Effect of lipid on physicochemical properties of solid lipid nanoparticle of paclitaxel

The aim of this study was to compare physicochemical properties of solid lipid nanoparticles (SLN) made from different lipids. To make small, stable, uniform and highly encapsulated SLNs, many factors such as the components (lipid, stabilizer) and preparation condition (sonication time, power) can be considered. Out of those, we selected solid lipid as lipid matrix to investigate an effect on SLNs. The SLNs were characterized by particle size, zeta potential, solubility and in vitro release study. In this study, SLNs showed different physicochemical properties and release profiles according to used solid lipid. In case of particle size, M-SLN showed biggest particle size (412.5?±?29.4?nm) and highest encapsulation efficiency (61.2?±?4.8?%). And, B-SLN showed highest cumulative drug percentage (85.0?±?1.7?%, 24?h) in release study. These results suggest that lipids type affect physicochemical properties and release profile of SLN.     

Effect of poloxamer on physicochemical properties of tacrolimus solid dispersion improving water solubility and dissolution rate

Tacrolimus (TCR; also FK-506 and trade name prograf^?), an antibiotic of macrolide family and a novel immunosuppressive agent, is a natural product of actinomycete Streptomyces tskubaensis. But TCR is poorly soluble in water (0.012?mg/mL), so its bioavailability is low and irregular. The aim of this study is to characterize physicochemical properties of TCR and investigate the improvement of solubility and dissolution rate of TCR solid dispersion (SD) with poloxamer. TCR SDs, consisting of various grades and ratios of poloxamer were prepared by hot-melting method and were characterized by DSC, PXRD, and FT-IR. The dissolution profile and solubility of TCR from the SDs were evaluated. SD of TCR prepared with poloxamer 188 at the ratio of 1:1 by the hot-melting method resulted in a significant increase in TCR solubility and enhanced dissolution profile over the TCR crystalline powder.     

Effect of gamma and neutron radiation on drugs

Effect of Gamma and Neutron Radiation on Drugs Gamma and neutron radiation induces decomposition reactions of many drugs in aqueous solution, leading to a number of reaction products. The decompositions of the compounds are usually proportional to the applied doses, and they are independent of dose rate. Na₂S₂O₅ was found not to be an efficient stabilisation agent of most solutions against ionizing radiation. Gamma and neutron irradiation of crystalline drugs often causes a change in colour and in only a few cases a slight amount of decomposition. Radioactivity will be induced by neutrons especially in cases where the molecules have as a part of their constitution the elements Na, K, P, Ca and S, but not in trace quantities. For the estimation of how much radioactivity can be permitted in the drug and still be tolerated by man, it was suggested that the maximum permissible radioactivity be applied to the drugs as is allowed in drinking water in case of emergency (200 μC). Calculations show that this value will not be reached by most drugs taking into account their maximum therapeutic daily doses and a neutron dose of 3.10¹³n/cm², with the exception of infusion solutions with Na²⁴ activity, but this activity decays in a few days.     

The effect of ionizing radiation on some derivatives of 1,4-dihydropyridine in the solid state

The effect of gamma and beta radiation in doses between 10 and 100 kGy on physico-chemical properties of four derivatives of 1,4-dihydropyridine (nifedipine, nitrendipine, felodipine and nimodipine) in the solid state was analysed. A number of qualitative and quantitative methods such as UV, IR, TLC, GLC, DSC, EPR as well as organoleptic and gravimetric analysis were used to determine and analyse any changes resulting from irradiation. In order to determine the effectiveness of sterilization with ionizing radiation of doses from 10 to 25 kGy, various microbiological tests were used. It was established that only doses 10-20 kGy of both kinds of radiation ensure total sterilization without any degradation of physico-chemical properties of the compounds studied. For the doses 50-100 kGy a decrease in the content of the compounds, appearance of the products of their decomposition and changes in the melting point and IR spectra appeared. Felodipine (with chlorophenyl substituent) was found to be much more sensitive to ionising radiation than nifedipine, nitrendipine and nimodipine (all with nitrophenyl substituent).     

Effect of gamma radiation and ethylene oxide on neomycin sulphate

Neomycin is affected by ethylene oxide but not by gamma radiation (2.75 Mrad). Differential refractometer is more advantageous in quantitating neomycin A, B and C than is the ninhydrin method.     

Effect of chitosan on physicochemical properties of exenatide-loaded PLGA nanoparticles

The aim of this study was to test stability of exenatide and compare physicochemical properties of PLGA nanoparticles. To make small, stable, uniform and highly encapsulated nanoparticles, various factors such as the components (polymer and stabilizer) and preparation condition (organic phase, temperature or sonication time) were considered. We tested the effect of organic phase, acid/base, ultrasonication time or temperature on exenatide to decide preparation condition of PLGA nanoparticles. And, PLGA nanoparticles were prepared by the double emulsion-solvent evaporation method and chitosan was selected as stabilizer. PLGA nanoparticles were characterized by yield, encapsulation efficiency, drug loading, particle size, zeta potential, polydispersity index and morphology. In this study, PLGA nanoparticles showed different physicochemical properties according to chitosan molecular weight. In case of particle size, PLGA nanoparticles using 0.5 g chitosan (4 kDa) showed biggest particle size (781.4 ± 24.1 nm) among PLGA nanoparticles prepared in this study and PLGA nanoparticles using 1 g chitosan (2 kDa) showed highest encapsulation efficiency (52.8 ± 1.7 %) among PLGA nanoparticles prepared in this study. And, all of PLGA nanoparticles using chitosan showed that polydispersity index was low and zeta-potential was increased. These results suggest that chitosan molecular weight affects physicochemical properties of PLGA nanoparticle.     

Effect of gamma radiation on amlodis and its potential for radiosterilization

In the present work, radiation sensitivity of amlodis (AML) and its active ingredient Amlodipin Besylate (AML-B) were separately investigated by electron spin resonance (ESR) spectroscopy using radiolytic products induced in these drugs. Irradiation in the dose range of 2.5-25kGy did not create any ESR resonance line in AML-B, but it create five characteristic ESR resonance lines associated with more than one radical species in the case of AML. This signal is attributed to the radical species created upon irradiation of inactive ingredients such as microcrystalline cellulose and sodium starch glycolate of AML. Five resonance lines were observed to be divided into three sub groups of different characteristic behaviors associable with three different radical species. Radical species responsible from observed ESR lines were unstable at room and above room temperatures, however, they conserved their identities over a storage period of 92 days. This permitted to discriminate irradiated AML from unirradiated one. A quadratic function was found to describe best the variations of the intensities of observed resonance lines with applied radiation dose. A model based on three tentative radical species with a pyranose ring formed by the rapture of CH bonds in positions 1 and 4 was proposed to explain the observed five lines experimental ESR spectra. AML was considered not providing the characteristic features of a good dosimetric material due to its low radiation yield and relatively fast decays of the created radical species, but very low radiation sensitivity of its active ingredient, namely AML-B makes AML a good candidate for radiosterilization.     

Impact of solid state properties on developability assessment of drug candidates

Solid state properties including polymorphism, solvate and salt formation can have a profound impact on two of the most important properties that are essential to the successful development of drug candidates: solubility and stability. To enable meaningful evaluations of drug candidates for their development risks, often referred to as developability, and provide input to the molecular design regarding the "drug-like" properties, one must take into account the impact of solid state properties on solubility and stability. This review examines the importance of solid state properties and their relationship to developability criteria. Phase appropriate characterization strategies and appropriate salt and crystal form screening and selection processes are discussed. These strategies and processes should balance the need for speed and throughput of modern discovery with the quality of data essential to the adequate developability assessment. Specific examples are given to illustrate the importance of understanding the solid state properties and their impact on developability.     

Effect of physicochemical properties on in vivo fate of nanoparticle-based cancer immunotherapies

Current advances of immunotherapy have greatly changed the way of cancer treatment.At the same time,a great number of nanoparticle-based cancer immunotherapies(...     

Solubilities and solid state properties of the sodium salts of drugs

The solubilities in water of a number of sodium salts of weakly acidic drugs were determined. The compounds examined included barbiturates, sulfonamides, and hydantoins. When the logarithm of the aqueous solubilities of the salts were plotted against their melting points, an inverse relationship was observed; however, a good correlation was not immediately apparent. Further studies were conducted on the solid phases of the drugs after equilibration with water, using calorimetric, spectrophotometric, and gravimetric methods. In many cases, hydrate formation was evident and, for some compounds, the stoichiometric amount of water in the crystal was different before and after equilibration with water. Multivariate analysis of the data indicated that the logarithms of the molar solubilities were inversely related to both the melting points and the stoichiometric amounts of water in the crystal hydrates, but were unrelated to the polarity of the corresponding acid forms of the drugs. Therefore, for the sodium salts of these drugs, the solubility is primarily controlled by the properties of the solid phase which exists in equilibrium with the solution phase.     

Influence of selected auxiliary substances on some physicochemical properties of solid dispersions containing magnesium salts

In this survey magnesium sails in the form of solid dispersions were studied to examine the interaction of the drug and lecithin or Tego Betain L-7. The results of thermal analysis of solid dispersions containing magnesium adipate Mg[Adip] and compounds of this salt with glycine substituent, and the partition coefficient (logP) of this salts applied for solid dispersion, have been presented in this paper. Lecithin (45% phosphatidylcholine) or Tego Betain L-7 (30% solution of amide betaine) have been added to magnesium salts to obtain a solid dispersion. The influence of auxiliary substances: Tego Betain L-7 and lecithin on physicochemical properties of the examined preparations has been assessed. The results of thermal analysis (DTA, DSC, TG) of magnesium complexes indicated their good thermal resistance up to the temperature of 375 K.     

Effect of position isomerism on the formation and physicochemical properties of pharmaceutical co-crystals

The effect of position isomerism on the co-crystals formation and physicochemical properties was evaluated. Piracetam was used as the model compound. Six position isomers, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5-dihydroxybenzoic acid (DHBA), were used as the co-crystal formers. Co-crystals were prepared on a 1:1 molar ratio by crystallization from acetonitrile. The solid-state properties of co-crystals were characterized using X-ray powder diffractometry (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR). All co-crystal formers formed co-crystal with piracetam except 2,6-DHBA. This failure was possibly due to steric hindrance of two bulk hydroxyl groups and preference of intra-molecular hydrogen bonding formation between hydroxyl group and carboxylic acid group. The XRD patterns of resulting co-crystal indicated that they are highly crystalline and different than parental compounds. Based on the single crystal data, P_23DHBA is orthorhombic while P_24DHBA, P_34DHBA, and P_35DHB belong to monoclinlic system. The hydrogen bonding network patterns of the co-crystals are also different. DSC data showed that the melting temperatures of resulting co-crystals are all lower than that of the starting materials. The melting point rank order of the co-crystals is: P_24DHBA > P_34DHBA > P_23DHBA > P_25DHBA > P_35DHBA. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:246–254, 2010     

Effect of biocompatible polymers on the physicochemical and dissolution properties of fenofibrate in nanoparticle system

This study aimed to evaluate the effect of biocompatible polymers on the physicochemical and dissolution properties of poorly water-soluble drugs in nanoparticle systems. Four types of nanoparticles containing poorly water-soluble fenofibrate were prepared using solvent evaporation technique with different biocompatible polymers such as polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC), carbopol and ethylcellulose. Their physicochemical properties were investigated using scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. The solubility and dissolution of nanoparticle-entrapped fenofibrate were compared with those of free drug powder. Biocompatible polymers affected the morphology and sizes of fenofibrate nanoparticles. PVP or carbopol-based nanoparticles showed spherical appearance, whereas HPMC or ethylcellulose-based nanoparticles formed aggregates with irregular shape. The particle sizes increased in the order of the nanoparticle prepared with carbopol ≤ PVP < HPMC < ethylcellulose. The size of PVP-based nanoparticles did not significantly differ from that of carbopol-based nanoparticles, showing the mean sizes of ca. 10 μm. As compared to free drug powder, the solubility and dissolution of the drug in nanoparticles increased in the order of PVP > HPMC > carbopol > ethylcellulose. The enhanced solubility and dissolution of poorly water-soluble fenofibrate via nanoparticle system did not depend on particle size but on crystallinity. In conclusion, in nanoparticle development of poorly water-soluble drugs such as fenofibrate, the nature of biocompatible polymers plays an important role in the physicochemical and dissolution of poorly water-soluble drugs in the nanoparticles.     

Evaluation of hypericin-loaded solid lipid nanoparticles: physicochemical properties, photostability and phototoxicity

Hypericin (HYP), a natural photosensitizer, has powerful photo-oxidizing ability, tumor-seeking characteristics, and minimal dark toxicity; nevertheless, it has proven high lipid solubility compared to its sparingly water soluble nature. Therefore, its formulation into solid lipid nanoparticles (SLNs) has attracted increasing attention as a potential drug-delivery carrier. Two HYP-loaded SLNs formulations were prepared utilizing microemulsion-based technique. Thereafter, the physicochemical properties of the formulations were investigated and evaluated. HYP-loaded SLNs showed spherical shape with mean particle size ranging from 200-300 nm for both formulations (FA and FB). The encapsulation efficiencies reached above 80% and FA showed significant higher encapsulation than FB (P<0.05), also, the thermal analysis using differential scanning calorimetry (DSC) indicated good compatibility between hypericin and lipids forming the cores in both formulations. Spectroscopic measurements of the photostability study showed that hypericin encapsulation into SLNs improved its photostability, compared to free HYP in 0.1% ethanolic solution. However, photocytotoxicity studies on HepG2 cells revealed an evident inhibition of the photodynamic efficacy of HYP-loaded SLNs, compared to free HYP. In conclusion, although the elevated entrapment efficiency of HYP into SLNs increased its photostability, it decreased its phototoxicity which might be due to the quenching deactivation of HYP molecules resulting from SLN compactness and thickness structure.     

Effect of wet milling process on the solid state of indomethacin and simvastatin

The aim of this study was to investigate the effect of wet milling on the solid state of indomethacin (IMC) and simvastatin (SIM). Wet milling was performed using high pressure homogenization (HPH). Polyvinylpyrrolidone-K25 (PVP) and poloxamer 407 (P407) were used as suspension stabilizers. Samples were characterized before and after wet milling using particle size analyzer, scanning electron microscopy (SEM), infrared (IR) spectroscopy and modulated temperature differential scanning calorimetry (MTDSC) techniques. After wet milling of IMC, physical appearance and IR spectra indicated surface amorphization; however, the solid state of SIM remained unaffected. MTDSC could not detect surface amorphization in IMC, suggesting that if present, it was only at very low levels. These results are in contradiction to the previous reports where dry milling of IMC and SIM resulted in amorphization of crystalline particles. Moreover, cryogrinding of IMC in the absence of water resulted in an amorphous form while presence of water using the same cryogrinding conditions resulted in a solid state similar to that obtained after wet milling. These results signify the role of water in inhibiting the amorphization during wet milling of crystalline drugs.     

Crystallization and solid state properties of molecules of pharmaceutical interest

Polymorphism characterizes the ability of a molecule to crystallize in different crystallographic systems (in the case of a simple atom the term allotropy is used). This phenomenon, known for a long time, leads to significantly different physicochemical properties between the different crystalline forms. In the pharmaceutical domain, the potential polymorphism of the active substances and the excipients could affect Since most of the pharmaceutical products consist of solid dosage forms administered by the oral route, it is not surprising that studies on polymorphism have become a mandatory chapter of any pharmaceutical dossier whether it concerns a new chemical entity or a generic. In fact, beyond the polymorphism phenomenon, it is the crystallization process which deserves to be highlighted. We will show how it controls the appearance of the polymorphism and the crystalline growth which is a second feature at least as important as the polymorphism itself (external aspect of the solid particles/habit) in terms of processability and dissolution. After having recalled some thermodynamic considerations which characterize the polymorphism, we will illustrate succinctly the impact of these phenomena on some important aspects of the pharmaceutical development such as the dissolution, the bioavailability and the stability.     

Effect of ciprofloxacin on the pharmacokinetics of ropivacaine

OBJECTIVE: To assess the effect of ciprofloxacin on the pharmacokinetics of ropivacaine. METHODS. In a double-blind, randomised, cross-over study, nine healthy volunteers were treated for 2.5 days with 500 mg oral ciprofloxacin or placebo twice daily. On day 3, they received a single dose of 0.6 mg/kg ropivacaine intravenously over 30 min. Ropivacaine, 3-hydroxyropivacaine (3-OH-ropivacaine), and (S)-2',6'-pipecoloxylidide (PPX) in venous plasma and urine were measured for up to 12 h and 24 h, respectively. RESULTS: Ciprofloxacin decreased the mean clearance (CL) of ropivacaine by 31% (P<0.05), with a considerable inter-individual variation (range from -52% to +39%). It also decreased the area under the plasma concentration-time curve (AUC) of 3-OH-ropivacaine by 38% (P<0.05) and urinary excretion of 3-OH-ropivacaine by 27% (P<0.05). Ciprofloxacin increased the AUC of PPX by 71% (P<0.01) and urinary excretion of PPX by 97% (P<0.01). CONCLUSION: Ciprofloxacin modestly decreased the mean ropivacaine CL by inhibiting the CYP1A2-mediated formation of 3-OH-ropivacaine. At the same time, the CYP3A4-mediated formation of PPX was increased. There was a marked inter-individual variation in the extent of the interaction, and, for some individuals, the concomitant use of ciprofloxacin with ropivacaine might produce toxic symptoms.