Development, optimization andin vitroevaluation of alginate mucoadhesive microspheres of carvedilol for nasal delivery

Abstract

The present research work was aimed at development and optimization of alginate mucoadhesive microspheres of carvedilol for nasal delivery to avoid first pass metabolism and to improve the therapeutic efficacy in the treatment of hypertension and angina pectoris. The microspheres were prepared by a water-in-oil (w/o) emulsification technique. A 2(3) factorial design was employed with drug : polymer ratio, calcium chloride concentration and cross-linking time as independent variables while particle size of the microspheres and in vitro mucoadhesion were the dependent variables. Regression analysis was performed to identify the best formulation conditions. Particle size was analysed by dynamic laser light diffraction technique and found to be in the range of 26.36-54.32 microm, which is favourable 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 in the range between 36.62-56.18. In vitro mucoadhesion was performed by adhesion number using sheep nasal mucosa and was observed in a range from 69.25-85.28. Differential scanning calorimetry and X-ray diffraction results indicated a molecular level dispersion of carvedilol in the microspheres. In vitro release studies in pH 6.2 phosphate buffer indicated non-Fickian or anomalous type of transport for the release of carvedilol from the microspheres.

Factorial design studies of antiretroviral drug-loaded stealth liposomal injectable: PEGylation, lyophilization and pharmacokinetic studies

“…Response surface modelling and evaluation of the quality of fit of the model for the current study were performed employing Design Expert Ò DX 8.0.7.1 trial version software (Dhiman et al 2008;Huang et al 2005;Patil and Sawant 2008). Polynomial models including linear, interaction and quadratic terms were generated for all the response variables using multiple linear regression analysis (MLRA).…”

Sustained release biodegradable solid lipid microparticles: Formulation, evaluation and statistical optimization by response surface methodology

“…Similarly, the interaction terms (X 1 X 3 ) and (X 2 X 3 ) were found to be negative, suggesting that the interaction of CW and GMS with T-20 was useful in decreasing/controlling the NEB release. Moreover, drug release studies at the gastric pH of 1.2 showed less than 10 % of NEB release, suggesting a gastro protective effect of lipids due to their insoluble nature, as also mentioned in the literature (26).…”

“…The EE and DL increased with an increase in lipid matrix concentration providing an equal increase in T-20 concentration as observed for F2, F3, F10 and F16. Formulations F3 and F9 had equal concentrations of CW and GMS but both formulations had different EE and DL because of the T-20 concentration difference applied in the preparation of these formulations (26). Formulations with lower percentage of CW or GMS at lower concentration of T-20 (F1, F12) showed minimum EE.…”

“…It was also observed that the connection between variables and observed responses was not linear. Furthermore, a change of more than one variable at the same time at different levels produced quite a different intensity of the response (24,26).…”

Formulation Development and in Vitro Evaluation of in Situ Lisinopril Gel for Nasal Administration

“…[1] In addition, nasal drug administration results in quick onset of action as compared to oral, sublingual and transdermal administrations area, porous endothelial basement membrane, highly vascularized epithelial layer, high total blood flow per cm 3, avoiding the first pass metabolism and easy access. [2] Nasal mucociliary clearance is one of the most important limiting factors for nasal drug delivery.…”