Comparison of the Systemic and Local Pharmacokinetics of Clonidine Mucoadhesive Buccal Tablets with Reference Clonidine Oral Tablets in Healthy Volunteers: An Open-Label Randomised Cross-Over Trial

Abstract

ClinicalTrials.gov identifier, NCT02548806.

Identifying Clinically Relevant Drug–Drug Interactions With Methadone and Buprenorphine: A Translational Approach to Signal Detection

“…Clonidine is an alpha‐2 adrenergic receptor agonist approved for the treatment of hypertension and attention‐deficit disorder, and is commonly used off‐label for the treatment of opioid withdrawal syndrome 32 . In pharmacokinetic screening, clonidine was predicted to increase buprenorphine AUC, based on an in vitro study suggesting that clonidine can inhibit CYP3A4 at high concentrations 33,34 . Whether these findings can be extrapolated in vivo is unclear, as doses that are used clinically result in lower serum concentrations compared with those studied in vitro 33,34 .…”

“…33,34 Whether these findings can be extrapolated in vivo is unclear, as doses that are used clinically result in lower serum concentrations compared with those studied in vitro. 33,34 The plausibility of an interaction is bolstered by the observation that clonidine was associated with a roughly two-fold increased risk of overdose in SCCS screening. In addition to CYP3A4 inhibition, the association with overdose may be due in part to additive CNS depression, as clonidine has well-characterized sedative effects, particularly at high doses.…”

Advances in Nanoparticulate Drug Delivery Approaches for Sublingual and Buccal Administration

“…For example, permeation enhancers (e.g., surfactants, bile salts, fatty acids, cyclodextrins, and chelators) have been shown to improve the mucosal permeability and absorption of various compounds (Tsutsumi et al, 1998; Shojaei et al, 1999; Bird et al, 2001; Burgalassi et al, 2006; Sohi et al, 2010; Tian et al, 2012; Prasanth et al, 2014; Patil and Devarajan, 2014; Ojewole et al, 2014; Marxen et al, 2018) by: (i) changing mucus rheology; (ii) increasing the fluidity of the lipid bilayer membrane; (iii) acting on the components at tight junctions; (iv) inhibiting mucosal enzymes; and (v) increasing the thermodynamic activity of drugs (Chinna Reddy and Chaitanya, 2011). In addition, the incorporation of mucoadhesive constituents has been demonstrated to enhance formulation retention time with the sublingual or buccal mucosa (Das and Das, 2004; Razafindratsita et al, 2007; Perioli and Pagano, 2013; Ikram et al, 2015; Yildiz Pekoz et al, 2016; El-Nabarawi et al, 2016; Ammar et al, 2017; Parodi et al, 2017; Celik, 2017; Salehi and Boddohi, 2017; Vasseur et al, 2017; Khan and Boateng, 2018; Razzaq et al, 2018; Sharma et al, 2018). This has been done primarily for solid dosage forms and semi-solid dosage forms.…”

Quality by Design (QbD) Assisted Fabrication of Fast Dissolving Buccal Film for Clonidine Hydrochloride: Exploring the Quality Attributes

“…It has a half-life of 12-16 h [3]. The daily effective dose of CLH is in the range of 0.1-0.2 mg, and nearly 65% of which is eliminated through kidney and 20% through faces [5]. Taking the above ideal properties of CLH into the consideration, to best of our knowledge, we have planned to prepare fast dissolving buccal film (FDBF) of CLH as no attempt has been reported in the literature.…”

“…The aim of preparation of FDBF is to reduce the dissolution time which gives quick onset of action and also avoid the first pass metabolism of model drug. The several studies reported the benefits of giving CLH by sublingual route over oral administration as later route associated with dry mouth, fatigue, hypotensive effect [5], and swallowing difficulty [7,8]. Further, sublingual administration of CLH was reported to be effective, simple, and safe [9].…”