Characterization of indomethacin-loaded lipid nanoparticles by differential scanning calorimetry

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are interesting nanoparticulate delivery systems produced from solid lipids. Both carrier types are submicron size particles but they can be distinguished by their inner structure. In the present paper, indomethacin (IND)-loaded SLN and NLC were prepared and the organization and distribution of the different ingredients originating each type of nanoparticle system were studied by differential scanning calorimetry (DSC) technique. Furthermore, mean particle size and percentage of drug encapsulation were also determined. From the results obtained, NLC lipid organization guaranteed an increased indomethacin encapsulation in comparison with SLN. DSC static and dynamic measurements performed on SLN and NLC showed that oil nanocompartments incorporated into NLC solid matrix drastically influenced drug distribution inside the nanoparticle system. Controlled release from NLC system could be explained considering both drug partition between oil nanocompartments and solid lipid and a successive partition between solid lipid and water.     

Characterization of dimethyldiacyloxysilanes by differential scanning calorimetry, Raman scattering and X-ray diffraction

The phase behaviour of diacyloxydimethylsilanes (DMS Cn; n = 10, 12, 14, 16, 18, 20, 22) was investigated by differential scanning calorimetry, X-ray diffraction and Raman spectroscopy. All DMS Cn melt from a crystalline phase to an isotropic liquid with a single sharp transition. On cooling, the homologous DMS C16 up to DMS C22 show a characteristic monotropic phase (L beta'H). In contrast to the calorimetrical investigations, it was not possible to analyse the monotropic phase of DMS C16 by X-ray diffraction. This behaviour is due to a two-phase region (gel phase--crystalline phase). The Raman spectra of all DMS are very similar. Only in the low frequency range we find different bands of the longitudinal acoustic modes. The Raman measurements demonstrate undoubtedly that in the solid state the alkyl chains are in all-trans conformation. The factor group splitting of the CH2 scissoring Raman mode show that the DMS Cn are arranged in a subcell packing with two molecules per unit cell. The highly ordered all-trans structure of the alkyl chains is present up to the melting transition. On melting there are changes in different regions of the Raman spectra: C-H stretching, CH2 scissoring mode, C-C skeletal stretching, CH3 rocking and longitudinal acoustic modes. On cooling DMS C18 and DMS C20 from the melt to the crystalline state, the gel phase is also proved by Raman scattering. Based on the results of the Raman and X-ray data the gel phase is characterized by a hexagonal subcell packing and by an ordered structure of the alkyl chain residues.     

Characterization of latex-antineoplastic drug complexes by differential scanning calorimetry and microphotography

Choline kinase inhibitors have recently been identified as potentially useful antitumoral agents. Here we determine the best conditions for obtaining drug-polymer complexes with 5-fluorouracil (5-FU), and JCR791B, a new drug representing a significant advance in the development of new molecules to inhibit tumour proliferation. As polymers we used the cellulose derivatives Aquacoat and Aquateric. The variables in the adsorption process measured were time to adsorbent-adsorbate equilibrium, pH and concentration. The drug-polymer complexes were characterized by differential scanning calorimetry and microphotography. Our results show that adsorption of 5-FU and JCR was similar with both polymers although slightly greater with Aquacoat. The chemical structure of the drug and its solubility in water and oil are fundamental characteristics that determine the performance of polymers as drug carriers able to provide controlled release.     

Characterization of lipophilic gemcitabine prodrug-liposomal membrane interaction by differential scanning calorimetry

Gemcitabine is an anticancer agent rapidly deaminated to the inactive metabolite 2',2'-difluorodeoxyuridine. Its stability as well as bioavailability can be increased by making prodrugs. A series of lipophilic prodrugs of gemcitabine were synthesized by linking the 4-amino group with valeroyl, lauroyl, and stearoyl linear acyl derivatives. We studied, by the differential scanning calorimetry technique, and compared the interaction of pure gemcitabine and its prodrugs with dimyristoylphosphatidylcholine and distearoylphosphatidylcholine vesicles with the aim of demonstrating if the gemcitabine prodrug is more able than the pure gemcitabine to interact with lipid vesicles employed both as model biomembranes and as carriers in the transport of antitumor drugs. These studies, carried out by static and kinetic calorimetric measurements, give evidence that the increase of the prodrug's lipophilic character improves the interaction with lipid bilayers, favoring the absorption through the lipid barriers and allowing the liposomes to work (when the prodrug is inserted inside the vesicles) as a lipophilic carrier which is able to deliver the drug near the cell surface. The use of different prodrugs modified in their lipophilic character, of different kinds of vesicles (multilamellar and unilamellar), and of different kinds of vesicles forming phospholipids permitted us to determine the better equilibrium between in-vesicle solubility and through-vesicle diffusion of the drug, important in the preformulative studies of antitumor carriers based on phospholipid formulations. Such studies suggest that the prodrug lipophilic tail should modulate the transport and the release of gemcitabine inside the cellular compartments, and the efficiency of the liposomal system is related to the length of the prodrug's acyl chain which has to match the phospholipid acyl chain allowing or retarding the migration through the lipid release device.     

Characterization of amorphous ketoconazole using modulated temperature differential scanning calorimetry

The objective of the present study was to characterize the glassy state of ketoconazole and to calculate its molecular mobility below the glass transition, with a view to further developing the use of modulated temperature differential scanning calorimetry (MTDSC) as a means of studying relaxation behavior. Particular emphasis is placed on identifying the influence of the choice of experimental parameters on the measured values of both the glass transition temperature (T(g)) and the relaxation enthalpy magnitude. Amorphous ketoconazole was studied using an amplitude of +/-0.212 K, a period of 40 s, and an underlying heating rate of 2 K/min. The correction required for the calculation of the relaxation endotherm magnitude (the "T(g) shift effect") was demonstrated and is discussed in terms of the mechanism underpinning this phenomenon. Similarly, the influence of the choice of MTDSC experimental parameters on the measured T(g) was studied by varying the amplitude from +/-0.011 to +/-0.424 K and the period from 25 to 50 s. The influence of the cooling rate from the melt on the magnitude of the relaxation endotherm and position of the glass transition was investigated. It was noted that the magnitude of the relaxation endotherm increased with slower cooling rates, this being ascribed to a combination of annealing during the cooling and heating cycle and a further facet of the T(g) shift effect. Annealing experiments were performed at aging temperatures T(g)-12--T(g)-42 K for periods ranging from 10 min up to 16 h. The relaxation behavior was characterized by fitting the calculated extent of relaxation to the Williams-Watts equation. Overall, the study has highlighted theoretical and experimental issues that need to be considered when using both DSC and MTDSC for the calculation of relaxation times.     

Simultaneous differential scanning calorimetry,X-ray diffraction and FTIR spectrometry in studies of ovalbumin denaturation

The new application of differential scanning calorimetry (DSC) and the susceptibility of ovalbumin to α-chymotrypsin gave a quantitative estimation of protein denaturation in solid ovalbumin. Solid ovalbumin in granules with 11% of water was heated at 100 °C in closed and nonclosed ampules. In order to compare effects of size and crystal structure, two proteins (bovine albumin and γ-globulin) were examined at similar conditions for the extent of denaturation. Ovalbumin and bovine albumin showed similar extents of denaturation, but γ-globulin, with a very different molecular mass, showed the maximal conformational changes. The enthalpy of denaturation was measured to elucidate the conformational changes in solid proteins. Its value was used for calculation of the degree of denaturation. The thermodynamic data associated with transition were calculated and the number of bonds broken during denaturation was determined. Intrinsic fluorescence was utilized in order to compare these two methods. Moreover, X-ray diffraction and FTIR spectrometry were applied to native and denatured proteins.     

Characterization of the thermal properties of microcrystalline cellulose by modulated temperature differential scanning calorimetry

The purpose of this study was to characterize the thermal properties of microcrystalline cellulose (MCC) and to investigate the influence of water on these properties. Differential scanning calorimetry (DSC), modulated temperature differential scanning calorimetry (MTDSC), thermomechanical analysis (TMA), and scanning electron microscopy (SEM) were used to characterize MCC. Three reproducible step transitions were detected in the dry material at 132, 159, and 184 degrees C; for these transitions the magnitude of the heat capacity change varied by a factor of two. Exposure of MCC to water lowers the transition temperature in a manner comparable to a glass transition. The effect of water was different for samples equilibrated to different atmospheric humidities versus water added by granulation. A change in the physical properties of MCC after granulation with high amounts of water was observed. In conclusion, it appears that MCC has glass transitions, which come in reproducible triplets, and these transitions are affected by the presence of water. Also, for the materials studied, the transition temperatures are not affected by particle size and pulp source.     

Characterization of moisture-protective polymer coatings using differential scanning calorimetry and dynamic vapor sorption

The aim of this study was to evaluate the moisture-protective ability of different polymeric coatings. Free films and film-coated tablets (with cores containing freeze-dried garlic powder) were prepared using aqueous solutions/dispersions of hydroxypropyl methylcellulose (HPMC), Opadry AMB [a poly(vinylalcohol)-based formulation] and Eudragit E PO [a poly(methacrylate-methylmethacrylate)]. The water content of the systems upon open storage at 75% relative humidity (RH) and 22 degrees C (room temperature) was followed gravimetrically. Furthermore, polymer powders, free films and coated tablets were analyzed by differential scanning calorimetry (DSC) and dynamic vapor sorption (DVS). The type of polymer strongly affected the resulting water uptake kinetics of the free films and coated tablets. DSC analysis revealed whether or not significant physical changes occurred in the coatings during storage, and whether the water vapor permeability was water concentration dependent. Using DVS analysis the critical glass transition RH of Opadry AMB powder and Opadry AMB-coated tablets at 25 degrees C could be determined: 44.0% and 72.9% RH. Storage below these threshold values significantly reduces water penetration. Thus, DVS and DSC measurements can provide valuable information on the nature of polymers used for moisture protection.     

X-ray diffraction, differential scanning calorimetry and thermogravimetry combined with infrared analysis of freeze-dried prednisolone hemisuccinate.

In this study, the thermal behaviour of freeze-dried prednisolone hemisuccinate (Prednisolut) was investigated by means of X-ray scattering, differential scanning calorimetry (DSC) and fourier transformation infra-red analysis (FT-IR).     

Differential scanning calorimetry studies on sunscreen loaded solid lipid nanoparticles prepared by the phase inversion temperature method

Solid lipid nanoparticles (SLN) are regarded as interesting carriers to improve sunscreens' safety and effectiveness. In this work, surfactant effects on the physico-chemical properties of SLN loading two of the most widely used UV-filters, octylmethoxycinnamate (OMC) and butylmethoxydibenzoylmethane (BMBM), were evaluated and the interactions between SLN components and loaded UV-filters were investigated by differential scanning calorimetry (DSC). All the SLN showed a mean size ranging from 30 to 95 nm, and a single peak in size distribution. The use of isoceth-20 or oleth-20 as primary surfactants did not provide SLN with suitable physico-chemical properties since: (a) OMC loaded SLN proved unstable; (b) BMBM could not be loaded. OMC or BMBM loaded SLN prepared using ceteth-20 as primary surfactant were stable but their loading capacity lowered when both sunscreens were loaded simultaneously. DSC analyses showed that OMC distributed inside the SLN and caused a decrease of the lipid matrix molecules cooperativity while BMBM did not affect SLN calorimetric behaviour. When OMC and BMBM were loaded together into these SLN, an interaction between BMBM and OMC occurred. These results suggest that the interactions between sunscreens and between sunscreens and SLN components deserve further investigation to evaluate their effect on UV-filter-loaded SLN effectiveness.     

Characterization of temperature-induced phase transitions in five polymorphic forms of sulfathiazole by terahertz pulsed spectroscopy and differential scanning calorimetry

The far-infrared properties of all five known polymorphic forms of the drug sulfathiazole have been studied by terahertz pulsed spectroscopy and low-frequency Raman spectroscopy. The observed spectra of the different polymorphs are distinctly different. Terahertz pulsed spectroscopy proves to be a rapid and complementary alternative to other physical characterization techniques reported in the literature for distinguishing between the five forms. Variable-temperature measurements (293-473 K) of all polymorphic forms have been performed. The phase transitions observed have been related to thermal analysis data. Form I is the form stable at high temperature of sulfathiazole with a melting point of about 475 K. Form II melts at around 470 K and recrystallizes at higher temperatures to form I. Forms III, IV, and V all convert to form I via a solid-solid phase transition at temperatures below 450 K. The phase transitions can be monitored by terahertz pulsed spectroscopy. Polymorphic impurities of the samples can be detected in the room temperature spectra and their effect on the phase transition behavior can be studied.     

Characterization of amorphous solids with weak glass transitions using high ramp rate differential scanning calorimetry

Measurement of the glass transition temperature (T(g)) of proteins and other high molecular weight polymers in the amorphous state is often difficult, since the transition is extremely weak, that is, the DeltaC(p) at the glass transition temperature is small. For example, little is known about the solid-state properties of hydroxyethyl starch (HES), which is beginning to become more commonly evaluated as a bulking agent in pharmaceutical products. For weak thermal events, such as the change in heat capacity at the T(g) of a pure protein or large synthetic polymer, increased heating rate should produce greater sensitivity in terms of heat flow. Recent innovations in rapid scanning technology for differential scanning calorimetry (DSC) allow measurements on materials where the thermal events are difficult to detect by conventional DSC. In the current study, measurements of the T(g) of proteins in the solid state, amorphous pharmaceutical excipients which have small DeltaC(p) at the glass transition temperature, and bacterial spores, have all been made using high ramp rate DSC, providing information on materials that was inaccessible using conventional DSC methods.     

Interaction of cortisol-21-palmitate with liposomes examined by differential scanning calorimetry

Liposomes have been suggested as carriers for corticosteroids in the local treatment of arthritis by intra-articular injection. The long chain 21-esters of Cortisol such as the palmitate or octanoate are taken up and retained by liposomes in higher concentration than cortisol itself. Differential scanning calorimetry has been used to show that the cortisol ester is anchored in the liposome phospholipid bilayer by the acyl side chain. In addition, the limiting concentration of cortisol-21-palmitate which can be incorporated into dipalmitoyl phosphatidylcholine liposomes has been measured by observing changes in the DSC spectrum at different steroid concentrations. Steroid in excess of this concentration limit forms a separate phase which can be identified by nuclear magnetic resonance. For optimum effect, the treatment of arthritis with liposomes must be carried out with liposomes containing steroid below the limiting concentration.