Formulation and in vitro evaluation of xanthan gum or carbopol 934-based mucoadhesive patches, loaded with nicotine

Abstract

Bilayer nicotine mucoadhesive patches were prepared and evaluated to determine the feasibility of the formulation as a nicotine replacement product to aid in smoking cessation. Nicotine patches were prepared using xanthan gum or carbopol 934 as a mucoadhesive polymers and ethyl cellulose as a backing layer. The patches were evaluated for their thickness, weight and content uniformity, swelling behavior, drug-polymers interaction, adhesive properties, and drug release. The physicochemical interactions between nicotine and the polymers were investigated by Fourier transform infrared (FTIR) spectroscopy. Mucoadhesion was assessed using two-arm balance method, and the in vitro release was studied using the Franz cell. FTIR revealed that there was an acid base interaction between nicotine and carbopol as well as nicotine and xanthan. Interestingly, the mucoadhesion and in vitro release studies indicated that this interaction was strong between the drug and carbopol whereas it was weak between the drug and xanthan. Loading nicotine concentration to non-medicated patches showed a significant decrease in the mucoadhesion strength of carbopol patches and no significant effect on the mucoadhesion strength of xanthan patches. In vitro release studies of the xanthan patches showed a reasonable fast initial release profile followed by controlled drug release over a 10-h period.

Fig. 1

The relationship between the cast volume of the xanthan gum solution and the thickness of the patch

Fig. 2

Water uptake of medicated and non-medicated xanthan and carbopol patches. a Medicated carbopol film (cast volume = 30 ml, nicotine = 2 mg/cm²); b non-medicated xanthan film (cast volume = 20 ml); c medicated xanthan film (cast volume = 30 ml, nicotine = 3.75 mg/cm²); d medicated xanthan film (cast volume = 30 ml, nicotine = 2 mg/cm²); e non-medicated xanthan film (cast volume = 30 ml); f non-medicated xanthan film (cast volume = 40 ml); h non-medicated carbopol film (cast volume = 30 ml)

Fig. 3

FTIR of carbopol 934 and nicotine–carbopol 934

Fig. 4

FTIR of xanthan and nicotine–xanthan

Fig. 5

Mucoadhesion strength of medicated and non-medicated carbopol and xanthan mucoadhesive patches [cast volume = 20 ml, drug content = 2 mg/cm²)

Fig. 6

Mucoadhesion strength of different film thickness of medicated xanthan patches (20 ml ≈ 0.101 mm, 30 ml ≈ 0.120 mm, 40 ml ≈ 0.147 mm, 50 ml ≈ 0.172 mm, and 60 ml ≈ 0.195 mm)

Fig. 7

Nicotine release profile across dialysis membrane from carbopol and xanthan gum patches having different drug loading concentration; a xanthan gum loaded with 1 mg/cm² nicotine, b xanthan gum loaded with 2 mg/cm² nicotine, c xanthan gum loaded with 2.75 mg/cm² nicotine, d xanthan gum loaded with 3.75 mg/cm² nicotine, and e carbopol loaded with 2 mg/cm² nicotine

Fig. 8

In vitro release profile of nicotine (2 mg/cm²) using different cast volume of xanthan gum to attain different medicated film thickness (20 ml, 0.101 mm; 30 ml, 0.120 mm; 40 ml, 0.147 mm; 50 ml, 0.172 mm; and 60 ml, 0.195 mm)