Extrusion 3D printing of minicaplets for evaluating in vitro & in vivo praziquantel delivery capability.

This study aimed to explore extrusion three dimensional (3D) printing technology to develop praziquantel (PZQ)-loaded minicaplets and evaluate their in vitro and in vivo delivery capabilities. PZQ-loaded minicaplets were 3D printed using a fused deposition modelling (FDM) principle-based extrusion 3D printer and were further characterized by different in vitro physicochemical and sophisticated analytical techniques. In addition, the % PZQ entrapment and in vitro PZQ release performance were evaluated using chromatographic techniques. It was in vitro observed that PZQ was fully released in the gastric pH medium within the period of gastric emptying, that is, 120 min, from the PZQ-loaded 3D printed minicaplets. Furthermore, in vivo pharmacokinetic (PK) profiles of PZQ-loaded 3D printed minicaplets were systematically evaluated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The PK profile of the PZQ-loaded 3D printed minicaplets was established using different parameters such as Cmax, Tmax, AUC0-t, AUC0-∞, and oral relative bioavailability (RBA). The Cmax value of pristine PZQ was found at 64.79 ± 13.99 ng/ml, while PZQ-loaded 3D printed minicaplets showed a Cmax of 263.16 ± 47.85 ng/ml. Finally, the PZQ-loaded 3D printed minicaplets showed 9.0-fold improved oral RBA compared with that of pristine PZQ (1.0-fold). Together, these observations potentiate the desired in vitro and improved in vivo delivery capabilities of PZQ from the PZQ-loaded 3D printed minicaplets.

Theoretical and experimental validation of praziquantel with different polymers for selection of an appropriate matrix for hot-melt extrusion.

The selection of an appropriate matrix for the preparation of amorphous extrudate in hot-melt extrusion (HME) deals with the study of various solid-state properties of drugs and polymers. Therefore, it is necessary to have an appropriate knowledge of drug-polymer miscibility, the interaction between the drug-polymer on mixing, and Gibb's free thermal energy of mixing to screen polymers through thermodynamic phase diagrams, to be suitable amorphous matrix system for HME. Here, we evaluated the possibility of three different polymers, namely, Eudragit®EPO, polyvinyl alcohol (PVA), Kollicoat®IR (KIR) with Praziquantel (PZQ), with proper validation of the Flory-Huggins theory and construction of the phase diagram using the melting point depression approach to determine a suitable matrix for HME. The solubility parameter theoretical calculation approach was used as a preliminary study to validate the miscibility of PZQ with three different polymers. Theoretical and experimental validation studies using the Flory-Huggins interaction parameter value using the melting point depression approach and the effect of PZQ loading on the interaction parameter were systematically validated to predict thermodynamic phase diagrams and Gibbs free energy of mixing for screening these polymers for the preparation of amorphous extrudate. Using the phase diagram, the thermal processing temperature for the HME was determined using a T-φ phase diagram to obtain an appropriate matrix. The obtained extrudates were further validated through physical appearance, microscopic structure, thermal and functional group characterizations, followed by the PZQ assay. Thus, considering the solid-state properties, the processing parameters of HME were selected to obtain stable extrudates and an appropriate matrix for PZQ loading.

3D printing of immediate-release tablets containing olanzapine by filaments extrusion.

In this work, hot-melt extrusion (HME) is coupled with fused deposition modeling (FDM) mediated 3D printing to demonstrate additive manufacturing to fabricate immediate release (IR) prototypes of olanzapine with the aim of enhanced solubility using a fast disintegrating polymer (Kollicoat® IR). Drug-polymer solubility and interaction parameters were estimated by Hansen solubility parameters and Hildebrand-Scott equation. The obtained values signified drug-polymer miscibility. The detailed in vitro physicochemical evaluations of the developed filament through HME and its derived 3D printed tablet by FDM technique were assessed thoroughly by several analytical means such as light microscopy, DSC, XRD, FT-IR, SEM, etc. The average disintegration time of this developed 3D printed IR tablet was found to be 63.33 (±3.6) sec complying with the USP limit. Additionally, in vitro dissolution study data revealed almost close correlations and both showed 100% of drug release within 15 min, thus complying with the definition of IR tablet. Thus, this study demonstrates the feasibility of directly using olanzapine-Kollicoat® IR through the HME process without the addition of any plasticizers, organic solvents, etc. and coupling of HME with 3D printing technology allowing prototypes of IR tablet of olanzapine.