Pediatric Suppositories of Sulpiride Solid Dispersion for Treatment of Tourette Syndrome: In Vitro and In Vivo Investigations
Journal Title: AAPS PharmSciTech - Year 2015, Vol 16, Issue 3
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.
Authors and Affiliations
Ahmed S. Zidan, Sherif E. Emam, Tamer M. Shehata, Fakhr-eldin S. Ghazy
Keywords
Related Articles
- EP ID EP682250
- DOI 10.1208/s12249-014-0250-4
- Views 65
- Downloads 0
Model Drug as Pore Former for Controlled Release of Water-Soluble Metoprolol Succinate from Ethylcellulose-Coated Pellets Without Lag Phase: Opportunities and Challenges
The objective of the present study was to evaluate the feasibility of using model drug metoprolol succinate (MS) as a pore former to modify the initial lag phase (i.e., a slow or non-release phase in the first 1–...
Mechanisms of Pharmaceutical Aerosol Deposition in the Respiratory Tract
Aerosol delivery is noninvasive and is effective in much lower doses than required for oral administration. Currently, there are several types of therapeutic aerosol delivery systems, including the pressurized metered-do...
Biodegradable Injectable In Situ Implants and Microparticles for Sustained Release of Montelukast: In Vitro Release, Pharmacokinetics, and Stability
The objective of this study was to investigate the sustained release of a hydrophilic drug, montelukast (MK), from two biodegradable polymeric drug delivery systems, in situ implant (ISI) and in situ microparticles (ISM)...
The Effect of Streptozotocin and Alloxan on the mRNA Expression of Rat Hepatic Transporters In Vivo
The effect of streptozotocin (STZ) and alloxan (ALX) on the hepatic messenger RNA (mRNA) expression of four transporters (Mrp2, Mdr1, Oct1, and Oatp1) was studied in the present work. After the healthy male Wistar rats w...
Quality-by-Design II: Application of Quantitative Risk Analysis to the Formulation of Ciprofloxacin Tablets
The online version of this article (doi:10.1208/s12249-015-0349-2) contains supplementary material, which is available to authorized users.