Purpose: The development of age appropriate pharmaceutical formulations for pediatric population is challenging. Extemporaneous formulations are generally prepared by manipulating adult formulation but medication errors can result in suboptimal efficacy and safety concerns due to absence of well characterized standardized procedures. The purpose of present work was to develop a modified release 3D printed minicaplets of baclofen for pediatric population and optimize it using 3-level 2-factor factorial design.
Methods: Different polymer blends were extruded by using a parallel twin screw extruder. The filaments prepared were characterized further for their elasticity and tensile strength by performing a 3-point bend test. Baclofen loaded filament were prepared by hot melt extrusion using an immediate release polyvinyl alcohol (Parteck®MXP) (PVA) and Sorbitol (Parteck®SI 150) as plasticizer to improve printability. Solid state characterization was performed. Minicaplets were printed in 3 different infill percentage and 4 different infill patterns using a MakerBot® 3D printer. Minicaplets were characterized for assay, friability, weight variation, tablet hardness and in vitro disintegration test. To systematically investigate the effect of infill density and caplet dimensions on drug release (D50 and D85), 3-level 2-factor full factorial design was used.
Results: The 3-Point bend test depicted that the extrudates of PVA and Sorbitol (10%) had optimum elasticity for 3D printing as the required breaking force was higher than the other placebo filaments (Fig No.1) . Absence of a melting endotherm and characteristic peak in DSC and XRPD confirmed that the drug was present in amorphized state. Minicaplets printed in 100% Diamond (Fast) infill pattern showed slowest disintegration in comparison to the different infill patterns and infill percentages. It was observed that infill density had marginal effect on the dissolution but dimension had a more significant effect on the (p<0.05) on dissolution profile of the minicaplets. (Fig No.2).
Conclusion: Thermostable drug loaded, and printable polymeric filaments of Baclofen were successfully developed using Polyvinyl Alcohol (Parteck®MXP) in combination with Sorbitol (Parteck®SI 150). The release profile and disintegration time required for the minicaplets can be individually altered based on the dimension, infill pattern and infill percentage. It can be inferred that the diamond (fast) infill is the accurate infill type with 100% infill to produce modified release minicaplet with a few modifications in the dimensions.
Pavan Kumar Nukala– Student, St. John's University, Flushing, New York
Thomas Kipping– Head of Drug Carriers, MilliporeSigma, Darmstadt, Hessen
Saurabh Mishra– Student, St. John's University, New York
Ketankumar Patel– Assistant Professor, St. John's university, Jamaica, New York