Sustained release dosage form of noscapine HCl using hot melt extrusion (HME) technique: formulation and pharmacokinetics

Sustained release formulation of noscapine (Nos) HCl could be useful in maintaining plasma Nos HCl level for prolonged period of time, which is important for chemo-sensitization. However, weakly basic drugs like Nos HCl have pH-dependent solubility. Therefore, the purpose of this study was to achieve pH-independent drug release by developing the sustained release dosage form of Nos HCl using biodegradable polymer Eudragit RLPO and FDA-approved pH modifier citric acid (CA) by hot melt extrusion (HME) technique. Nos HCl was successfully formulated using 10% CA with 91.2 ± 1.34% drug recovery through the extruder. X-ray diffraction (XRD) results showed that drug was completely dispersed in the polymer and changed to amorphous from its crystalline form. In vitro drug release studies in pH 6.8 buffer showed that formulation containing 10% CA released 70.99 ± 3.85% drug in 24 h after initial burst release of 40.04 ± 2.39% compared to formulation without CA. Furthermore, in vivo pharmacokinetic data showed the sustained release plasma concentration time curve with significant ( p < 0.05) increase in area under curve (AUC) in Nos HCl extrudate compared to Nos HCl solution. Overall, HME can be used to enhance the bioavailability and achieve the pH-independent solubility of weakly basic drugs like Nos HCl. Graphical abstract