsakorn Suchaoin ◽  
Irene Pereira de Sousa ◽  
Kesinee Netsomboon ◽  
Hung Thanh Lam ◽  
Flavia Laffleur ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Zeta Potential ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
In Vitro Evaluation

scholarly journals FORMULATION, DEVELOPMENT AND CHARACTERIZATION OF DRUG DELIVERY SYSTEMS BASED TELMISARTAN ENCAPSULATED IN SILK FIBROIN NANOSPHERE’S

2019 ◽  
Vol 11 (1) ◽  
pp. 247 ◽  
Author(s):  
Shahid Ud Din Wani ◽  
Gangadharappa H. V. ◽  
Ashish N. P.
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Zeta Potential ◽  
Silk Fibroin ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
Random Coil ◽  
Burst Release

Objective: The aim of the present work was to formulate silk fibroin (SF) nanospheres (NS’s) for drug delivery application. The current study was designed to advance the water solubility and bio-availability of telmisartan by nanoprecipitation method.Methods: SF NS’s loaded with TS were prepared by nanoprecipitation method. The drug was dissolved in aqueous solution of SF by using acetone as a non-solvent. The prepared NS’s were then characterized by FTIR, X-ray diffraction and zeta potential, and were evaluated for its, surface morphology, %drug content, encapsulation efficiency and in vitro drug release.Results: The evaluation results of SF NS’s loaded of TS showed 74.22±0.17 % entrapment efficiency, 35.21±0.02 % of drug loading, and-4.9 mV to-13.6 mV of zeta potential due to the proper bounding of TS with the β-sheets of SF, the particle size reported was within the size range of 160-186 nm having smooth surface and were spherical in shape. The SFNS’s pattern switched from random coil to β-sheet formation on treating with acetone. FTIR and DSC studies marked no such inter-molecular interactions between SF and drug molecules. The % cumulative in vitro drug release from SF NS’s exhibited quick burst release. The in vitro cumulative drug release of SF NS’s of TS it was found that about 74% of the drug was released within 8 h and about 96% of drug released at 24 hr. The rate of drug release increased with the increase in SF ratio.Conclusion: It is believed that these SF NS’s will find potential applications in drug delivery release as drug carriers, especially poor water-soluble drugs. All these results proposed that SF NS’s are eventuality handy in various drug delivery systems.

scholarly journals Development, Characterization, and Pharmacodynamic Evaluation of Hydrochlorothiazide Loaded Self-Nanoemulsifying Drug Delivery Systems

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Pankajkumar S. Yadav ◽  
Ekta Yadav ◽  
Amita Verma ◽  
Saima Amin
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Tween 80 ◽  
Delivery Systems ◽  
Dissolution Profile ◽  
Rate Of Dissolution ◽  
Capmul Mcm

The objective of the current work was to develop optimized self-nanoemulsifying drug delivery systems (SNEDDS) and evaluate theirin vitroandin vivoperformance. The research comprised various studies which includes solubility studies in various vehicles, pseudoternary phase diagram construction, and preparation and characterization of SNEDDS along within vitrodissolution andin vivopharmacodynamic profiling. Based on dissolution profile, a remarkable increase in rate of dissolution was observed in comparison with plain drug and marketed formulation. Optimized SNEDDS formulation was composed of Capmul MCM (19.17% w/w), Tween 80 (57.5% w/w), Transcutol P (12.7% w/w), and HCT (4.17% w/w).In vivopharmacodynamic evaluation in Wistar rats showed considerable increase in pharmacological effect of HCT by SNEDDS formulation as compared with plain HCT.

scholarly journals Core-shell poly(lactide-co-ε-caprolactone)-gelatin fiber scaffolds as pH-sensitive drug delivery systems

2018 ◽  
Vol 32 (8) ◽  
pp. 1105-1118 ◽  
Author(s):  
Qingqing Sang ◽  
Heyu Li ◽  
Gareth Williams ◽  
Huanling Wu ◽  
Li-Min Zhu
Keyword(s):  
Electron Microscopy ◽  
Drug Delivery ◽  
Sodium Bicarbonate ◽  
Drug Delivery Systems ◽  
Tumor Resection ◽  
Delivery Systems ◽  
Ph Sensitive ◽  
Core Shell ◽  
Fiber Scaffolds

Dual-drug-loaded pH-responsive fiber scaffolds were successfully prepared by coaxial electrospinning. These were designed with the aim of being sutured into the resection site after tumor removal, to aid recovery and prevent cancer recurrence. The shell was made up of a mixture of gelatin and sodium bicarbonate (added to provide pH-sensitivity), and was loaded with the anti-inflammatory drug ciprofloxacin; the core comprised poly(lactide-co-ε-caprolactone) with the chemotherapeutic doxorubicin hydrochloride. Scanning electron microscopy revealed most fibers were smooth and homogeneous. Transmission electron microscopy demonstrated the presence of a clear core/shell structure. The fiber scaffolds were further characterized using infrared spectroscopy and X-ray diffraction, which proved that both drugs were present in the fibers in the amorphous form. The gelatin shells were cross-linked with glutaraldehyde to enhance their stability, and water contact angle measurements used to confirm they remained hydrophilic after this process, with angles between 10 and 35°. This is important for onward applications, since a hydrophilic surface is known to encourage cell proliferation. During in vitro drug release studies, a rapid and acid-responsive release of ciprofloxacin was seen, accompanied by sustained and long-term doxorubicin release. Both the release profiles and the mechanical strength of the fibers can effectively be tuned through the sodium bicarbonate content of the fibers: for instance, the break stress varies from 2.00 MPa to 2.57 MPa with an increase in sodium bicarbonate content. The pH values of aqueous media exposed to the scaffolds decrease only slightly, by less than 0.5 pH units, over the two-month timescale, suggesting that only minimal fiber degradation occurs during this time. The fiber scaffolds also have good biocompatibility, as revealed by in vitro cytotoxicity experiments. Overall, our results demonstrate that the novel scaffolds reported here are promising pH-sensitive drug delivery systems, and may be candidates for use after tumor resection surgery.

Olmesartan Medoxomil-Loaded Self-Nanoemulsifying Drug Delivery Systems: Design, In-Vitro Characterization, and Pharmacokinetic Assessments in Rabbits Via LC-MS/MS

2017 ◽  
Vol 7 (03) ◽  
Author(s):  
El-Assal M. I. A. ◽  
El-Gendy M. A. ◽  
Tadros M. I. ◽  
El-Gazayerly O. N.
Keyword(s):  
Drug Delivery ◽  
Zeta Potential ◽  
Drug Delivery Systems ◽  
Oral Absorption ◽  
Systems Design ◽  
Olmesartan Medoxomil ◽  
Delivery Systems ◽  
Log P ◽  
Polyethylene Glycol 400

Olmesartan medoxomil (OLM) is a lipophilic (log P = 4.31) antihypertensive drug suffering from limited oral bioavailability in humans (26%) due to its low aqueous solubility, uncontrolled enzymatic conversion to the active metabolite (olmesartan; OL) and efflux by drug resistance pumps. Surmounting such limitations via incorporation of OLM into self-nanoemulsifying drug delivery systems (SNEDDS). Based on OLM-equilibrium solubility studies in various oils, surfactants and co-surfactants, Capmul® MCM, Tween® 20, Cremophor® EL and polyethylene glycol-400 (PEG) were combined in different ratios to plot ternary phase diagrams. OLM-loaded SENDDS were developed and evaluated for particle size, polydispersity index (PDI), zeta potential, self-emulsification time, morphology, drug released percentages after 5-min (Q5min%), 1-hour (Q1h%) and dissolution efficiency percentages (DE1h%). The OL pharmacokinetics from SNEDDS (F6) and Benicar® tablets were evaluated (LC-MS/MS) in rabbits. Spherical OLM-loaded SNEDDS were developed. The best-achieved SNEDDS (F6) showed short emulsification time (13 s), fine droplet size (60.00 nm), low PDI (0.25), negative zeta potential (-14.4 mV), promising dissolution parameters; Q5min% (29.78%), Q1h% (66.69%) and DE1h%(47.96%) and enhanced in vivo absorption characteristics; shorter Tmax, higher Cmax and larger AUC(0−48h; suggesting its potential for the enhancement of the oral absorption of practically insoluble drugs; like OLM.

scholarly journals DESIGN AND DEVELOPMENT OF SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEMS (SMEDDS) OF TELMISARTAN FOR ENHANCEMENT OF IN VITRO DISSOLUTION AND ORAL BIOAVAILABILITY IN RABBIT

2018 ◽  
Vol 10 (4) ◽  
pp. 117 ◽  
Author(s):  
Suvendu Kumar Sahoo ◽  
Padilam Suresh ◽  
Usharani Acharya
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Zeta Potential ◽  
Droplet Size ◽  
Oral Bioavailability ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
Poorly Water Soluble

Objective: The main purpose of this investigation was to prepare self-microemulsifying drug delivery system (SMEDDS) for enhancement of oral bioavailability of a poorly water soluble drug telmisartan (TLS), a BCS class II drug by improving its dissolution rate. Methods: Self-Emulsifying Drug Delivery Systems (SEDDS) of TLS were formulated using cinnamon essential oil as the oil phase, Gelucire 44/14 as the surfactant and Transcutol HP as co-surfactant. Drug-excipient interactions were studied by FTIR spectroscopy. The formulations were evaluated for its self-emulsifying ability, clarity, and stability of the aqueous dispersion after 48 h and the phase diagram was constructed to optimize the system. Selected formulations were characterized in terms of droplet size distribution, zeta potential, cloud point and were subjected to in vitro drug release studies. The bioavailability of optimized formulation was assessed in New Zealand white rabbits.Results: By considering smaller droplet size, higher zeta potential and faster rate of drug release the formulation TF9 was chosen as optimized SMEDDS formulations. TF9 was robust to different pH media and dilution volumes, remained stable after three cooling-heating cycles and after stored at 4 °C and 25 °C for 3 mo without showing a significant change in droplet size. The pharmacokinetic study in rabbits showed SMEDDS have significantly increased the Cmax and area under the curve (AUC) of TLS compared to suspension (P<0.05).Conclusion: SMEDDS can be an effective oral dosage form for enhancing aqueous solubility and improving oral bioavailability of poorly water soluble drugs.

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