Overdose and Alcohol Sensitive Immediate Release System (OASIS) for Deterring Accidental Overdose or Abuse of Drugs
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Research Article Theme: Pharmaceutical Thermal Processing - An Update Guest Editors: Feng Zhang, Michael Repka and Suresh Bandari
Overdose and Alcohol Sensitive Immediate Release System (OASIS) for Deterring Accidental Overdose or Abuse of Drugs Manali Patki,1 Siddhant Palekar,1 Pavan Kumar Nukala,1 Richa Vartak,1 and Ketankumar Patel1,2
Received 11 August 2020; accepted 12 November 2020 Abstract.
Death from an accidental or intentional overdose of sleeping tablets has increased exponentially in the USA. Furthermore, the simultaneous consumption of sleeping tablets with alcoholic beverages not only intensifies the effect of sleeping tablets but also leads to blackouts, sleepwalking, and death in many cases. In this article, we proposed a unique and innovative technology to prevent multi-tablet and alcohol-associated abuse of sleeping tablet. Agonist- and antagonist-loaded polymeric filaments of appropriate Eudragit® polymers were prepared using hot melt extrusion. Metoprolol tartrate and hydrochlorothiazide were used as model drugs in place of zolpidem tartrate (agonist-BCS class I) and flumazenil (antagonist-BCS class IV), respectively. Crushed filaments were converted into a tablet with a novel rapidly soluble co-processed alkalizing agent. Dissolution studies of single tablet and multiple tablets (5) in fasted state simulated gastric fluid (FaSSGF) confirmed that the release of the agonist was significantly (p < 0.0001) reduced in multi-tablet dissolution. Furthermore, the release of antagonist was significantly higher when tablet was exposed to FaSSGF+20% ethanol and various alcoholic beverages. Thus, appropriate use of Eudragit® polymer’s chemistry could help design a tablet to prevent the release of agonist in case of overdose and simultaneous release of antagonist when consumed with alcohol. KEY WORDS: sleeping tablet; zolpidem; drug abuse; hot melt extrusion; Eudragit polymer; abusedeterrent formulation.
INTRODUCTION A large part (around 70 million) of the American population has been reported to be affected with problems related to sleep (1,2). Sleep medications or sedatives are one of the most common treatments given to patients suffering from insomnia or anxiety. Various reports suggest that around 33% of the patients suffering from sleep disorders are prescribed either a benzodiazepine or Z-drugs (3,4). Due to a shorter duration of action and half-life of benzodiazepines, “Z-drugs” (zolpidem, zaleplon, zopiclone) have been reported to become the prescriber’s choice due to less severe side effects compared to benzodiazepines (5–8). Recent reports suggest that around 55% of patients taking prescrip-
Guest Editors: Feng Zhang, Michael Repka and Suresh Bandari 1
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, New York 11439, USA. 2 To whom correspondence should be addressed. (e–mail: [email protected])
tion medicine continue using sleeping tablet for a longer period. This is generally not recommended since the drug becomes less effective over a
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