The Effect of Adding PVP to the Binary Solid Dispersion (Indomethacin: Kaolin) on the Formation of Physically Stable Amorphous Drug

Abstract

Purpose In this work, we investigate the effect of adding polyvinylpyrrolidone (PVP K30) to the binary solid dispersion (indomethacin/kaolin) on the formation of physically stable amorphous drug. This aims to profit more effectively from the therapeutic effect of kaolin in the solid dosage forms of indomethacin. Methods Binary mixtures (indomethacin/kaolin) were ball milled at room temperature (≈ 25 °C) in presence of PVP K30 at different weight ratios (w/w). The characterization of the obtained materials was carried out using X-ray diffraction (XRD), infrared spectroscopy (FTIR), scanning electronic microscopy (SEM), high-performance liquid chromatography (HPLC), differential scanning calorimetry (DSC), and 13 C MAS NMR spectroscopy. Results Results have shown that indomethacin (IND) interacted with kaolin and PVP K30 in solid state via hydrogen bonds without any polymorphic transformations or chemical degradation. The PVP seems to play a role of linker between drug and kaolin leading to physical stability enhancement of amorphous IND even under high stress conditions (RH = 75% and T = 40 °C for 3 months). Such ternary system (IND/kaolin/PVP) has shown a considerable improvement of drug solubility at T = 37 ± 0.5 °C and pH = 7.0 compared to the binary solid dispersion (IND/kaolin). Conclusions The addition of PVP to the solid dispersion (IND/kaolin) was advantageous not only in terms of physical stabilization of the amorphous IND but also made it possible to overcome the solubility challenges associated with the presence of kaolin.

Multifunctional Roles of PVP as a Versatile Biomaterial in Solid State

“…In our recent published work [55], we have studied the solid dispersion of binary system (indomethacin/kaolin) in the presence of PVP K30 by co-milling technique [55]. The milling procedure was carried out in a high-energy planetary ball mill (Pulverisette 7, Fritsch), using the stable γ form of indomethacin (IND, Figure 3).…”

“…The milling procedure was carried out in a high-energy planetary ball mill (Pulverisette 7, Fritsch), using the stable γ form of indomethacin (IND, Figure 3). The milling parameters were optimized in order to avoid polymorphic transformations or chemical degradation of drug molecules [55].…”

“…Main results of characterization techniques are summarized in Table 4 (curves not shown, [55]). According to XRD results [55], the addition of variable amount of PVP to the binary mixture (IND:kaolin, in 1:1 ratio) led to the loss of drug crystallinity.…”

“…Main results of characterization techniques are summarized in Table 4 (curves not shown, [55]). According to XRD results [55], the addition of variable amount of PVP to the binary mixture (IND:kaolin, in 1:1 ratio) led to the loss of drug crystallinity. IND particles were totally coated by amorphous films of the polymer as shown by SEM micrographs (Table 4), and this was completely different to that observed in the binary mixture (IND:kaolin, in 1:1 ratio) [55].…”

“…According to XRD results [55], the addition of variable amount of PVP to the binary mixture (IND:kaolin, in 1:1 ratio) led to the loss of drug crystallinity. IND particles were totally coated by amorphous films of the polymer as shown by SEM micrographs (Table 4), and this was completely different to that observed in the binary mixture (IND:kaolin, in 1:1 ratio) [55]. Amorphous drug molecules maintain its physical stability even after exposure to stress conditions (RH: 75% and T = 40°C) for 6 months [55].…”