Preparation of Naringenin Nanosuspension and Its Antitussive and Expectorant Effects.

Naringenin (NRG) is a natural flavonoid compound abundantly present in citrus fruits and has the potential to treat respiratory disorders. However, the clinical therapeutic effect of NRG is limited by its low bioavailability due to poor solubility. To enhance the solubility, naringenin nanosuspensions (NRG-NSps) were prepared by applying tocopherol polyethylene glycol succinate (TPGS) as the nanocarrier via the media-milling method. The particle size, morphology, and drug-loading content of NRG-NSps were examined, and the stability was evaluated by detecting particle size changes in different physiological media. NRG-NSps exhibited a flaky appearance with a mean diameter of 216.9 nm, and the drug-loading content was 66.7%. NRG-NSps exhibited good storage stability and media stability. NRG-NSps presented a sustainable release profile, and the cumulative drug-release rate approached approximately 95% within 7 d. NRG-NSps improved the antitussive effect significantly compared with the original NRG, the cough frequency was decreased from 22 to 15 times, and the cough incubation period was prolonged from 85.3 to 121.6 s. Besides, NRG-NSps also enhanced expectorant effects significantly, and phenol red secretion was increased from 1.02 to 1.45 µg/mL. These results indicate that NRG-NSps could enhance the bioavailability of NRG significantly and possess a potential clinical application.

Exploring the Potential of Hydrophilic Matrix Combined with Insoluble Film Coating: Preparation and Evaluation of Ambroxol Hydrochloride Extended Release Tablets.

To explore the potential utility of combination of hydrophilic matrix with membrane-controlled technology, the present study prepared tablets of a water-soluble model drug (ambroxol hydrochloride), through process of direct compression and spray coating. Single-factor experiments were accomplished to optimize the formulation. In vivo pharmacokinetics was then performed to evaluate the necessity and feasibility of further development of this simple process and low-cost approach. Various release rates could be easily obtained by adjusting the viscosity and amount of hypromellose, pore-former ratios in coating dispersions and coating weight gains. Dissolution profiles of coated tablets displayed initial delay, followed by near zero-order kinetics. The pharmacokinetic study of different formulations showed that lag time became longer as the permeability of coating membrane decreased, which was consistent with the in vitro drug release trend. Besides, in vitro/in vivo correlation study indicated that coated tablets exhibited a good correlation between in vitro release and in vivo absorption. The results, therefore, demonstrated that barrier-membrane-coated matrix formulations were extremely promising for further application in industrialization and commercialization.

A new strategy for cyclopentenone synthesis.

[reaction--see text] A new strategy for the synthesis of 2,3-disubstituted cyclopentenones emerges from two key reactions-the ruthenium-catalyzed three-component coupling of an equivalent of HBr, an alkyne, and a vinyl ketone and the Ni-Cr Barbier type reaction. As a result, these important structures are readily accessed from an alkyne and a vinyl ketone (which derive directly from carboxylic acids). Syntheses of tetrahydrodicranenone B and rosaprostol illustrate the new strategy.

Capillary electrophoretic separation of N-acetylcysteine and its impurities as a method for quality control of pharmaceuticals.

Capillary electrophoresis has been applied to separate and determine N-acetylcysteine (NAC) and related impurities. Determination conditions were found to be optimum with 100 mmol/l borate as the buffer, pH 8.40. The limit of detection was established for each substance examined. The method has been validated by examining linearity ranges, precision and repeatability. The method was used to determine the content of NAC in, and purity of, pharmaceutical preparations. The major impurities (N,N-diacetylcystine, N,S-diacetylcysteine and cystine) were determined at levels of 0.1%.

Synthesis and some properties of two salsalate derivatives.

The synthesis of esters of 2-hydroxy benzoic acid-2-carboxyphenyl ester (salsalate) with guaiacol for the treatment of inflammatory bronchopneumopathies is reported. The antiinflammatory, analgesic and antipyretic activities of these derivatives were evaluated, together with their antioxidant, mucolytic and broncho-bacteriostatic properties in comparison to acetylsalicylic acid.

2-[(3-Pyridinylmethyl)thio]pyrimidine derivatives: new bronchosecretolytic agents.

2-[(3-Pyridinylmethyl)thio]pyrimidine derivatives (1a-n) promote the excretion of phenol red into the mouse trachea, indicating an increased tracheobronchial secretion. Furthermore, 2-[(3-pyridinylmethyl)thio]pyrimidine (1a) (tasuldine) produces greater excretion of phenol red into the mouse trachea after systemic administration than the known bronchosecretolytic ambroxol. Compound 1a also reduces the viscosity of canine bronchial mucus. Compound 1a has been selected for clinical investigations.

DL-S-(2-[N-3-(2-oxo-tetrahydrothienyl)acetamido])-thioglycolic acid: a novel mucolytic agent of the class of homocysteine thiolactone derivatives.

The synthesis and the characterization of some DL-homocysteine thiolactone derivatives are described. Rabbits, affected by acute bronchitis, treated orally with the title compounds showed a considerable reduction of the viscosity of the bronchial mucus. DL-S-(2-[N-3-(2-oxo-tetrahydrothienyl)acetamido]]thioglycolic acid (RV 144, Dithiosteine) was the most active compound and was thus selected for further experimental studies. The structure elucidation, physical and chemical parameters of RV 144 (Dithiosteine) were determined.

[New 2,4-dibromo-6-(N-cyclohexyl-N-methyl)-aminomethylanilides of derivatives of cysteine and cystine with expectorant activity]. / Nuove 2,4-dibromo-6-(N-cicloesil-N-metil)aminometilanilidi di derivati della cisteina e della cistina ad attività espettorante.

New 2,4-dibromo-6-(N-cyclohexyl-N-methyl)aminomethylanilides of N-acetylcysteine and N-acetyl-S-carboxymethylcisteine derivatives, N-benzyloxycarbonylcysteine and N,N'-bisbenzyloxycarbonylcystine were synthesized. The compounds were tested for the expectorant activity in rabbit and mouse. N,N'-Bisbenzyloxycarbonylcystin-bis [2,4-dibromo-6-(N-cyclohexyl-N-methyl)aminomethyl]anilide (XIX) was selected for further investigations.

[Histochemical investigation on the mechanism of action of a synthetic mucolytic compound (Na 872 Cl): preliminary results]. / Indagine istochimica sul meccanismo d'azione di un mucolitico di sintesi (Na 872 Cl): risultati preliminarai.

A histochemical study about mucolytic capacity of Na872Cl compound revealed its action upon epitelial mucins of mouse colonic and tracheal mucosa but the results depend on the chemical type of fixative employed (formalin or acetone fixed sections); the mode of action especially regarding the influence of fixatives and the nature of sensitive substrates are discussed.