ABSTRACT
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.
ABSTRACT
AIM : To prepare a phase-specific drug delivery system withfloating and pulsatile release of sinome-nine hydrochloride and evaluate in vitro drug release behavior. METHODS: The floating and pulsatile-release of coat-core tablets were prepared by press-coated technics. The effects of factors influencing release characteristic of the drug were investigated by dissolution test, and to elucidate the mechanism of drug releaseof the tablets with erosion and water-uptake test. RESULTS: The tablets had typical floating and pulsatile release properties with a lag time rapid release. The lag-time was shortened with the increase of expansion ratio of tablet core and rotation speed of stirrer. The lag-time was prolonged with the increase of pH and ionic strength of dissolution media.CONCLUSION: The tablet could float and rapidly release drug at the predetermined time.
ABSTRACT
Pulsatile drug delivery system,capable of releasing drug at the predetermined times according to clinical therapeutic requirements,can be used to treat several rhythmic diseases.Majority of individuals experience the rise in the blood pressure in the early morning hours,which potentially leads to serious cardiovascular complications.The purpose of the study was to develop pulsatile candesartan cilexetil core-in-cup tablets according to human circadian rhythm of blood pressure.The factors influencing t_(lag) were evaluated by in vitro drug release and tablet erosion observations.In addition,the jugular artery pressures vs times courses of rabbits were recorded after oral administration of commercial candesartan cilexetil tablets or the developed core-in-cup tablets.The quantity and characteristics of the excipients in top layers in the tablets were found to modify t_(lag).In vivo studies showed that the onset times indicating the decreases in the blood pressures of commercial tablets and core-in-cup tablets were (98 ± 17) min and (278 ±29) min,respevtively.In vivo t_(lag) of the prepared core-in-cup tablets was (180 ± 34) min in rabbits,which is consistent with the goal of design.
ABSTRACT
AIM: To prepare a phase-specific drug delivery system with floating and pulsatile release of sinomenine hydrochloride and evaluate in vitro drug release behavior. METHODS: The floating and pulsatile-release of coat-core tablets were prepared by press-coated technics.The effects of factors influencing release characteristic of the drug were investigated by dissolution test,and to elucidate the mechanism of drug release of the tablets with erosion and water-uptake test. RESULTS: The tablets had typical floating and pulsatile release properties with a lag time rapid release.The lag-time was shortened with the increase of expansion ratio of tablet core and rotation speed of stirrer.The lag-time was prolonged with the increase of pH and ionic strength of dissolution media. CONCLUSION: The tablet could float and rapidly release drug at the predetermined time.