Mannitol as Pharmaceutical Excipient

Mannitol is a sugar alcohol commonly used in the pharmaceutical industry for various purposes. It is a white, crystalline powder with a sweet taste and is known for its ability to act as an osmotic diuretic. Mannitol finds applications in pharmaceuticals due to its unique properties, including solubility, stability, and low toxicity. This article will delve into the sources, manufacturing process, and pharmaceutical uses of mannitol, along with pertinent information from the United States Pharmacopeia-National Formulary (USP-NF) and European Pharmacopoeia (EP) monographs.

Manufacturing of Mannitol

Mannitol can be naturally found in a variety of plants, fungi, and bacteria. Common sources include seaweed, fruits like apples, and certain types of mushrooms. However, for pharmaceutical purposes, mannitol is often commercially produced through chemical synthesis.

The industrial manufacturing of mannitol typically involves the hydrogenation of fructose or glucose. The process begins with the catalytic hydrogenation of glucose to sorbitol, which is then further hydrogenated to yield mannitol. The resulting product is then purified and crystallized to obtain the desired pharmaceutical-grade mannitol.

Function of Mannitol as Excipients

Mannitol is a sugar alcohol commonly used in pharmacy for various purposes. Some of its important functions include:

• Osmotic Diuretic: Mannitol is often used as an osmotic diuretic in medical settings. When administered intravenously, it increases the osmotic pressure of the glomerular filtrate, leading to increased urine production. This can be beneficial in the treatment of conditions such as cerebral edema and acute kidney injury.
• Reducing Intraocular Pressure: Mannitol is employed to reduce intraocular pressure in certain eye conditions, particularly in the treatment of glaucoma and before intraocular surgery. Its osmotic properties help draw fluid out of the eye, reducing pressure.
• Intravascular Volume Expansion: In some medical situations, mannitol is used to expand intravascular volume. It works by drawing fluid from the interstitial space into the vascular system, helping to increase blood volume.
• Excipient in Pharmaceuticals: Mannitol is widely used as an excipient in the pharmaceutical industry. It serves as a bulking agent, diluent, and sweetening agent in various oral dosage forms, including tablets, capsules, and powders.
• Stabilizing Agent: Mannitol is used as a stabilizing agent for certain drugs, particularly proteins and peptides. It helps prevent denaturation and aggregation of these substances, maintaining their stability during storage.
• Inhalation Therapy: In respiratory medicine, mannitol can be used as an inhalation powder to diagnose and manage conditions such as asthma. It is known as a bronchoconstrictor challenge agent.
• Cryoprotectant: Mannitol is employed as a cryoprotectant in the preservation of certain biological materials, such as cells and tissues. It helps prevent damage during freezing and thawing processes.
• Diagnostics: Mannitol is sometimes used in diagnostic tests, particularly in renal function studies. Its ability to increase urine production makes it useful in assessing kidney function.
• Sugar Substitute: Mannitol is also used as a sugar substitute in some sugar-free or reduced-calorie products. It has a sweet taste but is not metabolized in the same way as sugar, making it suitable for individuals with diabetes.

Factors to consider when selecting Mannitol Excipients

When selecting a mannitol excipient, several factors should be considered, including:

• Dosage Form: Consider the specific dosage form you are developing (e.g., tablet, capsule, powder, or liquid). Mannitol is versatile and can be used in various formulations, but its properties may be better suited for certain forms over others.
• Physical and Chemical Properties: Assess the physical and chemical properties of mannitol, including its particle size, crystalline structure, and solubility. These properties can impact the formulation’s flowability, compressibility, and dissolution characteristics.
• Compatibility with Active Ingredients: Evaluate the compatibility of mannitol with the active pharmaceutical ingredient (API) and other excipients in the formulation. Ensure that mannitol does not interact adversely with the drug substance.
• Stability: Consider the stability of the formulation over time. Mannitol can act as a stabilizing agent for certain drugs, but it’s essential to assess its impact on the long-term stability of the entire formulation.
• Manufacturability: Assess the ease of manufacturing with mannitol. Consider its flow properties during processing, compressibility for tableting, and other factors that may affect the efficiency of the manufacturing process.
• Dose Uniformity: Evaluate how well mannitol contributes to dose uniformity within the formulation. It should facilitate the uniform distribution of the active ingredient throughout the dosage form.
• Taste and Palatability: If the dosage form is intended for oral administration, consider the taste and palatability of mannitol. It is often used as a sweetening agent, but excessive amounts may impact the overall taste.
• Regulatory Considerations: Ensure that mannitol complies with regulatory standards and requirements for pharmaceutical excipients. Consider any limitations or restrictions on its use in certain regions or for specific applications.
• Patient Factors: Consider the target patient population and any specific requirements or preferences they may have. For example, if the formulation is for pediatric use, factors like taste and ease of administration become particularly important.
• Cost Considerations: Assess the cost-effectiveness of using mannitol in the formulation. Consider the overall cost of production and how it may impact the final pricing of the pharmaceutical product.
• Specialized Properties: Mannitol has unique properties, such as its ability to act as a bulking agent and its low hygroscopicity. Consider whether these properties align with the desired characteristics of the final dosage form.

By carefully considering these factors, formulators can make informed decisions about the use of mannitol as an excipient, ensuring that it contributes positively to the overall quality and performance of the pharmaceutical product.

Definitions according to the European Pharmacopeia and USP/NF

The United States Pharmacopeia-National Formulary (USP-NF) and the European Pharmacopoeia (EP) have established standards for mannitol to ensure their quality and safety in pharmaceutical applications.

USP-NF Monograph for Mannitol:

• CAS Number: 69-65-8
• Description:  The USP-NF monograph for Mannitol provides specifications for its identity, purity, and strength. The monograph includes tests and acceptance criteria to ensure compliance with pharmaceutical standards.

EP Monograph for Mannitol:

• CAS Number: 69-65-8
• Description: The EP monograph for Mannitol outlines similar specifications for identity, purity, and strength. It aligns with international pharmaceutical standards and facilitates global harmonization.

Mannitol Excipients

Mannitol, a sugar alcohol (polyol), finds extensive use in the pharmaceutical industry due to its unique properties and diverse applications. Here is a list of some common uses of mannitol in the pharmaceutical field:

• Excipient in Tablet Formulations: Mannitol is frequently employed as an excipient in tablet formulations. It serves as a diluent and a filler, contributing to the physical properties of the tablet, such as hardness and disintegration.
• Osmotic Diuretic: Mannitol is used as an osmotic diuretic in medical settings, particularly for the reduction of intracranial pressure and the prevention of acute renal failure. Its osmotic properties promote the removal of excess fluid from tissues.
• Lyoprotectant for Proteins and Vaccines: Mannitol is utilized as a lyoprotectant in the freeze-drying (lyophilization) process of pharmaceuticals, especially for proteins and vaccines. It helps maintain the stability and activity of these sensitive compounds during storage.
• Diagnostic Imaging Agent: In radiology, mannitol can be used as a contrast agent in certain imaging studies. It is employed to enhance visualization in procedures like magnetic resonance imaging (MRI) and computed tomography (CT) scans.
• Pulmonary Drug Delivery: Mannitol is sometimes utilized in inhalable formulations for respiratory conditions. It can be incorporated into dry powder inhalers to improve drug dispersion and lung deposition.
• Oral Care Products: Mannitol is found in some oral care products, such as sugar-free chewing gum and lozenges. Its sweet taste and sugar-like properties make it a suitable sugar substitute.
• Diagnostics and Testing: Mannitol can be used in certain diagnostic tests, such as the Mannitol Salt Agar test, which is employed for the selective isolation of Staphylococcus aureus bacteria.
• Wound Care Products: Mannitol may be included in certain wound care products, contributing to the formulation of gels or creams used in the treatment of burns or skin injuries.

Mannitol Excipients on pharmaexcipients.com – in alphabetical order

Products	Manufacturer
D(-)-Mannitol EMPROVE® EXPERT Ph Eur,BP,USP,JP	Merck KGaA
Parteck® Delta M (Mannitol) EMPROVE ESSENTIAL Ph Eur,BP,USP,JP,E 421	Merck KGaA
Parteck® M DPI EMPROVE EXPERT Ph Eur,BP,JP,USP,E 421	Merck KGaA
Parteck® M 100 (Mannitol) EMPROVE ESSENTIAL Ph Eur,BP,JP,USP,E 421	Merck KGaA
Parteck® M 200 (Mannitol) EMPROVE ESSENTIAL Ph Eur,BP,JP,USP,E 421	Merck KGaA
PEARLITOL® CR-H	Roquette
PEARLITOL® Flash	Roquette
PEARLITOL® PF (Mannitol PFG)	Roquette
PEARLITOL® SW-F 200	Roquette
PEARLITOL® 25 C (Mannitol 25)	Roquette
PEARLITOL® 50 C (Mannitol 35)	Roquette
PEARLITOL® 110 C	Roquette
PEARLITOL® 160 C (Mannitol 60)	Roquette
PEARLITOL® 300 DC	Roquette
PEARLITOL® 400 DC	Roquette
PEARLITOL® 500 DC	Roquette
PEARLITOL® 200 GT	Roquette
PEARLITOL® 100 SD	Roquette
PEARLITOL® 150 SD	Roquette
PEARLITOL® 200 SD	Roquette
Mannitol Spheres SANAQ®	Pharmatrans SANAQ

 

Mannitol’s role in the pharmaceutical industry as a versatile excipient underscores its significance in drug formulation. With defined standards provided by the USP-NF and EP monographs, mannitol continues to be a reliable and indispensable component in the development of pharmaceutical products. As technology advances and industry standards evolve, mannitol’s applications are likely to expand, further cementing its place in the realm of pharmaceutical science and medicine.