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  • Drug-polymer intermolecular interactions in hot-melt extruded solid dispersions.

Drug-polymer intermolecular interactions in hot-melt extruded solid dispersions.

International journal of pharmaceutics (2012-12-25)
Mohammed Maniruzzaman, David J Morgan, Andrew P Mendham, Jiayun Pang, Martin J Snowden, Dennis Douroumis
ABSTRACT

The purpose of the study was to investigate and identify the interactions within solid dispersions of cationic drugs and anionic polymers processed by hot-melt extrusion (HME) technique. Propranolol HCl (PRP) and diphenhydramine HCl (DPD) were used as model cationic active substances while pH sensitive anionic methacrylic acid based methyl methacrylate copolymers Eudragit L100 (L100) and ethyl acrylate copolymer Eudragit L100-55 (Acryl EZE) (L100-55) were used as polymeric carriers. The extrudates were further characterised using various physicochemical characterisation techniques to determine the morphology, the drug state within the polymer matrices and the type of drug-polymer interactions. Molecular modelling predicted the existence of two possible H-bonding types while the X-ray photon spectroscopy (XPS) advanced surface analysis of the extrudates revealed intermolecular ionic interactions between the API amino functional groups and the polymer carboxylic groups through the formation of hydrogen bonding. The magnitude of the intermolecular interactions varied according to the drug-polymer miscibility.

MATERIALS
Product Number
Brand
Product Description

Supelco
Diphenhydramine hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Poly(methyl methacrylate-co-methacrylic acid), average Mw ~34,000 by GPC, average Mn ~15,000 by GPC
Supelco
Diphenhydramine hydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material
Diphenhydramine hydrochloride, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Diphenhydramine hydrochloride, ≥98% (HPLC)