Spray-Dried Amorphous Solid Dispersions of Griseofulvin in HPC/Soluplus/SDS: Elucidating the Multifaceted Impact of SDS as a Minor Component

This study aimed to elucidate the impact of a common anionic surfactant, sodium dodecyl sulfate (SDS), along with hydroxypropyl cellulose (HPC) and Soluplus (Sol) on the release of griseofulvin (GF), a poorly soluble drug, from amorphous solid dispersions (ASDs). Solutions of 2.5% GF and 2.5%–12.5% HPC/Sol with 0.125% SDS/without SDS were prepared in acetone–water and spray-dried. The solid-state characterization of the ASDs suggests that GF–Sol had better miscibility and stronger interactions than GF–HPC and formed XRPD-amorphous GF, whereas HPC-based ASDs, especially the ones with a lower HPC loading, had crystalline GF. The dissolution tests show that without SDS, ASDs provided limited GF supersaturation (max. 250%) due to poor wettability of Sol-based ASDs and extensive GF recrystallization in HPC-based ASDs (max. 50%). Sol-based ASDs with SDS exhibited a dramatic increase in supersaturation (max. 570%), especially at a higher Sol loading, whereas HPC-based ASDs with SDS did not. SDS did not interfere with Sol’s ability to inhibit GF recrystallization, as confirmed by the precipitation from the supersaturated state and PLM imaging. The favorable use of SDS in a ternary ASD was attributed to both the wettability enhancement and its inability to promote GF recrystallization when used as a minor component along with Sol.


S.2. Details of the Characterization Methods Used for Drug Wettability
Penetration of a liquid into a packed powder bed inside a cylindrical column allows for measurement of the powder wettability, based on the Washburn method [1,2]. The method presented here was adapted from Bilgili et al. [3] and Li et al. [4]. In the current study, powder and liquids, respectively, refer to GF (griseofulvin) powder and GF-saturated aqueous solutions of 15% Soluplus (Sol)/HPC with or w/o 0.125% SDS and 0.125% SDS alone. All percentages are (% w/w) with respective to deionized water. This polymer concentration was selected in order to measure the viscosity accurately in our viscometer set-up instead of the maximum viscosity of 12.5% used in the feed solutions. The solutions and deionized water were saturated with griseofulvin (GF) and stirred overnight. The saturated solutions were used for further characterization.

S.2.1. Apparent Shear Viscosity of the Solutions
The apparent shear viscosity of the solutions was measured using an R/S Plus Rheometer (Brookfield Engineering, Middleboro, MA, USA) with a water jacket assembly Lauda Eco (Lauda-Brinkmann LP, Delran, NJ, USA). A coaxial cylinder (CC40) was used to provide a controlled shear rate on the samples and shear rate from 0 to 1000 1/s for 60 s was used for all samples. The temperature of the jacket was kept constant at 25 ± 0.5 °C. The raw data were analyzed using the Rheo 3000 software (Brookfield Engineering, Middleboro, MA, USA) of the equipment to obtain the apparent shear viscosity as a function of the shear rate. The apparent shear viscosity at ~100 1/s was used as a representative low shear rate value. The viscosity of water and SDS solution were taken from Korson et al. [5] and Kushner et al. [6], respectively.

S.2.2. Surface Tension of the Solutions
The surface tension of the GF-saturated deionized water and the GF-saturated aqueous solutions of the polymer/surfactant was measured using an Attension Sigma 700 (Biolin Scientific, Linthicum, MD, USA). The Attension software calculates surface tension from force measurements of interaction of the probe (Wilhelmy plate) at the boundary between air and a liquid.

S.2.3. Drug Wettability with the Solutions
The Attension Sigma 700 set-up (Biolin Scientific, Linthicum, MD, USA) was used to study the penetration of GF-saturated deionized water/GF-saturated aqueous solutions of the polymer/surfactant into a packed powder bed of GF inside a cylindrical column and determine the GF wettability, based on the modified Washburn method. The assembly consists of a sample holder in the form of a cylindrical metallic tube with small holes at the bottom as well as a hook at the top of the cover equipped with screw threads. About 0.8 g of GF powder was packed uniformly into the tube before each measurement. A filter paper was placed at the perforated end of the sample holder to support the GF powder sample. A petri dish containing deionized water or polymer/surfactant solution was placed below the perforated end of the holder on the mechanical platform.
Upon contact of the sample holder with the liquid, the liquid penetrated the GF powder bed, while the Attension Sigma 700 recorded the mass M of the liquid penetrated as a function of time T. The cosine of the contact angle θ for the GF-saturated deionized water/GF-saturated aqueous polymer/surfactant solution and drug can be determined using the modified Washburn equation, which provides a relationship between the mass of liquid penetration and contact angle, via where η, ρ, and γ stand for viscosity of the liquid, density of the liquid, and surface tension of the liquid, respectively. C is a characteristic parameter of the powder sample, which could have been determined independently using a completely wetting liquid such as hexane, heptane, etc. Since the same drug powder (GF) was used as the powder sample and C depends only on the powder's packing-particle size, C remained invariant for different liquids studied here. This allows us to calculate the ratio of cosθs/cosθw as a wetting effectiveness factor from the slopes of M 2 vs. T for deionized water and the polymer/surfactant solution. Here, θs is the contact angle between GF and the polymer-surfactant solution and θw is the contact angle between GF and deionized water. The wettability enhancement upon the use of different polymers/surfactant on the wetting of GF particles can be assessed by using this ratio, taking the wettability by water as a basis for comparison.
Experimental liquid penetration data (M 2 vs. T) for various liquids are presented in Figure 7 of the main text. The slope of the modified Washburn equation, i.e., 2 , was obtained by fitting the linear region of the liquid penetration curve. The initial ~20 s was not considered due to transient behavior; data points that deviated from the linear region were also excluded. The modified Washburn equation fitted the data well (R 2 ≥ 0.98). Using the slope for the different polymer/surfactant solutions and water, cosθs/cosθw was calculated separately for each solution. The viscosity, surface tension, and calculated wetting effectiveness factor are reported in Table S2.  Figure  7 of the main text).

S.3. X-Ray Powder Diffractograms of SDS and As-Received Griseofulvin
Three intense non-overlapping peaks were detected at diffraction angles of 5.6°, 6.8°, and 8.3° in the SDS diffractogram ( Figure S2, peaks shown in the orange dashed rectangle).