Preparation, release and pharmacokinetics of a risperidone elementary osmotic pump system

Abstract

Preparation and in vitro/in vivo evaluation of risperidone elementary osmotic pump (RIS-EOP) formulations were investigated. A method for the preparation of RIS-EOP tablets was developed by modulating RIS solubility with citric acid. The influence of osmotic agents and the compositions of semipermeable membrane on drug release profiles was evaluated. The formulation of RIS-EOP was optimized by orthogonal design. The in vitro release profile of the optimum formulation achieved to deliver RIS at an approximate zero-order up to 12 h. The pharmacokinetic profiles of RIS-EOP were evaluated compared with immediate release tablets in beagle dogs. The mean tmax and mean residence time of RIS-EOP for RIS and its active metabolite, 9-hydroxyrisperidone, were remarkably longer, compared with immediate release tablets. These results corroborated prolonged release of RIS from EOP formulations. Moreover, drug plasma levels with lower fluctuations could be achieved with RIS-EOP tablets. These results suggested that increasing drug solubility by adding or reacting with alkali/acid might be used for the preparation of EOP tablets of certain poorly water-soluble drugs.

Synchronous delivery of felodipine and metoprolol tartrate using monolithic osmotic pump technology

“…It could be indicated from the results in Figure 4 (F7 with 10 % coating weight, F10 with 11 % coating weight and F11 with 12 % coating weight) that the releases of both felodipine and metoprolol tartrate were reduced markedly with the increase of weight gain since f 2 among the release profiles of felodipine or metoprolol tartrate from different tablets were all below 50. This was perhaps related to the slower rate of water hydration and drug permeability caused by thicker coating layer 39 . As other factors decreasing drug release, higher coating gain also reduced the disparity in the release of felodipine and metoprolol tartrate since J U S T A C C E P T E D most agents lowering drug release usually had more fervent effect on water highly soluble metoprolol tartrate than water insoluble felodipine.…”

Preparation and evaluation of bilayer-core osmotic pump tablets contained topiramate

“…For further formulation optimization, single-factor experiments were carried out to screen the main formulation factors that affecting the drug release [10][11][12]19] greatly. Before the conducts of the single-factor experiment, formulation factors (e.g.…”

“…In order to achieve a constant plasma level, controlled drug delivery systems such as osmotic pump system can be utilized, which can release drugs at an approximate constant rate up to 24 h [11]. Distinguished by its ability to release drugs independently of the environment media composition and hydrodynamics, osmotic pump has many advantages, such as reducing the risk of adverse reactions, increasing the treatment tolerances of patients, diminishing the food effects and possessing comparable in vitro/in vivo drug release features [7,12]. Thereby, in the past several decades, various types of osmotic pump systems have been developed to deliver drugs with different aqueous solubilities [13].…”

Physiologically Based Pharmacokinetic Modeling to Understand the Absorption of Risperidone Orodispersible Film

“…Risperidone, a benzisoxazole derivative, is a secondgeneration antipsychotics which has a high affinity for multiple receptors including 5-HT 2A serotonin, D 2 dopamine, a 1 , a 2 adrenergic, and histamine receptors (Huang et al, 1993;Megens et al, 1994;Meuldermans et al, 1994;Gong et al, 2015). Risperidone has been widely used for acute and chronic schizophrenia (Huang et al, 1993;Mannens et al, 1993;Gong et al, 2015;Narayan et al, 2016). It can also alleviate the symptoms of schizophrenia and improve the social and personal performance (Huang et al, 1993;de Leon et al, 2010).…”