Pediatric Suppositories of Sulpiride Solid Dispersion for Treatment of Tourette Syndrome: In Vitro and In Vivo Investigations

Abstract

Abstract. Pharmaceutical development was adopted in the current study to propose a pediatric rectal formulation of sulpiride as a substitute to the available oral or parenteral formulations in the management of Tourette syndrome (TS). The goal was to formulate a product that is easy to use, stable, and highly bioavailable and to achieve a rapid clinical efficacy. Towards this aim, sulpiride solid dispersion (SD) with tartaric acid at a weight ratio of 1:0.25 was incorporated into different suppository bases, namely witepsol W25, witepsol H15, witepsol E75, suppocire NA, suppocire A, glycerogelatin, and polyethylene glycols. The formulae were evaluated in vitro using different pharmacotechnical methods such as visual, melting, weight and content uniformities, drug release, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray diffraction (XRD) analyses. In vivo bioavailability was also assessed in rabbits to compare the bioavailability of either raw sulpiride-incorporated or its SD-incorporated witepsol H15-based suppositories to its oral suspension (reference). Sulpiride SD-incorporated witepsol H15 formulation showed acceptable in vitro characteristics with a bioavailability of 117% relative to oral dosing, which excel that in humans (27% after dosing of oral product). In addition, the proposed formula not only passed the 6-month stability study but also proposed a promising scale-up approach. Hence, it showed a great potential for pediatric product development to manage TS in rural areas.

In vitro dissolution/release methods for mucosal delivery systems

“…Another setup includes the use of a glass cylinder containing the formulation, sealed at the bottom with the semipermeable membrane and vertically immersed into the dissolution medium. Such apparatus is used for in vitro release testing of rectal suppositories [49].…”

Solid Lipid Nanoparticles of Sulpiride: Improvement of Pharmacokinetic Properties

“…Animals were divided into two groups (n=4); the first group was administered Sul suspension while the second group received Sul SLNs (10% SA, 2.5% P188, 2% soy lecithin and 1% Sul) at a dose of 20 mg/Kg. 1 Blood samples were withdrawn at different time intervals from the sinus orbital and centrifuged at 3000 rpm for 10 min to separate the plasma which was stored at -20°C for analysis.…”

“…The amount of Sul in each sample was analyzed at room temperature according to Zidan et al after modification and validation. 1 The plasma (1 ml) was spiked with 0.1 ml of internal standard (metoclopramide 1.5 μg/ml in mobile phase) and 0.1 ml of a NaOH solution (1 N) with vortex mixing for 2 min. Then, mixing with 6 ml of ethyl acetate/ dichloromethane (5:1, v/v) and centrifuged at 3000 rpm for 10 min.…”

“…Previous studies claimed that Sul has a low bioavailability of 27% after oral administration. 1 Hence, in order to improve the bioavailability of Sul; different strategies have been investigated, including solid dispersion, microemulsion and nanoparticles. [1][2][3] Incorporation of drugs into nanoparticles boosts the bioavailability, prolongs plasma levels and minimizes the variability in the therapeutic outcome.…”

“…1 Hence, in order to improve the bioavailability of Sul; different strategies have been investigated, including solid dispersion, microemulsion and nanoparticles. [1][2][3] Incorporation of drugs into nanoparticles boosts the bioavailability, prolongs plasma levels and minimizes the variability in the therapeutic outcome. Among nanoparticles, Solid Lipid Nanoparticles (SLNs) were designed to encompass the merits of polymeric particles, liposomes and emulsions while circumventing some of their drawbacks.…”