Acoustic-like dynamics of amorphous drugs in the THz regime.

The high frequency dynamics of Indomethacin and Celecoxib glasses has been investigated by inelastic x-ray scattering, accessing a momentum-energy region still unexplored in amorphous pharmaceuticals. We find evidence of phonon-like acoustic dynamics, and determine the THz behavior of sound velocity and acoustic attenuation. Connections with ordinary sound propagation are discussed, along with the relation between fast and slow degrees of freedom as represented by non-ergodicity factor and kinetic fragility, respectively.

Formulation optimization of an indomethacin-containing photocrosslinked polyacrylic acid hydrogel as an anti-inflammatory patch.

Photocrosslinked polyacrylic acid hydrogel, made from polyacrylic acid (PAA) modified with 2-hydroxyethyl methacrylate (HEMA), is a promising candidate adhesive for dermatological patches. In this study, we investigated the further availability of hydrogel as an adhesive for dermatological patches using a hydrogel containing indomethacin (IDM) as a model anti-inflammatory patch. From an orthogonal experimental study, we clarified the relationships between formulation factors and characteristics of model formulation. Formulations with a lower degree of swelling were prepared by increasing the degree of HEMA modification and the addition of Tween 80. Apparent permeation rate was increased by addition of L-menthol and Tween 80. A tendency for higher HEMA modification to be accompanied by the prolongation of the lag time of IDM was observed. To obtain an applicable anti-inflammatory patch, we conducted a formulation optimization study using a novel optimization method, a response-surface method incorporating multivariate spline interpolation (RSM-S). Consequently, a highly functional anti-inflammatory patch in terms of its adhesive properties and bioavailability was successfully obtained. Since a wide range of functions can be fully controlled by manipulating the formulation factors, photocrosslinked polyacrylic acid hydrogel is an attractive candidate adhesive for dermatological patches.

Radiosterilisation of indomethacin PLGA/PEG-derivative microspheres: protective effects of low temperature during gamma-irradiation.

Currently, gamma-irradiation seems to be a good method for sterilising drug delivery systems made from biodegradable polymers. The gamma-irradiation of microspheres can cause several physicochemical changes in the polymeric matrix. These modifications are affected by the temperature, irradiation dose and nature of the encapsulated drug and additives. This study has aimed to evaluate the influence of temperature during the sterilisation process by gamma irradiation in indomethacin PLGA microspheres including a PEG-derivative. Microspheres were prepared by the solvent evaporation method from o/w emulsion and were then exposed to gamma-irradiation. A dose of 25 kGy was used to ensure effective sterilisation. Some microspheres were sterilised with dry ice protection that guaranteed a low temperature during the process whilst others were sterilised without such dry ice protection. The effects of gamma-irradiation on the characteristics of non-loaded PLGA/PEG-derivative and indomethacin loaded PLGA/PEG-derivative microspheres with and without protection were studied. Non-protected microspheres showed changes in their morphological surface, polymer glass transition temperature, molecular weight and release rate of indomethacin after sterilisation. However, microspheres sterilised with protection did not show significant differences after gamma-irradiation exposure. The sterilisation method was satisfactory when the indomethacin loaded microspheres including a PEG-derivative were exposed to gamma-irradiation at low temperature.

Electron transfer processes in the reactivity of nonsteroidal anti-inflammatory drugs in the ground and excited states.

The nonsteroidal anti-inflammatory drugs (NSAID), naproxen, sulindac and indomethacin, were shown to donate electrons to nitro blue tetrazolium (NBT) when irradiated with UV light in deoxygenated aqueous buffer solution (pH 7.4, 30 degrees C). The reaction was monitored spectrophotometrically by the appearance of the diformazan reduction product from NBT. The electron transfer process facilitates the decomposition of the drugs. Naproxen in the presence of NBT is photodegraded principally to the alcohol (2-[1-hydroxyethyl]-6-methoxynaphthalene) at a rate approximately 20-fold faster than when irradiated alone in deoxygenated conditions. The photoproduct from naproxen also participates in the electron transfer to NBT but at a much slower rate than naproxen. Irradiation of sulindac or indomethacin in the presence of NBT caused the slow photoreduction of NBT to diformazan. In the absence of NBT, indomethacin and sulindac are essentially unreactive when irradiated in aqueous solution. The ability of a number of NSAID to act as electron donors in their ground state was studied by observing their oxidation by potassium peroxodisulfate in pH 7.0 phosphate buffer at 50 degrees C. The HPLC analysis of the drug remaining showed that the 2-arylpropionic acid NSAID (naproxen, ibuprofen, ketoprofen and suprofen) reacted at a rate equivalent to the thermal decomposition of peroxodisulfate. The major products were the same as detected in the photooxidation of these drugs, resulting from decarboxylation and oxygen addition but also included a dimeric compound. On the other hand, the NSAID that do not contain the propionic acid substituent all reacted more slowly with peroxodisulfate, enabling specific reaction rate constants to be evaluated.

Kinetics of drug degradation. Part 58: a method of preparation and the stability of 3% aqueous indometacin solution.

A method was worked out which allows one to obtain 3% aqueous indometacin solution. The above can be done by solubilization of indometacin by means of ethyl carbamate and ethylurea in the concentration of 30% each and boiling the mixture for 30 s. The stability of indometacin in the above solution was checked with respect to elevated temperatures and exaggerated UV light conditions and compared with the stability of the same solution but without the solubilizing agents. It appears that the solubilizing agents diminish both the hydrolytic as well as the photochemical degradation processes of indometacin. 3% aqueous indometacin solution is stable for 25 months at 20 degrees C, and it is practically non-susceptible to the effects of diffused light for many years. The indometacin solution proposed shows low acidity (pH = 6.95). It is believed that the above solution can be introduced to everyday medical treatment.

Kinetics of drug decomposition Part 51: Kinetics of indometacine photodegradation.

Indometacine aqueous solution degradation was studied under the influence of UV light. Spectrophotometric readings of absorbances at lambdamax = 270 nm were taken in order to follow changes of the indometacine solutions as a function of irradiation time. It was found that the degradation of indometacine under influence of UV light proceeds according a sequential reaction A k2 leads to B k2 leads to C k3 leads to D in which each individual step is a zero-order process Individual zero-order rate constants were calculated for indomatacine photodegradation under anaerobic and aerobic conditions. They indicate the first step (A leads to B) to be oxygen independent and the other processes (B leads to C leads to D) to be oxygen catalyzed.

Kinetics of drug decomposition. Part 50: Graphic method for calculation of zero-order rate constants of sequential reaction of indometacine photodegradation.

Calculation of partial zero-order rate constants for a sequential reaction was presented following indometacine photochemical degradation according to the equation A k1 leads to B k2 leads to C k3 leads to D. When zero-order rate constants k1 not equal to k2 not equal to k3 and absorptivity coefficients a not equal to b not equal to c not equal to d, then individuell zero-order rate constants can be obtained from simple equations: k1 = [A]0/tA, k2 = [A]0/tB, k3 = [A]0/tC, where [A]0 is the initial concentration of a substrate, and tA, tB, tC are the starting times of the steps of the sequential reaction, which can be read from the plots for a relationship A = f(t).