Formulation Of Solid Lipid Microparticles Research Articles

Comparison of the In Vitro Drug Release Methods for the Selection of Test Conditions to Characterize Solid Lipid Microparticles

The release profiles of active substances from microspheres are one of the most important features in solid lipid microparticles (SLM) characterization. Unfortunately, the results of the dissolution tests are largely dependent on the chosen method and test conditions, which in relation to novel dosage forms, such as dispersions of lipid microspheres, are not clearly defined in international compendiums and guidelines. This makes it impossible to compare the results of different studies. The aim of the research was to identify the factors most influencing the variability of the obtained results. An attempt was also made to select the most appropriate method for testing drug substance release from SLM. Various dissolution methods were employed (method I: without a membrane, method II: in a dialysis bag, and method III: in a Side-Bi-Side chamber), and the obtained release profiles of cyclosporine and indomethacin from SLM dispersions were compared. In addition to the effect of membranes, the types of acceptor fluids were also investigated. Significant differences were observed when testing the SLM formulations under various test conditions. The results were significantly influenced by the selected membrane, the acceptor fluid, or the difference in the concentrations of active substance between the donor and acceptor compartments. The burst effect observed in some experimental methods was not noticed in other conditions. At this stage, the method with a dialysis bag has been selected as the most suitable, while the methods without the membrane can only play a complementary role.

Microfluidics-enabled particle engineering of monodisperse solid lipid microparticles with uniform drug loading and diverse solid-state outcomes

Lipids serve as excellent excipients for drug products. Solid lipid microparticles (SLMs) are relatively underexplored in drug delivery; these particles are conventionally prepared using processes yielding polydisperse size distributions, such as spray congealing or emulsification. In this paper, we demonstrate a microfluidics-enabled process for particle engineering of monodisperse solid lipid microparticles with size and content uniformity. To overcome low solubility, we use a volatile solvent to increase drug loading, making the drug-lipid solution a single phase, enabling identical drug loading across particles. We use microfluidic flow extrusion of the solution to generate uniform drug-loaded SLMs, substantially enhancing monodispersity. This method generalises across three drugs—ibuprofen, 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY), and naproxen, and two lipids—beeswax and hard fat (Suppocire NAI 25A), forming particles of various solid states: amorphous naproxen in crystalline lipids, crystalline ROY in crystalline lipids, and a eutectic mixture of ibuprofen-hard fat. In vitro dissolution studies on the ibuprofen-hard fat SLMs reveal gradual release, fitting the Higuchi model with 50–65% drug released over 72 h. This work expands the drug particle engineering toolbox to enable the formulation of SLMs with high precision in particle size and drug loading. Moreover, the diverse solid-state outcomes enabled by our method makes it applicable to various drugs having different formulation requirements (crystalline/amorphous).

Development of solid lipid microparticles by melt-emulsification/spray-drying processes as carriers for pulmonary drug delivery

The aim of this study was to optimize the parameters of the complex melt-emulsification process coupled with the spray-drying, in order to maintain the balance between solid lipid microparticles (SLMs) powders aerodynamic performance and salbutamol sulfate release rate. Quality target product profile was identified and risk management and principal component analysis were used to guide formulation development. Obtained dry powders for inhalation (DPIs) were evaluated in terms of SLMs size distribution, morphology, true density, drug content, solid state characterization studies, in vitro aerosol performance and in vitro drug release. SLMs micrographs indicated spherical, porous particles. Selected powders showed satisfactory aerosol performance with a mean mass aerodynamic diameter of around 3 μm and acceptable fine particle fraction (FPF). Addition of trehalose positively affected SLMs aerodynamic properties. The results of in vitro dissolution testing indicated that salbutamol sulfate release from the tested SLMs formulations was modified, in comparison to the raw drug release. In conclusion, SLMs in a form of DPIs were successfully developed and numerous factors that affects SLMs properties were identified in this study. Further research is required for full understanding of each factor's influence on SLMs properties and optimization of DPIs with maximized FPFs.

Solid lipid microparticles for enhanced dermal delivery of tetracycline HCl

Acne vulgaris (commonly called acne) is a most common skin disease during adolescence, afflicting more than 85% of teenagers. Topical tetracycline (Tc) is used for mild inflammatory acne and as an adjunct to systemic treatment in more severe forms. Solid lipid microparticles (SLMs) are useful tool for topical delivery because of their biodegradable, biocompatible and low toxic characteristic accompanying with excellent skin hydration, occlusiveness and controlled release properties. The purpose of this study was to prepare Tc-loaded SLMs were produced by the spray drying technique and characterized by scanning electron microscopy, powder X-ray diffractometry and differential scanning calorimetry. In vitro and ex vivo release characteristics of Tc through SLMs and control formulations (aqueous carbopol gel) were evaluated over 24h using a vertical Franz diffusion cell through cellulose acetate membranes and exercised rat skin, respectively. SLM formulations present high encapsulation values above 97% without significant different among formulations (p<0.05). The sustained release pattern of Tc through SLMs was illustrated by in vitro release study. The ex vivo drug skin permeation study revealed that Tc dermal deposition of optimum SLMs formulation was about 7 times that of the control formulations. The enhanced skin penetration and accumulation of Tc observed for Tc-loaded SLMs may increase the efficiency of acne therapy and decrease the associated Tc side effects.

Formulation, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles

Context: Formulation, characterization, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles (SLMs).Objective: The objective of the study was to formulate and evaluate halofantrine-loaded SLMs.Materials and methods: Formulations of halofantrine-loaded SLMs were prepared by hot homogenization and thereafter lyophilized and characterized using particle size, pH stability, loading capacity (LC) and encapsulation efficiency (EE). In vitro release of halofantrine (Hf) from the optimized SLMs was performed in SIF and SGF. In vivo study using Peter’s Four day suppressive protocol in mice and the mice thereafter subjected to histological studies in kidney and liver.Results: Results obtained indicated that EE of 76.32% and 61.43% were obtained for the SLMs containing 7% and 3% of Hf respectively. The SLMs loaded with 3% of Hf had the highest yield of 73.33%. Time-dependent pH stability analysis showed little variations in pH ranging from 3.49 ± 0.04 to 4.03 ± 0.05.Discussion: The SLMs showed pH-dependent release profile; in SIF (43.5% of the drug for each of H2 and H3) compared with SGF (13 and 18% for H2 and H3 respectively) after 8 h. The optimized SLMs formulation and Halfan® produced a percentage reduction in parasitemia of 72.96% and 85.71% respectively. The histological studies revealed that the SLMs formulations have no harmful effects on the kidney and liver.Conclusion: SLMs formulations might be an alternative for patients with parasitemia as there were no harmful effects on vital organs of the mice.

Preliminary Studies on Solid Lipid Microparticles of Loratadine for the Treatment of Allergic Reactions via the Nasal Route

Purpose: To formulate solid lipid microparticles (SLM) of loratadine (LRT) for the treatment of allergic reactions via the nasal route.Methods: Microparticles were prepared by emulsion congealing technique. The drug content of microparticles was analysed. Drug/excipient compatibility and crystallinity characteristics of microparticles were investigated by Fourier Transform Infrared Spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Particle size distribution was determined by laser diffraction (LD). Drug release from microparticles was compared to that from conventional vehicles (O/W emulsion, gel andoleageneous cream) using Franz-type diffusion cells.Results: Drug content of microparticles was &gt; 87.96 %. FT-IR and DSC analysis indicated that the drug and excipients were compatible for at least 6 months at room temperature after production. Microparticle size was between 86 ± 5.63 ìm and 184 ± 13.21 ìm while mean droplet size of O/Wemulsion was 76 ± 3.45 ìm. Release profiles of LRT from microparticles were significantly different from those of O/W emulsion, gel and oleageneous cream (p &lt; 0.05). In the case of conventional vehicles,increase in the hydrophilicity of the vehicles led to increase in drug release rate. Drug release fitted generally to zero order kinetics as well as Korsmeyer-Peppas model for one of the SLM formulations, indicating non-Fickian drug release (super case II transport).Conclusion: SLM provided LRT release for a longer period than the conventional vehicles. However, in vivo studies are required to ascertain the effectiveness of the formulations.Keywords: Loratadine, Solid lipid microparticles, Allergy, Controlled drug delivery, Transnasal delivery

Novel formulation of solid lipid microparticles of curcumin for anti-angiogenic and anti-inflammatory activity for optimization of therapy of inflammatory bowel disease

Abstract Objectives This project was undertaken with a view to optimize the treatment of inflammatory bowel disease through a novel drug delivery approach for localized treatment in the colon. Curcumin has poor aqueous solubility, poor stability in the gastrointestinal tract and poor bioavailability. The purpose of the study was to prepare and evaluate the anti-inflammatory activity of solid lipid microparticles (SLMs) of curcumin for the treatment of inflammatory bowel disease in a colitis-induced rat model by a colon-specific delivery approach. Methods We have developed a novel formulation approach for treating experimental colitis in the rat model. SLMs of curcumin were prepared with various lipids, such as palmitic acid, stearic acid and soya lecithin, with an optimized percentage of poloxamer 188. The SLMs of curcumin were characterized for particle size, drug content, drug entrapment, in-vitro release, surface morphology and infrared, differential scanning calorimetry and X-ray studies. The colonic delivery system of SLM formulations of curcumin were further investigated for their anti-angiogenic and anti-inflammatory activity using chick embryo and rat colitis models. Key findings Particle size, drug content, drug entrapment and in-vitro release studies showed that formulation F4 containing one part stearic acid and 0.5% surfactant had the smallest diameter of 108 μm, 79.24% entrapment and exhibited excellent in-vitro release characteristics when compared with other formulations and pure curcumin. SLMs of curcumin (F4) proved to be a potent angio-inhibitory compound, as demonstrated by inhibition of angiogenesis in the chorioallantoic membrane assay. Rats treated with curcumin and its SLM complex showed a faster weight gain compared with dextran sulfate solution (DSS) control rats. The increase in whole colon length appeared to be significantly greater in SLM-treated rats when compared with pure curcumin and DSS control rats. An additional finding in the DSS-treated rats was chronic cell infiltration with predominance of eosinophils. Decreased mast cell numbers in the mucosa of the colon of SLMs of curcumin and pure curcumin-treated rats was observed. Conclusions The degree of colitis caused by administration of DSS was significantly attenuated by colonic delivery of SLMs of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for inflammatory bowel disease patients.

Investigation of carnuba wax in the formulation of solid lipid microparticles for controlled release

Investigation of carnuba wax in the formulation of solid lipid microparticles for controlled release

Novel formulation of solid lipid microparticles of curcumin for anti-angiogenic and anti-inflammatory activity for optimization of therapy of inflammatory bowel disease

This project was undertaken with a view to optimize the treatment of inflammatory bowel disease through a novel drug delivery approach for localized treatment in the colon. Curcumin has poor aqueous solubility, poor stability in the gastrointestinal tract and poor bioavailability. The purpose of the study was to prepare and evaluate the anti-inflammatory activity of solid lipid microparticles (SLMs) of curcumin for the treatment of inflammatory bowel disease in a colitis-induced rat model by a colon-specific delivery approach. We have developed a novel formulation approach for treating experimental colitis in the rat model. SLMs of curcumin were prepared with various lipids, such as palmitic acid, stearic acid and soya lecithin, with an optimized percentage of poloxamer 188. The SLMs of curcumin were characterized for particle size, drug content, drug entrapment, in-vitro release, surface morphology and infrared, differential scanning calorimetry and X-ray studies. The colonic delivery system of SLM formulations of curcumin were further investigated for their anti-angiogenic and anti-inflammatory activity using chick embryo and rat colitis models. Particle size, drug content, drug entrapment and in-vitro release studies showed that formulation F4 containing one part stearic acid and 0.5% surfactant had the smallest diameter of 108 microm, 79.24% entrapment and exhibited excellent in-vitro release characteristics when compared with other formulations and pure curcumin. SLMs of curcumin (F4) proved to be a potent angio-inhibitory compound, as demonstrated by inhibition of angiogenesis in the chorioallantoic membrane assay. Rats treated with curcumin and its SLM complex showed a faster weight gain compared with dextran sulfate solution (DSS) control rats. The increase in whole colon length appeared to be significantly greater in SLM-treated rats when compared with pure curcumin and DSS control rats. An additional finding in the DSS-treated rats was chronic cell infiltration with predominance of eosinophils. Decreased mast cell numbers in the mucosa of the colon of SLMs of curcumin and pure curcumin-treated rats was observed. The degree of colitis caused by administration of DSS was significantly attenuated by colonic delivery of SLMs of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for inflammatory bowel disease patients.

Effect of Sonophoresis and Chemical Enhancers on Testosterone Transdermal Delivery from Solid Lipid Microparticles: An In Vitro Study

The main objective of the study was to investigate the effect of permeation enhancers and application of low frequency (LUS) and high frequency ultrasound (HUS) on testosterone (TS) transdermal permeation after application of testosterone solid lipid microparticles (SLM). SLM formulations contained 10% compritol and 5 mg TS /g of SLM. The permeation experiments were performed using Franz diffusion cells and abdomen rat skin. The examined permeation enhancers were 1% oleic acid (OA) or 1 % dodecylamine (DA). HUS (1 MHz) was applied in a continuous mode for 1h at intensity 0.5 W/cm(2). Different intensities and application time of pulsed LUS (20 kHz) were also examined. Additionally, the effect of combination of US and OA or DA was investigated. Skin irritation and histological changes were also evaluated. The results revealed that SLMs have an occlusive effect on the skin. Statistical analysis revealed the following order for the permeation of TS: 1% DA for 30 min>HUS +1% DA for 30 min= HUS=HUS + SLM containing 1% OA> SLM containing 1% OA=control. At total application time of LUS 6, 12, and 15 min the flux increased by 1.86, 4.63, and 4.77 fold, respectively. The enhancement effect of different intensities of LUS was not directly proportional to the magnitude of intensity. Skin exposure to HUS or LUS before application of 1% DA for 30 min had no superior enhancement effect over application of either LUS or HUS alone. Application of drug loaded SLM offered skin protection against the irritation effect produced by TS and 1% DA. Histological characteristics of the skin were affected to various extents by application of enhancers or ultrasound. In general, application of LUS gave higher TS permeation than HUS. However, safe application of LUS should be practiced by careful selection of exposure parameters.