Coamorphous Atorvastatin Calcium to Improve its Physicochemical and Pharmacokinetic Properties

Abstract

-Purpose: Atorvastatin calcium (ATC) is classified as class II (low solubility and high permeability) compound according to the biopharmaceutical classification system. The amorphous form of ATC possesses higher solubility, dissolution rate, and bioavailability than its crystalline form. Coamorphous drug system is a new and emerging method to prepare stable amorphous forms, in this case leading to the improved stability of ATC in dissolution medium. Methods: In this study, coamorphous form of ATC and nicotinamide (ATC-NIC) was prepared from solvent evaporation method and characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD). The intrinsic dissolution rate and solubility of ATC-NIC were determined along with plasma concentrations of ATC using HPLC after oral dosing in rats. Results: The crystalline ATC was converted to coamorphous form revealing a molecular interaction between ATC and NIC. The intrinsic dissolution rate, solubility and plasma concentration of coamorphous ATC-NIC are higher than those of crystalline ATC. ATC-NIC coamorphous system showed greater solution stability than those reported in the literature for amorphous ATC. Conclusions: Coamorphous ATC-NIC has improved physicochemical and pharmacokinetic properties as compared to ATC.

Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluation

“…Co-amorphous dispersions can be prepared from solutions of crystalline drugs, especially when rapid co-precipitation is pursued using carboxylic acids as plasticizing agents (12,13). Stable coamorphous systems have been prepared from low solubility drugs and small molecular mass amino acids (14) or neutral molecules capable of forming strong H-bonding such as saccharin (15) or nicotinamide (16). Although numerous successful plasticized formulations have been prepared using carboxylic acids (17)(18)(19)(20), plasticized co-amorphous dispersions prepared from crystalline drugs with polycarboxylic acids are rare.…”

Characterization and Stability of Amorphous Tadalafil and Four Crystalline Polymorphs

“…IDR was expected to correlate more closely with in vivo dissolution dynamics of drug than solubility, 28,29) which overcomes particle size and crystal habit effects during dissolution at the same time. 30) As shown in Fig.…”

Formulation and Evaluation of Tablet Prepared by Coamorphous System Containing Anti-Hypertensive and Anti-Hyperlipidemic Drug

“…A small amount of the triturated sample was taken into a pellet maker and was compressed at a 10 kg/cm 2 hydraulic press. The pellet was kept onto the sample holder and scanned from 4000 cm -1 to 600 cm -1 Preparation of amorphous precipitate of AML-ATR binary system [11,13] in FT-IR spectrophotometer (Shimadzu FTIR-8700). The spectra obtained were compared and interpreted for the functional group peaks.…”

“…These systems have been found to provide high stability and enhanced dissolution rates for the drugs. There are several publications in the area of amorphous binary systems like ritonavir with indomethacin, naproxen with cimetidine, simvastatin with glipizide, and atorvastatin with nicotinamide [11][12][13].…”