Co-processed Hydroxypropyl Methylcellulose – Mannitol as a Directly Compressible Excipient for Controlled Release

Introduction

Controlled release dosage forms deliver an effective dose of the active pharmaceutical ingredient over a prolonged duration, which is particularly advantageous to maintain a constant plasma drug concentration within the therapeutic window. This effectively overcomes the negative peak-trough effects associated with multiple dosing of immediate release formulations. In addition, controlled release formulations also feature significantly in patient-centric pharmaceutical design, given the reduced administration frequency hence improved patient compliance. The most common strategy involves dispersing the active ingredient homogeneously in a hydrophilic polymer matrix, which hydrates and swells upon contact with biological fluids to form a viscous diffusion gel barrier which limits drug release. Hydroxypropyl methylcellulose (HPMC) is among the most widely used excipients as a water-soluble, hydrophilic controlled release matrix. However, standard HPMC powders are associated with flow issues due to their fibrous nature, rendering it unsuitable for tableting via direct compression. In this work, PEARLITOL® CR-H HPMC co-processed with mannitol from Roquette Frères was evaluated based on critical quality attributes necessary for a directly compressible, controlled release excipient. In addition to texturization, mannitol also acts to modulate drug release from the polymer matrix.

Materials and Methods

Co-processed HPMC-mannitol was produced by spray-drying whereby HPMC particles were spray coated with mannitol solution. Particle morphology was assessed via scanning electron microscopy of powder samples sputter-coated with platinum. Moisture content was determined by loss on drying using a moisture analyzer (Ohaus® MB 45, USA). The flow properties of co-processed HPMC–mannitol (PEARLITOL® CR-H) were characterized via angle of repose, bulk/tapped density and flow through a 10 mm orifice measurements (Ph. Eur. Chapter 2.9.16), in comparison to direct compression grade HPMC (METHOCEL™ DC2 K4M, Colorcon, USA) and physical mixtures of HPMC–mannitol. The mannitol used in the physical mixture was PEARLITOL® 100 SD from Roquette Frères. Tabletability was evaluated by compacting 400 mg tablets using a compaction simulator (Styl’One Evolution, Medelpharm, France) following Korsch XL-400 simulation with compaction speeds of 63,000 tablets/hour (30 rpm) and 136,500 tablets/hour (65 rpm). A flat-faced, 11.28 mm tooling set, under external lubrication with magnesium stearate was used. Drug release was evaluated with drugs of differing solubilities, namely propranolol hydrochloride (high solubility, 50 mg/mL) and metformin (very high solubility, 300 mg/mL). The controlled release performance of drug-containing co-processed HPMC–mannitol tablets was benchmarked against corresponding commercial products. Tablet shape and drug content were matched with the marketed formulations Ciplar LA 40 mg (Cipla, India) and Glucophage XR 500 mg (Merck). Dissolution studies were conducted with USP dissolution apparatus II, using a physiologically relevant, pH transition method adapted from USP <711> Dissolution Method A.

Download the full study by Roquette here Co-processed Hydroxypropyl Methylcellulose–Mannitol as a Directly Compressible Excipient for Controlled Release

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Source: Roquette, Presented at the AAPS 2022 PHARMSCI 360, October 16-19, 2022, Boston, MA, https://www.roquette.com/innovation-hub/pharma/technical-illustration/co-processed-hydroxypropyl-methylcellulose,

See also this overview article on PEARLITOL CR-H: