Stable amorphous binary systems of glipizide and atorvastatin powders with enhanced dissolution profiles: formulation and characterization

Abstract

The aim of this study was to enhance the dissolution profile of the combination of glipizide and atorvastatin used for simultaneous treatment of hyperglycemia and hyperlipidemia. The strategy to formulate coamorphous glipizide-atorvastatin binary mixture was explored to achieve enhancement in dissolution. The coamorphous glipizide-atorvastatin mixtures (1:1, 1:2 and 2:1) were prepared by cryomilling and characterized with respect to their dissolution profiles, preformulation parameters and physical stability. Amorphization was found to be possible by cryomilling at various tried ratios of the two drugs. The data obtained from glass transition temperatures and from Raman spectroscopy point toward practically no interaction between the two drugs. The dissolution studies revealed the highest enhancement in dissolution profiles of cryomilled coamorphous mixtures containing GPZ:ATV in ratios 1:1 (B-5) and 2:1 (B-7). These two mixtures were, therefore, subjected to studies for the evaluation of precompression parameters in order to find their amenability to satisfactory compression into tablet dosage form. The selected formulation was found to be stable when subjected to accelerated stability testing at 40°. C/75% RH for six months as per ICH guidelines. Based on all these studies, it was concluded that GPZ:ATV (1:1) combination may be able to provide an effective therapy for the comorbidities of hyperglycemia and hyperlipidemia.

Advances in coamorphous drug delivery systems

“…Recently, using liquid nitrogen as a coolant, cryo-milling has received considerable interest in producing coamorphous formulations 16 , 22. , 23. , 24.…”

Co-Amorphous Solid Dispersions for Solubility and Absorption Improvement of Drugs: Composition, Preparation, Characterization and Formulations for Oral Delivery

“…Processing into a tablet or capsules form has the risk of crystallization due to the influence of environmental factors (moisture, temperature), while mechanical stresses during compression into tablets may alter the amorphous structure, the stability and the dissolution profile [ 18 , 23 , 99 ]. Other problems arising from the soft and sticky nature of the amorphous SDs may be difficulty in granulation and sieving, poor flowability and compressibility [ 100 ].…”

Coamorphous Active Pharmaceutical Ingredient–Small Molecule Mixtures: Considerations in the Choice of Coformers for Enhancing Dissolution and Oral Bioavailability

“…Tablets have been produced using coamorphous systems. 107,116,117 The first step is to determine excipient compatibility between the coamorphous solid and proposed excipients. 117 Precompression studies are commonly performed for tablet formulations, and an investigation of milled and unmilled coamorphous powders may include angle of repose, bulk density, tapped density, Carr's index, and Hausner's ratio.…”

“…In 1 study, the tablets were tested for hardness, friability, and disintegration time. 116 Another study with spray-dried indomethacin-arginine measured compaction pressure, porosity, tensile strength, and disintegration time for tablets. 107 Late formulation development can use Quality by Design principles as reported for the telepravir ASD drug product.…”