Erythromycin Stearate

The continuous feeding-mixing system ensures the composition uniformity down to the tableting continuous manufacturing line so that a quality end-product is consistently delivered. Near-infrared spectroscopy (NIRS) enables in-line assessment of the blend's critical quality attributes in real-time. In this study, the effect of total feed rate and impeller speed on the continuous blending process monitored in-line by NIRS was examined by principal component analysis (PCA), ANOVA simultaneous component analysis (ASCA) and partial least squares (PLS) regression. Process data were generated by a factorial experimental design with process parameters and a constant formulation comprised of: 30% (wt/wt) ibuprofen, 67.5% (wt/wt) microcrystalline cellulose, 2% (wt/wt) of sodium starch glycolate and 0.5% (wt/wt) of magnesium stearate. The PCA hinted at the prevalence of impeller speed effect on ibuprofen concentration due to path length variation of the NIR light caused by the fluidized behaviour in the powder blend as a result of high speed ranges (>300 rpm). The ASCA model indicated that while both impeller speed and total feed rate effects were statistically significant (p-value=0.004), the impeller speed was the factor that contributed the most to the spectral variance (55.5%). The PLS regression model for the ibuprofen content resulted in a RMSECV of 1.3% (wt/wt) and showed that impeller speed was yet again the factor that exerted the major influence on spectral variance, owing to its wavelength-dependent effect that prevents common pre-processing techniques from eliminating it across the entire NIR range. The best sample presentation to the NIR probe was achieved at low impeller speed ranges (<600 rpm) and low total feed rates (<15 kg/h), such that it enhanced the PLS model ability to predict the ibuprofen concentration in the blend.

The traditional drug delivery system is not much effective when treating chronopathological diseases like arthritis. Consequently, there is a gap in the market for a delivery system that can provide an explicit treatment following the chronopharmacology of this disorder. The present study is based on the objective to develop Eudragit coated dual release bilayer tablet designed by the quality by design (QbD) and based on the chronotherapeutic approach. The dual release tablet contained an immediate release layer of etoricoxib and a sustained release layer of thiocolchicoside.

The quality target product profile (QTTP) of the formulation was established along with critical quality attributes (CQA). The optimization of the dual release layer was done using a three-level, three-factor Box-Behnken design. A total of thirteen formulations of etoricoxib (ET1-ET13) and thiocolchicoside (TH1-TH13) were developed based on the design composition of etoricoxib, sodium starch glycolate and sodium bicarbonate for the immediate release (IR) layer and thiocolchicoside, HPMC E5 LV and magnesium stearate for the sustained release (SR) layer respectively. The developed dual release layers were compressed to form a bilayer tablet. The bilayer tablets were further coated with pH-dependent polymer Eudragit S-100 to avoid drug release in upper GIT. The initial characterization and drug-excipient interaction studies were performed initially using infra-red (IR) spectroscopy and X-ray diffraction studies (XRD). Formulations showing good micrometric properties, disintegration and drug release were selected for final compression of bilayer tablets.

Formulation ET13 showed the fastest drug release (88%) at 15minutes and quick disintegration time (21s). The sustained release thiocolchicoside tablet layer (TH1-TH13) had a hardness that varied from 4.01 to 4.45kg/cm². Formulation TH12 had the highest hardness, whereas TH6 showed the lowest hardness. The sustained release layer showing 97.63% of drug release after 8hours was selected for the compression to bilayer tablet. The developed dual layer tablets were investigated for quality parameters like hardness, percentage friability, weight variation, disintegration and dissolution.

A high level of patient compliance is ensured through the current design as the patient does not need to get out of bed at night to take the medication.