The aim of this work was to formulate and evaluate nalidixic acid for the first time in different topical ointment bases. Among different ointment formulations, hydrocarbon base achieved the lowest release, while water-soluble base achieved the highest release. The presence of both isopropanol as cosolvent and nalidixic acid-sodium benzoate solid dispersion in formula (W8) enhanced both the release and the antibacterial activity of nalidixic acid compared to ointment formula (W5) containing neither of them. A stability study was also performed where no significant change in pH or drug content was observed in all stored formulations (W5 and W8). Stability was further checked by thin-layer chromatography (TLC). After clinical application in impetigo, it was found that the presence of isopropanol and nalidixic acid-sodium benzoate solid dispersion in ointment formulation (W8) caused a significant reduction in the mean time of healing (only four days) in impetigo patients.

The aim of this work was to formulate and evaluate nalidixic acid for the first time in different topical ointment bases. Among different ointment formulations, hydrocarbon base achieved the lowest release, while water-soluble base achieved the highest release. The presence of both isopropanol as cosolvent and nalidixic acid-sodium benzoate solid dispersion in formula (W8) enhanced both the release and the antibacterial activity of nalidixic acid compared to ointment formula (W5) containing neither of them. A stability study was also performed where no significant change in pH or drug content was observed in all stored formulations (W5 and W8). Stability was further checked by thin-layer chromatography (TLC). After clinical application in impetigo, it was found that the presence of isopropanol and nalidixic acid-sodium benzoate solid dispersion in ointment formulation (W8) caused a significant reduction in the mean time of healing (only four days) in impetigo patients.

Nalidixic acid is practically insoluble in water therefore the aim of this study was to study the effect of both cosolvency and solid dispersionon its solubility. Among different cosolvents, the highest result was achieved by isopropanol (30% v/v). Through all studied solid dispersioncarriers in the ratio 1:1, sodium benzoate enhanced both the solubility and antibacterial activity of nalidixic acid and was therefore selected for further investigation. Increasing sodium benzoate ratio had significantly increased nalidixic acid solubility till a 1:8 ratio. Differential scanning calorimetry (DSC) showed a sharp endothermic peak of nalidixic acid which was slightly shifted to lower temperature accompanied by significant broadening in the case of solid dispersion. Further confirmation was obtained by X-ray powder diffraction (XRPD) whereas the peak heights were much reduced in the case of solid dispersion confirming the cause of increasing solubility.

Nalidixic acid is practically insoluble in water therefore the aim of this study was to study the effect of both cosolvency and solid dispersionon its solubility. Among different cosolvents, the highest result was achieved by isopropanol (30% v/v). Through all studied solid dispersioncarriers in the ratio 1:1, sodium benzoate enhanced both the solubility and antibacterial activity of nalidixic acid and was therefore selected for further investigation. Increasing sodium benzoate ratio had significantly increased nalidixic acid solubility till a 1:8 ratio. Differential scanning calorimetry (DSC) showed a sharp endothermic peak of nalidixic acid which was slightly shifted to lower temperature accompanied by significant broadening in the case of solid dispersion. Further confirmation was obtained by X-ray powder diffraction (XRPD) whereas the peak heights were much reduced in the case of solid dispersion confirming the cause of increasing solubility.

Naproxen (Nap) is an NSAID used as a neuroprotective agent to treat several neurodegenerative diseases. The observed limited brain bioavailability of the drug prompted the design of several chemical delivery systems. We report the synthesis and preliminary in vitro and in vivo investigations of Nap prodrugs with dihydropyridine (I) and ascorbic acid (II) through an ester spacer to target specific brain delivery of Nap. The purpose of this study was to determine the brain bioavailability of Nap after oral administration of the prodrugs in rats. The results showed moderate oral bioavailability of prodrugs (AUC = 53-94 h•µg/mL) in rats compared with parent Nap (AUC = 155 h•µg/mL) at equimolar doses. Contrarily, there was a twofold increase in Nap levels in the brain with the prodrugs compared to parent Nap. The enhanced brain bioavailability may be attributed to the specific carrier system in addition to the reduced percentage of plasma protein binding of Nap. Plasma protein binding of the tested prodrugs was investigated in vitro using equilibrium dialysis. The percentage of plasma free fraction of prodrugs (9-15%) was significantly greater than that of Nap (about 5%) when tested at 20 µM, illustrating more available prodrug to cross the blood brain barrier. A significant decrease in gastric ulcerogenicity of the prodrugs compared with parent Nap was also noted. In conclusion, oral dihydropyridine and ascorbate prodrugs for brain site-specific delivery of Nap may be promising candidates for safe, chronic use of NSAIDs for the treatment of neurodegenerative diseases.

A solid dispersion of Meloxicam (MX), a poorly soluble, non steroidal anti-inflammatory drug, and Gelucire 50/13 was prepared by spray drying. Spherical microparticles were yielded with smooth surfaces as observed by scanning electron microscopy. According to differential scanning calorimetry and powder X-ray diffractometry analysis, MX was transformed from the crystalline state to the amorphous state as confirmed by the disappearance of its melting peak and the crystalline peaks. The dissolution tests at pH 7.4 revealed that the dissolution rate of encapsulated MX was 2.5-fold higher than that of the corresponding physical mixture and fourfold higher than the drug alone, respectively. The microparticles prepared at a ratio of 1:4 (drug/Gelucire) exhibited a 4-fold higher anti-inflammatory activity on the paw edema of rats in comparison to the drug alone. All in all, this work reveals that spray drying is a suitable technique for preparation of solid dispersions with improved biopharmaceutical and pharmacological characteristics of MX.

Knowledge and control of the solid forms of active pharmaceutical ingredients are important aspects of drug development in the pharmaceutical industry. In this paper, the process of the molecular self-assembly of saccharin cocrystals and the 2-amino-5-methylpyridine salt of indomethacin, in terms of the hydrogen bonding patterns, has been studied in the solid-state using vibrational spectroscopy (Raman and infrared). Interaction patterns in the respective crystalline states were obtained from the single crystal data. The effects of cocrystal and salt formation on the frequencies of the vibrational modes of motion were explained by vibrational spectroscopy and supported by quantum chemical calculations at the density functional theory level, leading to unambiguous assignment of the vibrational spectra of the starting materials and their respective products. Both Raman and infrared spectroscopies were useful, reliable tools for characterizing and distinguishing the indomethacin cocrystals and salt.

Budesonide is a mixture of 22R and 22S epimers. The epimeric content of budesonide was reported in both British and European pharmacopoeias to be within the range of 60–49/40–51 for R and S epimers, respectively. In this work, contribution of the two epimers to the overall infrared spectrum of budesonide has been investigated by quantum chemical calculations.

Pharmaceutical solids exposed to thermal stress during manufacturing processes undergo various phase transformations in bulk drug substances or excipients, resulting in altered dosage form performance. Due to its relatively rapid spectral acquisition rate, as well as the possibility of incorporation into in-line monitoring, Raman spectroscopy is ideally suited to monitoring the transformation between different solid-state forms. In this study, we demonstrate that the transition temperature for polymorphs can be estimated from the transformation profiles obtained from real-time, in situ, simultaneous Raman spectroscopic, and differential scanning calorimetric data. Using this method, we have estimated the transition temperature of the solid-state transformation of the enantiotropically related sulfathiazole polymorphs III and I. These results suggest that this method is a useful approach to determine transition temperatures in systems that are not amenable to accessing other methods.

In this study, ipratropium bromide is investigated using vibrational spectroscopy and quantum chemical calculations. The structure of ipratropium bromide was optimised using density functional theory calculations and the geometry optimization has been carried out on two conformations with and without intramolecular hydrogen bonding. Infrared and Raman spectra were calculated from the optimised structures. Many modes in the calculated spectra could be matched with the experimental spectra and a description of the modes is given. By analysis of the theoretical vibrational modes, it is shown that ipratropium bromide specimens are likely to be a mixture of the two conformations with and without intramolecular hydrogen bonding. In addition, several spectral features and band intensities in the CH and OH stretching regions are explained. Quantum mechanical calculations allowed improved understanding of ipratropium bromide and its vibrational spectra.