Effect of the pH grade of silicates on chemical stability of coground amorphous quinapril hydrochloride and its stabilization using pH-modifiers

Complex Effects of Drug/Silicate Ratio, Solid-State Equivalent pH, and Moisture on Chemical Stability of Amorphous Quinapril Hydrochloride Coground with Silicates

“…Neat amorphous QHCl and QHCl/Neusilin coground amorphous samples were prepared using a cryo‐mill (6750 Freezer/Mill®; SPEX SamplePrep, Metuchen, New Jersey) under the optimized cryogrinding conditions reported previously 13. QHCl/Neusilin coground amorphous samples containing 5%, 25%, 50%, 75%, and 95% (w/w) of either Neusilin US2 or Neusilin FL2 were prepared.…”

“…As a control, neat amorphous QHCl was also stored at 40°C and 0%, 11.5%, 31.6%, and 48% RH. Because the glass transition temperature of the neat amorphous QHCl is 51°C at 48% RH and below 40°C at 75% RH,13 its stability was investigated at 40°C only up to 48% RH, that is, below the glass transition temperature ( T g ). In contrast to the neat amorphous drug, QHCl/Neusilin coground amorphous samples remained amorphous powders even at 40°C/75% RH and, therefore, stability of the coground samples was investigated up to 75% RH.…”

“…Preparation of amorphous drugs using silicates resulted in improved physical stability with corresponding enhanced dissolution rate and, in some cases, bioavailability of poorly soluble drugs 6–9. However, silicates may have detrimental effects on chemical stability of amorphous drugs 10–13. For instance, in our previous study, pH grade of silicates was identified as a major factor affecting the chemical stability of amorphous quinapril hydrochloride (QHCl) 13.…”

“…However, silicates may have detrimental effects on chemical stability of amorphous drugs 10–13. For instance, in our previous study, pH grade of silicates was identified as a major factor affecting the chemical stability of amorphous quinapril hydrochloride (QHCl) 13. Accordingly, the use of pH modifiers or selection of silicates with appropriate pH grades resulted in improved stability of the amorphous formulation.…”

Highly efficient amorphization of drugs by the participation of molecular complex

“…Apart from well established methods of drug amorphization by grinding with additives [4][5][6] or melt quenching [7,8], role of coexisting polymeric species has gathered increasing interests for this purpose [9]. Indeed, one of the authors with other coauthors recently reported that sorption of a solvent (methanol) by the drug, ibuprofen (IB), in the coexistence of hydrophilic polymeric species, hydroxypropyl methyl cellulose (HPMC) brought about autogenous amorphization without applying any external physical stimuli [10].…”