Interaction and Compatibility Studies in the Development of Olmesartan Medoxomil and Hydrochlorothiazide Formulations under a Real Manufacturing Process

Abstract

A drug–drug and drug–excipient interactions and compatibilities study was conducted for two fixed-dose combination (FDC) products containing olmesartan medoxomil (OLM)/hydrochlorothiazide (HCT) 20/12.5 mg and OLM/HCT 40/12.5 mg during their development including storage. The study consisted of the evaluation of samples retrieved during all stages of a real manufacturing process. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transform infrared spectroscopy (FT-IR), and contact angle techniques were applied to the samples to determine interactions and incompatibilities. Dissolution tests and long-term stability studies were conducted to evaluate dosage form performance. Results showed weak solid–state interactions able to obtain a eutectic mixture of OLM and HCT while microcrystalline cellulose (MC) impacted the thermal stability of both drugs. Reliable dissolution and long-term stability tests confirmed that the interactions observed were not considered incompatibilities because they were not influenced by the performance of the final products.

Potency and Powder X-ray Diffraction (PXRD) Evaluation of Levothyroxine Sodium Tablets under Ambient, Accelerated, and Stressed Conditions

“…PXRD was used as a technique to monitor the excipient compatibility of API [ 27 , 31 , 32 ]. The initial PXRD fingerprints obtained from the study samples were used as a baseline to monitor if changes in the formulation would be detectable through changes in their diffractograms.…”

“…A similar study used PXRD and other isothermal techniques to establish compatibility between propafenone HCl and lactose monohydrate [ 29 ]. Further studies reported PXRD as one of the spectroscopic methods for conducting API using excipient assessments to support the stability data for pharmaceutical products [ 30 , 31 , 32 ]. As there is evidence to support using PXRD to monitor formulation changes in pharmaceutical development, this study employed the technique as a tool to possibly detect changes in the diffractograms of the L-T 4 formulations used in the stability studies.…”

Host–Guest Interaction Study of Olmesartan Medoxomil with β-Cyclodextrin Derivatives

“…Other characteristic bands of OLM are noticed at 1225 and 1167 cm −1 due to C-O stretching from lactone and ester groups, at 1551, 1503 and 1474 cm −1 assigned to C=C stretching vibration of the aromatic ring, at 1389 cm −1 due to C=N stretching vibration, at 1136 cm −1 attributed to C-O stretching vibration from tertiary alcohol, at 953, 826, 816, 781, 770 cm −1 corresponding to C ar -H bending. The C-N stretching vibration appears at 1302 cm −1 , the NNN bending vibration arises at 1002 cm −1 and the NH wagging is shown at 760 and 741 cm −1 [42,43].…”

Modafinil-excipient compatibility study using differential scanning calorimetry

“…[ 22 ] However, there are many published articles concerning its incompatibility with pharmaceutical ingredients due to its hydrophobic nature, the presence of the positively charged magnesium ion, and its strong surface energetic behavior. [ 23 24 25 ] Gelucire 48/16 is a member of the Gelucire family, is a mixture of mono, di, and triglycerides with PEG esters of fatty acids, working as nonionic surfactants and used in lipid-based formulations to increase solubility and bioavailability of poorly soluble drugs. [ 26 ] However, there is a lack of research data regarding their compatibility behavior toward drugs.…”