Formulation and in-vitro Evaluation of Extended Release Metformin Hydrochloride Directly Compressible Tablets by Using ULTRAMOD Polymer Premix

Abstract

Aims: Different types of drug release modifying polymers, their grades and quantities have to be optimised in the formulation considering solubility characteristics and biological half-life of the drugs. Further, formulations containing such discrete ingredients processed by conventional, multi-step manufacturing techniques can be a resource-intensive and challenging task for the formulators. This necessitated development of ready-to-use, co-processed polymer premixes.

Methodology: Present study proposed to develop an optimised composition of a polymer premix, ULTRAMOD^TM and evaluate its performance in modifying release of highly water-soluble model drug (BCS Class III) having short biological half-life, metformin hydrochloride. Blend micromeritics and tablet physical properties and performance (in-vitro drug release) were evaluated by pharmacopeial methods.

Results: Such formulations showed excellent flow and compressibility properties, tablet physical properties and drug release compared to the pharmacopeial specifications. These quality attributes and release modifying performance of the polymer premix stored at accelerated stability conditions for 6 months also was unchanged.

Significance: The present research contributes to scientific formulation management by demonstrating how co-processed polymer premixes simplify extended-release tablet design, reduce formulation optimization trials, and enhance manufacturability. ULTRAMOD™ offers a scientifically robust and industrially scalable approach to developing matrix  tablets for highly water-soluble drugs, minimizing batch variability and reducing production cost and time.

Conclusions: Ready-to-use, co-processed polymer premix proved to be an advantageous substitute to conventional polymers. This reduced formula optimisation challenges, manufacturing complexity and promises quick commercialisation.

Introduction

The development of oral drug delivery systems that optimize therapeutic efficacy while enhancing patient compliance has been a significant focus of pharmaceutical research. Among these, modified release formulations have substantial interest, particularly in the management of chronic conditions such as diabetes mellitus, where maintaining consistent drug plasma levels is crucial for effective treatment (Brahmankar and Jaiswal, 2009). Oral drug delivery is the most widely utilized route of administration among all other routes that have been explored for systemic delivery of drugs. The oral route offers advantages such as ease of administration, patient acceptance, and cost-effective manufacturing process (Chein, 1992). The objective of designing modified drug release delivery systems is to reduce the frequency of dosing or to increase the drug’s effectiveness by localization at the site of the action, reducing the dose required, or providing uniform drug delivery (Rajarao and Rohini, 2020). The success of modified release formulations depends largely on the choice of polymer used in the tablet matrix. Polymers control the rate at which the drug is released from the formulation, and selecting the appropriate polymer is critical to achieving the desired release profile (Sousa et al., 2023). Traditional polymers like hydroxypropyl methylcellulose, ethyl cellulose, and carboxymethyl cellulose sodium have been widely used because of their predictable and reliable drug release modifying characteristics (Pockle et al., 2023).

Metformin hydrochloride (Metformin HCl), which is basically used in the treatment of type 2 diabetes, is often formulated in such extended release forms to overcome the limitations such as gastrointestinal side effects, frequent dosing, shorter duration of action associated with its immediate-release counter parts (Lalla, 1991). Metformin HCl popularly formulated into a modified drug release system because it is a highly water-soluble active pharmaceutical ingredient with short half life. Such formulations ensure more stable blood sugar levels, and reduced dosing frequency also, which improves patient adherence (Modi et al., 2011). While previous studies have modified the release of metformin HCl using wet granulation, this method presents significant formulation challenges, including drug-polymer incompatibility during aqueous processing, variability in granule particle size distribution, and prolonged processing time (Roy et al., 2013). Wet granulation often necessitates additional steps such as binder optimization, drying control, and moisture-sensitive stability testing, which complicate scale-up. In contrast, direct compression method using ready-to-use polymer premix eliminates these hurdles by avoiding water exposure, ensuring uniform drug-polymer blending, and streamlining manufacturing are critical advantages for robust extended-release metformin HCl tablets (Takasaki et al., 2015). This research explores the formulation and in vitro evaluation of extended release metformin hydrochloride tablets formulated with ready-to-use co-processed polymer premix.

ULTRAMOD™ is a proprietary polymer blend designed to achieve extended-release formulations. It comprises HPMC and carboxymethyl cellulose sodium, which work synergistically to control the drug release profile. It offers improved flow compressibility and hydration properties, making it suitable for direct compression tablet manufacturing. Its ability to form a consistent gel matrix that modulates drug release effectively. Development of ready-to-use co-processed excipients like ULTRAMOD™ marks a significant advancement in the field of pharmaceutical formulation development and their commercialization. This simplifies tablet manufacturing through its excellent micromeritics, eliminating the need for wet granulation (Takasaki et al., 2015). Use of such excipient offers several advantages, including reduced processing time, lower production costs, and enhanced batch-to-batch consistency (Rowe et al., 2023). ULTRAMOD™ also combines the desirable properties of various traditional polymers, providing a unique matrix that ensures extended drug release while maintaining the mechanical integrity of the tablet. Considering short biological half-life of metformin hydrochloride is 1.5-4.5 hours and high water solubility (>300 mg/mL), it was formulated into matrix type extended-release tablets to reduce the dosage frequency and enhance patient compliance using such novel approach (Van der Merwe et al., 2020). Our study, further proposes to introduce other grades of such co-processed excipient for modifying release of moderate to low soluble drugs also.

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Materials

ULTRAMOD™ polymer premix (release retarding agent) and HiCelTM LP200 MCC-based (binder) were manufactured at SIGACHI® Industries Limited, (Gujarat, India), Colloidal silicon dioxide (glidant) was purchased from Evonik Industries, (Germany). Metformin hydrochloride (API) was purchased from IOL Chemicals and Pharmaceutical Limited, (Punjab, India) and magnesium stearate (lubricant) was purchased from Sunshine Organics Private Limited, (Mumbai, India). Marketed tablet brand Cgmet-500 (metformin hydrochloride extended release tablet 500 mg, B. No. 22230E manufactured by CMG Biotech Private Limited, Himachal Pradesh, India) was purchased from local market. Other chemicals of analytical reagent grade used in this study were sourced locally.

Kulthe, Viraj, Rauf Pathan, and Amit Raj Sinha. 2025. “Formulation and in-Vitro Evaluation of Extended Release Metformin Hydrochloride Directly Compressible Tablets by Using ULTRAMODTM Polymer Premix”. Journal of Pharmaceutical Research International 37 (11):156-65. https://doi.org/10.9734/jpri/2025/v37i117772.

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