Preparation of Spray Dried Coamorphous Solids to Improve the Solubility and Dissolution Rate of Atorvastatin Calcium

Abstract

Atorvastatin calcium (AC) is a statin drug used to lower cholesterol. Its crystalline form is usually found in the market with low solubility properties. The amorphization of crystalline AC is a technique used to increase its solubility however; the amorphous form has less thermodynamic stability. Therefore, to increase the solubility properties of its crystalline form, an AC coamorphous solid was prepared. This coamorphous solid was prepared using spray drying techniques, and coformers such as isonicotinamide (INA) and maleic acid (MA). Furthermore, characterization was carried out using powder X-ray diffraction, differential scanning calorimetry, fourier transform infrared spectroscopy, and scanning electron microscopy, while the solubility properties test was conducted using the shake-flask and paddle method. The results showed that the spray-dried solids were coamorphous with single-phase homogeneous systems. Furthermore, the coamorphous solids, AC-INA and AC-MA were found to have a higher Tg than the melting points of other components, and formed intermolecular interactions between them. The higher Tg and presence of intermolecular interactions indicate that coamorphous solids are more stable than the amorphous form. Therefore, the results of the solubility and dissolution test showed that the coamorphous solid of AC-INA and AC-MA have better solubility properties compared to the AC crystalline form.

Preparation of Atorvastatin Calcium-Dipicolinic Acid Multicomponent Solids by Liquid-Assisted Grinding Method to Increase Solubility

“…Dipicolinic acid has a broad absorption peak at wave number 3254-2363 cm -1 (O-H stretching) and a sharp absorption peak at 1692 cm -1 (C=O stretching). The FTIR spectra of both materials showed the same specific absorption peaks as mentioned in the literature (Wicaksono et al, 2021;Hiendrawan et al, 2016). The FTIR spectra of atorvastatin calcium -dipicolinic acid multicomponent solids showed a change in the intensity and shift of the absorption peak in the functional groups of atorvastatin calcium and dipicolinic acid.…”

“…Previous studies have shown that the formation of multicomponent solids of atorvastatin calcium, carried out with maleic acid coformers using the spray drying method, can increase the solubility of atorvastatin calcium in water significantly when compared to its pure solids form (Wicaksono et al, 2021). However, in evaluating lipid-lowering activity, the atorvastatin calcium-maleic acid multicomponent solids did not show increased lipid-lowering activity when compared to the lipid-lowering activity of pure atorvastatin calcium (Wicaksono et al, 2022).…”

“…The presence of molecules of dipicolinic acid in multicomponent solids changes the crystal packing arrangement so that it is thought to reduce the crystal lattice energy. The decrease in crystal lattice energy causes the multicomponent solids to be easily hydrated, which leads to increased solubility (Wicaksono et al, 2021;Docherty et al, 2015;Bergström & Larsson, 2018;Ozaki et al, 2014).…”

“…Atorvastatin calcium is a potent lipid-lowering drug that acts through a competitive inhibitory mechanism against HMG-CoA reductase (Cao et al, 2017;Gaviria-Mendoza et al, 2019). However, based on the Biopharmaceutical Classification System (BCS), atorvastatin calcium is a class II drug compound with high permeability but low solubility (Kwon et al, 2019;Wicaksono et al, 2021). This solubility property causes problems in the formulation process of atorvastatin calcium; namely, the oral bioavailability of the resulting preparation is relatively low.…”

Preparation and Physicochemical Characterizations of p-Methoxycinnamic acid – Succinic Acid Cocrystal by Solvent Evaporation Technique

“…However, PMCA is an active ingredient that is very difficult to dissolve with a solubility of 0.71 mg/mL at 25°C [1], [2]. Low solubility is a major problem in the development of new drugs because it affects the rate of drug dissolution and limited the drug's absorption [3], [4]. Therefore, it urges to find a method to increase the solubility of PMCA.…”