Spray-Dried Amorphous Solid Dispersions of Atorvastatin Calcium for Improved Supersaturation and Oral Bioavailability

Abstract

Over the past few decades, the amorphous solid dispersions (ASDs) technique has emerged as a promising strategy to enhance the in vitro/in vivo characteristic of hydrophobic drugs. The low aqueous solubility and poor bioavailability of atorvastatin calcium (ATO), a lipid-lowering drug, present challenges for effective drug delivery. The objective of this work was to improve the aqueous solubility, in vitro dissolution, and oral absorption of ATO with amorphous solid dispersion technique prepared by spray-drying method. The optimized ternary formulation comprising of ATO; hydroxypropyl methylcellulose (HPMC), as a hydrophilic polymer; and sodium lauryl sulfate (SLS), as a surfactant, at a weight ratio of 1/1/0.1, showed significant improvement in aqueous solubility by ~18-fold compared to that of the free drug, and a cumulative release of 94.09% compared to a release of 59.32% of the free drug. Further, physicochemical studies via scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction revealed a change from the crystalline state of the free drug to its amorphous state in the ASD. Pharmacokinetic analysis in rats demonstrated 1.68- and 2.39-fold increments in AUC and Cmax, respectively, in the ASD over the free drug. Altogether, hydrophilic carrier-based ASDs prepared by the spray-drying technique represent a promising strategy to improve the biopharmaceutical performance of poorly soluble drugs.

Self-Micellizing Technology Improves the Properties of Ezetimibe and Increases Its Effect on Hyperlipidemic Rats

“…These results confirm the increase in crystallization of the MC carrier observed in the PXRD studies for PM and MS-K (1:0.1), and the decrease in crystallinity of the croscarmellose carrier for MS-K (1:0.3). Similar processes of partial amorphization of EZ have been used to obtain EZ nanoparticles [24] or micro/nanoparticles of poorly soluble drugs [25,26]. However, the inclusion of MS-K (1:0.6) and MS-K (1:0.75) surfactant ratios does not display the endothermic peak attributed to croscarmellose (Figure 3).…”

Mechanism and Improved Dissolution of Glycyrrhetinic Acid Solid Dispersion by Alkalizers

“…SEM, DSC, XPRD, FTIR, Raman, XPS, and a molecular model were used to perform solid-state characterizations and to study the dissolution mechanism of the TSDs. Among the known technologies, amorphous solid dispersions have become one of the most effective methods of enhancing the solubility and gastrointestinal absorption of poorly soluble drugs [18][19][20]. Hot melt extrusion technology has been widely adopted because it offers continuous control and because it is solvent free and less time consuming.…”

Improvement in the Oral Bioavailability and Efficacy of New Ezetimibe Formulations—Comparative Study of a Solid Dispersion and Different Micellar Systems

“…Amphiphilic polymers and surfactants in a solid state are currently mixed with SD to prepare micellar systems by dispersion in aqueous media, and are known as ternary SD or micellar systems (MS) [ 3 , 4 ]. Surfactants such as sodium dodecyl sulphate, Tween 80 or Kolliphor ® RH40 have been used in MS to increase the dissolution profile of poorly soluble drugs [ 4 ].…”

“…Amphiphilic polymers and surfactants in a solid state are currently mixed with SD to prepare micellar systems by dispersion in aqueous media, and are known as ternary SD or micellar systems (MS) [ 3 , 4 ]. Surfactants such as sodium dodecyl sulphate, Tween 80 or Kolliphor ® RH40 have been used in MS to increase the dissolution profile of poorly soluble drugs [ 4 ]. The presence of surfactants in MS increases the molecular dispersion of the drug within the polymer chains, producing an amorphous form of the drug with low drug-to-polymer ratios between 1:1 and 1:3 [ 4 ].…”