Hot liquid extrusion assisted drug-cyclodextrin complexation: a novel continuous manufacturing method for solubility and bioavailability enhancement of drugs

In this study, drug-cyclodextrin (CD) complexes were prepared using hot liquid extrusion (HLE) process with an aim to improve solubility and bioavailability of carbamazepine. Saturation solubility studies of CBZ in water and different pH media showed a pH-independent solubility. Phase solubility studies of CBZ at different molar concentrations of beta-cyclodextrin (β-CD) and hydroxypropyl beta-cyclodextrin (HP-β-CD) indicated A_L-type solubility profile with stability constants of 574 M⁻¹ and 899 M⁻¹ for β-CD and HP-β-CD. Drug-β-CD and drug-HP-β-CD complexes were prepared using HLE process and conventional methods (such as physical mixture, kneading method, and solvent evaporation) as well. Optimized complexes prepared using HLE viz. CBP-4 and CHP-2 showed a solubility of 4.27 ± 0.09 mg/mL and 6.39 ± 0.09 mg/mL as compared to plain CBZ (0.140 ± 0.007 mg/mL). Formation of drug-CD inclusion complexes was confirmed using DSC, FTIR, and XRD studies. Drug release studies indicated highest release of CBZ from CHP-2 (98.69 ± 2.96%) compared to CBP-4 (82.64 ± 2.45%) and plain drug (13.47 ± 0.54%). Complexes prepared using kneading showed significantly lesser drug release (KMB 75.52 ± 2.68% and KMH 85.59 ± 2.80%) as that of CHP-2 and CBP-4. Pre-clinical pharmacokinetic studies in Wistar rats indicated a significant increase in C_max, T_max, AUC, and mean residence time for CHP-2 compared to KMH and plain CBZ. All these results suggest that HLE is an effective method to increase the solubility of poorly water-soluble drugs.

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or continue reading here: cyclodextrin complexation: a novel continuous manufacturing method for solubility and bioavailability enhancement of drugs. Drug Deliv. and Transl. Res. (2020). https://doi.org/10.1007/s13346-020-00854-w