Improving drug loading of mucosal solvent cast films using a combination of hydrophilic polymers with amoxicillin and paracetamol as model drugs

Abstract

Solvent cast mucosal films with improved drug loading have been developed by combining carboxymethyl cellulose (CMC), sodium alginate (SA), and carrageenan (CAR) using paracetamol and amoxicillin as model drugs and glycerol (GLY) as plasticizer. Films were characterized using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), folding resilience, swelling capacity, mucoadhesivity, and drug dissolution studies. SA, CMC, and GLY (5 : 3 : 6) films showed maximum amoxicillin loading of 26.3% whilst CAR, CMC, and GLY (1 : 2 : 3) films had a maximum paracetamol loading of 40%. XRPD analysis showed different physical forms of the drugs depending on the amount loaded. Films containing 29.4% paracetamol and 26.3% amoxicillin showed molecular dispersion of the drugs while excess paracetamol was observed on the film surface when the maximum 40% was loaded. Work of adhesion was similar for blank films with slightly higher cohesiveness for CAR and CMC based films, but the differences were significant between paracetamol and amoxicillin containing films. The stickiness and cohesiveness for drug loaded films were generally similar with no significant differences. The maximum percentage cumulative drug release was 84.65% and 70.59% for paracetamol and amoxicillin, respectively, with anomalous case two transport mechanism involving both drug diffusion and polymer erosion.

Figure 1

Representative digital images showing (a) typically rejected patchy nonhomogeneous film, (b) optimised amoxicillin loaded film, and (c) optimised paracetamol loaded film.

Figure 2

XRPD patterns of CAR : CMC : GLY (1 : 2 : 3) films containing (a) 29.4% and 18.2% paracetamol (b) 40% paracetamol, and (c) SA : CMC : GLY (5 : 3 : 6) films containing 26.3% amoxicillin. The drug contents have been calculated as a percentage of total dry weight of the films.

Figure 3

Representative SEM images of (a) blank CAR : CMC : GLY film and (b) the corresponding paracetamol (40%) loaded film.

Figure 4

Hydration profile showing the % swelling for the blank and paracetamol loaded film containing CAR : CMC : GLY in phosphate buffer (mean ± s.d, n = 3).

Figure 5

In vitro drug dissolution profiles of paracetamol released from films containing CAR : CMC : GLY (1 : 2 : 3) and amoxicillin released from films containing SA : CMC : GLY (5 : 3 : 6).