Date of Award

2020

Document Type

Dissertation

Degree Name

Pharmaceutical Sciences(Ph.D.)

Department

Pharmaceutical Sciences

Second Advisor

Abu Serajuddin

Third Advisor

Vivek Gupta

Abstract

In recent years prescription drug diversion, misuse, abuse represent a growing problem for the United States. Oral ingestion, snorting, injection are most commonly employed routes of abuse. To circumvent this problem hot melt extrusion (HME) was employed to prepare abuse deterrent formulation (ADF). Abuse Deterrent Immediate Release Egg-Shaped Tablet Using 3D Printing Technology: Quality by Design to Optimize Drug Release and Extraction. In current work, we developed egg-shaped tablet (egglet) using fused deposition modeling (FDM) 3D printing. Drug-loaded polymeric filaments (1.5 mm) were prepared using HME followed by printing into egglets of different sizes and infill densities. Based on printability, crush resistance polyvinyl alcohol (PVA) was used further. Later, egglets were evaluated for abuse deterrence properties based on USFDA guidance. A multifactorial design was used to optimize solvent extraction, drug release. Extreme hardness (> 500 N), large particle size (> 1 mm) on mechanical manipulation established snorting deterring property while <20% drug extraction in 5 min (% Sext) demonstrated deterrence for injection abuse. Quality target product profile D85 < 30 min, % Sext < 20 was achieved with egglets of 6 mm diameter, 45% infill density, 15% w/w drug loading. Development of Multi-dose Oral Abuse Deterrent Formulation of Loperamide Using Hot melt extrusion. Loperamide, an over the counter anti-diarrheal drug, also referred as "poor man's methadone". Abusers consume more than 30 tablets to achieve euphoria and to combat opioid withdrawal. But supratherapeutic doses causes respiratory depression, cardiac dysrhythmia, mortality. Aim is designing a tablet which can immediate release loperamide in diarrheic patients (single tablet) while stops release in case of intentional multi-dose ingestion. Loperamide was molecularly dispersed into gastric soluble cationic polymers - Eudragit® EPO, Kollicoat® Smartseal 100P using HME to obtain filament. Filaments were milled and compressed into tablets ((Eudragit® EPO (SJU1) and Kollicoat® Smartseal (SJU2)) with optimized amount of L-arginine. Dissolution in 250 mL of Fasted state simulated gastric fluid (FaSSGF) revealed that single tablet of Imodium® (marketed formulation) and SJU1 showed >85% of release in 15 min. In multi-unit dissolution (15 tablets), Imodium® exhibited >90% release but SJU tablets showed <5% of release thus demonstrating its ability to deter multi-dose oral abuse.

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