Effect of cimetidine on the heart conduction system]

An effect of cimetidine on ECG records has been investigated in a group of 40 patients with gastric or duodenal ulcers and coexisting circulatory disorders. For this purpose ECG has been recorded with Holter's technique (Medilog 2000) together with ECG-recording using high amplifying technique. An intravenous injection of 200 mg of cimetidine produced in some of patients inhibition of the sinus rhythm atrio-ventricular conduction disturbances as well as changes in the end phase of ECG ventricular image. The authors suggest, that intravenous administration of cimetidine to patients with cardiac diseases should be monitored with ECG recording.     

Controlled Release of Oral Tetrahydrocurcumin from a Novel Self-Emulsifying Floating Drug Delivery System (SEFDDS)

The objectives of this study were to develop and evaluate a novel self-emulsifying floating drug delivery system (SEFDDS) that resulted in improved solubility, dissolution, and controlled release of the poorly water-soluble tetrahydrocurcumin (THC). The formulations of liquid self-emulsifying drug delivery system (SEDDS; mixtures of Labrasol, Cremophor EL, Capryol 90, Labrafac PG) were optimized by solubility assay and pseudo-ternary phase diagram analysis. The liquid SEDDS was mixed with adsorbent (silicon dioxide), glyceryl behenate, pregelatinized starch, sodium starch glycolate, and microcrystalline cellulose and transformed into pellets by the extrusion/spheronization technique. The resulting pellets with 22% liquid SEDDS had a uniform size and good self-emulsification property. The microemulsions in aqueous media of different self-emulsifying floating pellet formulations were in a particle size range of 25.9–32.5 nm. Use of different weight proportions of glyceryl behenate and sodium starch glycolate in pellet formulations had different effects on the floating abilities and in vitro drug release. The optimum formulation (F2) had a floating efficiency of 93% at 6 h and provided a controlled release of THC over an 8-h period. The release rate and extent of release of THC liquid SEDDS (80% within 2 h) and self-emulsifying floating pellet formulation (80% within 8 h) were significantly higher than that of unformulated THC (only 30% within 8 h). The pellet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. Controlled release from this novel SEFDDS can be a useful alternative for the strategic development of oral solid lipid-based formulations.     

Development,Characterization and Permeability Assessment Based on Caco-2 Monolayers of Self-Microemulsifying Floating Tablets of Tetrahydrocurcumin

Novel self-microemulsifying floating tablets were developed to enhance the dissolution and oral absorption of the poorly water-soluble tetrahydrocurcumin (THC). Their physicochemical properties and THC permeability across Caco-2 cell monolayers were assessed. The self-microemulsifying liquid containing THC was adsorbed onto colloidal silicon dioxide, mixed with HPMC, gas-generating agents (sodium bicarbonate and tartaric acid), lactose and silicified-microcrystalline cellulose and transformed into tablets by direct compression. The use of different types/concentrations of HPMC and sodium bicarbonate in tablet formulations had different effects on the floating characteristics and in vitro THC release. The optimum tablet formulation (F2) provided a short floating lag time (∼23 s) together with a prolonged buoyancy (>12 h). About 72% of THC was released in 12 h with an emulsion droplet size in aqueous media of 33.9 ± 1.0 nm while that of a self-microemulsifying liquid was 29.9 ± 0.3 nm. The tablet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. The THC released from the self-microemulsifying liquid and tablet formulations provided an approximately three- to fivefold greater permeability across the Caco-2 cell monolayers than the unformulated THC and indicated an enhanced absorption of THC by the formulations. The self-microemulsifying floating tablet could provide a dosage form with the potential to improve the oral bioavailability of THC and other hydrophobic compounds.KEY WORDS: Caco-2 cells, controlled release, permeability, self-microemulsifying floating tablets, tetrahydrocurcumin     

Thermal behavior of a pharmaceutical solid acetaminophen doped withp-aminophenol

Thermal behavior of a series of acetaminophen (APAP) doped withp-aminophenol (PANP) was studied by differential scanning calorimetry (DSC) to determine whether it exhibited a eutectic system. Within the temperature range of 120 to 200° C, accurately weighed (1–2 mg) samples sealed in hermetic pans were calorimetrically scanned with a low scanning rate of 1° C/min. The mixture formed a single eutectic with the composition ratio APAP/PANP of 0.6/0.4 at a temperature of 138° C, where it liquefied. Melting began as early as at the eutectic point, which was below the melting temperature of APAP (169° C). The melting point as well as heat of APAP fusion was depressed with the increase in doped PANP. It was postulated that there might be a deficit heat of APAP fusion in APAP doped with PANP, which was coincident with the heat consumed by early liquefaction. The deficit heat was used to correct fraction molten in the van’t Hoff law of purity determination. It was found that the purity determination of APAP doped with PANP was comparable to the UV-spectroscopic method up to the maximum doped PANP level of 8 mol percent. It was concluded that DSC was able to approach early heat of liquefaction of APAP doped with PANP. The van’t Hoff law may be applicable to the determination of APAP with the presence of PANP as a eutectic impurity.     

Development of Push–Pull Osmotic Tablets Using Chitosan–Poly(Acrylic Acid) Interpolymer Complex as an Osmopolymer

The objectives of this study were to prepare push–pull osmotic tablets (PPOT) of felodipine using an interpolymer complex of chitosan (CS) and poly(acrylic acid) (PAA) as an osmopolymer, and to study the mechanisms of drug release from these tablets. The interpolymer complexes were prepared with different weight ratios of CS to PAA. Preparation of PPOT involved the fabrication of bilayered tablets with the drug layer, containing felodipine, polyethylene oxide, and the polymeric expansion layer, containing the CS–PAA complex. The effects of polymer ratios, type of plasticizers, and compression forces on release characteristics were investigated. It was found that drug release from PPOT exhibited zero-order kinetics and could be prolonged up to 12 or 24 h depending on the plasticizer used. PPOT using dibutyl sebacate showed a longer lag time and slower drug release than that using polyethylene glycol 400. In the case of polyethylene glycol 400, an increase in the CS proportion resulted in an increase in the drug release rate. The compression force had no effect on drug release from PPOT. Drug release was controlled by two consecutive mechanisms: an osmotic pump effect resulting in the extrusion of the drug layer from the tablet and subsequent erosion and dissolution of the extruded drug layer in the dissolution medium. The mathematical model (zero-order) related to extrusion and erosion rates for describing the mechanism of drug release showed a good correlation between predicted and observed values.     

Extensive Miocene speciation in and out of Indochina: The biogeographic history of Typhonium sensu stricto (Araceae) and its implication for the assembly of Indochina flora

The Asian paleotropical flora is characterized by abundance of endemic species, high biodiversity, and complex geological and climatic histories. However, the main driving mechanism underlying such high tropical biodiversity remains unclear. Hence, the present study aimed to investigate the biogeographic origin of the Asian paleotropical flora by tracking the speciation and diversification history of a typical tropical perennial, Typhonium sensu stricto (s.s.) (Araceae), using a time-calibrated whole-plastome phylogeny. In particular, we tested whether the Asian paleotropic region is a macroevolutionary source or sink. We observed that Typhonium s.s. originated in Indochina during the early–middle Miocene epoch, ca. 17.24 Ma (95% highest posterior density [HPD]: 12.83 ̶ 21.99 Ma). Most of the in situ diversification within the genus Typhonium s.s. has been underway since 14.73 Ma, with an accelerated lineage diversification at ca. 15−17 Ma, which may have been triggered by the intensification of the Asian monsoon system around the middle Miocene. Furthermore, the underground tuberous stem of Typhonium s.s. might have played an essential role in the adaptation to the seasonality caused by the monsoon in Indochina. Our results also suggested that peripatric speciation may be important in the diversification of T. trilobatum and T. roxburghii. This study provides a framework for studies in biogeography and evolution of the Asian paleotropical flora.