In situ gels of Metoclopramide Hydrochloride for intranasal delivery: in vitro evaluation and in vivo pharmacokinetic study in rabbits.
Intranasal (IN) administration is a promising approach for rapid-onset delivery of medications and to circumvent their first-pass elimination when taken orally. Metoclopramide Hydrochloride (MET HCl) is a potent antiemetic, effective even for preventing emesis induced by cancer chemotherapy. The feasibility of developing an efficacious intranasal formulation of metoclopramide has been undertaken in this study. Formulations were modulated so as to have gelation at physiological ion content after intranasal administration. Gelation was determined by physical appearance. The mucoadhesive force in terms of detachment stress, determined using sheep nasal mucosal membrane, increased with increasing concentration of carbopol. The results of in vitro drug permeation studies across sheep nasal mucosa indicate that effective permeation could be significantly increased by using in situ gelling formulation with carbopol concentration 0.15% or greater. Histological examination did not detect any damage during in vitro permeation studies. Finally, the bioavailability study in rabbits revealed that the absolute bioavailability of MET HCl was significantly increased from 40.67% in the case of the oral drug solution to 54.61% in the case of the nasal in situ gel. This study points to the potential of mucoadhesive nasal in situ gel in terms of ease of administration, accuracy of dosing, prolonged nasal residence and improved drug bioavailability.
Mahajan
Hitendra S
HS
R.C. Patel Institute of Pharmaceutical Education and Research, Karvand Naka Shirpur, Dist Dhule, Shirpur 425405, India. hsmahajan@rediffmail.com
Gattani
Surendra
S
D000042:Absorption; D000179:Acrylates / Q000737:chemistry; D000268:Adhesiveness; D000281:Administration, Intranasal; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D005782:Gels; D008353:Mannitol / Q000737:chemistry; D008787:Metoclopramide / Q000008:administration & dosage / Q000493:pharmacokinetics; D009297:Nasal Mucosa / Q000378:metabolism*; D010539:Permeability; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D011817:Rabbits; D033081:Shear Strength; D012756:Sheep; D014018:Tissue Distribution; D014783:Viscosity
D000179:Acrylates; D000932:Antiemetics; D004337:Drug Carriers; D005782:Gels; D011135:Polysaccharides, Bacterial; D008353:Mannitol; C048288:gellan gum; C453622:carbopol 934P; D008787:Metoclopramide