Size Of Solid Lipid Nanoparticles Research Articles

Solid Lipid Nanoparticles Containing Dopamine and Grape Seed Extract: Freeze-Drying with Cryoprotection as a Formulation Strategy to Achieve Nasal Powders

(1) Background: DA-Gelucire® 50/13-based solid lipid nanoparticles (SLNs) administering the neurotransmitter dopamine (DA) and the antioxidant grape-seed-derived proanthocyanidins (grape seed extract, GSE) have been prepared by us in view of a possible application for Parkinson’s disease (PD) treatment. To develop powders constituted by such SLNs for nasal administration, herein, two different agents, namely sucrose and methyl-β-cyclodextrin (Me-β-CD), were evaluated as cryoprotectants. (2) Methods: SLNs were prepared following the melt homogenization method, and their physicochemical features were investigated by Raman spectroscopy, Scanning Electron Microscopy (SEM), atomic force microscopy (AFM) and X-ray Photoelectron Spectroscopy (XPS). (3) Results: SLN size and zeta potential values changed according to the type of cryoprotectant and the morphological features investigated by SEM showed that the SLN samples after lyophilization appear as folded sheets with rough surfaces. On the other hand, the AFM visualization of the SLNs showed that their morphology consists of round-shaped particles before and after freeze-drying. XPS showed that when sucrose or Me-β-CD were not detected on the surface (because they were not allocated on the surface or completely absent in the formulation), then a DA surfacing was observed. In vitro release studies in Simulated Nasal Fluid evidenced that DA release, but not the GSE one, occurred from all the cryoprotected formulations. Finally, sucrose increased the physical stability of SLNs better than Me-β-CD, whereas RPMI 2650 cell viability was unaffected by SLN-sucrose and slightly reduced by SLN-Me-β-CD. (4) Conclusions: Sucrose can be considered a promising excipient, eliciting cryoprotection of the investigated SLNs, leading to a powder nasal pharmaceutical dosage form suitable to be handled by PD patients.

OPTIMIZATION, CHARACTERIZATION AND IN VIVO STUDY OF RIVASTIGMINE TARTRATE NANOPARTICLES BY USING 22 FULL FACTORIAL DESIGN FOR ORAL DELIVERY

Objective: This research aims to optimize the solid lipid nanoparticles by using full factorial design to improve the delivery of rivastigmine tartrate (RT), which is used for the treatment of Alzheimer’s disease (AD). Solid lipid nanoparticles (SLNs) are attracting importance for drug developers due to their performance. The outcome of this research will lead to improvements in drug release and solubility of RT for better therapeutic effect. Methods: Four different methods were used to prepare solid lipid nanoparticles of rivastigmine tartrate, namely the modified solvent emulsification technique, the microemulsion cooling technique, the solvent injection technique, and the homogenization/ultrasonication technique. Glyceryl monostearate (GMS) was used as a lipid; Compritol 888, tween 80, and span 40 were used as surfactants, co-surfactants, and stabilizers, respectively. Results: SLNs were evaluated for zeta potential, particle size, polydispersity index, surface morphology, Fourier Transform Infrared Spectroscopy (FTIR), and differential scanning calorimetry (DSC). Entrapment efficiency and drug loading were also estimated. Solubility study of rivastigmine tartrate in different solid lipids as well as the in vitro drug release, was studied. The particle size of SLNs was found to range between 138.22+0.01 nm and 172.79+0.23 nm. The zeta potential of the optimized formulation was found to be in the the-24+0.01mV range, indicating a stable formulation. A scanning electron microscope indicates a clear spherical structure without any aggregation. Entrapment efficiency was determined to be 69.27+0.22%. The RT-SLNs showed significant retention in memory when compared with RT solution (standard formulation), which may be attributed to the lipid nature and nanostructure of the delivery system that may probably result in more accumulation of the drug in the brain to show better effect. Conclusion: The current study concludes that the microemulsion cooling technique is the best method for patient compliance and stability with all desired characteristics parameters.

Fabrication of Transdermal Gel Embedded with Solid Lipid Nanoparticles of Indomethacin

Rheumatoid/osteoarthritis is one of the most common causes for lacking behind in the health sector. Medication in the form of tablets are already available in the market but has disadvantages. When these medicines are taken orally it cause heartburn and discomfort. The introduction of transdermal drug delivery is expected to solve this problem of side eff ects associated with oral delivery of drug. In the present study, indomethacin was loaded in solid lipid nanoparticles (SLN) which are then embedded in Carbopol gel for transdermal application. The solvent evaporation ultrasonication method was used for making SLNs. The formulation was evaluated for various parameters such as ; particle size and zeta potential of SLN using zetasizer as an instrument and gel formulations were evaluated for pH, spreading coeffi cient, viscosity, visual appearance and clarity. Gel-embedded SLN formulation was found to be a potential transdermal drug delivery system for NSAIDs like indomethacin to treat ailments like rheumatoid arthritis or osteoarthritis.

Synthesis of Lipid Nanoparticles Incorporated with Ferula assa-foetida L. Extract

Solid Lipid Nanoparticles (SLN) have been prepared by high-pressure homogenization and optimized in order to protect ferulic acid from Ferula assa-foetida L. extract. The influence of lipid and surfactant concentration on the mean particle size (Z-Ave), polydispersity index (PDI), and zeta potential (ZP) of SLN was analyzed. In addition, other parameters for the preparation of ferulic acid-loaded nanoparticles, such as extract concentration and variable parameters for the synthesis method used (e.g., pressure), were adjusted to obtain the smallest particle size and polydispersity index, as well as the highest value for zeta potential, which are characteristic of the stable SLN. The established formulation obtained from the optimized synthesis was composed of 6.0 wt.% of the lipid phase and 1.5 wt.% of surfactant, giving stable SLN with Z-Ave, PDI, and ZP values of 163.00 ± 1.06 nm, 0.16 ± 0.01, and −41.97 ± 0.47 mV, respectively. The loading of ferulic acid from Ferula assa-foetida L. extract within the SLN resulted in particles with a mean size of 155.3 ± 1.1 nm, polydispersity index of 0.16 ± 0.01, zeta potential of −38.00 ± 1.12 mV, and encapsulation efficiency of 27%, the latter being quantified on the basis of RP-HPLC analysis. Our findings highlight the added value of SLN as a delivery system for phenolic phytochemical compounds extracted from Ferula assa-foetida L.

Physicochemical Characterization of Chitosan-Decorated Finasteride Solid Lipid Nanoparticles for Skin Drug Delivery.

Finasteride is considered the drug of choice for androgenic alopecia and benign prostate hyperplasia. The aim of the study was to formulate nanodrug carriers of finasteride with enhanced retentive properties in the skin. The finasteride was formulated as solid lipid nanoparticles that were decorated with different concentrations of chitosan for improved retentive properties. Solid lipid nanoparticles (SLNs) were synthesized by “high-speed homogenization technique” using stearic acid as a solid lipid while PEG-6000 and Tween-80 were used as surfactants. The SLNs were evaluated for particle size, polydispersity index (PDI), zeta potential, drug entrapment efficiency, and drug release behavior. The mean particle size of SLNs was in the range of 10.10 nm to 144.2 nm. The PDI ranged from 0.244 to 0.412 while zeta potential was in the range of 8.9 mV to 62.6 mV. The drug entrapment efficiency in chitosan undecorated formulations was 48.3% while an increase in drug entrapment was observed in chitosan-decorated formulations (51.1% to 62%). The in vitro drug release studies of SLNs showed an extended drug release for 24 hours after 4 hours of initial burst release. The extended drug release was observed in chitosan-coated SLNs in comparison with uncoated nanoparticles. The permeation and retention study revealed higher retention of drug in the skin and low permeation with chitosan-decorated SLNs that ranged from 39.4 μg/cm2 to 13.2 μg/cm2. TEM images depicted spherical shape of SLNs. The stability study confirmed stable formulations in temperature range of 5°C and 40°C for three months. It is concluded from this study that the SLNs of finasteride were successfully formulated and chitosan decoration enhanced the drug retention in the skin layers. Therefore, these formulations could be used in androgenic alopecia and benign prostate hyperplasia to avoid the side effects, drug degradation, and prolonged use of drug with conventional oral therapy.

Impact of Composition and Morphology of Ketoconazole-Loaded Solid Lipid Nanoparticles on Intestinal Permeation and Gastroplus-Based Prediction Studies.

Ketoconazole (KTZ) is a potential oral antifungal agent to control systemic and local infections. This study addresses the impact of composition (tween 80 and compritol as CATO) and morphology on permeation (stomach, jejunum, and ileum) profiles of KTZ-loaded solid lipid nanoparticles (SLNs) in rats followed by in vivo pharmacokinetic prediction and simulation using GastroPlus. The selected formulations were characterized for size, size distribution, zeta potential, entrapment efficiency, total drug content, morphology, in vitro drug release, ex vivo permeation and drug deposition, penetration potential, and GastroPlus-based in vivo prediction in rats. The results showed that there was considerable impact of pH, composition (CATO and tween 80), size, total drug content, and entrapment efficiency on in vitro drug release and permeation across the stomach, jejunum, and ileum. Ex vivo findings suggested pH, composition, size, and permeability coefficient-dependent permeation of SLNs across the stomach, jejunum, and ileum. Confocal laser scanning microscopy (CLSM) confirmed a relatively high degree of penetration of the optimized formulation “K-SLN4” (66.1% across the stomach, 51.5% across the jejunum, and 47.9% across the ileum) as compared to KSUS (corresponding values of 21.7%, 18.2%, and 17.4%). Finally, GastroPlus predicted in vivo dissolution/absorption as 0.012 μg/mL of K-SLN4 as compared to KSUS (the drug suspension with 0.0058 μg/mL) and a total regional absorption of 80.0% by K-SLN4 as compared to 60.1% of KSUS. There was only an impact of dose on Cmax (maximum plasma concentration) and area under the curve (AUC) in rats. Thus, the present strategy could be a promising alternative to parenteral and topical delivery systems for long-term therapy against systemic and local mycoses with high patient compliance.

Promising Larvicidal Efficacy of Solid Lipid Nanoparticles Containing Mentha longifolia L., Mentha pulegium L., and Zataria multiflora Boiss. Essential Oils Against the Main Malaria Vector, Anopheles stephensi Liston.

An attempt was made in the current study to develop a natural mosquito larvicide using nanotechnology. Solid lipid nanoparticles (SLNs) containing three essential oils were first prepared using the high-pressure homogenizer. Larvicidal effects of essential oils and the SLNs against Anopheles stephensi were then compared. The size of SLN containing Mentha longifolia, Mentha pulegium, Zataria multiflora essential oil was obtained as 105 ± 7, 210 ± 4, and 137 ± 8nm. Their zeta potentials were -7.8, -4.7, and -9.7mV. Besides, their efficacy with LC50 values of 24.79, 5.11, and 9.19µg/mL was significantly more potent than that of their un-formulated essential oils with LC50 values of 36.2, 27.55, and 33.33µg/mL. SLNs containing M. pulegium with the best efficacy (P < 0.05) could be considered as potent larvicides against other important species of mosquitoes and field trials.

Suppressed XIAP and cIAP expressions in human brain cancer stem cells using BV6- and GDC0152-encapsulated nanoparticles

BackgroundSmac mimetics functioned against inhibitors of apoptosis proteins (IAP) often fail to achieve sufficient ability in glioblastoma multiforme (GBM) treatment due to the obstruction of the blood-brain barrier (BBB). MethodsBV6- and GDC0152-encapsulated solid lipid nanoparticles (SLNs) with surface transferrin (Tf) and folic acid (FA) (BV6-GDC0152-Tf-FA-SLNs) were developed to downregulate IAP in U87MG cells and human brain cancer stem cells (HBCSCs) for GBM treatment. Significant findingsAn increase in stearic acid (SA) level enlarged SLNs with improved entrapment of BV6 and GDC0152. 1H NMR study revealed hydrogen bonding between SA and the two IAP antagonists, supporting controlled release of BV6 and GDC0152 from SLNs. Increasing sodium dodecyl sulfate concentration reduced the size of SLNs, and raised the particle stability. Conjugated Tf and FA on SLNs favored permeating the BBB as corroborated from decreased transendothelial electrical resistance, and raised BBB permeability of propidium iodide, BV6 and GDC0152. The ability of BV6-GDC0152-Tf-FA-SLNs to target IAP in U87MG cells and HBCSCs was validated from the downregulated XIAP and cIAP-1 expressions and upregulated caspase-3 expression in immunofluorescence staining, flow cytometry and western blot analysis. Hence, Tf- and FA-grafted SLNs can be an effective colloidal delivery system to deliver BV6 and GDC0152 across the BBB, facilitate IAP targeting, and enhanced drug bioavailability of the two Smac mimetics in GBM cells for potential clinical trials.

DEVELOPMENT OF NILOTINIB LOADED SOLID LIPID NANOPARTICLES AND OPTIMIZATION BY CENTRAL COMPOSITE DESIGN APPROACH

Objective: In current research, solid lipid nanoparticles (SLN) are formulated for the anticancer drug, nilotinib, to conquer the drawbacks associated with drug including low bioavailability and solubility. Methods: The formulation comprised of tripalmitin (lipid), poloxamer 188(surfactant) and glyceryl palmitostearate (cosurfactant) by solvent evaporation technique. The formulation and process variables of SLN were optimized by experimental design-Central composite design (CCD). The effect of drug to lipid ratio (A), concentration of Poloxamer 188 (B) and concentration of glyceryl palmitostearate(C), on particle size (Y1) and encapsulation efficiency (Y2) of SLN were evaluated. Three batches (F1-F3) of Nilotinib SLNs were formulated by desirability approach and evaluated. Results: The mean size of all the formulations ranged between 187–198 nm, PDI between 0. 291-0.652 and zeta potential between-21.8 to to-24.7 mV indicating the wide range of size distribution and stabiliity of the formulations. The total encapsulation efficiency of SLNs ranged between 85 to 86 %. The SEM analysis revealed the spherical shape of individual particles and PXRD results indicate amorphization of drug in SLN formulation. The drug release was continued for 24 h, indicative of controlled release drug delivery. Conclusion: From the above results it is concluded that the solubility and bioavailability of nilotinib is enhanced.

Formulation, characterization and in-vitro evaluation of solid lipid nanoparticles for the delivery of a new anticancer agent, 1H-pyrazolo[3,4-d] pyrimidine derivative

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To investigate the physicochemical properties and in vitro cytotoxic effect of a potent epidermal growth factor receptor-tyrosine kinase (EGFRWT-TK) inhibitor, 1H-pyrazolo [3,4-d] pyrimidine (FEP) derivative and formulated as solid lipid nanoparticles (SLNs) using stearic acid (ST) or glycerylmonostearate (GMS).&#x0D; Methods: The SLNs were prepared by hot homogenization and sonication method. The effect of formulation variables on particle size, zeta potential and polydispersity index (PDI) of SLNs were studied, and an optimized formulation selected. Drug-excipient interactions were assessed by differential scanning calorimetry (DSC) and Fourier Transform Infrared (FTIR). Mammary gland breast cancer (MCF-7) and human colon cancer (HCT116) human cell lines were used to evaluate the cytotoxic activity of the free and FEP-loaded SLNs.&#x0D; Results: The particle size of the SLNs was in the range of 138 - 819 nm, while zeta potential varied from -15 to -20 nm. FEP-loaded SLNs exhibited significant cytotoxic effect compared to the free drug and doxorubicin in the two cell lines (p &lt; 0.05). The activity was higher in HCT116 compared with MCF-7 cells (p &lt; 0.007). The concentration of FEP loaded SLNs, free drug and doxorubicin that showed 50 % inhibition (IC50) for breast cancer cells were 1.06 ± 0.09, 2.58 ± 0.16 and 3.75 ± 0.4 μg/ml, respectively.&#x0D; Conclusion: The findings show that FEP-loaded SLNs have greater in-vitro cytotoxic activity than the free FEP, and thus, might improve cancer therapy in humans.&#x0D; &#x0D; &#x0D; &#x0D;

Major difference in particle size, minor difference in release profile: a case study of solid lipid nanoparticles

Solid lipid nanoparticles (SLN) have been widely used in a variety of drug delivery routes, which have the outstanding advantage of controlled drug release. The release of SLN is dominated by many factors, among which the particle size of SLN is a critical one. The aim of this project was to explore the relationship between drug release profile and particle size of SLN. SLN were synthesized via the hot high-pressure homogenization (HPH) method, budesonide (BUD) was used as the model drug, and BUD-SLN1–BUD-SLN4 with increasing particle size was obtained, i.e. 120, 240, 360, and 480 nm. The prepared SLN has good encapsulation efficiency, drug loading capacity, and stability. In vitro release behavior studies showed that the cumulative release of BUD-SLN in Tris-Maleate (Tris-M) media was negligible, while that in Tris-M plus pancreatin media or Tris-M-ethanol media obeyed Ritger-Peppas model or first-order kinetic model, respectively. Noticeably, the release behavior of SLN was to some extent related to the average particle size of SLN, but the correlation was insignificant when the intersection degree of particle size distribution was great. This study provides a new idea for the understanding of in vitro release of SLN and has a certain referencing value for the research and development of novel nanomedicines.

Brain targeting of venlafaxine HCl as a hydrophilic agent prepared through green lipid nanotechnology

This study aimed to improve venlafaxine HCl brain delivery using solid lipid nanoparticles (SLNs) made by an ultrasonication method. The impact of the ratio of two surfactants (Tween:Span) on nanoparticle behaviors and their efficiency was examined to achieve optimal brain delivery for venlafaxine. To study the solid-state of venlafaxine in SLNs and detect any potential interactions between the drug and other formulation excipients, PCS, TEM, ATR-FTIR, and DSC were employed. By reducing the HLB (Hydrophilic–lipophilic balance) of the binary surfactants, the particle size of SLN increased. The optimized nanoparticles showed an average particle size of 311.33 ± 9.29 nm when the HLB of the ratio of the surfactants (Tween:Span) was adjusted to 8. The zeta potential of SLNs decreased from −15.90 ± 0.70 to −6.95 ± 0.42 mV when the HLB of the system was reduced from 14 to 8. According to the results, the highest entrapment efficiency of 76.05 ± 1.42% was observed for the formulation with the largest particle size and the lowest HLB value (HLB 8). DSC analysis showed that venlafaxine was in an amorphous state in SLN. The findings of the ATR-FTIR also excluded any chemical interactions between excipients and the drug. Venlafaxine-SLN had a prolonged release pattern, according to the in vitro diffusion process. Venlafaxine oral absorption from SLN was also substantially higher than venlafaxine solution after single-dose oral administration of venlafaxine preparations. This research demonstrated that the venlafaxine-SLN might be employed as a potential nano-vehicle for venlafaxine brain delivery and potentially opens up new avenues for depression treatment.

Formulation Development of Topical Preparation Containing Nanoparticles of Povidone-Iodine for Wound Healing.

Povidone-iodine (PVI) is an antiseptic drug that is used for wound healing or for repair of the damaged tissue. Studies on solid lipid nanoparticles (SLNs) indicate that this system could potentially be used as a delivery system with improved drug entrapment efficiency and controlled drug release for hydrophilic actives. This study focuses on developing a topical gel containing SLNs of PVI for wound healing. SLNs were prepared by using the solvent emulsification diffusion method. Lipids such as glycerol monostearate, palmitic acid, and stearic acid, and surfactants such as polysorbate 80, soyalecithin, and Pluronic F-68 were used for the preparation of SLN. These were screened out based on particle size and entrapment efficiency of SLN. Gel was prepared by using Carbopol 940 (1% w/w) and propylene glycol (10% w/w). Formulated SLNs were evaluated by various in vitro and in vivo techniques. Based on the results, the drug-to-lipid ratio (1:3) and 2% polysorbate 80 (surfactant) along with stirring rate (3,000 rpm) produced the desired particle size (285.4 nm) with good stability. 22.85% drug loading and 88.83% drug entrapment efficiency were found in the optimized formulation. In vitro drug release shows that it follows the Korsmeyer-Peppas model. The animal study shows that the period of epithelization produced by the test group was 17.14 ± 1.35 days, which was near to that of the standard group (16.25 ± 1.24 days). Clinical Trial Registration number: 1044/PO/Re/S/07/CPCSEA.

Preparation and evaluation of kojic acid dipalmitate solid lipid nanoparticles

IntroductionNatural dissolution of kojic acid dipalmitate (KAD) in oil medium makes it difficult to load pharmacologic dose in a stable penetrative drug delivery system as topical dosage form. This study aimed to evaluate solid lipid nanoparticles (SLNs) as a drug delivery platform for the topical delivery KAD. MethodsSLNs were made with five different lipids and homogenization methods. The particle size was analyzed and the best lipid was chosen. Fourier-transform infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry were done. Then, KAD cream, KAD hydrogel, SLN-based KAD cream, and SLN-based KAD hydrogel were prepared and their release and permeation profile were evaluated on rat skin by Franz cell. ResultThe particle size of SLNs prepared with glycerol monostearate was about 70 nm. The optimum formulation was the combination with GMS 100 mg, KAD 10 mg, and ethanol/acetone in 2.5:1.5; all of which had the KAD entrapment efficiency of about 47%. The release of KAD powder was the fastest, and release from the SLN-based KAD hydrogel was slower than others. The KAD loaded in the SLN had the highest concentration in the stratum corneum, and KAD loaded in hydrogel formulation had the most concentration in the epidermis layer. ConclusionKAD can be loaded in the SLN with fair entrapment efficiency and particle size of <100 nm. KAD loaded in SLN-based cream made the maximum concentration of KAD in the epidermis compared with other formulations. Thus, SLN-based KAD cream is suggested as a proper topical formulation.

Loading, release profile and accelerated stability assessment of monoterpenes-loaded solid lipid nanoparticles (SLN)

Glycerol monostearate solid lipid nanoparticles (SLN) were produced by hot high-pressure homogenization technique to load alpha-pinene, citral, geraniol or limonene. SLN were composed of 1 wt.% monoterpene, 4 wt.% of Imwitor® 900K as a solid lipid and 2.5 wt.% of Poloxamer188 as a surfactant. Empty SLN consisted of 5 wt.% of Imwitor® 900K and 2.5 wt.% of Poloxamer188. The mean particles size (Z-Ave) and polydispersity index (PDI) of SLN were analyzed by dynamic light scattering (DLS), while the zeta potential (ZP) of each formulation were measured by electrophoretic light scattering. LUMiSizer® was applied to calculate the velocity distribution in the centrifugal field and instability index. Drug release profile from SLN was analyzed using Franz cell diffusion cells assayed by UV–Vis spectrophotometry, whereas the gas chromatography technique was applied to determine the encapsulation parameters of volatile monoterpenes. The matrix state, polymorphism and phase behavior of SLN were studied by X-ray diffraction (XRD, low and wide angles) and differential scanning calorimetry (DSC). Selected monoterpenes were successfully loaded in glycerol monostearate SLN. A burst release profile within the first 15 min was observed for all formulations, being the modified release profile dependent on the type of monoterpene and on the encapsulation efficiency.

Nano-structured lipid particles for controlled transport of hydrophobic volatile and non-volatile molecules

Nano-structured lipid particles can be designed for tailored delivery of small molecules. Liquid lipid nanoparticles (LLN) stabilized by lecithin and solid lipid nanoparticles (SLN) stabilized by sodium caseinate were used to form self-assembled nano-emulsion structures (i.e., colloidosomes) via electrostatic deposition of a solid wall around a liquid reservoir. Particle size and zeta potential were measured at pH 3.5 and 7 to characterize the colloidal dispersions at selected mixing ratios (2:1 to 1:5). The partitioning, kinetic release, and reactivity of non-volatile (4-phenyl-2,2,5,5-tetramethyl-3-imidazoline-1-oxyl nitroxide; PTMIO) and volatile (limonene) molecules were studied using electron paramagnetic resonance (EPR) spectroscopy and atmospheric pressure chemical ionization-mass spectroscopy (APcI-MS), respectively, as a function of pH-change at the 1:3 mixing ratio. Particle size (d32) of LLN (134 nm) and SLN (166 nm) remained unchanged with pH adjustment, and colloidosome particle size (450 nm) was a combination of LLN and SLN particles at pH 3.5. The presence of the solid wall significantly reduced the diffusion rate (ca. 80 %) of PTMIO from the LLN core protecting the compound. APcI-MS measurements showed similar behavior for limonene release to air. These systems can be used for controlled delivery of various active compounds in food and pharmaceutical formulations.

Development, Characterization and In vitro Evaluation of Donepezil solid Lipid Nanoparticles

Solid lipid nanoparticles (SLNs) loaded with donepezil were prepared by hot homogenization followed by probe ultrasonication technique. Donepezil SLNs were composed of lipids (1 to 5%w/v) such as trimyristin, tristearin, glycerol monostearate and compritol which were stabilized by soya lecithin (0.5 to 2.5%w/v) and poloxamer 188 (0.5 to 2.5%w/v). Developed donepezil SLNs were characterized for size, zeta potential, entrapment efficiency and content uniformity. Selected method of preparation was able to produce nanoparticles of size range 102.5 to 179.3 nm possessing zeta potential -23.5 to -34.9 mV with entrapment efficiency 86.65 to 89.64%. FTIR and DSC studies showed that there was no interaction between donepezil and selected lipids. Sterilization by autoclave increased size of SLNs from 1.5 to 1.9 times, however, there was no decrease in the zeta potential of the formulations. Short term stability studies showed that size of SLNs maximum increased by 38 nm whereas their entrapment efficiency was lowered by 1.3% only. In vitro release studies revealed that 61.58 to 74.82% of donepezil released from developed SLNs after 24 hours and found that drug release followed non-Fickian transport (0.556 to 0.658).

Development, in-vitro and in-vivo evaluation of ezetimibe-loaded solid lipid nanoparticles and their comparison with marketed product

This study aims to develop ezetimibe-loaded solid lipid nanoparticles (SLNs) and compare them with marketed product and drug suspension for dissolution and bioavailability. Ezetimibe-loaded SLNs were fabricated using high pressure homogeniser (HPH). The content of SLNs were (drug, solid lipid and surfactant; 50/300/25 mg/ml of distilled water). They were characterized through particle size, poly dispersive index (PDI), zeta potential and entrapment efficiency (EE). Moreover, dynamic scattering calorimetry (DSC) and powder x-ray diffraction (PXRD) were also performed. Furthermore, in-vitro release study was performed followed by pharmacokinetics study in rats after oral administration of ezetimibe-loaded SLNs and compared with marketed product and powder drug suspension. The mean particle size, PDI and zeta potential of ezetimibe-loaded SLNs were 156.9 nm, 0.125 and −20.5 mV, respectively with 90.7% EE. DSC and PXRD study exhibited that the drug was crystalline in powder form, however converted into amorphous form when entrapped in SLNs. Enhanced dissolution and bioavailability of ezetimibe was observed from ezetimibe-loaded SLNs as compared to marketed product and drug suspension. Stability studies revealed that the formulation remains unchanged for 3 months. Thus SLN is a suitable carrier for ezetimibe with enhanced dissolution and bioavailability as compared to the marketed product.

Drug-Lipid-Surfactant Miscibility for the Development of Solid Lipid Nanoparticles.

This research aimed to study the correlation between miscibility of flutamide (FLT), lipids and surfactant on the particle size of solid lipid nanoparticles (SLNs). Physical mixtures (PMs) of lipids-glyceryl monooleate (GMO), Precirol® (glyceryl palmitostearate, PRE), glyceryl monostearate (GMS), and Compritol® (glyceryl dibehenate, COM) were prepared with surfactant-Gelucire® (stearoyl polyoxyl-32 glycerides, GEL) 50/13 and 44/14. PMs were prepared in 5:2 w/w ratio (lipid:surfactant) and 2:1 w/w (Flutamide (FLT):lipids/GEL 50/13) by co-melting. Miscibility of PMs was investigated using modulated differential scanning calorimetry (MDSC). SLNs with and without drug were prepared using GEL 50/13 by the ultra-sonication method and particle size analysis was conducted. PMs of GMO, GMS, and PRE with both surfactants showed a decrease in the melting temperature, no change in melting and crystallization peak was observed with COM-GELs, indicating immiscibility. Similarly, MDSC data suggests good miscibility of FLT in GMO, GMS, and GEL 50/13 but not in PRE and COM. The particle size of drug-loaded SLNs prepared from GMO and GMS with GEL 50/13 was found to be 70.2 ± 5.4 and 92.6 ± 8.5 compared to > 200-nm particles obtained from PRE and COM. On lyophilization, an increase in particles size was observed with COM only. The particle size of SLNs with PRE and COM was prominently increased during stability studies indicating SLNs prepared with GMO and GMS are more stable due to miscibility and ability to reduce the crystallinity of FLT. The results established a good correlation between drug, lipids, and surfactants miscibility to the obtained particle size of SLNs before and after lyophilization. Graphical Abstract ᅟ.

Novel Solid Lipid Nanocarrier of Glibenclamide: A Factorial Design Approach with Response Surface Methodology.

In the present investigation, a factorial design approach attempt was applied to develop the Solid Lipid Nanoparticles (SLN) of Glibenclamide (GLB) a poorly water-soluble drug (BCS -II) used in the treatment of type 2 diabetes. Prime objectives of this experiment are to optimize the SLN formulation of Glibenclamide and improve the therapeutic effectiveness of the developed formulation. Glibenclamide loaded SLNs (GLB-SLN) were fabricated by High speed homogenization technique. A 32-factorial design approach has been employed to assess the influence of two independent variables, namely amount of Poloxamer 188 and Glyceryl Monostearate on entrapment efficiency (% EE) (Y1), Particle Size (nm) (Y2), % drug release at 8hr Q8 (Y3) and 24 hr Q24 (Y4) of prepared SLNs. Differential scanning calorimetry analysis revealed the compatibility of the drug into lipid matrix with a surfactant, while Transmission electron and Scanning electron microscopy studies indicated the size and shape of SLN. The entrapment efficiency, particle size, Q8 and Q24 of the optimized SLNs were 88.93%, 125 nm, 31.12±0.951% and 86.07±1.291% respectively. Optimized GLB-SLN formula was derived from an overlay plot. Three-dimensional response surface plots and regression equations confirmed the corresponding influence of selected independent variables on measured responses. In vivo testing of the GLB-SLN in diabetic albino rats demonstrated the significant antidiabetic effect of GLB-SLN. The hypoglycemic effect obtained by GLB-SLN remained significantly higher than that given by drug alone and marketed formulation, further confirming the higher therapeutic effectiveness of the GLB-SLN formulation. Our findings suggested the feasibility of the investigated system for oral administration of Glibenclamide.