Granules are an oral solid dosage form that is small, discrete particles or aggregates of particles containing one or more active pharmaceutical ingredients (APIs) and other excipients. Granules offer several advantages in drug formulation. They can improve the flow characteristics of the drug, enhance compressibility, and provide uniform distribution of the API and excipients. Granules are commonly used as intermediates in manufacturing various solid dosage forms such as tablets and capsules.

Protheragen-ING is an expert in pharmaceutical formulation development and dosage form optimization. We can provide you with a one-stop service and can design granule formulations to meet your granule needs based on the characteristics of the API and the development goals of the customer.

Protheragen-ING's Granule Development Services

• Development and optimization of granule formulations - selection of appropriate excipients, determination of optimal granulation methods, and compatibility studies to ensure stability and efficacy.
• CMO development and optimization of manufacturing processes for commercial-scale production of granules - granulation methods, drying techniques, particle size, and other process parameters.
• Design and validate analytical methods for evaluating the content, solubility, and physical properties of granules
• Scale-up and manufacturing to transition from lab-scale production to commercial scale - technology transfer, equipment selection, etc.
• Regulatory support - assistance with documentation, data generation, and compliance with regulatory requirements to help customers successfully navigate the regulatory approval process for their particulate products.

Production Methods for Granule Formulations

Protheragen-ING uses a variety of technologies to produce granules. The choice of method depends on the nature of the drug and the desired characteristics of the final dosage form.

• Direct Tableting

It involves mixing the drug and excipient and pressing them directly into granules without the need for a wet or dry granulation step.

Direct compression is advantageous when the API and excipient have good flowability and compressibility.

• Dry Granulation

It involves the use of pressure or compaction rollers to press the drug and excipients into blocks or ribbons, which are then ground or sieved to obtain granules. It is a technique used when the drug or excipient is moisture or heat-sensitive.

• Wet Granulation

This involves mixing APIs and excipients with a liquid binder to form wet agglomerates, which are then dried and sieved to obtain granules of the desired size.

Advantages include improved flowability, enhanced compressibility and better content uniformity. Suitable for drugs that are heat sensitive or have poor flowability.

Fig. 1 Schematic presentation of the wet granulation process. (Kumar A, et al. 2014)

The Cases for Granules

Several drugs are commonly formulated into granules for oral administration. Here are some examples:

• Antibiotics: Antibiotic drugs such as amoxicillin, cefixime, and azithromycin can be formulated into granules, which are usually used in pediatric formulations to promote accurate dosing and improve palatability.
• Antacids: Antacid drugs such as omeprazole and ranitidine can be formulated as granules, usually used in sachets or packets that can be mixed with water to form an oral suspension.
• Analgesics and anti-inflammatories: Medications such as ibuprofen, naproxen, and diclofenac are usually available in oral granule form and are often used in pediatric preparations or in patients who have difficulty swallowing pills.
• Antihistamines: Antihistamines such as loratadine and cetirizine can be formulated as granules and are usually used in pediatric preparations or for individuals who have difficulty swallowing tablets or capsules.
• Proton pump inhibitors (PPIs): PPI drugs such as pantoprazole and lansoprazole can be formulated as granules and are usually used in delayed-release formulations to prevent degradation of the drug in the acidic environment of the stomach.
• Antidepressants: Antidepressants such as fluoxetine and sertraline can be formulated into granules, typically used in pediatric or geriatric formulations to promote accurate dosing and improve ease of administration.

Contact us today to learn more about our granule development services and how we can support your pharmaceutical product development needs.