Gelatin as Pharmaceutical Excipient

Gelatin is a versatile and widely used ingredient in the pharmaceutical industry, where it serves various critical functions in the formulation and production of pharmaceutical products. This article explores the sources, manufacturing process, and applications of pharmaceutical gelatin, shedding light on its significance in pharmaceuticals.

Pharmaceutical gelatin, like most gelatin types, is primarily derived from collagen-rich tissues of animals. Common sources for pharmaceutical-grade gelatin include porcine (pork skin and bones) and bovine (cowhide and bones). The choice of source depends on factors such as regional availability, cultural preferences, and specific requirements of the pharmaceutical product in question. To ensure purity and compliance with stringent quality standards, gelatin suppliers select high-quality raw materials and adhere to strict processing protocols.

Manufacturing of Gelatin

The manufacturing process of pharmaceutical gelatin is a carefully controlled series of steps, aimed at producing a consistent and high-quality product that meets the exacting standards of the pharmaceutical industry. The key steps in the production of pharmaceutical gelatin include:

Pre-treatment: Raw materials, such as pork skins or cowhide, are first treated to remove impurities, contaminants, and excess fat. This pre-treatment step ensures that the resulting gelatin is of high purity.
Acid or Alkali Treatment: The treated materials are subjected to acid or alkali treatment, which helps in the solubilization of collagen. This step is crucial for breaking down collagen into its constituent amino acids.
Extraction: The extracted collagen is then purified through various processes, including filtration, centrifugation, and precipitation, to remove any remaining impurities.
Drying: The purified gelatin solution is dried to produce the final gelatin product, which is typically available in powder or sheet form.

Function of Gelatin as Excipient

Gelatin finds numerous applications in the pharmaceutical industry due to its unique properties, including its ability to form gels, improve drug stability, enhance drug delivery, and facilitate the encapsulation of active pharmaceutical ingredients (APIs). Some common pharmaceutical applications of gelatin include:

Capsules: Gelatin capsules are widely used to encapsulate both solid and liquid medications. They provide a convenient and efficient way to administer drugs orally.
Coatings: Gelatin coatings are used to protect pharmaceutical tablets from environmental factors, mask unpleasant tastes, and control the release of the drug (e.g. particularly fast in the stomach vs. delayed in the small intestine).
Gel Formulations: Gelatin can be used to create gel-based drug formulations for applications like wound care, dermatological treatments, and ophthalmic solutions.
Vaccines: Gelatin is used as a stabilizing agent in the production of some vaccines, where it helps preserve the integrity of the vaccine during storage and transportation.
Hemostatic Sponges: Gelatin-based hemostatic sponges are used to control bleeding during surgical procedures.

Factors to consider when selecting Gelatin Excipients

When selecting gelatin as an excipient in pharmaceutical formulations, several factors should be carefully considered to ensure that it meets the specific requirements of the drug product. These factors include:

Gelatin Type: The type of gelatin (e.g., Type A, Type B, Type AB, fish gelatin) should be chosen based on its compatibility with the active ingredients and the intended use in the formulation (e.g., hard capsules, soft capsules, gelling agent, film coating).
Source and Purity: The source of gelatin (e.g., porcine, bovine, fish) should be selected with consideration for religious, cultural, and dietary requirements. The gelatin should also meet purity and safety standards to ensure it is free from contaminants and pathogens.
Gel Strength and Viscosity: The gel strength and viscosity of the gelatin should match the requirements of the formulation. Different types and grades of gelatin can have varying gel strengths and viscosities.
Solubility: The solubility of gelatin in the formulation medium (e.g., water, organic solvents) should be assessed to ensure it can dissolve properly and form a uniform solution or suspension.
Compatibility with Active Ingredients: Gelatin should be compatible with the active pharmaceutical ingredients (APIs) and other excipients in the formulation. It should not interact with or degrade the APIs.
Gelatin Concentration: The concentration of gelatin in the formulation should be optimized to achieve the desired product properties, such as capsule strength or film coating thickness.
pH Sensitivity: Some gelatins may be sensitive to changes in pH. It’s essential to choose a gelatin type that is stable within the pH range of the formulation.
Regulatory Requirements: Compliance with regulatory guidelines and quality standards, such as those set by pharmacopeias and health authorities, is crucial. Gelatin should meet established specifications and safety standards.
Allergenic Concerns: Consider potential allergenicity issues related to the gelatin source and take necessary precautions to address them. Some individuals may be allergic to certain types of gelatin.
Religious and Dietary Considerations: If applicable, choose gelatin types that meet religious and dietary requirements, such as halal or kosher gelatin.
Storage and Stability: Consider the storage conditions and shelf-life stability of the gelatin and the final pharmaceutical product. Gelatin should not undergo degradation or changes that affect product quality during storage. Cross-linking in pharmaceutical capsules plays a crucial role in the stability aspect by enhancing the structural integrity of the capsule matrix, ensuring prolonged shelf life, and protecting the pharmaceutical content. The cross-linking of materials increases mechanical strength, leading to improved resistance to environmental factors such as moisture and temperature fluctuations.
Manufacturing Process: Assess the quality and consistency of the gelatin production process, including factors like sanitation, traceability, and control over raw materials.
Safety and Risk Assessment: Evaluate any potential risks associated with gelatin use, such as the risk of transmitting animal diseases (e.g., bovine spongiform encephalopathy) and take measures to mitigate such risks.
Cost Considerations: Consider the cost of the gelatin excipient in relation to the overall manufacturing budget and the economics of the pharmaceutical product.
Supplier Reputation: Choose a reputable and reliable supplier for the gelatin to ensure consistent quality and traceability.

By carefully considering these factors, pharmaceutical manufacturers can select the most suitable gelatin excipient for their specific formulation needs while ensuring product safety, efficacy, and regulatory compliance.

Definitions according to the European Pharmacopeia and USP/NF

The United States Pharmacopeia-National Formulary (USP-NF) and the European Pharmacopoeia (EP) establish monographs and specifications for pharmaceutical-grade gelatin to ensure its quality and safety. These monographs outline the requirements and tests that gelatin must meet to be considered suitable for pharmaceutical use.

USP-NF Monograph for Gelatin:

Gelatin is defined as a protein derived from the partial hydrolysis of collagen, a natural protein found in the connective tissues, bones, and skin of animals, typically cattle and pigs. Gelatin is a versatile excipient used in pharmaceuticals for its gelling and thickening properties. It is also used in the manufacture of gelatin capsules and as a component in various oral and topical pharmaceutical formulations. The USP-NF sets specific standards for the quality, purity, and characteristics of gelatin used in pharmaceutical applications.

EP Monograph for Gelatin:

Gelatin is a protein obtained from collagen, a natural protein present in animal tissues. It is derived from animal by-products, typically from the skin, bones, or connective tissues of animals such as cattle and pigs. Gelatin is characterized by its ability to form gels when dissolved in water and then cooled. It is used as a gelling agent, stabilizer, and coating material in various pharmaceutical and food products.
Gelatine is a vitreous, brittle solid that is faintly yellow to white and nearly tasteless and odourless. It is supplied in various physical forms such as coarse granules, fine powders and leaves.

Gelatin Excipients

Gelatin is commonly used in the pharmaceutical industry for various purposes, including as a coating for capsules and tablets, as a gelling agent in drug formulations, and for other pharmaceutical applications. Different types of gelatin may be used, depending on the specific requirements of the pharmaceutical product. Some of the commonly used gelatins in the pharmaceutical industry include:

Type A Gelatin: This type of gelatin is derived from acid-cured animal collagen, typically from porcine or bovine sources. It is often used in the production of hard gelatin capsules, as it provides a transparent and stable coating for medications.
Type B Gelatin: Type B gelatin is derived from alkali-cured animal collagen and is used in various pharmaceutical applications, including soft gel capsules, as a gelling agent in oral and topical drug formulations, and as a stabilizing agent for suspensions.
Type AB Gelatin: Type AB gelatin is a mixture of type A and type B gelatins, combining their properties to suit specific pharmaceutical formulation requirements.
Hydrolyzed Gelatin: Hydrolyzed gelatin, also known as collagen hydrolysate, is used in various pharmaceutical applications due to its improved solubility and bioavailability. It can be found in formulations like oral supplements and topical products.
Fish Gelatin: In some cases, fish-derived gelatin may be used in pharmaceutical products, particularly for capsules, to address religious or dietary restrictions or allergen concerns associated with mammalian-derived gelatin.
Halal and Kosher Gelatin: Specialized gelatins certified as halal or kosher are used in pharmaceutical products to meet religious dietary requirements.

It’s important to note that the selection of gelatin type in pharmaceutical formulations is based on factors such as compatibility with the active ingredients, stability, and specific requirements, including dietary and cultural considerations. Additionally, manufacturers may need to adhere to regulatory and quality standards when using gelatin in pharmaceutical products to ensure safety and efficacy.

Take a look at the gelatin products by Gelita.

Many thanks to Jessica Pföhler from Gelita for reviewing the article.