Quality Assesment and Stability Studies of Metronidazole Tablets Formulations Obtained via Crystallo Co-Agglomeration Technique

Abstract

Stability studies are essential for assessing the quality, safety, and efficacy of pharmaceutical products, ensuring they maintain their properties over time. This study aimed to assess the stability of metronidazole tablets stored in a desiccator with charged silica gel following the International council for harmonization of Technical Requirements for Pharmaceuticals for Human Use guidelines. Metronidazole tablets were formulated from metronidazole co agglomerates using different excipients by direct compression method and stored for 6 and 12 months at 25±2°C/60±5% relative humidity. Quality parameters such as weight variation, diameter, thickness, hardness, friability, content uniformity, and dissolution rate were evaluated at intervals using the United States Pharmacopeia – National Formulary and British Pharmacopeia specifications. The tablets maintained uniformity in weight, diameter, thickness and content over 12 months, meeting pharmacopeial standards. They exhibited high crushing strength, low friability, and consistent disintegration times (<5 min), across formulations and storage durations with no significant changes after storage, indicating stable performance. The sustained high crushing strength, friability ratio (CSFR) and crushing strength, friability, disintegration time (CSFR/Dt) ratios suggested high tablet strength and quality. In-vitro dissolution studies showed release rates of 87.31 – 100.81 %, with a significant decrease at 6 months within pharmacopeial standards but no change at 12 months. Content uniformity was maintained throughout storage. Metronidazole tablets formulated from crystallo co-agglomerates demonstrated good stability and mechanical strength over 12 months of storage. Storage in air-tight containers with desiccants at controlled room temperature (25±2°C) or below their relative humidities is recommended for maintaining tablet quality.

Introduction

Stability studies are crucial for ensuring the quality, safety, and efficacy of pharmaceutical products throughout their shelf life. These studies are conducted according to predefined protocols established by organizations like the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the World Health Organization (WHO). They assess a product’s ability to maintain its properties and characteristics over time (Rencber et al., 2019). A pharmaceutical product is considered stable if it maintains its physical, chemical, microbiological, toxicological, protective, and informational specifications within a specific container/closure system (Panda et al., 2013; Noman et al., 2024). The United States Pharmacopeia (USP) defines stability as the extent to which a product retains its specified characteristics throughout its storage and usage period. Stability testing is conducted throughout various stages of product development to ensure that the product’s characteristics remain unchanged from production until patient use, making it a critical quality indicator (Punam et al., 2014; Rencber et al., 2019).

Stability testing involves assessing the impact of environmental factors such as light, heat, and moisture on the quality of the drug substance or formulated product during storage and use. It helps predict shelf life, determine storage conditions, and guide labeling instructions. Factors influencing pharmaceutical stability are numerous and complex. They include the stability of active ingredients, interactions between ingredients and excipients, manufacturing processes, type of dosage forms, packaging materials, and environmental conditions during handling and storage (Maclean et al., 2022). Chemical reactions like oxidations, reduction, hydrolysis, and degradation reactions can significantly impact stability of a pharmaceutical product, as can physical changes such as alterations in appearance, consistency, and particle size (Narayan and Manupriya, 2019). A pharmaceutical product may experience alterations in its appearance, consistency, content uniformity, clarity (in the case of solutions), moisture content, particle size and shape, pH, and package integrity, all of which can impact its stability.

These changes can result from factors such as impact, vibration, abrasion, and temperature fluctuations, including freezing, thawing, or shearing. Chemical reactions such as solvolysis, oxidation, reduction, and racemization can also occur in pharmaceutical products, leading to the formation of degradation products and a loss of potency in the active pharmaceutical ingredient (API) as well as a reduction in excipient activity, such as antimicrobial preservative action and antioxidant properties (Alfred-Ugbenbo et al., 2017). Additionally, microbiological changes, such as the growth of microorganisms in non-sterile products and alterations in preservative efficacy, can impact the stability of pharmaceutical products (Syukri et al., 2019). Stability testing primarily focuses on evaluating chemical degradation to ensure the safety of the product throughout its shelf life. Accelerated stability studies are commonly used to study chemical degradation, with the data extrapolated for long-term storage predictions (Faisal et al., 2013). Additionally, physical stability must be evaluated to ensure product performance remains unaffected during storage. The stability of a pharmaceutical dosage form refers to its ability to maintain its properties and characteristics over time. It is a critical quality indicator, expressed as shelf life or expiry period, essential for patient safety, drug efficacy, and overall product quality (Costa et al., 2021). Stability studies involve exposing samples to environmental factors like temperature, humidity, and light, with evaluations conducted at various time intervals (Faisal et al., 2013; Syukri et al., 2019).

Stable tablets are expected to maintain their original properties, including size, shape, weight, color, and texture,
under normal handling and storage conditions throughout their shelf life (Alderborn and Frenning, 2017, Salim et al.,
2023). Dosage forms must be evaluated under storage conditions that assess their thermal stability and sensitivity to
moisture, encompassing storage, shipment, and subsequent use (Qiu, 2018).

This study aims to assess the stability of directly compressible metronidazole tablets formulated from crystallo co-agglomerates of metronidazole. Stability parameters such as weight variation, dimensions, hardness, friability, content uniformity, and dissolution were evaluated at 0, 6, and 12 months under controlled temperature and relative humidity conditions.

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Materials

All excipients and chemicals were of pharmaceutical grade and directly obtained from the manufacturers. The tablet excipients included Ludipress® (BASF, Germany), Combilac® (Meggle Group, Megglestrasse, Wasserburg, Germany), Sodium starch glycolate (ATOZ Pharmaceuticals Ltd, Ambaltur, India), Microcrystalline cellulose PH 200 (Avicel®) (Dupont Nutrition Ltd, Ireland), Starlac® (Meggle Group, Megglestrasse, Wasserburg, Germany), Prosolv® (JSR Pharm, GmbH and Co. KG, Rosenberg, Germany), Talc powder (BDH Chemicals Ltd Poole, England), Magnesium stearate (BDH Chemicals Ltd Poole, England), Maize starch (BDH Chemicals Ltd, England). All other solvents and reagents were of analytical grade.

Table 1: Batch Formular for Metronidazole 500 mg tablet prepared using direct compression method

Abdullahi, A. K., Olowosulu, A. K., Allagh, T. S, Quality Assesment and Stability Studies of Metronidazole Tablets Formulations Obtained via Crystallo Co-Agglomeration Technique, ORCID: 0000-0002-8831-6661, FUDMA Journal of Sciences (FJS), Vol. 8 No. 3, June, 2024, pp 81 – 90

Read also our introduction article on “Talc“ here: