Stability and antimicrobial effect of amikacin-loaded solid lipid nanoparticles

Solid lipid nanoparticles (SLNs) of amikacin were designed in this study for pulmonary delivery to reduce the dose or its administration intervals leading to reduction of its toxicities especially in long term treatment. Nanoparticles of amikacin were prepared from cholesterol by solvent diffusion technique and homogenization. The size, zeta potential, loading efficiency, and release profile of the nanoparticles were studied. The conventional broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC) and minimum bacteriostatic concentration (MBC) of amikacin SLNs with respect to Pseudomonas aeruginosa in vitro. To guarantee the stability of desired SLNs, they were lyophilized using cryoprotectants. Results showed that considering the release profile of amikacin from the studied nanocarrier, MIC and MBC of amikacin could be about two times less in SLNs of amikacin compared to the free drug. Therefore, fewer doses of amikacin in SLNs can clear the infection with less adverse effects and more safety. Particle size enlargement after lyophilization of desired SLNs after two months storage was limited in comparison with non-lyophilized particles, 996 and 194 nm, respectively. Zeta potential of lyophilized particles was increased to +17 mV from +4 mV before lyophilization. Storage of particles in higher temperature caused accelerated drug release

Freeze-drying of ampicillin solid lipid nanoparticles using mannitol as cryoprotectant

Nanoparticulas lipídicas sólidas (NLSs) são sistemas coloidais de liberação interessantes, uma vez que reúnem todas as vantagens de nanopartículas lipídicas e poliméricas. A liofilização é um processo amplamente utilizado para melhorar a estabilidade das NLSs e os crioprotetores têm sido usados para diminuir a agregação destas durante esse processo. Neste estudo, a ampicilina foi escolhida para ser encapsulada em um carreador de colesterol de escala nanométrica. Para manter a estabilidade das NLSs, a liofilização foi realizada utilizando-se manitol. O tamanho de partícula, o perfil de liberação do fármaco e os efeitos antibacterianos foram estudados após a liofilização em comparação com a NLSs primária. De acordo com os resultados, as preparações que contêm 5% de manitol mostraram o menor aumento do tamanho de partícula. Os resultados de tamanhos médio foram de 150 e 187 nm antes e depois da liofilização, respectivamente. O perfil de liberação prolongada, bem como o efeito antimicrobiano da ampicilina NLSs não foram alterados após a liofilização. A análise por DSC evidenciou provável interação entre a ampicilina e o colesterol.Solid lipid nanoparticles (SLNs) are interesting colloidal drug-delivery systems, since they have all the advantages of the lipid and polymeric nanoparticles. Freeze-drying is a widely used process for improving the stability of SLNs. Cryoprotectants have been used to decrease SLN aggregations during freeze-drying. In this study Ampicillin was chosen to be loaded in a cholesterol carrier with nano size range. To support the stability of SLNs, freeze-drying was done using mannitol. Particle size, drug release profile and antibacterial effects were studied after freeze-drying in comparison with primary SLNs. Preparations with 5% mannitol showed the least particle size enlargement. The average particle size was 150 and 187 nm before and after freeze-drying, respectively. Freeze-drying did not affect the release profile of drug loaded nanopartilces. Also our study showed that lyophilization did not change the antimicrobial effect of ampicillin SLNs. DSC analysis showed probability of chemical interaction between ampicillin and cholesterol

Development and validation of a HPTLC method for analysis of Sunitinib malate

A simple high performance thin layer chromatography (HPTLC) has been developed and validated for determination of sunitinib malate and possible impurities. The samples were applied in forms of bands on an aluminum TLC plate pre-coated with silica gel and were separated using dichloromethane: methanol: toluene: ammonia solution as the mobile phase. Sunitinib malate was thoroughly separated from impurities including E-isomer, sunitinib N-oxide and impurity B with a retention factor (RF) of 0.35±0.02. Quantitative analysis of sunitinib was carried out using a mobile phase consisting of dichloromethane:methanol:ammonia solution, RF value was 0.53±0.02 for Z isomer. Detection was performed densitometrically in absorbance mode at 430 nm. This method was found to produce sharp, symmetrical, and well resolved peaks. Linear relationship with the coefficients of determination >; 0.99 was achieved over the concentration range of 27.34 to 437.5 ng/spot. This method provides robust, replicable and accurate results with acceptable sensitivity

Nanotechnology in Wound Healing; Semisolid Dosage Forms Containing Curcumin-Ampicillin Solid Lipid Nanoparticles, in-Vitro, Ex-Vivo and in-Vivo Characteristics

Purpose: Wound healing is a natural biologic process, but the duration of it may take too long. Trying to shorten this process is one of the challenges for scientists. Many technologies were applied to achieve this goal as well as nanotechnology. In this study semi solid formulations containing curcumin and ampicillin solid lipid nanoparticles (SLNs) were prepared to evaluate as burn wound healing agent. Methods: Curcumin as an anti-inflammatory and anti-bacterial agent and ampicillin as an antibiotic were applied. In-vitro and in-vivo evaluations were carried out. Particle size, loading efficiency, release profile, morphology and anti-bacterial efficacy of desired nanoparticles were evaluated at first. Then the remaining of the antibacterial effect in semi solid preparations was studied. Animal studies for both toxicology using rabbits and skin burn model using rats were designed. Pathology studies after applying of formulations was done too. Results: Desired nanoparticles were spherical in shape and particle size in range of 112-121 nm, with low zeta potential. For increasing stability of particles they were freeze dried using cryoprotectant. Lyophilized particles show no significant size enlargement. Results showed that both ointment and gel preparations have reasonable anti-bacterial effects, both of them cause increasing in the rate of wound healing in comparison with placebos and control groups and none of the formulations showed acute toxicity. Conclusion: It seems that using nanotechnology could shorten wound healing process to reduce treatment costs and increase compliance of patients

Preparation and Skin Permeation Study of N, N- Diethyl- meta-Toluamide Semi Solid Formulations

N,N-Diethyl meta Toluamide (DEET) is an insect repellent agent that contrary to its benefits, if is used in formulations with high skin permeation, will produce side effects of different severity. This study attempted to achieve a semi-solid DEET containing formulation with good appearance, sufficient spreadity, suitable viscosity for tube and jar filling, compatible pH with skin, reasonable stability, longer release time, and the less skin permeation. To obtain such a formulation, three types of DEET containing semi solids including gels (hydrophile), creams (emulsion) and ointments (lipophile), and their characteristics were compared with each other and with Off! Brand. Results showed that one of the prepared creams with the proper viscosity, stability, appearance and spreadity, had the least drug release in six hours and less skin permeation of DEET as compared with Off!. Hence the preparation was introduced as the optimal formulation

Sustained release Curcumin loaded Solid Lipid Nanoparticles

Purpose: curcumin is poorly water soluble drug with low bioavailability. Use of lipid systems in lipophilic substances increases solubility and bioavailability of poorly soluble drugs. The aim of this study was to prepare curcumin loaded Solid Lipid Nanoparticles (SLNs) with high loading efficiency, small particle size and prolonged release profile with enhanced antibacterial efficacy. Methods: to synthesize stable SLNs, freeze- Drying was done using mannitol as cryoprotectant. Cholesterol was used as carrier because of good tolerability and biocompatibility. SLNs were prepared using high pressure homogenization method. Results: optimized SLNs had 112 and 163 nm particle size before and after freeze drying, respectively. The prepared SLNs had 71% loading efficiency. 90% of loaded curcumin was released after 48 hours. Morphologic study for formulation was done by taking SEM pictures of curcumin SLNs. Results show the spherical shape of curcumin SLNs. DSC studies were performed to determine prolonged release mechanism. Antimicrobial studies were done to compare the antimicrobial efficacy of curcumin SLNs with free curcumin. DSC studies showed probability of formation of hydrogen bonds between cholesterol and curcumin which resulted in prolonged release of curcumin. Lipid structure of cholesterol could cause enhanced permeability in studied bacteria to increase antibacterial characteristics of curcumin. Conclusion: the designed curcumin SLNs could be candidate for formulation of different dosage forms or cosmeceutical products

A new exponential cluster validity index using Jaccard distance

Estimating the optimal number of clusters in an unsupervised partitioning of data sets has been a challenging area in recent years. These indices usually use two criteria called compactness and separation to evaluate the efficiency of the performed clustering. In this paper a new separation measure for ECAS cluster validity index, proposed by Fazel et al. [1] is identified, which uses Jaccard distance in order to consider the whole shape of clusters. Jaccard distance uses the size of intersection and union of fuzzy sets, giving the cluster validity index more information about the overlap and separation of clusters. This property results in high robustness of the proposed index dealing with various degrees of fuzziness in comparison with ECAS. To test the efficiency of the proposed index in comparison with nine other indices existing in the literature, 15 data sets (3 existing datasets and 12 artificial data sets) have been used. Computational results indicate robustness and high capability of the proposed index in comparison with previous indice

Development and validation of a HPTLC method for analysis of Sunitinib malate

ABSTRACT A simple high performance thin layer chromatography (HPTLC) has been developed and validated for determination of sunitinib malate and possible impurities. The samples were applied in forms of bands on an aluminum TLC plate pre-coated with silica gel and were separated using dichloromethane: methanol: toluene: ammonia solution as the mobile phase. Sunitinib malate was thoroughly separated from impurities including E-isomer, sunitinib N-oxide and impurity B with a retention factor (RF) of 0.35±0.02. Quantitative analysis of sunitinib was carried out using a mobile phase consisting of dichloromethane:methanol:ammonia solution, RF value was 0.53±0.02 for Z isomer. Detection was performed densitometrically in absorbance mode at 430 nm. This method was found to produce sharp, symmetrical, and well resolved peaks. Linear relationship with the coefficients of determination > 0.99 was achieved over the concentration range of 27.34 to 437.5 ng/spot. This method provides robust, replicable and accurate results with acceptable sensitivity