Formulation and Evaluation of Mucoadhesive Microspheres for Nasal Drug Delivery

Terbutaline sulphate loaded microspheres were prepared for Nasal administration with the aim of avoiding first pass effect. The microspheres were prepared by a water-in-oil (w/o) emulsification-cross-linking technique by using chitosan as a mucoadhesive polymer, liquid paraffin (heavy and light, ratio 1:1) as a external phase, dioctyl sodium sulfosuccinate (0.2% w/v) as a stabilizer, volume of cross-linking agent (Glutaraldehyde, 25% solution, 1 mL) and time of cross linking 2 hrs. A 23 full factorial design was constructed to study the effect of three independent variables i.e. drug: polymer ratio (X1), volume of cross linking agent (ml) (X2), cross linking time (Hrs)(X3) while Particle size of the microspheres (Y1) and In vitro mucoadhesion (Y2) were taken as response parameters as the dependent variables. Particle size was found to be 26.11 ± 1.98 mm, which is favorable for intranasal absorption. The shape and surface characteristics were determined by scanning electron microscopy (SEM) which depicted the spherical nature and nearly smooth surfaces of the microspheres. The percentage encapsulation efficiency was found to be 74.4 ± 0.604%. In vitro mucoadhesion was performed using sheep nasal mucosa and was observed 72.32 ± 0.25%. FTIR Spectroscopy indicates characteristic peaks of the functional groups present in the drug, Differential scanning calorimetry and X-ray diffraction results indicated a molecular level dispersion of Terbutaline sulphate in the microspheres. In vitro release studies in pH 6.2 phosphate buffer indicated the mechanism of drug release was of zero order.