Enhancement of dissolution profile of poorly aqueous soluble atorvastatin calcium by binary and ternary solid dispersion techniques

Atorvastatin calcium (ATV) is an HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitor commonly known as a cholesterol-lowering agent. As a poorly water-soluble drug its absolute bioavailability is very low. To increase the water solubility as well as oral bioavailability, different hydrophilic carriers were used in different ratios (1:0.5, 1:1 and 1:2) to prepare reproducible binary and ternary solid dispersion formulations of ATV by simple physical mixing (PM) and fusion or melting technique. In vitro dissolution studies results revealed that in all cases, the cumulative percent drug release from ATV ternary SD formulations were greater than binary formulations, some marketed products and pure ATV powder. The order of the carriers in enhancing the drug release was found as kollidon 90F > pregelatinized starch > lutrol> kollidon 12F (99.1%, 98.8%, 96% and 95% respectively) for ternary SD formulations whereas pure ATV powder and marketed products showed cumulative percentage release 70.8%, 68.9% (B1) and 73.1% (B2), respectively. The best-out performed ternary SD formulation ATV:Kollidon 90 F (1:2) were further characterized using FT-IR and SEM. SEM analyses indicated conversion of crystal drug to amorphous form and FT-IR data suggested that little or no interaction between the drug and polymer. Bangladesh J. Sci. Ind. Res.56(3), 165-176, 2021

FUNDAMENTAL ASPECTS OF A THIRD COMPONENT USED IN TERNARY SOLID DISPERSION: A REVIEW

Ternary solid dispersion (TSD) is one of the promising approaches used in recent studies to address the issues encountered by poorly water-soluble drugs. The binary solid dispersion (BSD) with the drug and the single polymer is not sufficient to satisfy all the criteria such as improved solubility, dissolution, stability, supersaturation, and recrystallization inhibition. Hence, the TSD with the third component/ternary agent aids in overcoming the limitations, thereby enhancing the solubility and bioavailability to a greater extent when compared to the BSD. Excipients that can be used as a third component includes surfactants, pH modulator, polymer and adsorbents. All these excipients have distinct benefits in improving the efficiency of the final dosage form. However, care must be taken in selecting suitable excipients for the research. This review highlights the impact of these excipients in improving the formulation complications and the therapeutic potential of the TSD.

Ternary Solid Dispersion Strategy for Solubility Enhancement of Poorly Soluble Drugs by Co-Milling Technique

Amorphous ternary solid dispersion has become one of the strategies commonly used for improving the solubility and bioavailability of poorly water soluble drugs. Such multicomponent solid dispersion can be obtained by different techniques, this chapter provides an overview of ternary solid dispersion by co-milling method from the perspectives of physico-chemical characteristics in vitro and in vivo performance. A considerable improvement of solubility was obtained for many active pharmaceutical ingredients (e.g., Ibuprofen, Probucol, Gliclazid, Fenofibrate, Ibrutinib and Naproxen) and this was correlated to the synergy of multiple factors (hydrophilicity enhancement, particle size reduction, drug-carrier interactions, anti-plasticizing effect and complexation efficiency). This enhanced pharmacokinetic properties and bioavailability of these drug molecules (1.49 to 15-folds increase in plasma drug concentration). A particular focus was accorded to compare the ternary and binary system including Ibuprofen and highlighting the contribution of thermal and spectral characterization techniques. The addition of polyvinylpyrrolidone (PVP K30), a low molecular weight molecule, into the binary solid dispersion (Ibuprofen/β-cyclodextrin), leads to a 1.5–2 folds increase in the drug intrinsic dissolution rate only after 10 min. This resulted from physical stabilization of amorphous Ibuprofen by reducing its molecular mobility and inhibiting its recristallization even under stress conditions (75% RH and T = 40°C for six months).

DEVELOPMENT OF AMORPHOUS BINARY AND TERNARY SOLID DISPERSIONS OF NATEGLINIDE FOR IMPROVED SOLUBILITY AND DISSOLUTION

Objective: Nateglinide is a commonly used oral hypoglycemic, biopharmaceutical classification system Class II drug, which shows relatively poor water solubility and variable bioavailability. The objective of the present investigation was to develop the binary and ternary solid dispersions of nateglinide for improved solubility and dissolution. Methods: Nateglinide solid dispersions were prepared by a common solvent evaporation method. Polymers like soluplus, kolliphor P188, sylloid 244FP, gelucire 48/16, affinisol (HPMCAS), HPβCD, βCD were used in different combinations. The physicochemical characterization of the optimized ternary dispersion was studied by using FT-IR, DSC, and PXRD. Solubility and dissolution behavior of all dispersions were studied. Result: From all prepared ternary solid dispersions, nateglinide dissolution was significantly faster than pure nateglinide. With ternary solid dispersion of NTG, soluplus and kolliphor P188 there was a big improvement in solubility and dissolution. This combination enhanced the solubility of NTG by 23 folds. Another ternary dispersion of NTG with soluplus and gelucire 48/16 enhanced solubility by 25 fold. Conclusion: Ternary solid dispersion found superior over binary dispersions. For the ternary dispersions, showing the best solubility, tablets were prepared. Dissolution and drug release from the formulated tablet was as good as a marketed product.