Design and development of microemulsion drug delivery system of acyclovir for improvement of oral bioavailability.

The main purpose of this work was to develop an oral microemulsion formulation for enhancing the bioavailability of acyclovir. A Labrafac-based microemulsion formulation with Labrasol as surfactant and Plurol Oleique as cosurfactant was developed for oral delivery of acyclovir. Phase behavior and solubilization capacity of the microemulsion system were characterized, and in vivo oral absorption of acyclovir from the microemulsion was investigated in rats. A single isotropic region, which was considered to be a bicontinuous microemulsion, was found in the pseudoternary phase diagrams developed at various Labrasol:Plurol Oleique:Labrafac ratios. With the increase of Labrasol concentration, the microemulsion region area and the amount of water and Labrafac solubilized into the microemulsion system increased; however, the increase of Plurol Oleique percentage produced opposite effects. The microemulsion system was also investigated in terms of other characteristics, such as interfacial tension, viscosity, pH, refractive index, diffusion, and bioavailability. Acyclovir, a poorly soluble drug, displayed high solubility in a microemulsion formulation using Labrafac (10%), Labrasol (32%), Plurol Oleique (8%), and water (50%). The in vitro intraduodenal diffusion and in vivo study revealed an increase of bioavailability (12.78 times) after oral administration of the microemulsion formulation as compared with the commercially available tablets.

Studies on Ender's intramedullary nailing for closed tibial shaft fractures.

Low cost multiple flexible Ender's nails can be used in tibial shaft fractures in a non-ideal operating room set-up in India, also because of easy methodology. It is commonly used in femur and humerus but not in tibia. So we made the study in which prospective and consecutive patients were taken based on selection criteria. Forty patients were treated by the technique from August 2004 to May 2006. Twenty-seven patients (67.5%) were male, 28 patients (70%) had fracture type 4-2A of AO classification, 37 patients (92.5%) had acute injuries, delay in surgery by 1-2 weeks in 21 patients (52.5%), 30 patients (75%) had closed nailing, 35 patients (87.5%) needed 2 nails, 36 patients (90%) were operated by antegrade nailing approach and 23 patients (57.5%) had fracture union within 16 weeks. All the patients were evaluated based on pain,range of movement of knee and ankle,shortening and radiological union along with ability to perform daily activities like squatting,sitting cross-legged and the ability to walk. There was excellent result in 34 patients (85%), good in 5 patients (12.5%), fair/poor result in 1 patient (2.5%). The complications observed were soft tissue irritation of the proximal part of tibia due to protruding nail in 5 patients,infection at the entry portal in one patient and non-union in one patient. Ender's nailing can be a safe and alternative method of fixation of fracture shaft of tibia in rural India for poor patients in 'not well set-up'.

A short term experience of management of open and osteoporotic intercondylar fractures of the distal humerus using a mini-external fixator.

Seven cases of intercondylar fractures of the distal humerus were treated by a mini-external fixation technique. The average range of motion was 30 degrees to 110 degrees. All fractures united with radiologic and clinical evidence of union at 10-12 weeks. Open wound sites healed in 6 cases. There were no evidence of any nerve palsies.

Interaction of 2-aminopyrimidine with dichloro-[I-alkyl-2-(naphthylazo) imidazole]palladium(II) complexes: kinetic and mechanistic studies.

BACKGROUND: The anticancer properties of cisplatin and palladium(II) complexes stem from the ability of the cis-MCl2 fragment to bind to DNA bases. However, cisplatin also interacts with non-cancer cells, mainly through bonding molecules containing -SH groups, resulting in nephrotoxicity. This has aroused interest in the design of palladium(II) complexes of improved activity and lower toxicity. The reaction of DNA bases with palladium(II) complexes with chelating N,N'donors of the cis-MCl2 configuration constitutes a model system that may help explore the mechanism of cisplatin's anticancer activity. Heterocyclic compounds are found widely in nature and are essential to many biochemical processes. Amongst these naturally occurring compounds, the most thoroughly studied is that of pyrimidine. This was one of the factors that encouraged this study into the kinetics and mechanism of the interaction of 2-aminopyrimidine (2-NH2-Pym) with dichloro-[1-alkyl-2-(alpha-naphthylazo)imidazole]palladium(II) [Pd(alpha-NaiR)Cl2, 1] and dichloro-[1-alkyl-2-(beta-naphthylazo)imidazole]palladium(II) [Pd(beta-NaiR)Cl2, 2] complexes where the alkyl R = Me (a), Et (b), or Bz (c). RESULTS: 2-NH2-Pym reacts with 1a, 1b, and 1c to yield [[1-alkyl-2-(alpha-naphthylazo)imidazole]bis(2-aminopyrimidine)]palladium(II) (3a, 3b, 3c) dichloride and with 2a, 2b, and 2c to yield [[1-alkyl-2-(beta-naphthylazo)imidazole]bis(2-aminopyrimidine)]palladium(II) (4a, 4b, 4c) dichloride in an acetonitrile (MeCN) medium. The products were characterized using spectroscopic techniques (FT-IR, UV-Vis, NMR). The ligand substitution reactions follow second order kinetics - first order dependence on the concentration of the Pd(II) complex and 2-NH2-Pym. Addition of LiCl to the reaction does not influence its rate. The thermodynamic parameters (standard enthalpy of activation, Delta(double dagger)H degrees and standard entropy of activation, Delta(double dagger)S degrees) were determined from variable temperature kinetic studies. The magnitude of the second order rate constant, k2, at 298 K, was shown to increase thus: b

6-mercaptopurine (6-MP) entrapped stealth liposomes for improvement of leukemic treatment without hepatotoxicity and nephrotoxicity.

6-mercaptopurine (6-MP) is a purine analogue used in childhood leukemia. Because of the oral bioavailability of 6-MP is low and highly variable, the aim of this study was to develop a new parenteral formulation that can prolong the biological half-life of the drug, improve its therapeutic efficacy, and its associated reduce side effects. Conventional and stealth 6-MP liposomes were prepared by a thin film hydration technique followed by a high-pressure homogenization process and characterized for percent entrapment efficiency (%EE), particle size, and stability in human plasma. Pharmacokinetic, tissue distribution, and biochemical analysis were performed after intravenous (IV) administration of all formulations of 6-MP on rats. The conventional liposomes were found less stable than stealth liposomes in human plasma at 37 degrees C. Stealth liposomes exhibited high peak plasma concentration (C(max)), and long circulating capacity in blood and biological half-life. The uptake of stealth liposomes by the liver and spleen and accumulation in the kidney were significantly less than that of conventional liposomes and the free drug. Serum urea, creatinine, GOT (Glutamic Oxaloacetic Transaminase), and GPT (Glutamic Pyruvic Transaminase) increased significantly in rats given an IV injection of conventional liposomes and the free drug, but not in those administered with the same dose of stealth liposomes. Stealth liposomes may help to increase therapeutic efficacy of 6-MP and to reduce total amount of dose as well as frequency of the dose. It also may reduce the possibility of the risk of toxicity to the liver and kidney generally associated with free 6-MP.