Influence of drug loading on the physical stability of phospholipid-stabilised colloidal lipid emulsions

The efficacy of current standard chemotherapy is suboptimal due to the poor solubility and short half-lives of chemotherapeutic agents, as well as their high toxicity and lack of specificity which may result in severe side effects, noncompliance and patient inconvenience. The application of nanotechnology has revolutionized the pharmaceutical industry and attracted increasing attention as a significant means for optimizing the delivery of chemotherapeutic agents and enhancing their efficiency and safety profiles. Nanostructured lipid carriers (NLCs) are lipid-based formulations that have been broadly studied as drug delivery systems. They have a solid matrix at room temperature and are considered superior to many other traditional lipid-based nanocarriers such as nanoemulsions, liposomes and solid lipid nanoparticles (SLNs) due to their enhanced physical stability, improved drug loading capacity, and biocompatibility. This review focuses on the latest advances in the use of NLCs as drug delivery systems and their preparation and characterization techniques with special emphasis on their applications as delivery systems for chemotherapeutic agents and different strategies for their use in tumor targeting.

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Fluorescence-based techniques to assess the miscibility and physical stability of a drug–lipid complex

Canadian Journal of Chemistry ◽

10.1139/cjc-2018-0404 ◽

2019 ◽

Vol 97 (6) ◽

pp. 496-503 ◽

Cited By ~ 1

Author(s):

Jiahao Huang ◽

Peter X. Chen ◽

Shawn Wettig

Keyword(s):

Infrared Spectroscopy ◽

Fluorescence Microscopy ◽

Drug Loading ◽

Physical Stability ◽

Solvent Free ◽

Lipid Complex ◽

Pharmaceutical Dosage Form ◽

Free Condition ◽

Solvent Free Condition ◽

Model Complex

The objective of this study was to evaluate the feasibility of using fluorescence-based techniques to assess the miscibility and physical stability of a drug–lipid complex pharmaceutical dosage form under a solvent-free condition. An indomethacin–phospholipid complex (IDM–DPC) was used as model complex for this study. The miscibility of indomethacin within the phospholipid was assessed by fluorescence spectroscopy, fluorescence microscopy, and infrared spectroscopy. The miscibility limit of the complex system was determined by fluorescence to be 20%–30% drug loading content, showing good correlation with infrared spectroscopy. The physical stability of the IDM–DPC stored at 40 °C was evaluated by fluorescence microscopy. Indomethacin formulated in the lipid complex with an indomethacin loading not more than 30% remained in an amorphous state within a period of 21 days, whereas the samples with a drug loading over 30% started to crystallize earlier with increasing drug content. IDM–DPC having higher miscibilities were found to be more resistant to recrystallization under heating, thus having better physical stability. Fluorescence-based techniques showed convenience and promise in characterizing drug–lipid miscibility and predicting storage stability under a solvent-free condition.

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Lipid-Polymer Hybrid Nanocarriers for Oral Delivery of Felodipine: Formulation, Characterization and Ex-Vivo Evaluation

Advanced Pharmaceutical Bulletin ◽

10.34172/apb.2022.081 ◽

2021 ◽

Author(s):

Hayder Kadhim Drais ◽

Ahmed Abbas Hussein

Keyword(s):

Oral Delivery ◽

Ph Value ◽

Ex Vivo ◽

Drug Loading ◽

Aqueous Media ◽

Physical Stability ◽

Entrapment Efficiency ◽

Light Transmittance ◽

Sustained Drug Delivery ◽

Polymer Hybrid

Purpose: Felodipine, is a calcium-channel antagonist used for hypertension and angina pectoris. It is practically insoluble in aqueous media and shows low oral bioavailability (15%-20%). This investigation aims to prepare and characterize oral felodipine lipid-polymer hybrid nanocarriers (LPHNs) to increase solubility and control delivery for increasing bioavailability and enhance patient compliance. Methods: The newly microwave-based method was prepared with felodipine LPHNs (H1-H35) successfully. The (H1-H35) were subjected to thermodynamic stability experiments. After that, select nine felodipine LPHNs (F1-F9) that have smart physical stability for further optimization of different characterization processes. Results: The felodipine LPHNs (F4) are considered the most optimized formula. It was characterized by lower particle size (33.3 nm), lower PDI (0.314), high zeta potential (13.6 mV), entrapment efficiency is (81.645 %w/w), drug loading is (16.329 % w/w), the pH value is 4, excellent percent of light transmittance (95.5%), pseudoplastic rheogram, significantly high (p< 0.05) dissolution rate with sustained drug delivery and success ex-vivo intestinal permeation attributes. The (F4) subject for further investigations of fourier transformed infrared spectroscopy (FTIR), atomic force microscopy (AFM), and transmission electron microscopy (TEM). The results of FTIR, AFM, and TEM indicate there is no interaction between the felodipine and excipients and that the particulate system in the nanoscale dispersion system confirms the high stability. Conclusion: The optimized felodipine LPHNs (F1-F9) formulations were smart formulations for sustained oral delivery of felodipine and that F4 was the most optimized formula according to its characterization processes.

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Optimization of Hydroxypropyl Methylcellulose and Dextrin in Development of Dried Nanosuspension for Poorly Water-Soluble Drug

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2020.17659 ◽

2020 ◽

Vol 20 (9) ◽

pp. 5813-5818

Author(s):

Eun-Ji Heo ◽

Sang Yeob Park ◽

Hye-In Kim ◽

Ji-Hun Sung ◽

Hyeok Jin Kwon ◽

...

Keyword(s):

Particle Size ◽

Dissolution Rate ◽

Oral Absorption ◽

Drug Loading ◽

Hydroxypropyl Methylcellulose ◽

Physical Stability ◽

Tween 80 ◽

Water Soluble

The purpose of this study is to identify the effects of a stabilizer and matrix former in the development of a celecoxib dried nanosuspension (DNS) for high dissolution rate and drug loading. Tween 80 and Hydroxypropyl Methylcellulose (HPMC) were used as stabilizers in the bead-milling process and dextrin was used as the matrix former in the spray-drying. Various nanosuspensions (NS) were prepared by varying the ratio of HPMC and dextrin, and the physicochemical properties of each formulation were evaluated for particle size, morphology, drug loading, crystallinity, redispersibility, physical stability and dissolution rate. HPMC efficiently stabilized the NS system and reduced the particle size of NS. The mean particle size of the NS with 0.5% HPMC (w/v) was the smallest (248 nm) of all formulations. Dextrin has been shown to inhibit the increase of particle size efficiently, which is known to occur frequently when NS is being solidified. As the dextrin increased in DNS, the dissolution rates of reconstituted NS were significantly improved. However, it was confirmed that more than the necessary amount of dextrin in DNS reduced the dissolution and drug loading. The dissolution of celecoxib in DNS prepared at the ratio (drug:dextrin, 1:2.5) was almost the highest. The dissolution of optimal formulation was 95.8% at 120 min, which was 2.0-fold higher than that of NS dried without dextrin. In conclusion, these results suggest that the formulation based on Tween 80, HPMC and dextrin may be an effective option for DNS to enhance its in vitro dissolution and in vivo oral absorption.

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Evaluation and Comparison of Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) as Vectors to Develop Hydrochlorothiazide Effective and Safe Pediatric Oral Liquid Formulations

Pharmaceutics ◽

10.3390/pharmaceutics13040437 ◽

2021 ◽

Vol 13 (4) ◽

pp. 437

Author(s):

Paola Mura ◽

Francesca Maestrelli ◽

Mario D’Ambrosio ◽

Cristina Luceri ◽

Marzia Cirri

Keyword(s):

Particle Size ◽

Solid Lipid Nanoparticles ◽

Drug Loading ◽

Physical Stability ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

Nanostructured Lipid Carriers ◽

Particle Size Reduction ◽

Solid Lipid ◽

Oral Liquid

The aim of this study was the optimization of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in terms of physicochemical and biopharmaceutical properties, to develop effective and stable aqueous liquid formulations of hydrochlorothiazide, suitable for paediatric therapy, overcoming its low-solubility and poor-stability problems. Based on solubility studies, Precirol® ATO5 and Transcutol® HP were used as solid and liquid lipids, respectively. The effect of different surfactants, also in different combinations and at different amounts, on particle size, homogeneity and surface-charge of nanoparticles was carefully investigated. The best formulations were selected for drug loading, and evaluated also for entrapment efficiency and release behaviour. For both SLN and NLC series, the use of Gelucire® 44/14 as surfactant rather than PluronicF68 or Tween® 80 yielded a marked particle size reduction (95–75 nm compared to around 600–400 nm), and an improvement in entrapment efficiency and drug release rate. NLC showed a better performance than SLN, reaching about 90% entrapped drug (vs. 80%) and more than 90% drug released after 300 min (vs. about 65%). All selected formulations showed good physical stability during 6-month storage at 4 °C, but a higher loss of encapsulated drug was found for SLNs (15%) than for NLCs (<5%). Moreover, all selected formulations revealed the absence of any cytotoxic effect, as assessed by a cell-viability test on Caco-2 cells and are able to pass the intestinal epithelium as suggested by Caco-2 uptake experiments.

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Drug localization and its effect on the physical stability of poloxamer 188-stabilized colloidal lipid emulsions

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2021.120394 ◽

2021 ◽

pp. 120394

Author(s):

Nadine Francke ◽

Heike Bunjes

Keyword(s):

Physical Stability ◽

Lipid Emulsions ◽

Poloxamer 188 ◽

Drug Localization

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Analytical and Computational Methods for the Estimation of Drug-Polymer Solubility and Miscibility in Solid Dispersions Development

Pharmaceutics ◽

10.3390/pharmaceutics11080372 ◽

2019 ◽

Vol 11 (8) ◽

pp. 372 ◽

Cited By ~ 13

Author(s):

Djordje Medarević ◽

Jelena Djuriš ◽

Panagiotis Barmpalexis ◽

Kyriakos Kachrimanis ◽

Svetlana Ibrić

Keyword(s):

Shelf Life ◽

Drug Concentration ◽

Single Phase ◽

Drug Loading ◽

Solid Dispersions ◽

Physical Stability ◽

Solubility Limit ◽

Drug Dissolution ◽

Phase System ◽

Polymer Solubility

The development of stable solid dispersion formulations that maintain desired improvement of drug dissolution rate during the entire shelf life requires the analysis of drug-polymer solubility and miscibility. Only if the drug concentration is below the solubility limit in the polymer, the physical stability of solid dispersions is guaranteed without risk for drug (re)crystallization. If the drug concentration is above the solubility, but below the miscibility limit, the system is stabilized through intimate drug-polymer mixing, with additional kinetic stabilization if stored sufficiently below the mixture glass transition temperature. Therefore, it is of particular importance to assess the drug-polymer solubility and miscibility, to select suitable formulation (a type of polymer and drug loading), manufacturing process, and storage conditions, with the aim to ensure physical stability during the product shelf life. Drug-polymer solubility and miscibility can be assessed using analytical methods, which can detect whether the system is single-phase or not. Thermodynamic modeling enables a mechanistic understanding of drug-polymer solubility and miscibility and identification of formulation compositions with the expected formation of the stable single-phase system. Advance molecular modeling and simulation techniques enable getting insight into interactions between the drug and polymer at the molecular level, which determine whether the single-phase system formation will occur or not.

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