The Impact of Hypromellose on Pharmaceutical Properties of Alginate Microparticles as Novel Drug Carriers for Posaconazole

Abstract

Fungal infections are a group of diseases which are challenging to treat because of drug-resistant fungi species, drug toxicity, and often severe patient conditions. Hence, research into new treatments, including new therapeutic substances and novel drug delivery systems, is being performed. Mucoadhesive dosage forms are beneficial to improving drug bioavailability by prolonging the residence time at the site of application. Sodium alginate is a natural polymer with favorable mucoadhesive and gelling properties, although its precipitation in acidic pH significantly disrupts the process of drug release in gastric conditions. Hypromellose is a hydrophilic, semi-synthetic cellulose derivative with mucoadhesive properties, which is widely used as a control release agent in pharmaceutical technology. The aim of this study was to evaluate the impact of hypromellose on alginate microparticles with posaconazole, designed to modify drug release and to improve their mucoadhesive properties for both oral or vaginal application.

Keywords: alginate; hypromellose; microparticles; mucoadhesive formulations; posaconazole.

Figure 1

Representative SEM images of microparticle formulations A1 (a), F6 (b) under magnification 5000×, H1 (c), and H5 (d) under magnification 10,000×.

Figure 2

Three-dimensional response surface plots: (a) percent loading vs. ALG and POS concentrations and (b) percent loading vs. HPMC and POS concentrations.

Figure 3

Three-dimensional response surface plots: (a) production yield vs. ALG and POS concentrations and (b) production yield vs. ALG and HPMC concentrations.

Figure 4

Swelling ratio (SR) of ALG (A1 to F6) formulations assessed in gastric (a) and vaginal (b) conditions (0.1 M HCl and SVF, respectively) (mean ± SD, n = 3).

Figure 5

Swelling ratio (SR) of ALG/HPMC formulations (H1 to H6) assessed in gastric (a) and vaginal (b) conditions (0.1 M HCl and SVF, respectively) (mean ± SD, n = 3).

Figure 6

Mucoadhesive properties of ALG formulations (A1 to F6) assessed in gastric (a) and vaginal (b) conditions (0.1 M HCl and SVF, respectively), (mean ± SD, n = 6), * significant differences (p < 0.05) compared to formulation A2.

Figure 7

Mucoadhesive properties of ALG/HPMC formulations (H1 to H6) in gastric (a) and vaginal (b) conditions (mean ± SD, n = 6), * significant differences (p < 0.05) compared to formulation A2.

Figure 8

POS release profiles from ALG (a) and ALG/HPMC (b) microparticles in 0.1 M HCl imitating gastric conditions (mean ± SD, n = 3).

Figure 9

POS release profiles from ALG (a,b) and ALG/HPMC (c) microparticles in SVF imitating vaginal conditions within 24 h (a), and within 45 min (b,c) (mean ± SD, n = 3).

Figure 10

DSC thermograms of ALG, POS, A3, and F6 formulations (a); and ALG, HPMC, H3, and H6 formulations (b).

Figure 11

Antifungal activity of ALG placebo microparticles (A1–A3) and drug-containing formulations (F1–F6) against C. albicans, C. krusei, and C. parapsilosis with POS in dimethylsulphoxide (DMSO) as a control (mean ± SD, n = 3) * significant differences (p < 0.05) compared to formulation A2.

Figure 12

Antifungal activity of ALG/HPMC microparticles (H1–H6) against C. albicans, C. krusei, and C. parapsilosis with POS in DMSO as a control (mean ± SD, n = 3) * significant differences (p < 0.05) compared to formulation A2.