Abuse Deterrent Immediate Release Egg-Shaped Tablet (Egglets) Using 3D Printing Technology: Quality by Design to Optimize Drug Release and Extraction.

Opioid abuse is a growing problem and has become a national health crisis over the past decade in the USA. Oral ingestion, snorting, and injection are the most commonly employed routes of abuse for an immediate release product. To circumvent these issues, we have developed an egg-shaped tablet (egglet) using fused deposition modeling (FDM) 3D printing technology. Drug-loaded polymeric filaments (1.5 mm) were prepared using hot melt extrusion (HME) followed by printing into egglets of different sizes and infill densities. Based on printability and crush resistance, polyvinyl alcohol (PVA) was found to be the most suitable polymer for the preparation of abuse deterrent egglets. Further, egglets were evaluated and optimized for mechanical manipulation using household equipment, milling, particle size distribution, solvent extraction, and drug release as per the FDA guidance (November 2017). A multifactorial design was used to optimize egglets for solvent extraction and drug release. Extreme hardness (> 500 N) and very large particle size (> 1 mm) on mechanical manipulation confirmed the snorting deterring property while less than 15% drug extraction in 5 min (% Sext) demonstrated the deterrence for injection abuse. Quality target product profile D85 < 30 min and % Sext < 15 was achieved with egglets of 6 mm diameter, 45% infill density, and 15% w/w drug loading. Dose of drug can be easily customized by varying dimension and infill density without altering the composition. HME coupled with FDM 3D printing could be a promising tool in the preparation of patient-tailored, immediate release abuse deterrent formulation.

Development of a safe pediatric liquisolid self-nanoemulsifying system of triclabendazole for the treatment of fascioliasis.

Fascioliasis, a common parasitic infection observed in the pediatric patient population, is a leading cause of concern in countries with poor/unhealthy water resources. To treat this condition first line agent such as triclabendazole (TBZ) has been the choice therapy. However, there is a major hurdle in exploiting TBZ. Characterized with poor aqueous solubility (0.1 mg/L), its solubility has been the rate limiting factor, rendering requirement of large doses of TBZ. To address the same, the focus of the current study was to develop a self-nano emulsifying drug delivery system (TBZ-SNEDDS) for TBZ and developing dose customizable pediatric dispersible color-coded tablets. TBZ-SNEDDS were successfully formulated by using Kolliphor®EL, as a surfactant, a lipid phase of medium chain triglyceride and α-tocopherol in the ratio of (1:1), with dimethylacetamide (DMA) as a solvent. It was observed during in vitro release studies that there was a significant effect of fed conditions on the rate of TBZ release from the formulation. greater than 85 % TBZ was observed to release in fed conditions in comparison to fasted conditions. As currently TBZ is prescribed on a weight-based dosage regimen, it is imperative to develop a dose-customizable fast dissolving pediatric formulation. Hence, TBZ-SNEDDS could prove to be pivotal in helping countless children around the world in desperate conditions to get cheap yet effective therapy.