Recent Technologies for Amorphization of Poorly Water-Soluble Drugs

Abstract

Amorphization technology has been the subject of continuous attention in the pharmaceutical industry, as a means to enhance the solubility of poorly water-soluble drugs. Being in a high energy state, amorphous formulations generally display significantly increased apparent solubility as compared to their crystalline counterparts, which may allow them to generate a supersaturated state in the gastrointestinal tract and in turn, improve the bioavailability. Conventionally, hydrophilic polymers have been used as carriers, in which the amorphous drugs were dispersed and stabilized to form polymeric amorphous solid dispersions. However, the technique had its limitations, some of which include the need for a large number of carriers, the tendency to recrystallize during storage, and the possibility of thermal decomposition of the drug during preparation. Therefore, emerging amorphization technologies have focused on the investigation of novel amorphous-stabilizing carriers and preparation methods that can improve the drug loading and the degree of amorphization. This review highlights the recent pharmaceutical approaches utilizing drug amorphization, such as co-amorphous systems, mesoporous particle-based techniques, and in situ amorphization. Recent updates on these technologies in the last five years are discussed with a focus on their characteristics and commercial potential.

A New Challenge for the Old Excipient Calcium Carbonate: To Improve the Dissolution Rate of Poorly Soluble Drugs

“…Unfortunately, their use is limited by their instability. In fact, due to the high energy state of the amorphous form, it has a strong tendency to convert to the crystalline state, with a loss of the acquired advantages [ 40 ]. Among the strategies proposed for stabilizing the amorphous solids, the use of mesoporous compounds, such as ordered mesoporous silica, has been largely proposed.…”

Benchmarking the Solubility Enhancement and Storage Stability of Amorphous Drug–Polyelectrolyte Nanoplex against Co-Amorphous Formulation of the Same Drug

“…Approximately 40% of marketed drugs and 70% of newly discovered drugs possess poor aqueous solubility [ 1 ], resulting in their low systemic bioavailability upon administration and consequently low therapeutic efficacy. Amorphization represents a well-established solubility enhancement strategy of poorly soluble drugs by virtue of the metastable form of amorphous drugs that results in a lower energy barrier for dissolution compared to crystalline drugs [ 2 ]. In addition to faster dissolution, amorphous drugs are capable of generating a highly supersaturated drug concentration, resulting in a drug’s kinetic solubility that is multifold higher than its thermodynamic solubility [ 3 ].…”

Prediction and Preparation of Coamorphous Phases of a Bislactam

“… 1 A COAM material is defined as a mixture of multiple low-molecular-weight components in a single-phase homogeneous amorphous system. 2 − 6 The main research interest for COAM systems is for pharmaceutical products; therefore, at least one of the components is usually an active pharmaceutical ingredient (API) and the other is either an inactive coformer or another API. 3 , 7 , 8 COAM materials are of interest to the pharmaceutical industry due to the increased stability of COAM systems compared to the amorphous solids while retaining the dissolution advantage of an amorphous form.…”

“…The term coamorphous (COAM) system was first introduced by Rades and co-workers in 2009 based on an amorphous material comprising a mixture of ranitidine hydrochloride and indomethacin, which was initially described as a “comilled amorphous sample” . A COAM material is defined as a mixture of multiple low-molecular-weight components in a single-phase homogeneous amorphous system. − The main research interest for COAM systems is for pharmaceutical products; therefore, at least one of the components is usually an active pharmaceutical ingredient (API) and the other is either an inactive coformer or another API. ,, COAM materials are of interest to the pharmaceutical industry due to the increased stability of COAM systems compared to the amorphous solids while retaining the dissolution advantage of an amorphous form. − The COAM systems also help overcome some of the key issues of polymeric amorphous solid dispersions (PASDs), including the hygroscopicity and large ratio of polymers required to stabilize the API. − …”