title: Mucoadhesive chitosan microspheres of carvedilol for nasal administration.
abstract: The aim of the present study was to develop and characterize chitosan mucoadhesive microspheres of carvedilol (CRV) for nasal delivery to improve bioavailability for treatment of hypertension and angina pectoris. The microspheres were prepared by emulsification-cross-linking method and evaluated for size, shape, entrapment efficiency (EE), in vitro mucoadhesion, in vitro drug release, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The mucoadhesive properties were also evaluated by Freundlich and Langmuir adsorption isotherms. In vivo tests were carried out in rabbits. The microspheres were spherical with size of 20-50 microm, which is favorable for intranasal absorption. The EE was observed from 42% to 68% while percentage mucoadhesion was from 74% to 88%. A strong interaction between mucin and chitosan microspheres was detected explaining adsorption with electrostatic interaction. The microspheres released around 75% of drug in 8 h. DSC and XRD studies revealed that CRV was molecularly dispersed. The absorption rate was rapid and the absolute bioavailability was high, 72.29%. The gamma scintigraphy indicated that the microspheres cleared slowly from the nasal cavity. It was concluded that chitosan microspheres could be used to deliver CRV following nasal administration for improving the bioavailability.
authors.affiliation: New Drug Delivery Systems Laboratory, TIFAC Center of Relevance and Excellence in NDDS, Pharmacy Department, The M. S. University of Baroda, Fatehgunj, Vadodara-390002, Gujarat, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Patil
authors.forename: Anil
authors.initials: A
authors.lastname: Babbar
authors.forename: Rashi
authors.initials: R
authors.lastname: Mathur
authors.forename: Anil
authors.initials: A
authors.lastname: Mishra
authors.forename: Krutika
authors.initials: K
authors.lastname: Sawant
mesh_terms: D000281:Administration, Intranasal; D000327:Adsorption; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D002152:Calorimetry, Differential Scanning; D002227:Carbazoles / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D000077261:Carvedilol; D048271:Chitosan / Q000737:chemistry*; D008863:Microspheres; D009077:Mucins / Q000737:chemistry; D009297:Nasal Mucosa / Q000378:metabolism*; D011412:Propanolamines / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D011817:Rabbits; D055672:Static Electricity; D014961:X-Ray Diffraction
chemical_list: D000959:Antihypertensive Agents; D002227:Carbazoles; D009077:Mucins; D011412:Propanolamines; D000077261:Carvedilol; D048271:Chitosan