Atypical effects of incorporated surfactants on stability and dissolution properties of amorphous polymeric dispersions

Abstract

We suggest that surfactants can hinder the dissolution by promoting aggregation of polymeric chains, however that effect depends mainly on how the particles were prepared.

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

“…The temperatures ranged from 2°C to 60°C and the relative humidity varied between 0% and 100%. The duration also varied significantly, with stability studies lasting from 24 h to two years (73,74,81,82,84,86,88,92,93,104,105,109,110,113,115,116,118,120,123,124,126,127,129,130,132,134,135,139,143,146,149,153,158,166,169,172,175,176). While most of the studies did not mention the container used for the physical stability test, a few specified, for example, whether a closed or open container was used (88,92,113,123,132,146).…”

“…In the reviewed articles, no specific method was used in the investigation of amorphous solubility and dissolution behavior, even though different pharmacopoeia methods provide general guidance on how they should be performed. Ninety-two of the 101 studies reported solubility and dissolution studies (71–74,77–79,81–92,95,97–107,109–111,113–119,121,123,124,126–133,135–139,141–154,156,157,160,161,166,168–176). The USP in vitro dissolution type II apparatus was the most commonly used instrument (67%), followed by the USP type I apparatus (6%), while the remaining 27% used various other apparatuses, including modified versions of the USP type I only (148) or paired with confocal Raman microscopy (98), USP types I and II apparatus (72), USP type IV (152), closed loop of USP types II and IV (152), a perspex flow cell (73,142), a rotary mixer (131), a Chinese pharmacopoeia type III apparatus (118), an in-house miniaturized USP type II apparatus (175), Sirius T3 apparatus (146), μFLUX dissolution-permeation apparatus (141), Raman UV-Vis flow cell system (99), a centrifuge (88), high throughput screening using a 96-well plate (82,115,157), Wood’s apparatus (99,137), an orbital shaking incubator (156), and another shake-flask method (171) (Fig.…”

Pulmonary Drug Delivery of Antimicrobials and Anticancer Drugs Using Solid Dispersions

“…Most solid APIs exist in a crystalline state held together by strong intermolecular bonds, and therefore, display good stability profiles ( Figure 3 ). However, the crystalline state often shows poor solubility, due to the high energy required to break the crystalline lattice which creates a major problem for developing new APIs [ 112 , 113 ]. There has been much interest in the process of ‘drug amorphisation’, to address poor solubility, which involves the conversion from a crystalline state to an amorphous solid state.…”

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

“…The negative impact of the surfactant is believed to be due to reduction in T g (Table 2) and also may be due to molecular effects possibly promoting polymer chain entanglements and polymeric globule formation. 51 The globules formed in the spray drying solution seemed to be present in the solid state, and therefore, diffusion of the drug is reduced. This indicates the presence of a memory where incorporation of surfactant in the liquid state (spray drying solution) in the polymer chain remained even after the solid particles had formed.…”

“…29,30 However, currently there is very limited literature available on the preparation and characterization of spray-dried drug−polymer−surfactant dispersions, and therefore, it is of interest to study the effect of surfactants on ASD properties when incorporated within spray-dried ASDs. 31,32 Furthermore, the role of surfactants on drug release from ASDs has also been reviewed, with some studies finding a positive impact on the release kinetics of hydrophobic APIs, and others reporting a negative effect of surfactants on the dissolution of amorphous drugs from solid dispersions. 33,34 It is therefore reasonable to suggest that surfactants, like polymers, may have an impact on the physical stability and dissolution behavior of ASDs, and it is of interest to explore this possibility.…”