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Background The time rhythm of human body is associated with the occurrence and development of manydiseases, and it also affects the efficacy and pharmacokinetic characteristics of the corresponding therapeuticdrugs. Therefore, the chronopharmacological drug delivery system has potential applications. Aim In this work, it is proposed to develop a kind of pulsatile release tablet of simple structure and preparingprocess, thus to provide an alternative drug delivery system for therapeutic agents used in treatment of diseasesof typical onset biorhythm at period inconvenient to take drug.Methods Metoprolol tartrate (MT), a drug widely used clinically to treat cardiovascular diseases was selected asa model drug for developing pulsatile tablets of time-controlled explosive system (TES). The MT pulsatile tabletswere ethyl cellulose (EC) coating tablets produced by pan coating process, and the core tablets were preparedby direct compression. The formulation and process was optimized by single factor test and orthogonal design.Also, the pulsatile release mechanism of the tablets was discussed through investigating the water absorptionand swelling capacity of tablets as well as the mechanical properties of EC free film.Results A kind of pulsatile tablets of MT were developed with a drug release lag time around 7 h and a fastrelease of drug after lag time. When the swelling force of core tablet caused by water uptake was high enoughover the tensile strength of EC coating film, the MT pulsatile tablets demonstrated a shell-type exploding rupturedue to the great rigidity and weak flexibility of EC film, and then a fast pulsatile release of drug was observed.Both the swelling capacity of core tablet and the thickness of coating film together controlled the lag time of drugrelease. The lag time showed a good linear relationship with the thickness of coating film (r = 0.9984, P < 0.01).The sort and amount of fillers and disintegrants dominated the release behaviour after lag time.Conclusion The developed MT pulsatile tablets can exert a timely release of drug before peak onset period ofhypertension and angina pectoris early in the morning after drug taking around 22:00 P.M the night before. Thegood linear relationship between lag time and coating thickness enabled the pulsatile tablets to be used fordelivery of other therapeutic agents of similar chronotherapy demand by adjusting the coating thickness toachieve the appropriate lag time of drug release to match the different high attack rhythm of the exact diseases.
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Background Apocynin, a main component extracted from the root of Picrorhiza kurroa Royle, was a well-knownNADPH oxidase inhibitor and reported to have effect on lung injury, liver injury, diabetes and asthma. AN-1, anitrone derivative of apocynin, was found to exhibit significant effect on treatment of acute lung injury.Aim In order to carry out further preclinical study, it is important to reveal in vivo disposition of AN-1. A simple andrapid high-performance liquid chromatography (HPLC) method was developed to disclose the tissue distributionbehavior of AN-1 in Sprague-Dawley (SD) rats.Methods A HPLC method was developed and validated to measure the concentration of AN-1 in tissue sampleswith carbamazepine as internal standard (IS). The mobile phase consisted of water and methanol (47:53, v/v), theflow rate was 1 mL/min, and an ultraviolet (UV) detector was used at wavelength of 279 nm. The tissue distributionstudy of AN-1 was performed in Sprague-Dawley (SD) rats after a single intravenous dose of 40 mg/kg.Results The developed HPLC-UV method was of good specificity, precision (< 4%), accuracy (90-97%) and recovery(88-104%) for analysis of AN-1 in tissue samples of rats. The linear range was established over a concentrationrange 0.2-50 µg/mL (r2 > 0.998) in tissues including heart, liver, spleen, lung, kidney and brain. After administration,AN-1 was rapidly distributed in tissues and reached peak concentration with time, which showed a high distribution
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Background Apocynin (4-hydroxy-3-methoxyacetophenone), an important active ingredient contained in root ofPicrorhiza kurroa Royle, has been widely investigated as an antioxidative and anti-inflammatory agent in kinds ofdisease models, and exerted certain efficacy deserving further research. However, little was known about thedisposal process of apocynin in vivo, which is important information required in drug research and development.Aim In this work, a tissue distribution study of apocynin was performed in Sprague-Dawley (SD) male rats to helpfurther understanding well the disposition of apocynin in vivo.Methods A simple HPLC-UV method was developed for measurement of apocynin concentration in rat tissues. Amixture of water-methanol (47:53, v/v) was used as solvent system, the flow rate was 1 mL/min, and the detectedwavelength was 279 nm. The method was validated and applied to the tissue distribution study of a single bolusintravenous administration of apocynin in SD male rats.Results The developed HPLC-UV method showed good specificity, precision, accuracy and extraction recovery. Thegood linearity was achieved within 0.8-32 μg/mL in tissues including heart, liver, spleen, lung, kidney and brain. Thelower limit of quantification (LLOQ) was 0.8 μg/mL. The method was well used in the study of tissue distribution ofapocynin. The results demonstrated that apocynin was distributed fast into the tested tissues and reached peakconcentration at 5 min after injection. Apocynin was mainly distributed in liver, kidney and lung within 15 minutesafter administration, and eliminated from the tissues with no sample be detected more than 2 h after dose