Evaluation of carvedilol-loaded microsponges with nanometric pores using response surface methodology

Abstract

This study demonstrates the use of factorial design for the preparation of microsponges of carvedilol with nanometric pores using the response surface methodology and to establish the functional relationships between two operating variables of Eudragit RS100 and sucrose. The response variables selected for this study were percent drug entrapment (Y1), time taken to release 35% of drug (Y2), percent drug release after 24 h (Y3), percent dissolution efficiency (DE) (Y4) and the angle of repose (Y5). The overall calculated desirability was found to be 0.8065 for the optimised formulation OF1. The response surface analysis of the desirability function with the independent levels indicated that the overall desirability increases with high levels of Eudragit RS100 and sucrose content. The optimum robust formulation (OF1) contains high levels of Eudragit RS100 (400.0 mg) and sucrose (350.21 mg), satisfying the predetermined constraints and goals of all the selected response variables. The scanning electron microscopy of OF1 indicated the spherical shape of microsponges with numerous pores on the surface. The atomic force microscopic study suggested the presence of nanometric pores on the surface of microsponges which may facilitate the release of the drug. Compatibility studies using the Fourier transform infrared spectroscopy, X-ray diffraction and differential scanning calorimeter indicated the absence of any incompatibility between carvedilol and excipients used to prepare microsponges.

Microsponge: An emerging drug delivery strategy

“…Dispersion is centrifuged for sufficient time for complete solubilization of entrapped drug and supernatant is analyzed with suitable analytical technique. The percent loading efficiency can be calculated using the following formula (Osmani et al, ; Saini, Singh, & Verma, ). …”

“…Thin Layer Chromatography (TLC) and Fourier Transform Infra‐Red (FTIR) spectroscopy are used to study the compatibility of the drug with other formulation ingredients. Powder X‐ray diffraction (XRD) and Differential Scanning Colorimetry (DSC) techniques can be used to study thermal analysis and polymerization effect on crystallinity (Osmani, Aloorkar, Thaware, et al, ; Saini et al, ).…”

“…The increase in drug: polymer ratio indicates the increase in the amount of polymer in the microsponges. More amount of polymer in microsponges thickens the matrix network, minimizing the drug release (Saini et al, ). Suitable dissolution apparatus is used to perform the drug release.…”

Morphological and in vitro investigation of core–shell nanostructures of carvedilol using quality by design

“…The technique of optimization of pharmaceutical formulations is primarily focused to decide the levels of the variable from which a robust formulation with excellent characteristics can be evolved (Saini et al 2012) . A few of the measured responses have to be minimized while some others to be maximized.…”

“…CVD is practically insoluble in water and exhibits pHdependent solubility (Bhagat et al 2013). CVD undergoes significant stereoselective first-pass metabolism, resulting in low absolute bioavailability (30 % or less) (Singh et al 2009;Saini et al 2012).The low oral dose (6.25-25.0 mg), suitable log P (octanol/water) of 4.19, low oral bioavailability, and being a BCS class II drug strongly provide a rational to develop nanocapsules of CVD.…”