Factors Affecting the Stability of Paracetamol in Packaged Tablet and Liquid Formulations and as an Active Pharmaceutical Ingredient (API)


Paracetamol, also known as acetaminophen, is a widely used analgesic and antipyretic medication. It is available in various formulations, including tablets and liquid suspensions, and is commonly used as an active pharmaceutical ingredient (API) in the pharmaceutical industry. Ensuring the stability of paracetamol is crucial to maintain its potency, efficacy, and safety throughout its shelf life. In this article, we will explore the factors that can influence the stability of paracetamol in packaged tablet and liquid formulations, as well as its stability as an API.

Temperature and Humidity

Temperature and humidity are two critical environmental factors that can significantly impact the stability of paracetamol. High temperatures can accelerate chemical degradation processes, leading to the formation of impurities and degradation products. Conversely, low temperatures can slow down degradation but may lead to physical instability, such as crystal growth or agglomeration. Similarly, high humidity levels can increase the likelihood of moisture absorption, resulting in chemical and physical instability. Therefore, it is essential to store paracetamol-containing formulations and APIs under controlled temperature and humidity conditions to maintain their stability.

The recommended storage temperature for paracetamol API is generally between 15°C and 30°C (59°F and 86°F). This temperature range helps to maintain the stability and integrity of the active pharmaceutical ingredient. It is important to avoid exposure to extreme temperatures, such as freezing or excessive heat, as they can potentially degrade the quality of the paracetamol API.

It is crucial to store paracetamol API in a dry place, protected from moisture, and away from direct sunlight. Additionally, it is advisable to follow any specific storage instructions provided by the manufacturer or regulatory guidelines to ensure the optimal stability of the API.

It is worth noting that storage conditions may vary depending on the specific formulation or manufacturer’s recommendations. Therefore, it is always recommended to consult the product labelling or package insert for precise storage instructions for a particular brand or supplier of paracetamol API.

pH and Buffering Capacity

The pH of a formulation can influence the stability of paracetamol. Paracetamol is more stable in slightly acidic to neutral pH ranges. Extreme pH values can accelerate the degradation of paracetamol and lead to the formation of impurities. Buffering agents can be employed to maintain the desired pH and provide stability to paracetamol-containing formulations. Careful selection of buffering agents and their concentrations is crucial to ensure the desired pH range and stability of the product.

The ideal pH for a paracetamol suspension with a concentration of Paracetamol-250mg/5ml is typically slightly acidic to neutral. Paracetamol is generally stable in the pH range of 4 to 7. A pH within this range helps to maintain the stability and integrity of the paracetamol suspension.

To ensure the stability of the paracetamol suspension, it is recommended to conduct compatibility studies and stability testing during the formulation development process. These studies help to assess the impact of pH on the stability, appearance, taste, and other quality attributes of the paracetamol suspension. By conducting appropriate tests, manufacturers can determine the optimal pH range for their specific formulation to maintain the stability and efficacy of the product.

Packaging Material

The choice of packaging material is crucial for maintaining the stability of paracetamol in packaged tablet and liquid formulations. Packaging materials should provide an effective barrier against moisture, oxygen and light. Moisture ingress can lead to hydrolytic degradation and physical instability, while oxygen exposure can promote oxidative degradation. Additionally, exposure to light, especially ultraviolet (UV) light, can accelerate the degradation of paracetamol. Packaging materials with appropriate moisture and light barrier properties, such as blister packs or amber-colored bottles, can help protect paracetamol from degradation and maintain its stability.


Paracetamol is susceptible to oxidation, which can result in the formation of impurities and decrease its stability. Oxidation can occur through exposure to air, especially in liquid formulations. To mitigate oxidation, antioxidant agents can be added to the formulation to scavenge free radicals and inhibit oxidative processes. Commonly used antioxidants include ascorbic acid, sodium bisulfite, and sodium metabisulfite. The selection and concentration of antioxidants should be carefully determined to ensure their compatibility with paracetamol and their effectiveness in maintaining stability.

Light Sensitivity

Paracetamol is sensitive to light, particularly UV light. Exposure to UV radiation can induce photochemical reactions, leading to the degradation of paracetamol and the formation of impurities. Therefore, it is crucial to protect paracetamol-containing formulations from direct sunlight and UV radiation during storage and transportation. Light-resistant packaging, such as amber-coloured containers or coloured or opaque blister packs, can provide the necessary protection against light-induced degradation.

Interaction with Excipients

Paracetamol can interact with excipients used in the formulation of tablets and liquid suspensions, which can impact its stability. Excipients such as binders, disintegrants, lubricants, and surfactants should be carefully selected to ensure compatibility with paracetamol. Incompatibilities can lead to chemical reactions, physical instability, or reduced drug release. Compatibility studies should be conducted to assess the interactions between paracetamol and the excipients to ensure formulation stability.

Manufacturing Process

The manufacturing process can also influence the stability of paracetamol. Factors such as temperature, moisture, and processing time during manufacturing can affect the stability of the API. Proper control of these parameters, adherence to good manufacturing practices (GMP), and appropriate process validation are essential to maintain the stability of paracetamol throughout the manufacturing process.


The stability of paracetamol in packaged tablet and liquid formulations, as well as its stability as an API, is influenced by various factors, including temperature, humidity, pH, packaging materials, oxidation, light sensitivity, excipient interactions, and the manufacturing process. Understanding and mitigating these factors are crucial for maintaining the potency, efficacy, and safety of paracetamol-containing pharmaceutical products. Proper storage conditions, appropriate packaging, careful formulation design and adherence to GMP guidelines are essential to ensure the stability of paracetamol throughout its shelf life.