Studies On Salbutamol Sulfate Delayed-release Tablets

Chronopharmacology indicates that Asthma has daily rhythmicity. Asthma does not have a attack at the time to fall asleep. The disease is more pronounced in early morning, and since most of the patients need a peak value of drug concentration in plasma during nighttime or after waking up. Time-controlled systems are characterized by two release phases. The first phase is no or little drug being released, followed by the second phase, during which the drug is released completely within a short period of time after a lag time. According to rhythmicity of invasion, the patients can take drug ahead of schedule. Then the disease can be prevented, and drug adverse effect can be diminished. Tolerance is not to bring about, and the compliance of the patients enhance. It is a new mode of modern pharmaceutics study. In this paper, salbutamol sulfate time-controlled release press-coated tablet was prepared, and preparation technology, in vitro drug release performance and in vivo behavior were studied.In the current study, the external homogeneous barrier layer was composed of various PEG 6000-Eudragit S100 blends made by fusion method. Based on the results of single-factor tests, orthogonal tests were used to optimize the formulation. The result showed that the proportion of PEG 6000 influenced drug release significantly. The lag time was 4 h, achieving the aim of design. The stability test and influential factor experiment were investigated, and the results showed that SS time-controlled release press-coated tablets were unstable under high temperature (60℃) and high humidity (RH92.5%), whereas good stability was found under light, the accelerating test and room temperature. So the tablets should be stored seal up and dry.Fourier transform infrared (FTIR) analysis, differential scanning calorimetric (DSC) and powder X-ray diffraction (PXRD) were carried out to characterize PEG 6000-Eudragit S100 polymer blends. The results indicated that the two polymers were complete miscibility and a new polymer matrix was formed.γ-Scintigraphy was used for the study of in vivo performance of 99mTcO4- labeled SS time-controlled release press-coated tablets. As the results have shown, the tablets can release the drug after lag time, achieving the aim of design. It was correlated with direct observation of in vitro dissolution.HPLC with fluorescence detection method was preformed to detect the concentration of SS in plasma of beagle dogs and using quick release core tablets as the reference. Pharmacokinetics study of SS time-controlled release tablets were performed in three healthy beagle dogs. Compare with quick release core tablets, Tmax was delayed and SS time-controlled release tablets had conspicuous delayed release characteristics. There was good delayed release effect in beagle dogs. For reference tablets and time-controlled release tablets, Cmax was 9.61 ng·mL-1 and 8.29 ng·mL-1; Tmax was 1.83 h and 7.33 h respectively. The other pharmacokinetic parameters had no difference.