Formulation and In Vitro Evaluation of Salbutamol Sulphate In Situ Gelling Nasal Inserts

Abstract

The aim of this study was to formulate salbutamol sulfate (SS), a model drug, as mucoadhesive in situ gelling inserts having a high potential as nasal drug delivery system bypassing the first-pass metabolism. In situ gelling inserts, each containing 1.4% SS and 2% gel-forming polymer, hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose sodium (CMC Na), sodium alginate (AL), and chitosan (CH) were prepared. The inserts were investigated for their different physicochemical properties. The weight of inserts was 16-27 mg, drug content was 3.9-4.2 mg, thickness ranged between 15 and 28 μm and surface pH was 5-7. Cumulative drug released from the inserts exhibited extended release for more than 10 h following the decreasing order: CH>AL>CMC Na>HPMC. The drug release from CMC Na and AL inserts followed zero-order kinetics while HPMC and CH inserts exhibited non-Fickian diffusion mechanism. The inserts exhibited different water uptake (7-23%) with the smallest values for CH. Differential scanning calorimetry study pointed out possible interaction of SS and oppositely charged anionic polymers (CMC Na and AL). The mucoadhesive in situ gelling inserts exhibited satisfactory mucoadhesive and extended drug release characteristics. The inserts could be used for nasal delivery of SS over about 12 h; bypassing the hepatic first-pass metabolism without potential irritation.

Influence of excipients on spray-dried powders for inhalation

“…Analysis of the kinetics of drug release suggested zero-order release controlled by matrix relaxation and diffusion of drug through the gel layer formed as the insert swelled [40].…”

Nasal Inserts for Drug Delivery: An Overview

“…The interaction observed by differential scanning calorimetry between drug and oppositely charged polymers (carboxymethylcellulose sodium, sodium alginate) resulted in zero order release of the drug for > 10 h. However inserts prepared with all the polymers gave acceptable mucoadhesive and extended release properties which could be useful for nasal delivery of salbutamol sulfate [46].…”

“…In the context of the foregoing, nasal delivery studies are few despite its many advantages, probably owing to some limitations. However, studies on nasal inserts of some active molecules and proteins using mucoadhesive polymers such as cellulose derivatives, acrylic acid derivatives, polysaccarides and gums are outlined here [38,[46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62].…”

How to characterize a nasal product. The state of the art of in vitro and ex vivo specific methods

“…The formulation is then deposited on the plate and the displacement factor is measured (Nakamura et al, 1996). This displacement factor is defined as the distance in centimetres measured between the initial deposition site of the formulation and its position at the moment of measurement (Farid et al, 2013). The mucoadhesion is thus inversely proportional to the displacement factor.…”

“…The displacement of the inserts on the agar/mucin gel was evaluated to assess potential bioadhesion. This method was also used to evaluate the mucoadhesion of nasal in situ gelling inserts containing salbutamol (Farid et al, 2013) or liquid formulation containing amantadine and a thermosensitive polymer (Lungare et al, 2016). This method therefore L. Salade, et al International Journal of Pharmaceutics 561 (2019) 47-65 makes it possible to measure easily the potential of a formulation to adhere and to compare different excipients with each other.…”