A sustain-release lipid-liquid crystal containing risperidone based on glycerol monooleate, glycerol dioleate, and glycerol trioleate: In-vitro evaluation and pharmacokinetics in rabbits

The present study intends to develop an in-situ forming gel (ISFG) vehicle for the sustained and gradual delivery of risperidone to schizophrenic patients for longer drug dosing intervals. Initial burst release (IBR) was evaluated for the lipid liquid crystals (LLCs) containing glycerol monooleate (GMO), glycerol dioleate (GDO), and glycerol trioleate (GTO), along with different percentages of phosphatidylcholine (PC) as the oil phase, and N-methyl-2-pyrrolidone (NMP) as the solvent. In vitro evaluations, pharmacokinetics, and histopathological studies in rabbits were done to find the optimal LLC formulation. The formulation containing GDO had lower IBR in comparison with the other formulations, including Risperdal CONSTA®. Microscopy assessment indicated that the structures of LLC formulations containing GMO, GDO, and GTO cubic (Q2) were hexagonal (HII) and an intermediate form of HII and Q2, respectively. Comparison of the pharmacokinetic data showed that the optimal LLC containing GDO/PC with the ratio of 2.2:1 and 30% NMP created more consistent release profiles in vitro and in vivo during 60 days. Histopathology results in rabbits showed almost no side effects for the formulations. This study emphasized the better drug delivery potential of GDO-based gel-forming systems compared to Risperdal CONSTA®, which would increase patient compliance and decrease the inconvenience of frequent drug oral administrations.