Risperidone Monolayer Penetration Of The Pump Tablets

In this paper, water-insoluble risperidone with low dose was selected as a model drug to prepare mono-layer osmotic pump tablets (MOPT). Then, pharmacokinetic study of risperidone mono-layer osmotic pump tablets was performed in six beagle dogs.For preparation of elementary osmotic pump tablets with the poorly water-soluble drug, citric acid was used to modulate the solubility of risperidone within the core. In this paper, Similarity factors (f₂) was used as the evaluation standard. Based on single-factor experiments, the amount of citric acid in the tablet core, the content of PEG 4000 in coating membrane and coating thickness were selected as the causal factors, the synthetical mark was used as the evaluation to optimize the formulations according to orthogonal experiment design. The results indicated that the optimal formulation had the excellent zero-order release character, good reproducibility of different batches, and its drug release was almost complete. The primary stability test showed that risperidone osmotic pump tablets were sensible to humidity, so the tablets should be stored hermetically.With the commercial common risperidone tablet as the reference, the pharmacokinetics study of self-prepared risperidone MOPT was performed in six Beagle dogs. With two-preparation and two-period crossover design, LC-MS-MS was employed to detect the plasma drug concentration of dogs administered with single dose. The pharmacokinetic parameters of the testing and reference tablets were as below: AUC_0-∞ were 101.32±20.18 and 116.01±24.38 (ng·h·mL^-1),ρ_max werel2.87±3.15 and 73.51±11.86 (ng·mL^-1), t_max were 3.70±0.52 and 0.71±0.10 (h), relative bioavailability was 89.74±21.79% of risperidone; AUC_0-∞ were 1409.92±141.39 and 1447.53±171.09 (ng·h·mL^-1),ρ_max were 86.37±6.26 and 200.42±29.68(ng·mL^-1), t_max were 9.2±0.41�'�0.71±0.10(h), relative bioavailability was 98.80±16.51% of 9-hydroxyrisperidone. AUC_0-∞ were 1511.99±159.51 and 1560.03±189.05 (ng·h·mL^-1),ρ_max were 94.24±7.18 and 270.58±38.28 (ng·mL^-1), t_max were 9.0±0.63 and 0.71±0.10 ( h ), relative bioavailability was 98.31±16.33% of active moity(risperidone+ 9-hydroxyrisperidone). The relation between in vitro drug release rate and in vivo drug release rate calculated, the results showed that the correlationship was excellent and the correlation factor was 0.9950.