title: Effects of excipients and curing process on the abuse deterrent properties of directly compressed tablets.
abstract: The objective of the present investigation was to understand the effects of excipients and curing process on the abuse deterrent properties (ADP) of Polyox™ based directly compressible abuse deterrent tablet formulations (ADFs). The excipients investigated were lactose (monohydrate or anhydrous), microcrystalline cellulose and hydroxypropyl methylcellulose. The ADPs studied were tablet crush resistance or hardness, particle size distribution following mechanical manipulation, drug extraction in water and alcohol, syringeability and injectability. Other non-ADPs such as surface morphology and tablet dissolution were also studied. It was found that presence of 50% or more of water soluble or swellable excipient in the ADF tablets significantly affected the tablet hardness, particle size distribution following mechanical manipulation and drug extraction while small amount (5%) of excipients had either minimal or no effect on ADPs of these tablets. Addition of high molecular weight HPMC (K 100M) affected syringeability and injectability of ADF. Curing process was found to affect ADPs (hardness, particle size distribution, drug extraction and syringeability and injectability) when compared with uncured tablet. In conclusion, addition of large amount of excipients, especially water soluble ones in Polyox™ based ADF tablets increase the risk of abuse by various routes of administration.
authors.affiliation: Division of Product Quality and Research, Center for Drug Evaluation and Research, Food and Drug Administration, MD, United States; Irma Lerma Rangel College of Pharmacy, Texas A&M University, United States. Electronic address: rahman.ziyaur@gmail.com.
authors.forename: Ziyaur
authors.initials: Z
authors.lastname: Rahman
authors.affiliation: Division of Product Quality and Research, Center for Drug Evaluation and Research, Food and Drug Administration, MD, United States.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Zidan
authors.affiliation: Division of Product Quality and Research, Center for Drug Evaluation and Research, Food and Drug Administration, MD, United States.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Korang-Yeboah
authors.affiliation: Division of Product Quality and Research, Center for Drug Evaluation and Research, Food and Drug Administration, MD, United States.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Product Quality and Research, Center for Drug Evaluation and Research, Food and Drug Administration, MD, United States.
authors.forename: Akhtar
authors.initials: A
authors.lastname: Siddiqui
authors.affiliation: Division of Product Quality and Research, Center for Drug Evaluation and Research, Food and Drug Administration, MD, United States.
authors.forename: Diaa
authors.initials: D
authors.lastname: Shakleya
authors.affiliation: Division of Product Quality and Research, Center for Drug Evaluation and Research, Food and Drug Administration, MD, United States; Irma Lerma Rangel College of Pharmacy, Texas A&M University, United States.
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Division of Product Quality and Research, Center for Drug Evaluation and Research, Food and Drug Administration, MD, United States.
authors.forename: Celia
authors.initials: C
authors.lastname: Cruz
authors.affiliation: Division of Product Quality and Research, Center for Drug Evaluation and Research, Food and Drug Administration, MD, United States.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
mesh_terms: D002482:Cellulose / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D006244:Hardness; D065347:Hypromellose Derivatives / Q000737:chemistry; D007267:Injections; D007785:Lactose / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013015:Sotalol / Q000737:chemistry / Q000493:pharmacokinetics; D013607:Tablets / Q000737:chemistry*
chemical_list: D005079:Excipients; C098305:Polyox WSR-301; D013607:Tablets; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D002482:Cellulose; D013015:Sotalol; D007785:Lactose; C109691:microcrystalline cellulose
keywords: Abuse deterrent properties; Abuse deterrent tablet formulations; Crush resistance; Sotalol; Syringeability and injectability