Bakhtiari, Sara E; Zhu, Zilan; Magdysyuk, Oxana V; Brocchini, Steve; Williams, Gareth R; (2023) Amorphous Solid Dispersions of Lidocaine and Lidocaine HCl Produced by Ball Milling with Well-Defined RAFT-Synthesised Methacrylic Acid Polymers. International Journal of Pharmaceutics , 644 , Article 123291. 10.1016/j.ijpharm.2023.123291.

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Abstract

This study focuses on the use of methacrylic acid polymers synthesised via the Reversible Addition Fragmentation chain Transfer (RAFT) polymerisation method for the production of amorphous solid dispersions (ASDs) by ball milling, to kinetically solubilize a poorly water-soluble model drug. The solid-state characteristics and the physical stability of the formulations were investigated using X-ray diffraction, differential scanning calorimetry, and infrared spectroscopy. This was followed by dissolution studies in different media. It was discovered that the acidic polymers of methacrylic acid were capable of interacting with the weakly basic drug lidocaine and its hydrochloride salt form to produce ASDs when a polymer to drug ratio of 70:30 w/w was used. The ASDs remained amorphous following storage under accelerated aging conditions (40 °C and 75% relative humidity) over 8 months. Fast dissolution and increased lidocaine solubility in different media were obtained from the ASDs owing to the reduced microenvironment pH and enhanced solubilization of the drug caused by the presence of the acidic polymer in the formulation. Production of ASDs using well-defined RAFT-synthesised acidic polymers is a promising formulation strategy to enhance the pharmaceutical properties of basic poorly water-soluble drugs.

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