Determination of drug-polymer solubility from supersaturated spray-dried amorphous solid dispersions: A case study with Efavirenz and Soluplus®

Abstract

Amorphous solid dispersions (ASDs) are found to be a well-established strategy for overcoming limited aqueous solubility and poor oral bioavailability of active pharmaceutical ingredients (APIs). One of the main parameters affecting ASDs physical stability is the API solubility in the carrier, because this value determines the maximal API load without a risk of phase separation and recrystallization. Phase-diagrams can be experimentally obtained by following the recrystallization of the API from a supersaturated homogeneous API-polymer solid solution, commonly produced by processes as solvent casting or comilling, which are very time-consuming (hours). The work deals with the construction of a temperature-composition EFV-Soluplus® phase diagram, from a thermal study of recrystallization of a supersaturated solid solution (85 wt% in EFV) generated by spray drying. This supersaturated solution is kept at a given annealing temperature to reach the equilibrium state and the amount that still remains dispersed in the polymer carrier at this equilibrium temperature is determined by means of the new glass transition temperature of the binary mixture. From our knowledge, this is the first study employing a fast process (spray drying) to prepare a supersaturated solid solution of an API in a polymer aiming to determine a temperature-composition phase diagram. The EFV solubility in Soluplus ranges from 20 wt% at 25°C to 30 wt % at 40°C. It can be a very useful preformulation tool for researchers studying amorphous solid dispersions of Efavirenz in Soluplus, to assist for predicting the stability of EFV-Soluplus ASDs at different EFV loadings and under different thermal conditions.

Amorphous Form of Carvedilol Phosphate—The Case of Divergent Properties

“…It was shown that Pluronic ® F-127 showed a delay in release at acidic pH; however, at alkaline pH, it showed a significant improvement in API solubility, which was confirmed in the tests performed [54]. On the other hand, Soluplus shows the lowest solubility in acidic pH and the highest in alkaline pH; in the study, it was shown that the systems containing the polymer showed better solubility at higher pH, which confirms the assumption that the solubility of the entire system will depend on the solubility of the polymer used to compose the physical mixture [55,56]. The obtained results indicate the potential development of formulations containing carvedilol as an active substance based on selected polymers, allowing API release in a selected pH-dependent environment.…”

Effect of High-Energy Milling on the Dissolution of Anti-HIV Drug Efavirenz in Different Solvents

“… 1 − 3 The solubility of a drug substance is one of the significant parameters impacting absorption 4 as well as bioavailability, defined as the fraction of the administered dose of a drug that enters the systemic circulation, thereby accessing the site of action. 5 It is reported that EFV has a low aqueous solubility (9.2 μg mL –1 ) (pH 8.7) at 25 °C, 6 − 8 higher as the pH increases above 9, for the proton loss on the carbamate group’s amine. 6 Unfortunately, EFV tends to be eliminated in the human systemic circulation before the dissolution and absorption into the systemic circulation processes are completed, therefore requiring an increased dosage to achieve therapeutic levels in the body, often implying adverse effects for the patient.…”

Improved Bioavailability of Poorly Water-Soluble Drug by Targeting Increased Absorption through Solubility Enhancement and Precipitation Inhibition

“…Hydrophilic polymers, such as Soluplus ® , hydroxypropyl methylcellulose phthalate (HPMCP), and polyvinyl alcohol (PVA) enhance supersaturation and inhibit precipitation by employing hydrophobic interactions with drugs or intermolecular interactions, such as hydrogen bonds, ionic bonds, and van der Waals interactions [7][8][9][10]. Solvent evaporation and melting are mainly used to prepare amorphous SDs.…”