Carbopol-incorporated thermoreversible gel for intranasal drug delivery

Abstract

The present study describes the preparation and evaluation of a poloxamer 407 (P407)-based thermoreversible gel using Carbopol 934P (C934P) as a mucoadhesive polymer and hydroxypropyl-β-cyclodextrin (HP-β-CD) for enhancing the aqueous solubility and intranasal absorption of fexofenadine hydrochloride (FXD HCl). The prepared gels were characterized by gelation temperature, viscoelasticity, and drug release profile. Thermoreversibility of P407/C934P gel was demonstrated by rheological studies. The incorporation of carbopol into P407 gel also reduced the amounts of drug released from the gel formulations (p < 0.05). In vivo pharmacokinetic results of the prepared gel formulations in rabbits (at 0.5 mg/kg dose) showed that the relative bioavailability of drug from P407/C934P gel was 11.3 and 2.7-fold higher than those of drug solution and P407 gel group, respectively. These findings suggested that developed thermoreversible gels could be used as promising dosage forms to improve intranasal drug absorption.

Figure 1

Shear stress (σ) and steady shear viscosity (η) as a function of shear rate for P407/C934P gel at 35 °C.

Figure 2

Storage modulus (G') and loss modulus (G'') as a function of strain amplitude (γ₀, %) for P407/C934P gel at 35 °C.

Figure 3

Storage modulus modulus (G') and loss modulus (G'') as a function of angular frequency (ω, rad/s) for P407/C934P gel at 35 °C.

Figure 4

Drug release profiles from thermoreversible gel formulations. ^# p < 0.05, compared to P407 gel group. Each point represents the mean ± S.D. (n = 3).

Figure 5

Mean drug concentration in plasma-time profiles after intranasal administration of thermoreversible gel formulations in rabbits. Dose was 0.5 mg/kg. Each point represents the mean ± S.D. (n ≥ 3).