Preparation, Characterization and Evaluation of Quetiapine Fumarate Solid Lipid Nanoparticles to Improve the Oral Bioavailability

Quetiapine fumarate is an antipsychotic drug with poor oral bioavailability (9%) due to first-pass metabolism. Present work is an attempt to improve oral bioavailability of quetiapine fumarate by incorporating in solid lipid nanoparticles (SLN). Six quetiapine fumarate SLN formulations were developed using three different lipids by hot homogenisation followed by ultrasonication. The drug excipient compatibility was studied by differential scanning calorimetry (DSC). Stable quetiapine fumarate SLNs having a mean particle size of 200–250 nm with entrapment efficiency varying in between 80% and 92% were developed. The physical stability of optimized formulation F3 was checked at room temperature for 2 months. Comparative bioavailability studies were conducted in male Wistar rats after oral administration of quetiapine fumarate suspension and SLN formulation. The relative bioavailability of quetiapine fumarate from optimized SLN preparation was increased by 3.71 times when compared with the reference quetiapine fumarate suspension. The obtained results are indicative of SLNs as potential lipid carriers for improving the bioavailability of quetiapine fumarate by minimizing first-pass metabolism.

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Quality by Design Approach for Development and Characterisation of Solid Lipid Nanoparticles of Quetiapine Fumarate

Current Computer - Aided Drug Design ◽

10.2174/1573409915666190722122827 ◽

2020 ◽

Vol 16 (1) ◽

pp. 73-91 ◽

Cited By ~ 2

Author(s):

Shweta Agarwal ◽

Rayasa S. Ramachandra Murthy ◽

Sasidharan Leelakumari Harikumar ◽

Rajeev Garg

Keyword(s):

Solid Lipid Nanoparticles ◽

Quality By Design ◽

Lipid Nanoparticles ◽

Lymphatic Transport ◽

Quetiapine Fumarate ◽

Solid Lipid ◽

First Pass Metabolism ◽

First Pass ◽

Quality By Design Approach ◽

Pass Metabolism

Background: Quetiapine fumarate, a 2nd generation anti-psychotic drug has oral bioavailability of 9% because of hepatic first pass metabolism. Reports suggest that co-administration of drugs with lipids affects their absorption pathways, enhances lymphatic transport thus bypassing hepatic first-pass metabolism resulting in enhanced bioavailability. Objective: The present work aimed at developing, and characterising potentially lymphatic absorbable Solid Lipid Nanoparticles (SLN) of quetiapine fumarate by Quality by Design approach. Method: Hot emulsification followed by ultrasonication was used as a method of preparation. Precirol ATO5, Phospholipon 90G and Poloxamer 188 were used as a lipid, stabilizer and surfactant respectively. A32 Central Composite design optimised the 2 independent variables, lipid concentration and stabilizer concentration and assessed their effect on percent Entrapment Efficiency (%EE: Y1). The lyophilized SLNs were studied for stability at 5 ±3οC and 25 ± 2οC/60 ± 5% RH for 3 months. Results: The optimised formula derived for SLN had 270mg Precirol ATO5 and 107mg of Phospholipon 90G giving %EE of 76.53%. Mean particle size was 159.8nm with polydispersity index 0.273 and zeta potential -6.6mV. In-vitro drug release followed Korsmeyer-Peppas kinetics (R2=0.917) with release exponent n=0.722 indicating non-Fickian diffusion. Transmission electron microscopy images exhibited particles to be spherical and smooth. Fourier-transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction studies ascertained drug-excipient compatibility. Stability studies suggested 5οC as appropriate temperature for storage and preserving important characteristics within acceptable limits. Conclusion: Development and optimisation by Quality by Design were justified as it yielded SLN having acceptable characteristics and potential application for intestinal lymphatic transport.

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Development and Optimization of Mirabegron of Solid Lipid Nanoparticles as an Oral Delivery for Overactive Bladder

Pharmaceutical Nanotechnology ◽

10.2174/2211738509666210127143107 ◽

2021 ◽

Vol 09 ◽

Author(s):

Prajakta Raut ◽

Makarand Gambhire ◽

Dhruvi Panchal ◽

Vaishali Gambhire

Keyword(s):

Overactive Bladder ◽

Solid Lipid Nanoparticles ◽

Oral Bioavailability ◽

Lipid Nanoparticles ◽

Correlation Spectroscopy ◽

Solid Lipid ◽

Peg 400 ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

Background: Mirabegron (MBN), a β-3 adrenergic agent, is used in the treatment of overactive bladder. MBN has alow water solubility, high first-pass metabolism, and low bioavailability, consequently, having poor absorption in the gastrointestinal tract. Objective: The present study is intended at formulating Mirabegron-loaded solid lipid nanoparticles (MBN-SLN) coated with PEG-400 to bypass hepatic first-pass metabolism and to improve its oral bioavailability. Methods: MBN-SLNs were developed using glyceryl monostearate by pre-emulsion- ultrasonication method which was then optimized applying Box-Behnken Design. The optimized batch of MBN-SLN was selected for surface-modification with PEG-400 (MBN-PEG-SLN) and characterized by photon correlation spectroscopy, DSC, and XRD. Bioavailability studies were conducted in Wistar rats after oral administration of plain MBN dispersion, MBN-SLN, and MBN-PEG-SLN. Results: Stable MBN-SLNs and MBN-PEG-SLN of the optimized batch having a mean particle size of 162.7 nm and 149.9 nm; Zeta potential of -39.1 mV and -30.9 mV; %entrapment of 89.90% and 90.12%, respectively, were developed. The results of the in-vitro drug release studies demonstrated a significant slow release of MBN from MBN-SLN (69.38%) and MBN-PEG-SLN (61.33%) as compared to the dispersion of pure drug (92.10%). The relative bioavailability, as a result of the invivostudies, of MBN from MBN-PEG-SLN increased by 2-fold, based on the Cmax values, in comparison with the plain MBN dispersion. Conclusion: Thus, the study established that the oral bioavailability of MBN could be improved by the administration of MBN-PEG-SLN. The obtained results indicate SLNs as a potential drug delivery system for improving the bioavailability of poorly bioavailable drugs such as MBN by abating the first-pass metabolism.

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Solid lipid nanocarriers as alternative drug delivery system for improved oral delivery of drugs

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i6-s.4410 ◽

2020 ◽

Vol 10 (6-s) ◽

pp. 168-172

Author(s):

Gorre Thirupathi ◽

Samanthula Kumara Swamy ◽

Alli Ramesh

Keyword(s):

Oral Bioavailability ◽

Oral Delivery ◽

Lipid Nanoparticles ◽

Delivery Systems ◽

Chemical Degradation ◽

Solid Lipid ◽

First Pass Metabolism ◽

First Pass ◽

Lipid Nanocarriers ◽

Pass Metabolism

Oral bioavailability of drugs is mainly limited due to the poor aqueous solubility, enhanced chemical degradation, reduced permeation and/or first pass metabolism. Various novel delivery systems are developed for improved oral bioavailability of these drugs such as modified orals, buccal, transdermal and osmotic delivery systems. Colloidal carrier systems such as nanoparticles, lipid nanoparticles, nanoemulsions, microspheres, liposomes, resealed erythrocytes and transfersomes were also developed to enhance the oral delivery. Among these, solid lipid nanocarriers (SLNs) also gain much attention on the enhancement of oral bioavailability. SLNs are submicron sized nanoparticles and composed of solid lipid, surfactants and cosurfactants. The enhanced oral bioavailability of poorly soluble drugs from SLNs might be due to the reduced particle size, bypassed presystemic metabolism, and enhanced gastric mucosa permeability. Vast literature is available for the advantages, limitations, preparation methods, evaluation parameters and application of SLNs in different routes. This review mainly focused on list of drugs developed as SLNs and considered as an alternative approach to enhance the oral bioavailability based on pharmacokinetic as well as pharmacodyanmic parameters was discussed. Keywords: Oral bioavailability, solubility, first-pass metabolism, solid lipid nanoparticles, pharmacokinetics, pharmacodynamics.

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Transmucosal Solid Lipid Nanoparticles to Improve Genistein Absorption via Intestinal Lymphatic Transport

Pharmaceutics ◽

10.3390/pharmaceutics13020267 ◽

2021 ◽

Vol 13 (2) ◽

pp. 267

Author(s):

Antonella Obinu ◽

Giovanni Pietro Burrai ◽

Roberta Cavalli ◽

Grazia Galleri ◽

Rossana Migheli ◽

...

Keyword(s):

Intestinal Mucosa ◽

Solid Lipid Nanoparticles ◽

Biological Effects ◽

Lipid Nanoparticles ◽

Neuroprotective Activity ◽

Testing Time ◽

Solid Lipid ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

Genistein (GEN) is a soy-derived isoflavone that exhibits several biological effects, such as neuroprotective activity and the prevention of several types of cancer and cardiovascular disease. However, due to its poor water solubility and the extensive first-pass metabolism, the oral bioavailability of GEN is limited. In this work, solid lipid nanoparticles (SLN) were developed to preferentially reach the intestinal lymphatic vessels, avoiding the first-pass metabolism of GEN. GEN-loaded SLN were obtained by a hot homogenization process, and the formulation parameters were chosen based on already formulated studies. The nanoparticles were characterized, and the preliminary in vitro chylomicron formation was evaluated. The cell uptake of selected nanocarriers was studied on the Caco-2 cell line and intestinal mucosa. The SLN, characterized by a spherical shape, showed an average diameter (about 280 nm) suitable for an intestinal lymphatic uptake, good stability during the testing time, and high drug loading capacity. Furthermore, the intestinal mucosa and Caco-2 cells were found to uptake SLN. The approximately two-fold increase in particle size suggested a possible interaction between SLN and the lipid components of chylomicrons like phospholipid; therefore, the results may support the potential for these SLN to improve oral GEN bioavailability via intestinal lymphatic absorption.

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Preparation, Characterization and in vivo Evaluation of Felodipine Solid-Lipid Nanoparticles for Improved Oral Bioavailability

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2015.8.4.1 ◽

2015 ◽

Vol 8 (4) ◽

pp. 2995-3002

Author(s):

Kishan V ◽

Usha Kiranmai Gondrala ◽

Narendar Dudhipala

Keyword(s):

Solid Lipid Nanoparticles ◽

Oral Bioavailability ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

Scanning Calorimetry ◽

In Vivo Evaluation ◽

Solid Lipid

Felodipine is an antihypertensive drug with poor oral bioavailability due to the first pass metabolism. For improving the oral bioavailability, felodipine loaded solid lipid nanoparticles (SLNs) were developed using trimyristin, tripalmitin and glyceryl monostearate. Poloxamer 188 was used as surfactant. Lipid excipient compatibilities were confirmed by differential scanning calorimetry. SLN dispersions were prepared by hot homogenization of molten lipids and aqueous phase followed by ultrasonication at a temperature, above the melting point. SLNs were characterized for particle size, zeta potential, drug content, entrapment efficiency and crystallinity of lipid and drug. In vitro release studies were performed in 0.1N HCl and phosphate buffer of pH 6.8 using dialysis method. Pharmacokinetics of felodipine-SLNs after oral admini-stration in male Wistar rats was studied. The bioavailability of felodipine was increased by 1.75 fold when compared to that of a felodipine suspension.

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Preparation, characterization and scale-up of sesamol loaded solid lipid nanoparticles

Nanotechnology Development ◽

10.4081/nd.2012.e8 ◽

2012 ◽

Vol 2 (1) ◽

pp. 8 ◽

Cited By ~ 5

Author(s):

Vandita Kakkar ◽

Indu Pal Kaur

Keyword(s):

Solid Lipid Nanoparticles ◽

Scale Up ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Solid Lipid ◽

Transmission Electron ◽

The Brain

Sesamol loaded solid lipid nanoparticles (SSLNs) were prepared with the aim of minimizing its distribution to tissues and achieving its targeting to the brain. Three scale-up batches (100x1 L) of S-SLNs were prepared using a microemulsification technique and all parameters were statistically compared with the small batch (1x;10 mL). S-SLNs with a particle size of less than 106 nm with a spherical shape (transmission electron microscopy) were successfully prepared with a total drug content and entrapment efficiency of 94.26±2.71% and 72.57±5.20%, respectively. Differential scanning calorimetry and infrared spectroscopy confirmed the formation of lipidic nanoparticles while powder X-ray diffraction revealed their amorphous profile. S-SLNs were found to be stable for three months at 5±3°C in accordance with International Conference on Harmonisation guidelines. The SLN preparation process was successfully scaled-up to a 100x batch on a laboratory scale. The procedure was easy to perform and allowed reproducible SLN dispersions to be obtained.

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Preparation, Characterization and Optimization of Irbesartan Loaded Solid Lipid Nanoparticles for Oral Delivery

Asian Journal of Pharmacy and Technology ◽

10.52711/2231-5713.2021.00016 ◽

2021 ◽

pp. 97-104

Author(s):

Kumara Swamy S ◽

Ramesh Alli

Keyword(s):

Drug Release ◽

Solid Lipid Nanoparticles ◽

Oral Bioavailability ◽

Oral Delivery ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

Sustained Drug Release ◽

Bioavailability Enhancement ◽

Solid Lipid

The purpose of this study was to develop and evaluate irbesartan (IS) loaded solid lipid nanoparticles (SLNs; IS-SLNs) that might enhance the oral bioavailability of IS. IS, an angiotensin-receptor antagonist, used to treat hypertension. However, poor aqueous solubility and poor oral bioavailability has limited therapeutic applications of IS. Components of the SLNs include either of trimyristin/tripalmitin/tristearin/trilaurate/stearic acid/beeswax, and surfactants (Poloxamer 188 and soylecithin). The IS-SLNs were prepared by hot homogenization followed by ultrasonication method and evaluated for particle size, poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), drug content and in vitro drug release. The physical stability of optimized formulation was studied at refrigerated and room temperature for two months. The optimized IS-SLN formulation (F4) had a mean diameter of about 217.6±3.62 nm, PDI of 0.163±0.032, ZP of -28.5±4.12, assay of 99.8±0.51 and EE of 93.68±2.47%. The formulation showed sustained drug release compared with control formulation over 24 h. Optimized formulation was found to be stable over two months. IS-SLN showed nearly spherical in shape using and converted to amorphous form by DSC. Thus, the results conclusively demonstrated SLNs could be considered as an alternative delivery system for the oral bioavailability enhancement of IS.

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Central Composite Design for Formulation and Optimization of Solid Lipid Nanoparticles to Enhance Oral Bioavailability of Acyclovir

Molecules ◽

10.3390/molecules26185432 ◽

2021 ◽

Vol 26 (18) ◽

pp. 5432

Author(s):

Haniza Hassan ◽

Siti Khadijah Adam ◽

Ekram Alias ◽

Meor Mohd Redzuan Meor Mohd Affandi ◽

Ahmad Fuad Shamsuddin ◽

...

Keyword(s):

Central Composite Design ◽

Solid Lipid Nanoparticles ◽

Oral Bioavailability ◽

Oral Drug Delivery ◽

Entrapment Efficiency ◽

Fold Increase ◽

Lipid Nanoparticles ◽

Oral Drug ◽

Solid Lipid ◽

Central Composite

Treatment of herpes simplex infection requires high and frequent doses of oral acyclovir to attain its maximum therapeutic effect. The current therapeutic regimen of acyclovir is known to cause unwarranted dose-related adverse effects, including acute kidney injury. For this reason, a suitable delivery system for acyclovir was developed to improve the pharmacokinetic limitations and ultimately administer the drug at a lower dose and/or less frequently. In this study, solid lipid nanoparticles were designed to improve the oral bioavailability of acyclovir. The central composite design was applied to investigate the influence of the materials on the physicochemical properties of the solid lipid nanoparticles, and the optimized formulation was further characterized. Solid lipid nanoparticles formulated from Compritol 888 ATO resulted in a particle size of 108.67 ± 1.03 nm with an entrapment efficiency of 91.05 ± 0.75%. The analyses showed that the optimum combination of surfactant and solid lipid produced solid lipid nanoparticles of good quality with controlled release property and was stable at refrigerated and room temperature for at least 3 months. A five-fold increase in oral bioavailability of acyclovir-loaded solid lipid nanoparticles was observed in rats compared to commercial acyclovir suspension. This study has presented promising results that solid lipid nanoparticles could potentially be used as an oral drug delivery vehicle for acyclovir due to their excellent properties.

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Formulation and Evaluation of Solid Lipid Nanoparticles of Bifonazole

International Journal of Scientific Research in Science and Technology ◽

10.32628/ijsrst207522 ◽

2020 ◽

pp. 105-120

Author(s):

Botre P.P ◽

Maniyar M.G.

Keyword(s):

Drug Release ◽

Solid Lipid Nanoparticles ◽

Fungal Infections ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

Gelling Agent ◽

Rheological Parameters ◽

Scanning Calorimetry ◽

Solid Lipid

The objective of this study was to develop suitable solid lipid nanoparticles for topical delivery of Bifonazole. Bifonazole is an imidazole antifungal drug used in form of ointments. It was patented in 1974 and approved for medical use in 1983. Bifonazole having broad spectrum activity against dermatophytes, moulds, yeasts, fungi and some gram positive bacteria. BFZ SLNs systems were developed by melt emulsification followed by solvent evaporation technique using Compritol 888ATO (Glyceryl behenate) as a solid lipid and Tween 80 as a surfactant. Developed SLNs were evaluated for particle size, polydispersity index (PI), entrapment efficiency (EE) and drug release profiles. Process and formulation parameters were optimized. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies were carried out on SLNs to mark the changes in the drug and lipid modifications. The BFZ SLNs based gels were prepared using Carbopol 940 as a gelling agent. The SLNs based gels were evaluated for rheological parameters, in vitro drug release and permeation studies. In vitro antifungal study suggested that the SLNs based gel was more effective in inhibiting growth of Candida albicans. Thus the study concludes that SLNs based gel of BFZ gives a sustained release profile of BFZ and has the potential for treatment of topical fungal infections.

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