ABSTRACT
Pharmacokinetics (PK) is the science of the kinetics of drug absorption, distribution and elimination. Statistical methods are usually used for PK parameter estimation producing nonlinear responses where drug effect mechanism is modeled using compartmental approach. In the present study, PK parameters were estimated with nonlinear fixed effects one compartment open model where drug dose and sampling time are covariates and the plasma drug concentration is dependent variable. The PK parameters namely absorption rate constant (a), elimination rate constant (b) and apparent volume of distribution (V) were estimated using nonlinear least square method for each individual separately and for all individuals collectively with longitudinal or multiple response plasma drug concentration-time data obtained from 24 healthy human volunteers with reference drug product of Atorvastatin. The estimates for combined data were â =0.13±0.13hr-1, =0.49±0.13hr-1, =248±0.05L. All the individuals were again stratified into three categories based on Body Mass Index (BMI) and the PK parameters were estimated for each stratum accordingly (stratum-normal: â=0.12±0.17hr-1, =0.47±0.17hr-1, =250.24±0.07L; stratum-overweight: â =0.15±0.24hr-1, =0.47±0.25hr-1, =267.25±0.09L; stratumunderweight: â =0.13±0.13hr-1, =0.49±0.13hr-1, =245±0.05L).
ABSTRACT
The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug by a solid dispersion technique, in order to investigate the effect of these polymers on release mechanism from solid dispersions. Diazepam was used as a model drug to evaluate its release characteristics from different matrices. Solid dispersions were prepared by using polyethylene glycol 6000 (PEG-6000), HPMC, HPC and Poloxamer in different drug-to-carrier ratios (1:2, 1:4, 1:6, 1:8, 1:10). The solid dispersions were prepared by solvent method. The pure drug and solid dispersions were characterized by in vitro dissolution study. Distilled water was used as dissolution media, 1000 ml of distilled water was used as dissolution medium in each dissolution basket at a temperature of 37°C and a paddle speed of 100 rpm. The very slow dissolution rate was observed for pure Diazepam and the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. SEM (Scan-ning Electron microscope) studies shows that the solid dispersion having a uniform dispersion. Solid dispersions prepared with PEG-6000, Poloxamer showed the highest improvement in wettability and dissolution rate of Diaze-pam. Solid dispersion containing polymer prepared with solvent method showed significant improvement in the release profile as compared to pure drug, Diazepam.
ABSTRACT
The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug by a solid dispersion technique, in order to investigate the effect of these polymers on release mechanism from solid dispersions. Diazepam was used as a model drug to evaluate its release characteristics from different matrices. Solid dispersions were prepared by using polyethylene glycol 6000 (PEG-6000), HPMC, HPC and Poloxamer in different drug-to-carrier ratios (1:2, 1:4, 1:6, 1:8, 1:10). The solid dispersions were prepared by solvent method. The pure drug and solid dispersions were characterized by in vitro dissolution study. Distilled water was used as dissolution media, 1000 ml of distilled water was used as dissolution medium in each dissolution basket at a temperature of 37°C and a paddle speed of 100 rpm. The very slow dissolution rate was observed for pure Diazepam and the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. SEM (Scan-ning Electron microscope) studies shows that the solid dispersion having a uniform dispersion. Solid dispersions prepared with PEG-6000, Poloxamer showed the highest improvement in wettability and dissolution rate of Diaze-pam. Solid dispersion containing polymer prepared with solvent method showed significant improvement in the release profile as compared to pure drug, Diazepam.