Development of oral solid self-emulsifying lipid formulations of risperidone with improved in vitro dissolution and digestion.
Liquid adsorption on solid adsorbent carriers is an emerging technique for oral lipid-based drug delivery systems. The purpose of the current study is to convert liquid into solid self-emulsifying lipid formulations (SELFs) using an inorganic adsorbent Neusilin® grade US2 (NUS2) and investigate in vitro dissolution and digestion performance of the model antipsychotic compound risperidone.


METHODS
The liquid SELFs were designed using various oils, nonionic surfactants and converted into solid at various SELF: NUS2 (%m/m) mixing ratios. The characterization of solid SELF powder was performed by using SEM, XRD, FT-IR & DSC to investigate the physical nature of the drug. The in vitro dissolution experiments were conducted to compare the representative formulations with marketed product risperdal®. In vitro digestion experiments were performed using a pH-stat at pH 6.8 for 30mins to predict the fate of risperidone in the GI tract after exposure of the solid SELF to pancreatic enzymes and bile.


RESULTS
The results from the characterization studies showed that NUS2 with SELF at 1:1 (%m/m) yield superior flowability of the powder. The SEM revealed that pure risperidone was in irregular crystal shape whereas the drug loaded solid SELFs were in smooth regular shape. The XRD and DSC analyses of pure risperidone also confirmed the intense peaks due to the native crystalline form of the drug. However, the absence of sharp peaks in solid SELFs indicated the amorphous form of the drug. From the dissolution studies it was found that solid SELFs provided significant release profiles (>95%) compared to marketed product risperdal®. The digestion experiments suggested that risperidone was in a supersaturated state which could be maintained in the presence of mixed bile salt micelles.


CONCLUSIONS
Solid SELF of risperidone with improved dissolution and digestion profile was successfully prepared using Neusilin® US2 as an adsorbent carrier.
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: mkazi@ksu.edu.sa.
Mohsin
M
Kazi
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Hassan
H
Al-Qarni
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Fars K
FK
Alanazi
D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D010316:Particle Size; D018967:Risperidone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D004655:Emulsions; D005079:Excipients; D008055:Lipids; D018967:Risperidone
In vitro dissolution and lipolysis; Lipid-based self-emulsifying formulations; Risperidone; Solidification technique