Lamivudine salts with improved solubilities

To optimize solubility of drugs, current strategies mainly focus on engineering and screening of smart crystal phases. Two salts of the anti-human immunodeficiency virus (HIV) drug lamivudinenamely, lamivudine hydrochloride and lamivudine hydrochloride monohydrate, were prepared in the course of screening the crystallization conditions of lamivudine duplex, an uncommon DNA-mimic, double-stranded helical structure made up of partially protonated drug pairs. Here, water solubilities of lamivudine hydrochloride, lamivudine hydrochloride monohydrate, and lamivudine duplex are reported. The aqueous solubility of this anti-HIV drug was significantly increased in both salts and also in lamivudine duplex in relation to the water solubility of lamivudine form II. In comparison with the lamivudine form II incorporated into therapeutic formulations, the drug solubility was increased at a temperature of 299 +/- 2 K by factors of 1.2, 3.3, and 4.5 in lamivudine hydrochloride, lamivudine hydrochloride monohydrate, and lamivudine duplex, respectively, demonstrating that this solid-state property of lamivudine can be improved by crystal engineering strategies. Solubility profiles were understood on the basis of structural and solventsolute interaction approaches. At last, correlations between solubility and crystal structures allowed for a rational approach to understand how this physicochemical feature could be enhanced by engineering new salts of the drug. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:21432154, 2012

Effects of curing protocol and storage time on the micro-hardness of resin cements used to lute fiber-reinforced resin posts

Objectives: To determine the micro-hardness profile of two dual cure resin cements (RelyX - U100 (R), 3M-ESPE and Panavia F 2.0 (R), Kuraray) used for cementing fiber-reinforced resin posts (Fibrekor (R) - Jeneric Pentron) under three different curing protocols and two water storage times. Material and methods: Sixty 16mm long bovine incisor roots were endodontically treated and prepared for cementation of the Fibrekor posts. The cements were mixed as instructed, dispensed in the canal, the posts were seated and the curing performed as follows: a) no light activation; b) light-activation immediately after seating the post, and; c) light-activation delayed 5 minutes after seating the post. The teeth were stored in water and retrieved for analysis after 7 days and 3 months. The roots were longitudinally sectioned and the microhardness was determined at the cervical, middle and apical regions along the cement line. The data was analyzed by the three-way ANOVA test (curing mode, storage time and thirds) for each cement. The Tukey test was used for the post-hoc analysis. Results: Light-activation resulted in a significant increase in the microhardness. This was more evident for the cervical region and for the Panavia cement. Storage in water for 3 months caused a reduction of the micro-hardness for both cements. The U100 cement showed less variation in the micro-hardness regardless of the curing protocol and storage time. Conclusions: The micro-hardness of the cements was affected by the curing and storage variables and were material-dependent.

Effect of Temperature on the Degree of Conversion and Working Time of Dual-Cured Resin Cements Exposed to Different Curing Conditions

Objectives: This study evaluated the degree of conversion (DC) and working time (WT) of two commercial, dual-cured resin cements polymerized at varying temperatures and under different curing-light accessible conditions, using Fourier transformed infrared analysis (FTIR). Materials and Methods: Calibra (Cal; Dentsply Caulk) and Variolink II (Ivoclar Vivadent) were tested at 25 degrees C or preheated to 37 degrees C or 50 degrees C and applied to a similar-temperature surface of a horizontal attenuated-total-reflectance unit (ATR) attached to an infrared spectrometer. The products were polymerized using one of four conditions: direct light exposure only (600 mW/cm(2)) through a glass slide or through a 1.5- or 3.0-mm-thick ceramic disc (A2 shade, IPS e.max, Ivoclar Vivadent) or allowed to self-cure in the absence of light curing. FTIR spectra were recorded for 20 min (1 spectrum/s, 16 scans/spectrum, resolution 4 cm(-1)) immediately after application to the ATR. DC was calculated using standard techniques of observing changes in aliphatic-to-aromatic peak ratios precuring and 20-min postcuring as well as during each 1-second interval. Time-based monomer conversion analysis was used to determine WT at each temperature. DC and WT data (n=6) were analyzed by two-way analysis of variance and Tukey post hoc test (p=0.05). Results: Higher temperatures increased DC regardless of curing mode and product. For Calibra, only the 3-mm-thick ceramic group showed lower DC than the other groups at 25 degrees C (p=0.01830), while no significant difference was observed among groups at 37 degrees C and 50 degrees C. For Variolink, the 3-mm-thick ceramic group showed lower DC than the 1-mm-thick group only at 25 degrees C, while the self-cure group showed lower DC than the others at all temperatures (p=0.00001). WT decreased with increasing temperature: at 37 degrees C near 70% reduction and at 50 degrees C near 90% for both products, with WT reduction reaching clinically inappropriate times in some cases (p=0.00001). Conclusion: Elevated temperature during polymerization of dual-cured cements increased DC. WT was reduced with elevated temperature, but the extent of reduction might not be clinically acceptable.

Kinetic resolution of alpha-bromophenylacetamides using quinine or Cinchona alkaloid salts

The kinetic resolution of racemic alpha-bromophenylacetamides 1 was achieved in the presence of benzenethiolate and Cinchona alkaloid salts as phase-transfer catalysts or benzenethiol and quinine, yielding (S)-enantioenriched alpha-sulfanylated products. The observed stereoselection was rationalized on the basis of the best fitting of 1 and the resolving agent in the ternary complexes. (C) 2012 Elsevier Ltd. All rights reserved.

Salts of the anti-HIV drug lamivudine with phthalic and salicylic acids

Salts of the anti-HIV drug lamivudine, with phthalic acid and salicylic acid as counterions, were investigated in this study. Neither the packing of the (lamivudine)(+)(phthalic acid)(-) ion pairs nor the conformation of the lamivudine moiety itself were similar to those found in other multicomponent molecular salts of the drug, such as hydrogen maleate and saccharinate ones, even though all three salts crystallize in the same P2(1)2(1)2(1) orthorhombic space group with similar unit cell metrics. Lamivudine salicylate assumes a different crystal structure to those of the hydrogen maleate and saccharinate salts, crystallizing in the P2(1) monoclinic space group as a monohydrate whose (lamivudine)(+)(salicylic acid)(-) ion pair is assembled through two hydrogen bonds with cytosine as a dual donor to both oxygens of the carboxylate, such as in the pairing of lamivudine with a phthalic acid counterion. In lamivudine salicylate monohydrate, the drug conformation is related to the hydrogen maleate and saccharinate salts. However, such a conformational similarity is not related to the intermolecular interaction patterns. Lamivudine and water molecules alternate into helical chains in the salicylate salt monohydrate.

The effect of curing light and chemical catalyst on the degree of conversion of two dual cured resin luting cements

The aim of this study was to evaluate the influence of different curing lights and chemical catalysts on the degree of conversion of resin luting cements. A total of 60 disk-shaped specimens of RelyX ARC or Panavia F of diameter 5 mm and thickness 0.5 mm were prepared and the respective chemical catalyst (Scotchbond Multi-Purpose Plus or ED Primer) was added. The specimens were light-cured using different curing units (an argon ion laser, an LED or a quartz-tungsten-halogen light) through shade A2 composite disks of diameter 10 mm and thickness 2 mm. After 24 h of dry storage at 37A degrees C, the degree of conversion of the resin luting cements was measured by Fourier-transformed infrared spectroscopy. For statistical analysis, ANOVA and the Tukey test were used, with p a parts per thousand currency signaEuro parts per thousand 0.05. Panavia F when used without catalyst and cured using the LED or the argon ion laser showed degree of conversion values significantly lower than RelyX ARC, with and without catalyst, and cured with any of the light sources. Therefore, the degree of conversion of Panavia F with ED Primer cured with the quartz-tungsten-halogen light was significantly different from that of RelyX ARC regardless of the use of the chemical catalyst and light curing source. In conclusion, RelyX ARC can be cured satisfactorily with the argon ion laser, LED or quartz-tungsten-halogen light with or without a chemical catalyst. To obtain a satisfactory degree of conversion, Panavia F luting cement should be used with ED Primer and cured with halogen light.

Effect of light sources and curing mode techniques on sorption, solubility and biaxial flexural strength of a composite resin

Adequate polymerization plays an important role on the longevity of the composite resin restorations. Objectives: The aim of this study was to evaluate the effect of light-curing units, curing mode techniques and storage media on sorption, solubility and biaxial flexural strength (BFS) of a composite resin. Material and Methods: Two hundred and forty specimens were made of one composite resin (Esthet-X) in a stainless steel mold (2 mm x 8 mm 0), and divided into 24 groups (n=10) established according to the 4 study factors: light-curing units: quartz tungsten halogen (QTH) lamp and light-emitting diodes (LED); energy densities: 16 J/cm(2) and 20 J/cm(2); curing modes: conventional (CM) and pulse-delay (PD); and permeants: deionized water and 75% ethanol for 28 days. Sorption and solubility tests were performed according to ISO 4049:2000 specifications. All specimens were then tested for BFS according to ASTM F394-78 specification. Data were analyzed by three-way ANOVA followed by Tukey, Kruskal-Wallis and Mann-Whitney tests (alpha=0.05). Results: In general, no significant differences were found regarding sorption, solubility or BFS means for the light-curing units and curing modes (p>0.05). Only LED unit using 16 J/cm(2) and PD using 10 s produced higher sorption and solubility values than QTH. Otherwise, using CM (16 J/cm(2)), LED produced lower values of BFS than QTH (p<0.05). 75% ethanol permeant produced higher values of sorption and solubility and lower values of BFS than water (p<0.05). Conclusion: Ethanol storage media produced more damage on composite resin than water. In general the LED and QTH curing units using 16 and 20 J/cm(2) by CM and PD curing modes produced no influence on the sorption, solubility or BFS of the tested resin.

Kinetic of water diffusion and color stability of a resin composite as a function of the curing tip distance

The influence of curing tip distance and storage time in the kinetics of water diffusion (water sorption-W SP, solubility-W SB, and net water uptake) and color stability of a composite were evaluated. Composite samples were polymerized at different distances (5, 10, and 15 mm) and compared to a control group (0 mm). After desiccation, the specimens were stored in distilled water to evaluate the water diffusion over a 120-day period. Net water uptake was calculated (sum of WSP and WSB). The color stability after immersion in a grape juice was compared to distilled water. Data were submitted to three-way ANOVA/Tukey's test (α = 5%). The higher distances caused higher net water uptake (p < 0.05). The immersion in the juice caused significantly higher color change as a function of curing tip distance and the time (p < 0.05). The distance of photoactivation and storage time provide the color alteration and increased net water uptake of the resin composite tested.