Randomized, open-label, crossover trial comparing the pharmacokinetic profile of a novel oral aspirin solution and a chewed aspirin tablet.

OBJECTIVES: The primary objective of this study was to assess the pharmacokinetic profiles of acetylsalicylic acid (ASA) and salicylic acid (SA) after administration of two different formulations of aspirin under fasting and fed conditions. MATERIALS AND METHODS: The study was a randomized, open-label, parallel-group, 2-arm crossover study conducted at a single center. Healthy subjects were randomized to receive 300 mg of aspirin in either a 15-mL oral solution (pre-packaged vial containing powder and solvent that are combined at the time of administration) or a single solid tablet to be chewed and swallowed with 150 mL of water. Treatment visits were separated by a 10-day wash-out period. RESULTS: At 3 minutes, ASA concentrations for the oral solution fed state and fasting state arms exceeded those for the chewed tablet (fed 299 vs. 139 ng/mL; fasting 356 vs. 204 ng/mL). Compared to the chewed tablet, the mean plasma ASA concentration was 74% greater with the oral solution under fasting conditions, and 115% greater under fed conditions. Similarly, at 3 minutes, the mean SA plasma concentration with the oral solution under fed and fasting conditions exceeded those for the chewed tablet (fed 310 vs. 160 ng/mL; fasting 330 vs. 185 ng/mL). Under fasting conditions, the mean plasma ASA AUC0-last, with the oral solutions was 168,076.8 min.ng/mL compared to 163,726.3 min.ng/mL with the chewed tablet. Under fed conditions, the mean plasma ASA AUC0-last, with the oral solutions was 179,116.7 min.ng/mL compared to 164,704.3 min.ng/mL with the chewed tablet. CONCLUSION: This phase 1 study showed that use of an aspirin oral solution provided more rapid exposure to higher plasma concentration levels of ASA and SA than chewing a solid tablet.

Study of the Influence of Bone Cement Type and Mixing Method on the Bioactivity and the Elution Kinetics of Ciprofloxacin.

The objectives of this study were to examine ciprofloxacin release from three trademarks of bone cements (Simplex®, Lima® and Palacos®) and its bioactivity using as variables, the mixing method, the chemical form of the antibiotic and the antibiotic combination. The antibiotic amount released in base form represents 35% of antibiotic amount released when hydrochloride form is incorporated. Moreover, the combination (vancomycin and ciprofloxacin) shows a stronger release (132%) than hydrochloride ciprofloxacin alone. Three cements show equal drug release profile (P > 0.05). A bioactivity simulation exercise showed that until 72 hours post-surgery, ciprofloxacin concentrations in the implant would be higher than 0.1 µg/mL in 100% of the patients. After drain removal, it is expected that bioactivity would increase since drug clearance from implant would decrease.

Improving oral bioavailability and pharmacokinetics of liposomal metformin by glycerolphosphate-chitosan microcomplexation.

The purpose of this study was to develop a new delivery system capable of improving bioavailability and controlling release of hydrophilic drugs. Metformin-loaded liposomes were prepared and to improve their stability surface was coated with chitosan cross-linked with the biocompatible ß-glycerolphosphate. X-ray diffraction, differential scanning calorimetry, as well as rheological analysis were performed to investigate interactions between chitosan and ß-glycerolphosphate molecules. The entrapment of liposomes into the chitosan-ß-glycerolphosphate network was assessed by scanning electron microscopy and transmission electron microscopy. Swelling and mucoadhesive properties as well as drug release were evaluated in vitro while the drug oral bioavailability was evaluated in vivo on Wistar rats. Results clearly showed that, compared to control, the proposed microcomplexes led to a 2.5-fold increase of metformin T(max) with a 40% augmentation of the AUC/D value.

Hydroxypropylmethylcellulose films for the ophthalmic delivery of diclofenac sodium.

OBJECTIVES: The aim of this study was to prepare diclofenac/hydroxypropylmethylcellulose (HPMC) and diclofenac-loaded nanoparticles/HPMC films as potential systems for ocular delivery. METHODS: Two different concentration of the polymer were used: 1.5 and 2.0% w/v. Chitosan-hyaluronic acid nanoparticles were prepared by the ionotropic gelation technique. Nanoparticles were characterized by transmission electron microscopy, dynamic light scattering, drug encapsulation efficiency and rheological studies. In-vitro drug studies and corneal penetration release studies were carried out. Drug release mechanism was finally evaluated by fitting the Ritger and Peppas equation to data. In addition corneal hydration level was calculated to determine whether films could damage the corneas. KEY FINDINGS: Diclofenac HPMC films presented a faster drug release and a higher drug penetration than nanoparticles; on the contrary nanoparticles containing films were able to give a more sustained release of the drug and thus a slower diclofenac permeation through the cornea than HPMC films. CONCLUSIONS: Nanoparticles loaded with diclofenac sodium in HPMC films may be a valuable alternative for the treatment of ocular inflammatory diseases, since these formulations offer the benefit of sustained releasing directly to the site of action.

Metronidazole prodrugs: synthesis, physicochemical properties, stability, and ex vivo release studies.

The aim of the present study was to develop a colon targeted delivery system for metronidazole using polymeric prodrug formulation. Two chitosan amide conjugates of metronidazole were prepared by using two different spacers to covalently link the drug to the amino group of the chitosan glucosamine units. Glutaric and succinic hemiesters of metronidazole were thus prepared and then coupled to chitosan to obtain metronidazole-glutaryl- and metronidazole-succinyl-chitosan conjugates. Polymeric prodrugs were characterized by solid state NMR method, namely carbon 13 cross polarization magic angle spinning ((13)C NMR CPMAS). Prodrug stability study was carried out in acid (pH = 1.2) and in alkaline (pH = 7.4) buffers in a thermostatic bath at 37 °C. Drug release from the two prodrugs was studied by incubating each of them with 10% w/v cecal and colonic content of rats. Obtained results showed that both prodrugs were adequately stable in acid environment, while the succinyl conjugate was more stable than the glutaryl one in alkaline buffer. Both the prodrugs released the drug in cecal and colonic content, showing that the two systems could serve as colon specific delivery systems of metronidazole.