How to Improve Solubility and Dissolution of Irbesartan by Fabricating Ternary Solid Dispersions: Optimization and In-Vitro Characterization

Abstract

The purpose of this study is to improve the solubility and dissolution of a poorly soluble drug, Irbesartan, using solid dispersion techniques. For that purpose, different polymers such as Soluplus^®, Kollidon^® VA 64, Kolliphor^® P 407, and Polyinylpyrrolidone (PVP-K30) were used as carriers at different concentrations to prepare solid dispersion formulations through the solvent evaporation method. In order to prepare binary dispersion formulations, Soluplus^® and Kollidon^® VA 64 were used at drug: polymer ratios of 1:1, 1:2, 1:3, and 1:4 (w/w). Saturation solubility of the drug in the presence of used carriers was performed to investigate the quantitative increase in solubility. Dissolution studies were performed to explore the drug release behavior from the prepared dispersions. Additionally, the characterization of the prepared formulations was carried out by performing DSC, SEM, XRD, and FTIR studies. The results revealed that among binary systems, K₄ formulation (Drug: Kollidon^® VA 64 at ratio of 1:4 w/w) exhibited optimal performance in terms of increased solubility, drug release, and other investigated parameters. Furthermore, ternary dispersion formulations of the optimized binary formulation were prepared with two more polymers, Kolliphor^® P 407 and Polyvinylpyrrolidone (PVP-K30), at (Drug: Kollidon^® VA 64:ternary polymer) ratios of 1:4:1, 1:4:2, and 1:4:3 (w/w). The results showed that KPVP (TD₃) exhibited the highest increase in solubility, as well as dissolution rate, among ternary solid dispersion formulations. Results of solubility enhancement by ternary solid dispersion formulations were also supported by FTIR, DSC, XRD, and SEM analysis. Conclusively, it was found that the ternary solid dispersion-based systems were more effective compared to the binary combinations in improving solubility as well as dissolution of a poorly soluble drug (Irbesartan).

Keywords: Irbesartan; Kollidon® VA 64; Kolliphor® P 407; Polyinylpyrrolidone (PVP-K30); Soluplus®; dissolution; health care; solid dispersion; solubility.

Figure 1

Structures of (A) Irbesartan, (B) Soluplus^®, (C) Kollidon^® VA 64, (D) PVP-K30, and (E) Kolliphor^® P 407.

Figure 2

(A) Preparation of binary solid dispersions, (B) Preparation of ternary solid dispersions.

Figure 3

Saturation solubility data of pure Irbesartan and solid dispersions in (a) pH 6.8 phosphate buffer, (b) 0.1 N HCl (pH 1.2) (n = 3, mean ± SD).

Figure 4

Dissolution profile of binary solid dispersions prepared with Soluplus^® in (a) pH 6.8 phosphate buffer (b) 0.1 N HCl (n = 3, mean ± SD).

Figure 5

Dissolution profile of pure Irbesartan and binary solid dispersions prepared with Kollidon^® VA 64 in (a) pH 6.8 phosphate buffer (b) 0.1 N HCl (n = 3, mean ± SD).

Figure 6

Dissolution profile of pure Irbesartan and ternary solid dispersions prepared with Kolliphor^® P 407 in (a) pH 6.8 phosphate buffer (b) 0.1 N HCl (n = 3, mean ± SD).

Figure 7

Dissolution profile of pure Irbesartan and ternary solid dispersions formulated with PVP- K30 in (a) pH 6.8 phosphate buffer (b) 0.1 N HCl (n = 3, mean ± SD).

Figure 8

SEM micrographs of (A,B) pure Irbesartan, (C) S_1, (D) K_4, (E) KP407 (TD₃), and (F) KPVP (TD₃) formulations.

Figure 9

PXRD data of (A) Irbesartan and binary solid dispersions: (a) pure Irbesartan, (b) Kollidon^® VA 64, (c) binary solid dispersion of drug and Kollidon^® VA 64 at ratio 1:4 [K₄], (d) Soluplus^®, (e) binary dispersion of drug and Soluplus^® at ratio 1:1 [S₁]. (B) Irbesartan and ternary solid dispersions: (a) pure Irbesartan, (b) Kollidon^® VA 64, (c) Kolliphor^® P 407, (d) Polyvinylpyrrolide- K30, (e) ternary solid dispersion KP407 (TD₃), (f) ternary solid dispersion KPVP (TD₃).

Figure 9

PXRD data of (A) Irbesartan and binary solid dispersions: (a) pure Irbesartan, (b) Kollidon^® VA 64, (c) binary solid dispersion of drug and Kollidon^® VA 64 at ratio 1:4 [K₄], (d) Soluplus^®, (e) binary dispersion of drug and Soluplus^® at ratio 1:1 [S₁]. (B) Irbesartan and ternary solid dispersions: (a) pure Irbesartan, (b) Kollidon^® VA 64, (c) Kolliphor^® P 407, (d) Polyvinylpyrrolide- K30, (e) ternary solid dispersion KP407 (TD₃), (f) ternary solid dispersion KPVP (TD₃).

Figure 10

FTIR data of (A) Soluplus^®-based solid dispersion formulation: (a) pure Irbesartan, (b) Soluplus^®, (c) binary system of drug and Soluplus^® at ratio 1:1 [S₁]. (B) Kollidon^® VA 64-based solid dispersion formulation: (a) pure Irbesartan, (b) Kollidon^® VA 64, (c) binary solid dispersion of drug and Kollidon^® VA 64 at ratio 1:4 [K₄]. Note: Background noise may be present along with signals of compounds in FTIR display.

Figure 11

FTIR data of (A) Kolliphor^® P 407-based ternary solid dispersions formulation: (a) pure Irbesartan, (b) Kolliphor^® P 407, (c) Kollidon^® VA 64, (d) ternary system KP407 (TD₃). (B) Polyvinylpyrrolidone-K30-based ternary solid dispersions formulation: (a) pure Irbesartan, (b) Polyvinylpyrrolidone-K30, (c) Kollidon^® VA 64, (d) ternary solid dispersion KPVP (TD₃). Note: Background noise may be present along with signals of compounds in FTIR display.

Figure 12

DSC curves of (A) Irbesartan and binary solid dispersions: (a) pure Irbesartan, (b) Soluplus^®, (c) Kollidon^® VA 64, (d) binary dispersion of drug and Soluplus^® at ratio 1:1 [S₁], (e) binary solid dispersion of drug and Kollidon^® VA 64 at ratio 1:4 [K₄]. (B) Irbesartan and ternary solid dispersions: (a) pure Irbesartan, (b) Kollidon^® VA 64, (c) Kolliphor^® P 407, (d) Polyvinylpyrrolide- K30 (PVP-K30), (e) ternary solid dispersion KP407 (TD₃), (f) ternary solid dispersion KPVP (TD₃).