Witepsol E75 is an inert hard fat used as base for drug release from suppositories progesterone.

Witepsol E75 is a hard fat base primarily used in the pharmaceutical and cosmetic industries. It is a type of semi-synthetic fat derived from natural sources, typically used for the production of suppositories, creams, and ointments. Known for its stability, smooth melting profile, and easy handling, Witepsol E75 is a popular choice for creating solid dosage forms and topical products that require a stable, non-reactive base.

Chemical Composition and Structure
Witepsol E75 is composed mainly of triglycerides and partial glycerides of saturated fatty acids, derived from vegetable oils. The formulation is carefully designed to have specific melting points and consistency. Its structure allows it to melt at body temperature, making it ideal for suppositories, while remaining solid at room temperature. This balance between solid and melting properties is crucial for its pharmaceutical applications.

Physical Properties
Witepsol E75 appears as a white, waxy solid at room temperature. It has a smooth texture, melts easily at body temperature, and offers excellent stability across a range of temperatures. Its melting point ranges between 33°C and 35°C. It is non-reactive, odorless, and has a neutral pH, making it suitable for use with a wide range of active ingredients without affecting their stability or effectiveness.

Production Process
Witepsol E75 is produced through the esterification of glycerol with fatty acids derived from natural vegetable oils. The manufacturing process is carefully controlled to ensure the uniformity of the fat composition, which guarantees consistent performance in pharmaceutical and cosmetic applications.

The name defines the structure of the molecule

• "Witepsol" is a trade name for a range of suppository bases made primarily of fatty acid esters and saturated triglycerides.
• "E75" is a specific identifier within the Witepsol product range. It indicates a specific formulation or variant of the product.

Description of raw materials used in production

• Fatty Acids - Mainly derived from vegetable or animal sources.
• Alcohol - Such as ethanol or other fatty alcohols.
• Antioxidants - Added to enhance the stability of the product.

Step-by-step summary of industrial chemical synthesis process.

• Extraction of Fatty Acids - Fatty acids are extracted from vegetable or animal sources.
• Neutralization - The fatty acids are neutralized with a base to form triglycerides.
• Mixing - The triglycerides are mixed with other components to achieve the desired consistency and properties.
• Refinement - The mixture undergoes refinement to remove impurities and achieve a homogeneous product.
• Quality Control - Witepsol E75 is tested to ensure it meets desired specifications.

The quantities normally used are 1.1275 g for 125 mg suppositories, 1.15 g for 250 mg oral medicines (1).

Safety

The only problem with this grease is its oxidation when left in contact with air for a long time. It is therefore necessary to use the drugs that contain it in a short time.

Commercial applications

Suppositories. Witepsol E75 is commonly used as a base for the preparation of pharmaceutical suppositories due to its ability to melt at body temperatures.

Base for Pessaries. Acts as a base for pessaries, often used for vaginal or rectal applications.

Vehicle for Active Ingredients. Used as a vehicle to deliver active ingredients into the body when it melts at body temperature.

Stability. Offers a stable and consistent structure for various medications.

Consistency Modifier. It can be used in conjunction with other ingredients to modify the consistency of pharmaceutical or cosmetic products.

Health and Safety Considerations

Safety in Use
Witepsol E75 is considered safe for use in pharmaceutical and cosmetic products. It is well tolerated by the skin and mucous membranes and has a long history of safe use, particularly in suppository formulations. There are no known significant adverse effects when used as directed.

Allergic Reactions
Allergic reactions to Witepsol E75 are extremely rare. It is derived from vegetable sources and does not contain known allergens, making it safe for most users, even those with sensitive skin.

Toxicity and Carcinogenicity
Witepsol E75 is considered non-toxic and non-carcinogenic. It is used in medical and cosmetic applications without posing any health risks when used at recommended levels. The fats used in its production are generally regarded as safe (GRAS) by regulatory agencies.

Environmental and Safety Considerations
Witepsol E75 is biodegradable and derived from renewable natural sources, making it environmentally friendly. The production and disposal of products containing Witepsol E75 have a minimal environmental impact.

Regulatory Status
Witepsol E75 is approved for use in pharmaceutical and cosmetic products in many regions, including the European Union and the United States. It complies with regulatory standards for purity, safety, and performance, ensuring its suitability for use in both medical and cosmetic formulations.

Studies

Aminolevulinic acid-loaded Witepsol microparticles manufactured using a spray congealing procedure: implications for topical photodynamic therapy.  Al-Kassas R, Donnelly RF, McCarron PA.  J Pharm Pharmacol. 2009 Sep;61(9):1125-35. doi: 10.1211/jpp/61.09.0001.

Preparation and in vitro-in vivo evaluation of Witepsol H35 based self-nanoemulsifying drug delivery systems (SNEDDS) of coenzyme Q(10).
Nepal PR, Han HK, Choi HK.
Eur J Pharm Sci. 2010 Feb 19;39(4):224-32. doi: 10.1016/j.ejps.2009.12.004.

Release property of progesterone from a mixed-base suppository consisting of Witepsol W35 and Witepsol E85.  Iwata M, Komiya S, Nakamura K, Kiuchi M, Andoh N, Hirahara F, Maitani Y, Takayama K.  Drug Dev Ind Pharm. 2001 Nov;27(10):1039-45.

Optimization of the production of solid Witepsol nanoparticles loaded with rosmarinic acid.  Campos DA, Madureira AR, Gomes AM, Sarmento B, Pintado MM.  Colloids Surf B Biointerfaces. 2014 Mar 1;115:109-17. doi: 10.1016/j.colsurfb.2013.10.035

Effect of different bile salts on the relative hypoglycemia of witepsol W35 suppositories containing insulin in diabetic Beagle dogs.  Hosny EA, Al-Shora HI, Elmazar MM.  Drug Dev Ind Pharm. 2001 Sep;27(8):837-45.

Investigation of diazepam lipospheres based on Witepsol and lecithin intended for oral or rectal delivery.  Sznitowska M, Janicki S, Gajewska M, Kulik M.  Acta Pol Pharm. 2000 Jan-Feb;57(1):61-4.

References_____________________________________________________

(1) Ba B, Gaudin K, Désiré A, Phoeung T, Langlois MH, Behl CR, Unowsky J, Patel IH, Malick AW, Gomes M, White N, Kauss T. Ceftriaxone Absorption Enhancement for Noninvasive Administration as an Alternative to Injectable Solutions. Antimicrob Agents Chemother. 2018 Nov 26;62(12):e01170-18. doi: 10.1128/AAC.01170-18. PMID: 30348664; PMCID: PMC6256799.