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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).
Characterization of the thermodynamics of binding interactions is important in improving our understanding of bimolecular recognition and forms an essential part of the rational drug design process. Isothermal titration calorimetry (ITC) is rapidly becoming established as the method of choice for undertaking such studies. The power of ITC lies in its unique ability to measure binding reactions by the detection of the heat change during the binding interaction. Since heat changes occur during many physicochemical processes, ITC has a broad application, ranging from chemical and biochemical binding studies to more complex processes involving enthalpy changes, such as enzyme kinetics. Several features of ITC have facilitated its preferential use compared to other techniques that estimate affinity. It is a sensitive, rapid, and direct method with no requirement for chemical modification or immobilization. It is the only technique that directly measures enthalpy of binding and so eliminates the need for van't Hoff analysis, which can be time consuming and prone to uncertainty in parameter values. Although ITC has facilitated the measurement of the thermodynamics governing binding reactions, interpretation of these parameters in structural terms is still a major challenge.
Human sebum is a mixture of triglycerides, fatty acids, wax esters, squalene, cholesterol, and cholesterol esters. P. acnes, a bacterium that is normally found on the skin, hydrolyzes certain triglycerides to fatty acids, thereby changing the sebum composition. The objective of this study was to examine the physical state of a model sebum and the effect of variations in its composition on its physical properties including (a) the carbon chain length of the components, (b) the ratio of unsaturated to saturated components, and (c) the ratio of triglycerides to fatty acids. A model sebum mixture was prepared based on a composition reported in the literature and evaluated by differential scanning calorimetry (DSC). Since cholesterol and cholesterol esters contribute insignificantly to sebum composition, they were not included. Squalene was kept constant (13%), while the concentration of the rest of the components was varied. Variations of sebum were prepared by dissolving all components in a 3:1 chloroform-methanol mixture for uniformity. Subsequently the solvent was evaporated at room temperature. The samples were then analyzed using DSC. Four distinct endotherms (namely, Mp-1, Mp-2, Mp-3, and Mp-4) were observed between -50 degrees C and 100 degrees C. Mp-1 and Mp-2 occurred below 0 degrees C and were contributed by unsaturated components. Mp-3 and Mp-4, which represent the saturated components, occurred above 30 degrees C. Thus, at normal skin temperature (skin surface temperature is 32 degrees C), sebum contains both a solid and a liquid phase. All the transition temperatures increased with an increase in carbon chain length for the same ratio of unsaturation to saturation. A replacement of unsaturated components with corresponding saturated components led to a decrease in the transition temperatures for the former (Mp-1 and Mp-2) and an increase in the transition temperatures for the latter (Mp-3 and Mp-4). Replacement of triglycerides with corresponding fatty acids (mimicking the action of anaerobic bacteria) caused an increase in Mp-2 and a decrease in Mp-4. In all cases, the final melting temperature (Mp-4) was greater than the temperature of the human skin surface (32 degrees C); thus components contributing to these endotherms are still solids at skin temperature. All variations in the sebum model led to mixtures of solids and liquids at skin temperature. Considering a reduction in Mp-3 and/or Mp-4 to represent sebum "fluidization," it was achieved by a decrease in carbon chain length, an increase in unsaturation, or a substitution of triglycerides by corresponding fatty acids. Preferential enrichment with the saturated species will lead to enrichment of solids versus liquids in the sebum, presumably making it difficult for the liquid phase to dissolve the solids. It seems plausible that perturbation of the balance of solid and liquid components of sebum, such as by P. acnes action, may lead to blockage of the follicle. Future research will investigate strategies to dissolve and/or liquify the solid phase of sebum.
The interaction of crystalline and amorphous amylopectin with the plasticisers glycerol and ethylene glycol in the absence of water was studied with differential scanning calorimetry (DSC) and solid state NMR. At room temperature glycerol interacts mainly with the amorphous regions, while for ethylene glycol the amylopectin crystallinity does not effect the interaction. After heating the mixtures, an additional immobilisation of the plasticiser occurs.
By applying differential scanning calorimetry (DSC) on human hair in water, the thermal stability of hair' major morphological components is determined. Against the background of the two-phase model for alpha-keratins, these components are identified as the partially helical, fibrous intermediate filaments (IF) and the intermediate filament associated-proteins (IFAP) as a cross-linked, amorphous matrix. DSC yields the denaturation enthalpy deltaH(D), which depends on the amount and structural integrity of the alpha-helical material, and the temperature T(D), which is kinetically controlled by the cross-link density of the matrix. To assess the effects of cosmetic treatments, hairs were investigated that had undergone either multiple bleaching or perm-waving treatments. The respective dependencies between denaturation temperature and enthalpy show that both morphological components are similarly affected by bleaching, while reductive damage, in comparison, is more pronounced in the IFs. For both types of treatments, changes in enthalpy follow apparent first-order kinetics with respect to the number of treatments as well as treatment time (perm-waving), yielding characteristic reaction rate constants. It appears that DSC in water is an especially suitable method to determine the kinetics of damage formation in human hair resulting from cosmetic treatments.
1. The accuracy of measurements of flow rate and concentrations of O2 and CO2 in expiratory gas by indirect calorimetry (IC) using paediatric and adult circuits were assessed by mass spectrometry and a pneumotachogram, which have been proven as the most reliable instruments for these purposes. 2. In the paediatric circuit, all measurements were demonstrated to be reliable: error rates for flow rate, O2 concentration and CO2 concentration were +3.13, +2.66 and -6.63%, respectively. All were within the 10%, which is acceptable as a biological error. 3. However, in the adult circuit of IC, all measurements were reliable except for measurements of CO2 concentration: error rates for flow rate, O2 concentration and CO2 concentration were +2.82, +1.64 and +11.42%, respectively. 4. A fluctuation phenomenon of expiratory gas concentration was observed only in IC. Mass spectrometry did not show this phenomenon. This phenomenon seems to be derived from the IC machine itself.
The compatibility between ciprofloxacin hydrochloride (CFX) and some excipients was evaluated using differential scanning calorimetry (DSC). Physical mixture, coground mixture, compressed mixture and kneaded mixture were prepared to study the effect of sample manipulation. In addition, the samples of physical mixture were also accelerated at 55 degrees C for three weeks to obtain more reliable conclusions. Different types of excipients currently used in tablet or capsule formulations namely, calcium phosphate dibasic dihydrate (Emcompress), magnesium stearate lactose, sorbitol, mannitol, croscarmellose sodium (Ac-Di-Sol), sodium carboxymethyl starch (Primojel), microcrystalline cellulose (Avicel PH 101, Emcocil) were examined. The DSC scan of CFX displayed two endothermic peaks probably as a result of a fusion process followed by a decomposition process. CFX appeared to interact with sorbitol, mannitol, Ac-Di-Sol, Primojel, Avicel PH 101 and Emcocil.
Kinetic and thermodynamic studies were made on the effect of caffeine on the activity of adenosine deaminase in 50 mM sodium phosphate buffer, pH 7.5, using UV spectrophotometry and isothermal titration calorimetry (ITC). An uncompetitive inhibition was observed for caffeine. A graphical fitting method was used for determination of binding constant and enthalpy of inhibitor binding by using isothermal titration microcalorimetry data. The dissociation-binding constant is equal to 350 microM by the microcalorimetry method, which agrees well with the value of 342 microM for the inhibition constant that was obtained from the spectroscopy method. Positive dependence of caffeine binding on temperature indicates a hydrophobic interaction.
Hair hydration is one of the effects that consumers most expect when using a cosmetic hair product. The purpose of this study was to combine differential scanning calorimetry (DSC) and gas chromatography (GC) techniques for a precise evaluation of the water content in hair fiber. DSC allowed determination of the bonding strength of water to hair fibers by quantifying the amount of energy required to remove the water. The amount of water thus removed was determined by GC. Post-treatment sensory evaluations of hair tresses were conducted to determine whether the values obtained with these techniques correspond to the moisturizing sensation perceived by consumers.
The physico-chemical compatibility of solid-state pharmaceuticals is mainly determined by their interaction. The "Three-point-test" of differential scanning calorimetry in which three samples of different ratios are determined is proposed to study this interaction, and the simplified judging rules are as follows: If there are two or less than two endotherm peaks in DSC thermogram for all 3 ratio samples, we may mainly consider the peaks at lower temperature. If these temperatures are the same, which would be monotectic system or simple eutectic mixture, there will be very weak interaction in their solid state, and these could be compatible. If the temperatures are different, which would be solid solution system or solid complex system, there would be interaction in their solid state. If there is no endotherm peak, or there are exotherm peaks or there are more than two endotherm peaks, they all indicate that there is a stronger interaction in their solid state and they are incompatible. As an example, the interaction between water-soluble vitamins--Vit B1, Vit B2, Vit C and nicotinamide was determined. The results indicated that only Vit C is incompatible with nicotinamide, as there is a stronger interaction, and with Vit B1, there is a weak interaction.
This study investigates in detail the freezing events during cooling of solutions of various size classes of antifreeze glycoproteins. Differential scanning calorimetry and nanolitre osmometry were used to observe ice growth at temperatures within the hysteresis gap between the melting point and non-equilibrium freezing point (hysteresis freezing point) of solutions of the various sized antifreeze glycoproteins (AFGPs). The ice growth within the hysteresis gap is presumably due to both the expression of primary or near primary prism planes and also some growth at the basal plane. The binding of the AFGPs to the ice causes a particular ice crystal morphology. With the smaller AFGPs, substantial microscopic ice growth was observed in the form of a hexagonal bipyramids within the hysteresis gap.
The formulation and processing variables required for the effective freeze-drying of labile biologicals can be determined from an understanding of the physics of freeze-concentration. Three measurable values, Tg' (the glass temperature associated with maximum freeze-concentration), Wg' (the unfrozen water at this temperature) and Tg (the glass temperature of the dried product) are the keystones. These can be obtained by differential scanning calorimetry. This paper describes their measurement. Techniques to increase the detectability of glass transitions are discussed. Method of calculating Wg' from DSC power-time curves are critically reviewed. An example is presented in which it is demonstrated how failure to perform primary drying below the glass transition results in products on inferior quality. Finally, it is described how measurements of the glass temperature of the "dry" product can be used to predict storage stability. The limitation of using moisture determination to predict stability is high-lighted.
The interaction of dipalmitoylphosphatidylcholine, dipalmitoylphosphatidic acid and dipalmitoylphosphatidylethanolamine with some DNA substructures such as cytidine, uridine, adenosine 5'di- and triphosphate, guanosine 5'mono- and diphosphate, cytidine 5'mono- and triphosphate, uridine 5'mono- and triphosphate and inosine 5'monophosphate was studied with differential scanning calorimetry. The dependence of pretransition and main transition temperatures and the enthalpy of main transition on the molecular characteristics of the interacting molecular species was calculated by stepwise regression analysis. Nucleosides and nucleotides increased the main transition temperature and peak half width of phospholipids and they decreased the enthalpy of main transition proving the existence of interaction between phospholipids and DNA substructures. Calculation proved that the interaction is mainly of hydrophilic character but the involvement of hydrophobic forces or steric conditions cannot be ruled out.
The present study was conducted to examine the physicochemical changes during passage of drug through polymeric membranes and observe the surface morphology features of the coated pellets using scanning electron microscopy (SEM). Drug solution was first sprayed around inert pellets to form drug-layered pellets that were coated with two commercial aqueous dispersions namely, Eudragit NE30 and Kollicoat SR30 using bottom-spray fluidized bed technique. Differential scanning calorimetry (DSC) confirmed that no interactions existed between drug and polymers. Small peak of drug was observed in the DSC thermograms of Eudragit NE30 coated pellets indicating that small amount of drug was still present in the polymeric membrane after dissolution. Views of SEM revealed as the coating levels of two types of aqueous dispersions were increased the surface of the pellets become more uniform and compact. Therefore, the diffusion length for dissolution medium to enter the drug layer and dissolved drug to diffuse out would be increased at higher coating levels. The polymer surface of coated pellets after 12 hours dissolution testing seemed to be shrunk and size of the pellets were also reduced indicating the depletion of reservoir layer.
In this study, high sensitivity micro differential scanning calorimetry (MDSC) in the scanning of dynamic mode was compared to X-ray powder diffractometry (XRPD) for quantifying amorphous nifedipine in mixtures crystalline nifedipine. This technique was also compared with FTIR for quantifying polymorph A of chloramphenicol palmitate (CAP) and poly DL-lactide-co-glycolide) (PLGA) in pharmaceutical formulations. The limit of determination (LOD) achieved by MDSC were 0.06% compared to 5% for XRPD quantification of amorphous nifedipine and 0.02% compared to 7% for IR quanitfication of polymorph A of CAP. As little as 0.165 mg PLGA could be measured in excipients mixtures. Desirable linearity and repeatability were established in all cases.
Peripheral effects of thyroid hormones were examined using an indirect calorimetry in 18 patients with thyroid cancer before and after total thyroidectomy. Peripheral effects of exogenous thyroid hormones in TSH-suppression therapy after thyroidectomy were also studied. The subjects were maintained without hormone replacement for 3 weeks after total thyroidectomy. The ratio of resting energy expenditure to basal energy expenditure (REE/BEE) was determined before operation, before hormone replacement, and 1 and 5 weeks after the beginning of replacement, and the values were compared with changes in the blood thyroid hormone levels. Positive correlations were observed between the changes in endogenous thyroid hormone levels before and after total thyroidectomy and those in REE/BEE (free T3 vs. REE/BEE; r = 0.756, p less than 0.01), suggesting that evaluation of REE/BEE is clinically useful as an index of peripheral effects of thyroid hormones. Five weeks after the beginning of hormone replacement, T4 and free T4 were slightly range, and no enhancement of energy metabolism was noted. From these findings, the post-operative TSH suppression therapy carried out at our department is considered to be justifiable also from the viewpoint of energy metabolism.
The results of theoretical and experimental investigations of the interaction of ligands to DNA permit to suggest the method of "tie" calorimetry by means of which the thermodynamic parameters of the cooperative transitions of DNA such as helix-coil, B-A and B-Z transitions were obtained. The prominence of the method is that the experimental samples contain such concentration of DNA that intermolecular interaction may be neglected. Moreover the smaller is the magnitude of the measured parameter the greater is the accuracy of the experimentally obtained data.
The binding of alpha-, omega-amino acids, which are important effectors of human plasminogen activation, to the isolated kringle 4 (K4) peptide region of this protein has been investigated by high sensitivity titration calorimetry. The titration curve of the heat changes accompanying binding of the widely employed ligand, epsilon-aminocaproic acid (EACA), to K4 were deconvoluted to yield the following binding characteristics: n = 0.87 +/- 0.08 mol/mol; Ka = 3.82 +/- 0.37 x 10(4) M-1; delta H = -4.50 +/- 0.22 kcal/mol; delta S = 6.01 +/- 0.7 entropy units; and delta G = 6.29 +/- 0.06 kcal/mol. Here, both delta H and delta S provide the driving force of the interaction, with both hydrogen bonds and hydrophobic interactions, the latter which may result from an induced conformational change in K4 upon ligand binding, as well as possible alterations in peptide-bound water structure, providing the stabilizing forces for complex formation. The thermodynamic binding parameters were not greatly influenced by pH between the values of 5.5 and 8.2, suggesting that titratable groups on K4 in this pH region did not influence the binding. Investigations of the binding properties of structural analogues of EACA to K4 demonstrated that definable steric requirements existed for a maximal interaction, with spacing between the functional groups on EACA, as well as a hydrophobic region of this molecule, being important. This rapid and reliable method for measuring all thermodynamic parameters of formation of this complex at a given temperature can now be employed to investigate this important interaction with a wide variety of kringles and modified kringles to provide a more complete understanding of the necessary factors for this binding to occur.