Formulation and characterisation of self-microemulsifying drug delivery systems based on biocompatible nonionic surfactants

Development of self-dispersing drug delivery systems (SMEDDS) is a modern strategy for oral delivery improvement of poorly soluble drugs. Self-microemulsifying drug delivery systems (SMEDDS) are isotropic mixtures of oils and hydrophilic surfactants, which form oil-in-water (o/w) microemulsions by dilution in aqueous media (e.g., gastrointestinal fluids). Formulation of SMEDDS carriers requires consideration of a large number of formulation parameters and their influences on process of self-microemulsifying and releasing of drug. The aim of this work was formulation and characterisation of SMEDDS for oral administration of ibuprofen. In the experimental work, two series of potential SMEDDS were prepared (M1-M10), using surfactant (Labrasol?, Gattefosse), cosurfactant (PEG-40 hydrogenated castor (Cremophor? RH40), and oil (medium chain triglycerides (Crodamol? GTCC) and olive oil (Cropur? Olive)), at surfactant-to-cosurfactant mass ratios (Km) 9:1, 7:3, 5:5, 3:7, and 1:9, and 10 % or 20 % of the oil phase. Ibuprofen was dissolved in formulations in concentration of 10 %. Characterisation of the investigated formulations included evaluation of physical stability, self-microemulsification ability in 0,1M HCl (pH 1.2) and phosphate buffer pH 7.2 (USP) and in vitro drug release. Formation of o/w microemulsions with the average droplet size (Z-ave) up to 100 nm, was observed in dispersions of formulations prepared with 10% w/w of medium chain triglycerides, within the entire investigated range of the Km values (M1-M5). These formulations were selected as SMEDDS. Results of characterisation pointed out the importance of the type and concentration of the oil as well as the Km value for the self-microemulsying ability as well as drug release kinetics from the investigated SMEDDS. Ibuprofen relase was in accordance with the request of USP 30-NF 25 (at least 80 %, after 60 min) from the formulations M1 (Km 9:1) and M5 (Km 1:9). Furthermore, ibuprofen release was completed after 10 minutes from formulation M1, while the release from the carrier M5 (~30 %) as well as from the commercial tablets Brufen? (~55%) and soft capsules Rapidol? (~65 %), examined under the same conditions, was significantly slower. The present study revealed that the formulation M1 represents a potential SMEDDS which efficiently solubilises ibuprofen in acidic media, with potential to minimise the side effects, while on introduction into alkaline intestinal environment, the drug may rapidly release from the carrier and undergo apsorption.

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Correlating in vitro degradation and drug release kinetics of biopolymer-based drug delivery systems

International Journal of Biobased Plastics ◽

10.1080/24759651.2018.1563358 ◽

2019 ◽

Vol 1 (1) ◽

pp. 8-21 ◽

Cited By ~ 4

Author(s):

R. Harting ◽

K. Johnston ◽

S. Petersen

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery Systems ◽

Release Kinetics ◽

Delivery Systems ◽

In Vitro Degradation ◽

Drug Release Kinetics ◽

Kinetics Of

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Nanoporous anodic titanium dioxide layers as potential drug delivery systems: Drug release kinetics and mechanism

Colloids and Surfaces B Biointerfaces ◽

10.1016/j.colsurfb.2016.03.073 ◽

2016 ◽

Vol 143 ◽

pp. 447-454 ◽

Cited By ~ 30

Author(s):

Magdalena Jarosz ◽

Anna Pawlik ◽

Michał Szuwarzyński ◽

Marian Jaskuła ◽

Grzegorz D. Sulka

Keyword(s):

Drug Delivery ◽

Titanium Dioxide ◽

Drug Release ◽

Drug Delivery Systems ◽

Release Kinetics ◽

Delivery Systems ◽

Kinetics And Mechanism ◽

Potential Drug ◽

Drug Release Kinetics

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pH-Responsive Release of Ruthenium Metallotherapeutics from Mesoporous Silica-Based Nanocarriers

Pharmaceutics ◽

10.3390/pharmaceutics13040460 ◽

2021 ◽

Vol 13 (4) ◽

pp. 460

Author(s):

Minja Mladenović ◽

Ibrahim Morgan ◽

Nebojša Ilić ◽

Mohamad Saoud ◽

Marija V. Pergal ◽

...

Keyword(s):

Drug Delivery ◽

Mesoporous Silica ◽

Inductively Coupled Plasma ◽

Drug Delivery Systems ◽

Mesoporous Silica Nanoparticles ◽

Release Kinetics ◽

Delivery Systems ◽

Emission Spectrometry ◽

Ph Responsive

Ruthenium complexes are attracting interest in cancer treatment due to their potent cytotoxic activity. However, as their high toxicity may also affect healthy tissues, efficient and selective drug delivery systems to tumour tissues are needed. Our study focuses on the construction of such drug delivery systems for the delivery of cytotoxic Ru(II) complexes upon exposure to a weakly acidic environment of tumours. As nanocarriers, mesoporous silica nanoparticles (MSN) are utilized, whose surface is functionalized with two types of ligands, (2-thienylmethyl)hydrazine hydrochloride (H1) and (5,6-dimethylthieno[2,3-d]pyrimidin-4-yl)hydrazine (H2), which were attached to MSN through a pH-responsive hydrazone linkage. Further coordination to ruthenium(II) center yielded two types of nanomaterials MSN-H1[Ru] and MSN-H2[Ru]. Spectrophotometric measurements of the drug release kinetics at different pH (5.0, 6.0 and 7.4) confirm the enhanced release of Ru(II) complexes at lower pH values, which is further supported by inductively coupled plasma optical emission spectrometry (ICP-OES) measurements. Furthermore, the cytotoxicity effect of the released metallotherapeutics is evaluated in vitro on metastatic B16F1 melanoma cells and enhanced cancer cell-killing efficacy is demonstrated upon exposure of the nanomaterials to weakly acidic conditions. The obtained results showcase the promising capabilities of the designed MSN nanocarriers for the pH-responsive delivery of metallotherapeutics and targeted treatment of cancer.

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In vitro evaluation of drug release from self micro-emulsifying drug delivery systems using a biodegradable homolipid from Capra hircus

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2005.08.018 ◽

2005 ◽

Vol 304 (1-2) ◽

pp. 4-10 ◽

Cited By ~ 37

Author(s):

Anthony A. Attama ◽

Megg O. Nkemnele

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Capra Hircus ◽

In Vitro Evaluation

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Nanoparticles vs. nanofibers: a comparison of two drug delivery systems on assessing drug release performance in vitro

Designed Monomers & Polymers ◽

10.1080/15685551.2015.1070500 ◽

2015 ◽

Vol 18 (7) ◽

pp. 678-689 ◽

Cited By ~ 14

Author(s):

Xiaoqian Shan ◽

Changsheng Liu ◽

Fengqian Li ◽

Chunfa Ouyang ◽

Qun Gao ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery Systems ◽

Delivery Systems

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A hydrogel based quasi-stationary test system for in vitro dexamethasone release studies for middle ear drug delivery systems

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2021-2176 ◽

2021 ◽

Vol 7 (2) ◽

pp. 692-695

Author(s):

Thomas Eickner ◽

Michael Teske ◽

Natalia Rekowska ◽

Volkmar Senz ◽

Klaus-Peter Schmitz ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery System ◽

Delivery System ◽

Drug Concentration ◽

Drug Delivery Systems ◽

Test System ◽

Delivery Systems ◽

In Vitro Drug Release

Abstract For the investigation of in vitro drug release, methods have been used in which samples of drug delivery systems are immersed in release medium. The medium is used to measure drug concentration via chromatography or photometry. These systems are suitable to investigate the drug release of different systems or to simulate tissue environments. When considering predominantly humid regions, e.g. for drug release into the cochlea through the round window membrane by a drug delivery system placed at that membrane, reproducible in vitro determination of drug release becomes particularly challenging. In this study the development of a system is reported that allows the investigation of the in vitro drug release simulating such conditions. The presented test system consists of an alginate hydrogel in glass vials simulating the biological membrane, which separates the drug delivery system from the medium filled compartment. Saline is used as release medium and injected under the hydrogel. The samples are placed on top of the hydrogel, which slightly contacts the medium surface. The drug concentration in the release medium was determined by HPLC measurements. This system allows for testing the release of dexamethasone without the samples being completely surrounded by medium. The hydrogel mediates the diffusion of the drug by ensuring the contact with the medium. Release was monitored for more than 23 days. The presented concept was successfully designed and manufactured. The system is inexpensive and can be duplicated easily. In this study, it was used to monitor the drug release of dexamethasone from PEGDA700 derived polymer. One challenge that remains to be considered is the low mechanical stability of the hydrogel, which results in a need for repeated manufacturing during the handling of the system.

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Self-emulsifying drug delivery systems with atorvastatin adsorbed on solid carriers: formulation and in vitro drug release studies

Colloids and Surfaces A Physicochemical and Engineering Aspects ◽

10.1016/j.colsurfa.2019.05.062 ◽

2019 ◽

Vol 577 ◽

pp. 281-290 ◽

Cited By ~ 2

Author(s):

Agnieszka Snela ◽

Barbara Jadach ◽

Anna Froelich ◽

Marcin Skotnicki ◽

Kasylda Milczewska ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery Systems ◽

Delivery Systems ◽

In Vitro Drug Release ◽

Release Studies

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Towards the development of Self-Nano-Emulsifying Drug Delivery Systems (SNEDDS) containing trimethyl chitosan for the oral delivery of amphotericin B: In vitro assessment and cytocompatibility studies

Journal of Drug Delivery Science and Technology ◽

10.1016/j.jddst.2020.101524 ◽

2020 ◽

Vol 56 ◽

pp. 101524 ◽

Cited By ~ 5

Author(s):

Eleni Kontogiannidou ◽

Thomas Meikopoulos ◽

Christina Virgiliou ◽

Nikolaos Bouropoulos ◽

Helen Gika ◽

...

Keyword(s):

Drug Delivery ◽

Amphotericin B ◽

Oral Delivery ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Trimethyl Chitosan ◽

In Vitro Assessment

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Comparison of Polydopamine-Coated Mesoporous Silica Nanorods and Spheres for the Delivery of Hydrophilic and Hydrophobic Anticancer Drugs

International Journal of Molecular Sciences ◽

10.3390/ijms20143408 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3408 ◽

Cited By ~ 5

Author(s):

Anna-Karin Pada ◽

Diti Desai ◽

Kaiyao Sun ◽

Narayana Prakirth Govardhanam ◽

Kid Törnquist ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Mesoporous Silica ◽

Cellular Uptake ◽

Drug Delivery Systems ◽

Mesoporous Silica Nanoparticles ◽

Drug Distribution ◽

Delivery Systems ◽

Hydrophilic Drugs

Mesoporous silica nanoparticles (MSNs) have been widely studied as drug delivery systems in nanomedicine. Surface coating of MSNs have enabled them to perform efficiently in terms of bioavailability, biocompatibility, therapeutic efficacy and targeting capability. Recent studies have suggested the use of polydopamine (PDA) as a facilitative coating for MSNs that provides sustained and pH-responsive drug release, owing to the adhesive “molecular-glue” function of PDA. This further endows these hybrid MSN@PDA particles with the ability to carry large amounts of hydrophilic drugs. In this study, we expand the feasibility of this platform in terms of exploring its ability to also deliver hydrophobic drugs, as well as investigate the effect of particle shape on intracellular delivery of both a hydrophilic and hydrophobic anticancer drug. MSN@PDA loaded with doxorubicin (hydrophilic) and fingolimod (hydrophobic) was studied via a systematic in vitro approach (cellular internalization, intracellular drug distribution and cytotoxicity). To promote the cellular uptake of the MSN@PDA particles, they were further coated with a polyethylene imine (PEI)-polyethylene glycol (PEG) copolymer. Drug-loaded, copolymer-coated MSN@PDA showed effective cellular uptake, intracellular release and an amplified cytotoxic effect with both doxorubicin and fingolimod. Additionally, rods exhibited delayed intracellular drug release and superior intracellular uptake compared to spheres. Hence, the study provides an example of how the choice and design of drug delivery systems can be tuned by the need for performance, and confirms the PDA coating of MSNs as a useful drug delivery platform beyond hydrophilic drugs.

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