An acetyl salicylic acid-caffeine complex was prepared and evaluated for the potential use in rectal administration. The results revealed the formation of a complex between acetyl salicylic acid and caffeine in a 1:1 molar ratio by a charge transfer mechanism. The effects of acetyl salicylic acid and complex on the rectal tissues showed destruction in the mucosal epithelium in case of acetyl salicylic acid; however, no change in the rectal tissues was noticed upon the administration of the complex. The effect of suppository bases on the release of the complex was studied using Witepsol H15 as fatty base and polyethylene glycols (PEG) 1000 and 4000 as a water soluble suppository base. The release profiles of acetyl salicylic acid and the complex were faster from PEG than from that of Witepsol H15. The percent release for the complex and acetyl salicylic acid from PEG base were 45.8, and 34.9%, respectively. However, it was 8.7 and 7.8%, respectively, from Witepsol H15 fatty base. The release kinetic was found to follow the non-Fickian diffusion model for complex from the suppository bases. It was concluded that acetyl salicylic acid caffeine complex can be used safely for rectal administration.

Gastrointestinal side effects may interrupt essential therapy with indomethacin, a non-steroidal anti-inflammatory drug. Formulation of this drug into sustained release multiparticulate form may reduce some of these side effects by avoiding contact of drug crystals with gastrointestinal mucosa at high concentrations, as may happen with immediate release dosage forms. Indomethacin (IM) sustained release pellets containing 5 or 10% w/w of the drug were prepared using an extrusion-spheronization technique. Different concentrations of hydrophilic polymers, polyethylene glycol 4000 (PEG 4000), hydroxypropyl methylcellulose E5 LV premium (HPMC) and polyvinyl pyrrolidone (PVP K30), were mixed at different concentrations (5,10 and 20%) with Avicel PH 101 to prepare the sustained release formulae. Moreover, a mixer torque rheometer was used to quantitatively determine the suitable moisture content in the pastes before the extrusion process. The resulting pellets were characterized for content, particle size, shape and dissolution profile. The studies on the effect of the polymers used on Avicel rheological properties revealed that the magnitude of torque for the system was decreasing as the polymer concentration increased. The in vitro release of IM from the prepared Avicel pellets was found to be dependent upon the type and concentration of the added polymer. The rank order of IM release in the presence of the investigated polymers was as follows: PEG > HPMC > PVP. Furthermore, the magnitude of IM release rate from the pellet formulations was found to be dependent on the magnitude of the peak torque of the pellet forming paste, which in turn depends on the type and concentration of the added polymer. Increasing IM loading from 5 to 10% has led to an increase in dissolution rates. At least two of the prepared pellet formulations showed dissolution profiles similar to the commercial product Bonidon 75 SR capsules. In conclusion, the formulation of IM sustained release pellets successfully controlled the drug release which might be beneficial in lowering the risk of side effects and improving patient convenience as an advantage of the pellets as a drug delivery system.

Aminoglycoside antibiotics are effective in the treatment of infections caused by aerobic Gram negative bacilli, but their widespread use is hampered by serious side effects that may be alleviated through the use of tailored delivery systems. Robust polyion complex (PIC) micelles, incorporating up to 50 weight % drug, were prepared using two aminoglycosides: paromomycinand neomycin, and a dihydrophilic block copolymer consisting of a poly(ethyleneglycol) (PEG) chain linked to a carboxymethyldextran fragment (CMD) lightly grafted with n-dodecyl groups. The micelles were stable under physiological conditions (pH 7.4, 150 mM NaCl), in contrast to micelles formed by the unmodified CMD-PEG and the aminoglycosides or their guanidinylated derivatives. The aminoglycosides were released from the n-dodecyl-CMD-PEG micelles in a pharmacologically active form as indicated by their ability to kill test micro-organisms in culture. This study opens up new opportunities in the biomedical applications of PIC micelles with inherently enhanced stability.

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.