Studies On Enteric-coated Sustained Release Preparation Of Paroxetine Hydrochloride

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) currently used as an antidepressant drug [1–3]. The lower acute toxicity and improved tolerability of SSRI compared to previously frequently use tri- and tetra-cyclic antidepressants have been major reasons for the recommendation of its use as first-line treatment of depression in the elderly [2]. In this article, the preparation of enteric-coated sustained release tablets and pellets were included to avoid the gastrointestinal tract irritation.In this study, UV spectrophotometry was used for assay the partition coefficient and solubility of paroxetine. The experiment results showed that paroxetine is easily soluble in water, 0.lmol/L HCl aqueous solution, and pH7.5 TRIS-NaCl buffer solutions. The n-octanol/water partition coefficients increase with pH rising in various physiological pH solutions. And HPLC method was used for in vitro assay during the studies of release and content in tablets and pellets.Based on single factor investigation and orthogonal design, Hydroxy-propylmethyl cellulose and cellulose microcrystallisate were used to make the sustained tablet core by wet granulation compression; the wetting agent and the compression pressure can make paroxetine release rate change. Based on the quality investigation of the sustained release tablets, the self-prepared tablets between batches have good reproducibility of drug release behavior. The conditions affecting drug release were investigated. No significant difference in drug release behavior was observed for release study by using basket or paddle method. The mechanism of drug release from this sustained release tablet was investigated. Drug release rate followed the Higuchi equation. And the releasing parameter of the Ritger-Peppas equation equaling to 0.7632(0.45 < n < 0. 89) meant that the release mechanism was a synergism of diffusion and matrix erosion.The sustained release tablets were coated with Eudragit L100 to avoid to be destroying in the gastric juice. The coating formulation was optimized, having good resistance to acid and the dissolution of the tablet can last 5 hours in artificial intestinal liquid.The result of stability test showed that the enteric-coated tablet was unstable when exposed to strong light and high temperature. The appearance and drug release did not change, but the quantity decrease significantly. As it exposed to 75% humidity condition, drug release change and quantity decrease slightly.A fluid-bed spray processor was adopted for coating the pellets. Based on single factor investigation, the coating process variables of drug lay, sustained release lay, and enteric-coated lay were determined. Ethyl cellulose was selected as the main material for sustained release lay. And the categories and dosage of ethyl cellulose, curing time, etc were investigated. The coating formulation was optimized; the dissolution of the pellets can last 5 hours in artificial intestinal liquid. Eudragit L100 was selected for the excellent drug release. The coating formulation was optimized, having good resistance to acid and quickly dissolving in artificial intestinal liquid. The anti-tacking agent talc, curing time were studied.