Preparation of ion-activated in situ gel systems of scopolamine hydrobromide and evaluation of its antimotion sickness efficacy.
OBJECTIVE
To develop a novel, in situ gel system for nasal delivery of scopolamine hydrobromide (SCOP) and study its efficacy on motion sickness.


METHODS
SCOP in situ gels at 0.2%, 0.5%, and 1.0% gellan gum concentration (w/v) were prepared, respectively, and characterized in terms of viscosity, in vitro release, and nasal ciliotoxicity. Single photon emission computing tomography technique was used to evaluate the nasal residence time of gel containing (99m)Tc tracer. The antimotion sickness efficacy produced by the in situ gel formulation was investigated in rats and compared with those achieved after subcutaneous and oral administration.


RESULTS
The viscosity of the gellan gum formulations either in solution or in gel increased with increasing concentrations of gellan gum. Its release in vitro was moderate in artificial nasal fluid. The micrographic results showed that in situ gels were safe, without nasal ciliotoxicity. In comparison with phosphate buffer saline, a prolonged radioactivity of (99m)Tc in the rabbit nasal cavity was observed after administration of the gellan gum formulation. Intranasal SCOP in situ gel at a dose of 100 microg/kg decreased symptoms of motion sickness significantly in comparison with subcutaneous and oral administration (P<0.01).


CONCLUSIONS
SCOP nasal in situ gel is a safe and promising therapeutic alternative to existing medications for motion sickness.
Cao
Shi-lei
SL
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China.
Zhang
Qi-zhi
QZ
Jiang
Xin-guo
XG
D000281:Administration, Intranasal; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D002923:Cilia / Q000187:drug effects; D005079:Excipients; D005782:Gels; D008297:Male; D009041:Motion Sickness / Q000188:drug therapy*; D009297:Nasal Mucosa / Q000378:metabolism; D011135:Polysaccharides, Bacterial; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D014783:Viscosity
D000932:Antiemetics; D005079:Excipients; D005782:Gels; D011135:Polysaccharides, Bacterial; C048288:gellan gum; D012601:Scopolamine