Solvent injection-lyophilization of tert-butyl alcohol/water cosolvent systems for the preparation of drug-loaded solid lipid nanoparticles (original) (raw)
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Molecules, 2020
Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have emerged as potential drug delivery systems for various applications that are produced from physiological, biodegradable, and biocompatible lipids. The methods used to produce SLNs and NLCs have been well investigated and reviewed, but solvent injection method provides an alternative means of preparing these drug carriers. The advantages of solvent injection method include a fast production process, easiness of handling, and applicability in many laboratories without requirement of complicated instruments. The effects of formulations and process parameters of this method on the characteristics of the produced SLNs and NLCs have been investigated in several studies. This review describes the methods currently used to prepare SLNs and NLCs with focus on solvent injection method. We summarize recent development in SLNs and NLCs production using this technique. In addition, the effects of solvent injection pro...
Colloids and Surfaces B: Biointerfaces, 2013
Raloxifene HCl (RH), a selective estrogen receptor modulator (SERM), is indicated for the prophylaxis or treatment of postmenopausal osteoporosis. RH shows extremely poor bioavailability due to limited solubility and an extensive intestinal/hepatic first-pass metabolism. Solid lipid nanoparticles (SLNs) are valuable carriers that can enhance drug bioavailability. However, in the case of RH, the encapsulation of the drug in SLNs remains a challenge because of its poor solubility in both water and lipids. In this study, a series of RH-containing SLNs (RH-SLNs) were generated using a modified double emulsion solvent evaporation (DESE) method. Briefly, RH with various drug/lipid ratios was solubilized in the inner core of a double emulsion using different water/organic solvent mixtures. Our best formulation was achieved with the formation of negatively charged nanoparticles, 180 nm in diameter, with an encapsulation and loading efficiency of 85% and 4.5%, respectively. It also showed a Fickian mechanism of the drug release in the basic dissolution media. Thermal analysis revealed a distinct decrease in the crystallinity of lipids and RH in comparison with the unprocessed materials. The results of a cell viability assay also showed a better antiproliferative effect of the drug-loaded SLNs versus the free drug solution. Thus, these results indicated that the modified DESE method could be proposed for the effective encapsulation of RH in SLNs with appropriate physicochemical and biological properties.
LIPID BASED NANOPARTICLES: SLN/NLCS - FORMULATION TECHNIQUES, ITS EVALUATION AND APPLICATIONS
IJCIRAS`, 2019
This review represents the usage of SLN and NLCs regarding their advantages, formulation methodology, characterization and applications. If suitably investigated, SLNs/NLCS may open new prospects in therapy of complex diseases. Solid lipid nanoparticles (SLN) were formulated at the emergence of the 1990s as a replaced carrier system to emulsions, liposomes and polymeric nanoparticles. SLN are aqueous colloidal dispersions, the matrix of which consists of solid biodegradable lipids. Nanostructured lipid carriers (NLCs) are drug-delivery systems consists of both solid and liquid lipids as a core matrix. It was shown that NLCs has some advantages for drug therapy over conventional carriers, including higher solubility, the ability to enhance storage stability, improved permeability and bioavailability, reduced adverse effect, prolonged half-life, and tissue-targeted delivery. SLN and NLCs are manufactured by techniques like high pressure homogenization, solvent diffusion method ultrasonication, solvent emulsification etc. Both SLN/NLCs have applications in for parenteral, nasal, respiratory, ocular, rectal, and topical, in chemotherapy, etc.
Current Nanoscience, 2013
Introduction: Premise of the present study was to suitably select or modify the constitution of the lipid matrix to achieve significantly high entrapment of hydrophilic drugs within solid lipid nanoparticles (SLNs). Methods and Materials: Isoniazid was selected as a representative hydrophilic drug with a high solubility of 230 mg/ml and a log P of-0.402 at 25°C (determined as per OECD TG 105 and 107 respectively). Three lipids/fatty acids (Glyceryl monostearate, Compritol 888 ATO ® and stearic acid) were evaluated out of which Compritol 888 ATO ® and stearic acid showed favorable interactions (FTIR and DSC studies) with isoniazid. The two lipids were used alone or in combination for preparing SLNs. Formulation of SLNs by microemulsification, method involved pouring the hot microemulsion into cold water under constant stirring, which may result in expulsion of the hydrophilic drug from the lipid matrix; hence, partitioning of isoniazid from the hot lipid melts into cold water was also determined. Results and Discussion: Results indicate that combining stearic acid with Compritol 888 ATO ® in certain ratio (1:4) led to significant entrapment efficiency (EE) of 84.0±1.1%. The formulations were subjected to morphological, physiochemical and in vitro drug release studies. Developed SLNs were found to be stable for 1 year at 4 °C. Conclusion: The study demonstrates the benefit of excipient screening techniques in improving entrapment efficiency of a hydrophilic drug.
AAPS PharmSciTech, 2016
Lipid-core nanocapsules (LNC) were designed and prepared as a colloidal system for drug targeting to improve the stability of drugs and allow their controlled release. For parenteral administration, it is necessary to ensure formulation sterility. However, sterilization of nanotechnological devices using an appropriate technique that keeps the supramolecular structure intact remains a challenge. This work aimed to evaluate the effect of autoclaving on the physicochemical characteristics of LNC. Formulations were prepared by the self-assembling method, followed by isotonization and sterilization at varying times and temperatures. The isotonicity was confirmed by determining the freezing temperature, which was −0.51°C. The formulation was broadly characterized, and the diameter of the particles was determined utilizing complementary methods. To evaluate the chemical stability of poly(ε-caprolactone), its molecular weight was determined by size exclusion chromatography. The physicochemical characteristics (average diameter, viscosity, and physical stability) of the formulation were similar before and after adding glycerol and conducting the sterilization at the highest temperature (134°C) and the shorter exposure time (10 min). After autoclaving, the sterility test was performed and showed no detectable microbial growth. Multiple light scattering demonstrated that the formulations were kinetically stable, and the mean diameter was constant for 6 months, corroborating this result. The polymer was chemically stable in the sterilized formulation. Isotonic and sterile LNC aqueous suspensions were produced using glycerol and autoclaving. Briefly, the results open an opportunity to produce an isotonic and sterile LNC aqueous dispersion applicable as nanomedicine for intravenous administration in clinical trials.
International Journal of Pharmacy and Pharmaceutical Sciences, 2015
The aim of the present study was to formulate and evaluate the Solid Lipid Nanoparticles (SLNs) of Ropinirole Hydrochloride (ROP). Methods: ROP-loaded SLNs were prepared by a double emulsion method using glyceryl monostearate (GMS) as lipid and soya lecithin as a stabilizer. All formulated ROP-loaded SLNs were characterized for its particle size and size distribution, zeta potential, % Entrapment Efficiency (EE) and drug loading. The formulations were optimized in terms of GMS to soya lecithin ratio and sonication time of primary emulsion. Shape and surface morphology of the optimized formulation was studied using optical microscopy and scanning electron microscopy. In vitro and ex vivo Study of optimized formulation was also performed and compared with a pure drug solution. Results: The particle size and polydispersity index (PDI), zeta potential and EE of optimized formulation were found to be 320±5.15 nm, 0.260±0.012,-37.9±1.43, 56.13±2.33% respectively. In vitro and ex vivo permeation study revealed that percentage cumulative drug release of optimized formulation was found to be 58.45±1.75% and 53.75±1.34 % respectively in 24 h and more than 90% drug release from pure drug solution was found to be within 6 h. Drug release from the formulation is sustained as compared to the plain drug solution which release 97.74 % (in vitro) and 88.15 % (ex vivo) of the drug within 6 h. Conclusion: From the results, it concludes that drug released from SLNs follows sustained release pattern and it will enhance the overall activity of the drug.
European Journal of Pharmaceutics and Biopharmaceutics, 2010
The objective of the present paper is to develop lipidic nanoparticles (NP) able to encapsulate drugs presenting limited solubility in both water and lipids, with high loading rates, and without using organic solvents. In this goal, a solubility enhancer, a macrogolglyceride (Labrasol Ò), was incorporated in a formulation process based on a low-energy phase inversion temperature method. From electrical conductivity through the temperature scans, it appears that presence of Labrasol Ò does not prevent the phase inversion, and it takes part in the microemulsion structuring, probably of bicontinuous type. After screening pseudo-ternary diagrams, the feasibility of NP was established. From results of a partial least square analysis, it appears that these NP present a core-shell structure where Labrasol Ò is well encapsulated and contributes to the formation of the oily liquid core of the NP. The diameter of the NP, assessed by dynamic light scattering, remains kinetically stable. These NP, smaller than 200 nm, spherical in shape as attested by cryo-transmission electron micrographs, are able to encapsulate a tripentone, a new anticancer agent, with drug loading rates up to 6.5% (w/w). So highly drug-loaded lipidic nanocarriers were developed without using the slightest organic solvent trace, and making it easily possible dose adjustment.
Pharmaceutical Development and Technology, 2011
The present study describes an in Silico solubility behavior of drug, lipids and solvents, an essential screening study in preparation of solid lipid nanoparticles (SLN). Ciprofloxacin HCl was selected as a model drug along with 11 lipids and 5 organic solvents. In Silico miscibility study of drug/lipid/solvent was performed using Hansen solubility parameter approach calculated by group contribution method of Van Krevelen and Hoftyzer. Predicted solubility was validated by determining solubility of lipids in various solvent at different temperature range, while miscibility of drug in lipids was determined by apparent solubility study and partition experiment. The presence of oxygen and OH functionality increases the polarity and hydrogen bonding possibilities of the compound which has reflected the highest solubility parameter values for Geleol and Capmul MCM C8. Ethyl acetate, Geleol and Capmul MCM C8 was identified as suitable organic solvent, solid lipid and liquid lipid respectively based on a solubility parameter approach which was in agreement with the result of an apparent solubility study and partition coefficient. These works demonstrate the validity of solubility parameter approach and provide a feasible predictor to the rational selection of excipients in designing SLN formulation.
Solid lipid nanoparticles (SLN) for controlled drug delivery – a review of the state of the art
European Journal of Pharmaceutics and Biopharmaceutics, 2000
Solid lipid nanoparticles (SLN) introduced in 1991 represent an alternative carrier system to traditional colloidal carriers, such as emulsions, liposomes and polymeric micro-and nanoparticles. SLN combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews the present state of the art regarding production techniques for SLN, drug incorporation, loading capacity and drug release, especially focusing on drug release mechanisms. Relevant issues for the introduction of SLN to the pharmaceutical market, such as status of excipients, toxicity/tolerability aspects and sterilization and long-term stability including industrial large scale production are also discussed. The potential of SLN to be exploited for the different administration routes is highlighted. References of the most relevant literature published by various research groups around the world are provided. q
Design and characterization of a new drug nanocarrier made from solid–liquid lipid mixtures
Journal of Colloid and Interface Science, 2005
The classical lipid nanoparticles that have been proposed for drug delivery are composed of solid lipids. Due to their composition, these nanoparticles have a limited drug loading and controlled release capacity. The present work was aimed at modifying the inner structure of nanoparticles made of tripalmitin, lecithin, and poly(ethylene glycol) (PEG)-stearate with the incorporation of a liquid lipid (Miglyol 812 oil). The composition and structural organization of the components of the resulting nanoparticles were characterized by 1 H NMR spectroscopy. Any possible changes in the crystalline domains of individual components when in the form of the nanoparticles were investigated by differential scanning calorimetry (DSC) and X-ray diffraction spectroscopy. The results of the NMR analysis indicated a significant incorporation of the oil to the solid nanoparticle matrix. Furthermore, the relaxation time constants as well as the peak width of the 1 H NMR spectrum of the nanoparticles suggest the presence of the oil in the form of phase-separated liquid nanoreservoirs within the nanoparticles. This conclusion was supported by the observation of restricted diffusion dynamics for the oil molecules. Interestingly, the incorporation of the oil did not interfere with the crystallization of the solid lipids (tripalmitin and PEG-stearate). In conclusion, a new nanostructure consisting of solid lipids and oily nanodomains was developed. This structural modification of the solid lipid nanoparticles may have an effect on their encapsulation capacity and controlled release properties. 2004 Elsevier Inc. All rights reserved.