Stearic acid and high molecular weight PEO as matrix for the highly water soluble metoprolol tartrate in continuous twin-screw melt granulation

Abstract

Granules with release-sustaining properties were developed by twin screw hot melt granulation (HMG) using a combination of stearic acid (SA) and high molecular weight polyethylene oxide (PEO) as matrix for a highly water soluble model drug, metoprolol tartrate (MPT). Earlier studies demonstrated that mixing molten SA and PEO resulted in hydrogen bond formation between hydroxyl groups of fatty acid molecules and ether groups in PEO chains. These molecular interactions might be beneficial in order to elevate the sustained release effect of drugs from a SA/PEO matrix. This study aims to investigate the continuous twin screw melt granulation technique to study the impact of a SA/PEO matrix on the dissolution rate of a highly water soluble drug (MPT). Decreasing the SA/PEO ratio improved the release-sustaining properties of the matrix. The solid state of the granules was characterized using differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared (FTIR) and near infrared chemical imaging (NIR-CI) in order to understand the dissolution behavior. The results revealed a preferential interaction of the MPT molecules with stearic acid impeding the PEO to form hydrogen bonds with the stearic acid chains. However, this allowed the PEO chains to recrystallize inside the stearic acid matrix after granulation, hence, elevating the release-sustaining characteristics of the formulation.

Twin-Screw Melt Granulation for Oral Solid Pharmaceutical Products

“…The use of a molten binder avoids the challenge of drying these hydrophilic polymers after wet granulation. Some examples of this formulation approach are: zolpidem tartrate with HPMC K4M or PVP as a rate-controlling polymer and PEG 6000 as a meltable binder using the benchtop heat and mix method followed by sieving and compression [ 159 ], lovastatin granulated with HPMC K4M and PEG 6000 as a binder using HSMG [ 160 ], TSMG of metoprolol hydrochloride with stearic acid and PEO WSR N12K [ 72 ], and verapamil hydrochloride which was TSMG with either Compritol 888 or Precirol with HPMC K4M or PEO 1M [ 54 ]. Melt granules have been blended with another matrix forming excipient and tableted, for example, tenofovir and Gelucire melt granules were combined with HPMC or chitosan to make mucoadhesive tablets with a 7 day release for HIV prophylaxis [ 62 ].…”

An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part II

“…Monteyne et al [59] developed metoprolol tartrate (MPT) granules via TSMG by employing stearic acid (SA) and SentryPolyox ® WSR N12K (PEO; M.W 1,000,000 g). The TSMG process was carried at 60°C, except for the last segment, at a screw speed of 150 RPM.…”

Experimento Didático De Quimiometria Para O Mapeamento De Pellets Farmacêuticos Utilizando Espectroscopia De Imagem Na Região Do Infravermelho Próximo E Resolução Multivariada De Curvas Com Mínimos Quadrados Alternantes: Um Tutorial, Parte Iv

“…25,[40][41][42][43][44][45] O que se propõe então, nesse tutorial, é apresentar uma opção para o ensino desses tópicos em disciplinas experimentais de Química Analítica, baseando-se em experiências bem-sucedidas no Instituto de Química da Unicamp.…”