Preparation and Pharmacokinetics of Huperzine A Micro-porous Osmotic Pump Pellets / 中国药学杂志

OBJECTIVE: To prepare huperzine A micro-porous osmotic pump pellets and to investigate the pharmacokinetic properties in Beagle dogs. METHODS: The extrusion-spheronisation method was used to prepare the core of huperzine A pellets which then coated by fluid-bed coating technology. Central composite design-response surface method was used to optimize the prescription of coating layer.Then Zero-order, First-order and Higuchi equation of cumulative release with time were fitted to study its release characteristics.The commercially available huperzine A tablets were used as reference preparations to investigate the in vivo pharmacokinetics of huperzine A micro-porous osmotic pump pellets, and the bioequivalence of the two preparations were compared. RESULTS: The formula of coating was optimized as followsEC of 61.5%, PEG400 of 10.5%. Zero-order kinetics existed in the release of the pellets in 24 h. Moreover, the osmotic pressure-controlled delivery was greatly responsible for drug release. In vivo study showed that tmax and ρmax of huperzine A micro-porous osmotic pump pellets were significantly lower than that of the reference preparation, and its t1/2 was significantly prolonged compared with the reference preparation, the relative bioavailability was 95.8%. CONCLUSION: Huperzine A micro-porous osmotic pump pellets had a better sustained release effect in the Beagle dog and have a good correlation in vivo.

Preparation and in vitro evaluation of pregabalin controlled porosity osmotic pump tablets / 中国药科大学学报

@#In this study, pregabalin controlled porosity osmotic pump tablets which are taken once a day were prepared. Single-factor tests were carried out to investigate the influence of excipients and manufacturing process. The formulation was optimized through orthogonal experiment on three levels of three significant factors including the amount of sodium citrate, and polyethylene glycol 400 and coating weight gain. On the basis of the results of the single-factor tests and the orthogonal experiment, optimal formulation and manufacturing process were obtained. The final tablet formulation contained pregabalin(82. 5 mg), microcrystalline cellulose(40%), sodium citrate(27. 5%), magnesium stearate(0. 5%)and 5% povidone K30 solution as the tablet binder; the coating formulation consisted of cellulose acetrate and 60% of polyethylene glycol 400 as a porogen; the coating weight gain was 3%. In vitro drug release kinetic study suggested that the drug release from controlled porosity osmotic pump tablets was mainly driven by osmotic pressure, which was barely affected by the pH of the release medium. The drug release behavior of the tablets within 12 hours complied with zero-order release rule and the linear correlation coefficient was 0. 991 6. The obtained porosity osmotic pump tablets could effectively slow the drug release rate, reduce concentration fluctuation and improve the safety and convenience for the patients, hence with broad prospects.

Preparation of microporous osmotic pump tablets of marine / 中国药科大学学报

Aim: To develop marine microporous osmotic pump tablets and to investigate drug release in vitro of the optimized formulation and the release mechanism.Methods: Wet granulation and film-coating were used to develop marine micro-osmotic pump tablets.In vitro release studies were applied to evaluate the impacts of various factors on the release of the formulation.Central-composite design was exploited to aid the optimization of the formulation,and the mechanism of in vitro release was characterized.Results: There existed fairly good reproducibility in the preparation of marine micro-osmotic pump tablets.It was found that no change in the release rate of the tablets were elicited by the pH of the release media,the rotating speed selected,the hardness of the tablet core,and the amount of the plasticizer incorporated into the coating formulation.It was proved that the release of marine micro-osmotic pump tablets was closely related to the magnitudes of NaCl amount in the tablet core and the pore former in the coating formulation as well as the coating level.In addition,there existed 12-hr zero-order kinetics in the in vitro release study of the tablets.Moreover,it was shown that the osmotic pressure-controlled delivery is greatly responsi-ble for the release of the developed tablets.Conclusion: The prepared marine microporons osmotic pump tablets are expected to be a new sustained-release medication.

Preparation and Drug Release Mechanism of Tetramethylpyrazine Phosphate Porosity Osmotic Tablet / 中国药房

OBJECTIVE:To prepare Tetramethylpyrazine phosphate porosity osmotic tablet (TMPP) and to optimize its formulation and investigate its mechanism of drug release. METHODS: The formulation was optimized by the orthogonal experiment design through investigation of one factor; the accumulative drug release rates of preparations of different formulation were measured, and the mechanism of drug release of the tablets was discussed. RESULTS: The dosage of PEG 400 in coating solution, the content of hydroxy-propyl methyl cellulose (HPMC) in tablet core, the dosage of dibutylphthalate as plasticizer, and the weight gain of coating membrane were four important factors influencing drug release. The optimal formulation was to use 10% of PEG400, 5% of HPMC, 10% of dibutylphthalate and 12 mg coating membrane. The release behavior in vitro of the porosity osmotic tablets prepared in the above condition within 10 h complied with zero order release rule(r=0.999 81), with accumulative release rate of 94.2%. The tablets had good reproducibility in interassay and which was independent of the influence of gastrointestinal condition. The mechanism of drug release included osmotic pump mechanism and diffusion mechanism, but osmotic pump one was the main type. CONCLUSION: The formulation and preparation technology of the porosity osmotic tablets were simple but effective, showing an obvious zero order release within 12 h and good reproducibility, thus suitable for the industrial production of porosity osmotic tablets.

Pharmacokinetics of zero-order release and first-order release of mono-compar tment drugs administered by non-parenteral route / 中国药理学通报

Aim To establish the pharmacokinetic principles of the zero-order release and the first-order release of mono-compartment drugs administered by non-parenteral route based on the release kinetics of the dosage forms and the intrinsic pharmacokinetic parameters of the active drug, such as the rate constants of the absorption and elimination, and the distribution volume of the drug. Methods By the Laplace transform and the compartmental analysis method, the pharmacokinetic behaviors of the zero-order release and the first-order release of mono-compartment drugs administered by non-parenteral routes were deduced with divisions of the dose being absorbed during the release phase and after the release has terminated. Results The pharmacokinetics of the non-parenteral administration of the zero-order release and the first-order release of mono-compartment drugs were established. Conclusion The pharmacokinetic theories of the zero-order release and the first-order release of mono-compartment drugs administered by non-parenteral route have been established. Since the zero-order release and the first-order release are the primary release patterns, the theory should be a key to explore the pharmacokinetics of the controlled/sustained release dosage forms.