Physicochemical Characterization of a Co-Amorphous Atorvastatin-Irbesartan System with a Potential Application in Fixed-Dose Combination Therapy

Abstract

The aim of this study was to characterize a 1:1 molar ratio of a pharmacologically relevant co-amorphous atorvastatin-irbesartan (ATR-IRB) system obtained by quench cooling of the crystalline ATR/IRB physical mixture for potential use in the fixed-dose combination therapy. The system was characterized by employing standard differential scanning calorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and intrinsic dissolution rate studies. Quantum mechanical calculations were performed to obtain information regarding intermolecular interactions in the studied co-amorphous ATR-IRB system. The co-amorphous formulation showed a significant improvement in the intrinsic dissolution rate (IDR) of IRB over pure crystalline as well as its amorphous counterpart. An unusual behavior was observed for ATR, as the IDR of ATR in the co-amorphous formulation was slightly lower than that of amorphous ATR alone. Short-term physical aging studies of up to 8 h proved that the ATR-IRB co-amorphous system remained in the amorphous form. Furthermore, no physical aging occurred in the co-amorphous system. FT-IR, density functional theory calculations, and analysis of Tg value of co-amorphous system using the Couchman–Karasz equation revealed the presence of molecular interactions between APIs, which may contribute to the increased physical stability.

Understanding the Effect of Energy Density and Formulation Factors on the Printability and Characteristics of SLS Irbesartan Tablets—Application of the Decision Tree Model

“…Crystalline irbesartan shows characteristic absorption bands at 1730 and 1620 cm −1 , assigned to the carbonyl moiety of the carboxyl group and the C=N bond in the diazaspiro ring vibrations, respectively (Figure 7). These values are similar to those reported by Skotnicki et al (1733 and 1617 cm −1 ) and Yan et al (1732 and 1616) [38,39]. The FT-IR spectrum of HPMC displays a peak at 3450 cm −1 , revealing the presence of hydroxyl group (OH) stretching.…”

Thermodynamic Mechanism of Physical Stability of Amorphous Pharmaceutical Formulations

“…Calculations were performed using a relatively small system on behalf of the entire ASDs (one API molecule and two polymer monomers). Structural optimization and energy calculations were performed using the B3LYP functional (6-31G­(d,p)) of Gaussian G16 software. , To reliably calculate the binding energy ( E binding ) between the API and the polymer, it was corrected by the basis set superposition error (BSSE). , E binding was analyzed according to eq . Furthermore, the electrostatic potential (ESP) and independent gradient model (IGM) analysis were performed with Multiwfn wavefunction program to visualize the surface ESP and E binding …”

“…Structural optimization and energy calculations were performed using the B3LYP functional (6-31G(d,p)) of Gaussian G16 software. 41,42 To reliably calculate the binding energy (E binding ) between the API and the polymer, it was corrected by the basis set superposition error (BSSE). 43,44 E binding was analyzed according to eq 14.…”

Pemilihan Jenis Koformer dan Metode Preparasi dalam Sistem Penghantaran Sediaan Ko-Amorf

“…Pemberian obat secara simultan dalam satu unit dosis menghasilkan kepatuhan pasien yang lebih baik dan bahan pengisi yang minimal. Telah banyak dilakukan penelitian pembentukan ko-amorf dengan kombinasi dua zat aktif yaitu diantaranya Simvastatin-Glipizide [23], Ritonavir-Indomethacin [24], Ezetimibe-Indapamide [25], Ezetimibe-Lovastatin [26], Curcumin-Piperazine [27], Simvastatin-Nifedipine [28], Indomethacin-Naproxen, Nifedipine-Paracetamol dan Paracetamol-Celecoxib [29], Valsartan-Nifedipine [30], Febuxostat-Indomethacin [31], Atorvastatin-Irbesartan [32]. Ko-amorf Atenolol-Hydrochlorothiazide (1:1 M) berhasil dibentuk dengan metode cryogenic milling, dengan disolusi Hydrochlorothiazide meningkat 12,5 kali lipat dari Hydrochlorothiazide kristal, yang secara fisik stabil selama penyimpanan 30 hari pada suhu 4 °C dan 25 °C.…”

“…Suhu transisi gelas (Tg) merupakan parameter fisik penting zat aktif amorf karena menunjukkan batas antara fase mobilitas molekul rendah dan tinggi. Oleh karena itu, suhu transisi gelas dapat menyimpulkan kondisi penyimpanan zat aktif amorf [32].…”