Albuterol in situ Bioadhesive Nasal Inserts

Mohamed Etman1, Ragwa Farid2, Aly Nada3, Abdelazim Ebian1

1Faculty of Pharmacy, Alexandria University, Alexandria, Egypt2Faculty of Pharmacy & Drug Manufacturing, Pharos University, Alexandria, Egypt

3Faculty of Pharmacy, Kuwait University, Kuwait (alynada@hsc.edu.kw)

�In situ gelling inserts of AL (1.4%)

were prepared by film casting method

using aqueous solutions of AL and

different bioadhesive polymers (2%):

�Carboxymethyl cellulose sodium

(CMC-Na, FI), hydroxypropyl-

methylcellulose (HPMC, FII), Na

alginate (FIII), chitosan (FIV) and 1:1 mixture of FI and FII (FV).

�The inserts were investigated for:

content uniformity, thickness, surface

pH, weight uniformity, water uptake

and in vitro drug release.

�Bioadhesion was tested In vitro by

modified balance method and

displacement method:

�The inserts were placed on a hydrated surface of agar/mucin and the

displacement on the vertical surface

due to gravity was taken as an inverse

measure of the bioadhesion potential.

The drug release from CMC-Na and

sodium alginate inserts followed zero-

order kinetics while HPMC and

chitosan inserts showed non-Fickian

diffusion mechanism. The inserts

exhibited high water uptake with the

smallest values for chitosan (Fig. 2).

Fig.( 2): Water uptake profiles of the in situ

gelling mucoadhesive nasal inserts

prepared from different polymers at 25 0C

�The bioadhesive in situ gelling inserts

have shown satisfactory bioadhesive characteristics, water uptake and

extended drug release.

�The inserts could be used for nasal

delivery of AL over about 12 hours;

bypassing the hepatic first-pass

metabolism without potential

irritation.

Cumulative drug released exhibited

extended release for more than 10

hours with the order of chitosan>

Na alginate >CMC Na >HPMC (Fig. 1).

Fig. (1): Albuterol sulphate release from

the nasal inserts from different polymers

in simulated nasal fluid at 37 0C.

The bioadhesion force was in the

rank of sodium alginate = CMC-Na>HPMC > chitosan (Fig 3).

Fig.( 3): Adhesion force profiles of the

prepared insitu gelling mucoadhesive

nasal inserts from different polymers.

To formulate albuterol sulphate (AL)

bioadhesive nasal inserts, based on in situ gel release-controlling

polymers, having a high potential as

nasal drug delivery system.

Fig.( 4): Swelling index profiles of the

prepared in situ gelling mucoadhesive

nasal inserts at 250C in simulated nasal

fluid after 8 hours.

No displacement was observed for

all formulae except for FII (Fig. 5).

Fig.( 5 ): Adhesion profiles of the in situgelling mucoadhesive nasal inserts

prepared from different polymers.

The swelling indices ranged

between 0.1 and 0.4 (Fig. 4).

Objectives

Methods

RESULTS

CONCLUSION