title: Optimization of combinational intranasal drug delivery system for the management of migraine by using statistical design.
abstract: Migraine is a chronic disorder characterized by significant headache and various associated symptoms which worsen with exertion. Zolmitriptan approved for use in the acute treatment of migraine and related vascular headaches but are limited by high pain recurrence due to rapid drug elimination. Combinationalformulationof triptans and a nonsteroidal anti-inflammatory drug may provide a quicker and longer duration of relief from the subsequent pain during the attack. In this study, we formulate a Zolmitriptan (ZT) & ketorolac tromethamine (KT) loaded thermo reversible in-situ mucoadhesive intranasal gel (TMISG) formulation which gels at the nasal mucosal temperature and contains a bioadhesive polymer (Xyloglucan) that lengthens the residence time will enhance the bioavailability of the combinational drugs. This study uses Box-Behnken design for the first time to develop, optimize the TMISG and assess factors affecting the critical quality attributes. Histopathological study of the nasal mucosa suggested that the formulation was safe for nasal administration. The statistical difference in absolute bioavailability between oral and intranasal route suggested that intranasal route had almost 21% increases in bioavailability for ZT and for KT there was 16% increase over oral formulations. Optimized formulation would help mitigate migraine associated symptoms much better over the currently available formulations.
authors: Department of Pharmaceutical Quality Assurance, I.S.F. College of Pharmacy, Moga 142001, Punjab, India.
authors: Animesh
authors: A
authors: Kumar
authors: Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga 142001, Punjab, India.
authors: Tarun
authors: T
authors: Garg
authors: Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga 142001, Punjab, India.
authors: Ganti S
authors: GS
authors: Sarma
authors: Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga 142001, Punjab, India.
authors: Goutam
authors: G
authors: Rath
authors: Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga 142001, Punjab, India. Electronic address: amitkumargoyal1979@gmail.com.
authors: Amit Kumar
authors: AK
authors: Goyal
mesh_terms: D000269:Adhesives / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000281:Administration, Intranasal; D000818:Animals; D019468:Disease Management; D016503:Drug Delivery Systems / Q000379:methods*; D005782:Gels; D020910:Ketorolac / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D008881:Migraine Disorders / Q000188:drug therapy / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D012756:Sheep; D014363:Tryptamines / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000269:Adhesives; D005782:Gels; D023303:Oxazolidinones; D014363:Tryptamines; C089750:zolmitriptan; D020910:Ketorolac
keywords: Bioavailability; Box-Behnken design; Controlled drug delivery; Muco-adhesion; Nasal drug delivery