Advances in Nanoparticulate Drug Delivery Approaches for Sublingual and Buccal Administration

Abstract

The sublingual and buccal routes of administration have significant advantages for both local and systemic drug delivery. They have shown to be an effective alternative to the traditional oral route, especially when fast onset of action is required. Drugs can be rapidly and directly absorbed into the systemic circulation via venous drainage to the superior vena cava. Therefore, they are useful for drugs that undergo high hepatic clearance or degradation in the gastrointestinal tract, and for patients that have swallowing difficulties. Drugs administered via the sublingual and buccal routes are traditionally formulated as solid dosage forms (e.g., tablets, wafers, films, and patches), liquid dosage forms (e.g., sprays and drops), and semi-solid dosage forms (e.g., gels). Conventional dosage forms are commonly affected by physiological factors, which can reduce the contact of the formulation with the mucosa and lead to unpredictable drug absorption. There have been a number of advances in formulation development to improve the retention and absorption of drugs in the buccal and sublingual regions. This review will focus on the physiological aspects that influence buccal and sublingual drug delivery and the advances in nanoparticulate drug delivery approaches for sublingual and buccal administration. The clinical development pipeline with formulations approved and in clinical trials will also be addressed.

Transmucosal drug administration as an alternative route in palliative and end-of-life care during the COVID-19 pandemic

“…The composition and thickness of the oral epithelium depends on the site in the oral cavity. The buccal region refers to the lining of the cheek and has a surface area of ~50 cm 2 [ 82 ]. The buccal epithelium is composed of non-keratinised stratified squamous epithelial cells of around 40–50 cells thick (500–800 μm).…”

“…Like other mucosal surfaces, the oral mucosa is coated with a thin layer of mucus which is part of the saliva. The mucus layer, which is 70–100 μm thick, presents a barrier to drug absorption by impeding drug penetration [ 82 ].…”

“…Formulations that are unpalatable or cause local irritation may lead to voluntary expulsion or swallowing. There is also a risk of choking and aspiration in young and elderly patients, and when patients are unconscious or uncooperative [ 82 , 90 ]. Table 4 summarises the advantages and disadvantages of oral transmucosal drug delivery.…”

Mucoadhesive Electrospun Fibre-Based Technologies for Oral Medicine

“…Nanoparticle drug delivery vectors, such as liposomes and polymersomes, have previously been incorporated into electrospun materials for a variety of non-oromucosal applications [ 89 , 90 , 91 ]. Research on oromucosal films containing nanoparticles has shown improvements to absorption and drug solubility and may protect certain drugs from enzymatic degradation [ 92 ]. However, due the additional manufacturing and regulatory complexity, these materials rarely make it to late stage clinical development.…”

<p>Transdermal Asenapine in Schizophrenia: A Systematic Review</p>

“…13 Peak plasma concentration of sublingual formulation (Cmax) is 4 ng/ mL and occurs within 1 hr (Tmax); 11 elimination half-life (t 1/2 ) is 24 hrs (range 13.4 to 39.2 h). [14][15][16] Asenapine is highly bound (95%) to albumin and α 1 -acid glycoprotein. 14 Asenapine has weak affinity to the permeability glycoprotein (P-gp), and so would be unlikely to cause an inordinate increase in prolactin like risperidone, paliperidone, and amisulpride.…”