Investigation into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: A Rational Step toward the Design and Development of a Multicomponent Amorphous System

Abstract

The formulation of oral amorphous solid dispersions (ASD) includes the use of excipients to improve physical stability and enhance bioavailability. Combinations of excipients (polymers and surfactants) are often employed in pharmaceutical products to improve the delivery of poorly water-soluble drugs. However, additive interactions in multicomponent ASD systems have not been extensively studied and may promote crystallization in an unpredictable manner, which in turn may affect the physical stability and dissolution profile of the product. The main aim of this study was to understand the effect of different surfactant and polymer combinations on the solid-state properties and dissolution behavior of ternary spray-dried solid dispersions of dipyridamole and cinnarizine. The surfactants chosen for this study were sodium dodecyl sulfate and poloxamer 188, and the model polymers used were polyvinylpyrrolidone K30 and hydroxypropyl methylcellulose K100. The spray-dried ternary dispersions maintained higher supersaturation compared to either the crystalline drug equilibrium solubility or their respective physical mixtures. However, rapid and variable dissolution behavior was observed for different formulations. The maximum supersaturation level was observed with drug-polymer-polymer ternary dispersions. On the other hand, incorporating the surfactant into binary (drug-polymer) and ternary (drug-polymer-polymer) ASDs adversely affected the physical stability and dissolution by promoting crystallization. On the basis of these observations, a thorough investigation into the impact of combinations of additives on amorphous drug crystallization during dissolution and stability studies is recommended in order to develop optimized formulations of supersaturating dosage forms.

Evaluation of Dissolution Enhancement of Aprepitant Drug in Ternary Pharmaceutical Solid Dispersions with Soluplus® and Poloxamer 188 Prepared by Melt Mixing

“…Therefore, the present study attempts to extent the prior preliminary efforts made for the preparation of an effective APT SD system. Specifically, an in-depth evaluation of the binary SD of APT with Soluplus ® (an amphiphilic copolymer and solubilizer), recently studied by several different research groups [18][19][20][21], with the addition of a surface active compound like Poloxamer 188, a nonionic polyoxyethylene-polyoxypropylene copolymer widely used as an additive in temperature-based SD preparation methods [48,49,[51][52][53], and the preparation of ternary APT-based SD systems, are being evaluated for the first time. One additional advantage of our study is that these solid dispersions have been prepared my melt extrusion procedure, which is a new technique applied in pharmaceutical technology.…”

Evaluation of Dissolution Enhancement of Aprepitant Drug in Ternary Pharmaceutical Solid Dispersions with Soluplus® and Poloxamer 188 Prepared by Melt Mixing

“…Therefore, the present study attempts to extent the prior preliminary efforts made for the preparation of an effective APT SD system. Specifically, an in-depth evaluation of the binary SD of APT with Soluplus ® (an amphiphilic copolymer and solubilizer), recently studied by several different research groups [18][19][20][21], with the addition of a surface active compound like Poloxamer 188, a nonionic polyoxyethylene-polyoxypropylene copolymer widely used as an additive in temperaturebased SD preparation methods [48,49,[51][52][53], and the preparation of ternary APT-based SD systems, are being evaluated for the first time. One additional advantage of our study is that these solid dispersions have been prepared my melt extrusion procedure, which is a new technique applied in pharmaceutical technology.…”

<p>Improvements in the Oral Absorption and Anticancer Efficacy of an Oxaliplatin-Loaded Solid Formulation: Pharmacokinetic Properties in Rats and Nonhuman Primates and the Effects of Oral Metronomic Dosing on Colorectal Cancer</p>

“…Moreover, the amorphous solid powder consists of a chemically homogenous phase in which all components were uniformly mixed at the molecular level. 42 Several studies have suggested that the transformation of the crystalline form of drug to an amorphous form significantly increases its aqueous solubility, dissolution rate, and solid-state stability. 42 In addition, polymers used in the formulation could act as crystallization inhibitors and reduce the particle size, thereby achieving better wettability and preventing recrystallization.…”