Development and Evaluation of Novel Multi-unit Pellet System Formulation of Metoprolol Succinate for Extended Release

Abstract

Metaprolol succinate is a highly water-soluble drug with extensive first-pass metabolism. It needs to be administered about 3-4 times a day for optimum therapeutic effect. Conventional extended-release formulations are available but have their own disadvantages. The study was to designed formulate and evaluate the prolonged-release compressed multiple-unit pellet system (MUPS) of Metoprolol succinate. MUPS are novel formulations with benefits of both single and multi unit dosage forms and can provide extended drug delivery release profile and increase the efficiency profile of the drug. Metaprolol succinate pellets were prepared, coated with a different polymer, and compressed into tablets with suitable excipients. The tablet MUPS disintegrates after ingestion into extended-release pellets. MUPS formulations prepared with polymers like ECN50, Surelease, Kollicoat. Pellets formulation with Kollicoat coating (7.5%) was found to be the best formulation. MUPS prepared using this formulation of pellets and lubritab were found to be most promising formulation with acceptable limits of all physicochemical properties, dissolution profile and stability. Thus from the results, it can concluded that multiple-unit pellet systems (MUPS) can be ideal formulations for drugs like Metaprolol succinate.

Introduction

Metoprolol succinate (MS), a BCS-I class drug, blocks cardiac beta 1-adrenergic receptors and lowers heart rate, a force of contraction and thus the cardiac output.1 Decreasing the renin secretion, aldosterone secretion, other sympathetic activities, and blood angiotensin II level reduces vaso-constriction.2-5 Due to high water solubility and higher permeability, directly – indirectly, it affects the absorption through intestinal tract and undergoes extensive first-pass metabolism and thus only 50% of drug shows bioavailability. After administration in conventional form orally, it shows peak plasma concentration after 1–2 hours and readily eliminated within a 3–4 hours. The frequency of dosing is four times a day and may leads to patient non-compliance.6,7 Literature survey reveals that, there are various formulations developed for metoprolol which includes Mucoadhesive extended-release sustained release tablets8-10 Pellets11,12 Buccal patches.13,14 But none of the methods is developed to prepare and evaluate Metoprolol Succinate extended release Multi Unit Particulate System (MUPS) to overcome tablet defects and resolve poor bioavailability.15,16 The single unit controlled drug release formulations are avoided as sometimes it shows dose dumping. Multiple unit pellet system (MUPS) are compressed tablets containing small coated pellets of Metoprolol succinate which will disintegrate and distributed uniformly from the stomach to the small intestine, release drug for extended period resulting in less localized irritation, uniformity in drug absorption and more bioavailability.17-19 It also helps to avoid dose dumping or poor drug release. Also, it improves patient compliance in both paediatric and geriatric patients.20-25 Hence, the study’s main objective was to formulate and evaluate the prolonged-release compressed multi-unit pellet system (MUPS) of Metoprolol succinate. MUPS-based new drug delivery system that provides extended drug delivery release profile and increases efficiency profile of a drug.

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Materials

Metoprolol succinate was gifted as research sample by Sun Pharmaceutical Industries Ltd.India. Sugar pellets (50-60) and Sucrose Blend was procured from Shiva Shakthi Pharma. Aerosil (Aerosil 200 Pharma) procured from Evonik. HPMC 6cps (Hypromellose) procured from ShinEtsu. Ethylcellulose N50 was procured from Aqualon Hercules. Kollicoat SR 30D and Surelease were procured from Colorcon, Stearic acid was procured from Oleo Chemicals, PEG 6000 was procured from Clarient Chemicals and Isopropyl Alcohol from R.A. Chem Pharma Ltd.

Khobragade, DS, Vighneshwar, K, Potbhare, MS. Development and Evaluation of Novel Multi-unit, Pellet System Formulation of Metoprolol Succinate for Extended Release. International Journal of Drug Delivery Technology.
2022;12(3):1219-1227.